Abstract:
The present invention relates to compounds of Formula I, or a pharmaceutically acceptable salt, ester, or prodrug, thereof: 
     
       
                 
         
             
             
         
       
     
     which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
       [0001]    This application claims benefit of U.S. provisional application 60/914,175 filed on Apr. 26, 2007, the entire contents of which is herein incorporated by reference. 
     
    
     TECHNICAL FIELD 
       [0002]    The present invention relates to novel hydroxyamic peptides having activity against the hepatitis C virus (HCV) and useful in the treatment of HCV infections. More particularly, the invention relates to hydroxyamic peptide compounds, compositions containing such compounds and methods for using the same, as well as processes for making such compounds. 
       BACKGROUND OF THE INVENTION 
       [0003]    HCV is the principal cause of non-A, non-B hepatitis and is an increasingly severe public health problem both in the developed and developing world. It is estimated that the virus infects over 200 million people worldwide, surpassing the number of individuals infected with the human immunodeficiency virus (HIV) by nearly five fold. HCV infected patients, due to the high percentage of individuals inflicted with chronic infections, are at an elevated risk of developing cirrhosis of the liver, subsequent hepatocellular carcinoma and terminal liver disease. HCV is the most prevalent cause of hepatocellular cancer and cause of patients requiring liver transplantations in the western world. 
         [0004]    There are considerable barriers to the development of anti-HCV therapeutics, which include, but are not limited to, the persistence of the virus, the genetic diversity of the virus during replication in the host, the high incident rate of the virus developing drug-resistant mutants, and the lack of reproducible infectious culture systems and small-animal models for HCV replication and pathogenesis. In a majority of cases, given the mild course of the infection and the complex biology of the liver, careful consideration must be given to antiviral drugs, which are likely to have significant side effects. 
         [0005]    Only two approved therapies for HCV infection are currently available. The original treatment regimen generally involves a 3-12 month course of intravenous interferon-α (IFN-α), while a new approved second-generation treatment involves co-treatment with IFN-α and the general antiviral nucleoside mimics like ribavirin. Both of these treatments suffer from interferon related side effects as well as low efficacy against HCV infections. There exists a need for the development of effective antiviral agents for treatment of HCV infection due to the poor tolerability and disappointing efficacy of existing therapies. 
         [0006]    In a patient population where the majority of individuals are chronically infected and asymptomatic and the prognoses are unknown, an effective drug would desirably possess significantly fewer side effects than the currently available treatments. The hepatitis C non-structural protein-3 (NS3) is a proteolytic enzyme required for processing of the viral polyprotein and consequently viral replication. Despite the huge number of viral variants associated with HCV infection, the active site of the NS3 protease remains highly conserved thus making its inhibition an attractive mode of intervention. Recent success in the treatment of HIV with protease inhibitors supports the concept that the inhibition of NS3 is a key target in the battle against HCV. 
         [0007]    HCV is a flaviridae type RNA virus. The HCV genome is enveloped and contains a single strand RNA molecule composed of circa 9600 base pairs. It encodes a polypeptide comprised of approximately 3010 amino acids. 
         [0008]    The HCV polyprotein is processed by viral and host peptidase into 10 discreet peptides which serve a variety of functions. There are three structural proteins, C, E1 and E2. The P7 protein is of unknown function and is comprised of a highly variable sequence. There are six non-structural proteins. NS2 is a zinc-dependent metalloproteinase that functions in conjunction with a portion of the NS3 protein. NS3 incorporates two catalytic functions (separate from its association with NS2): a serine protease at the N-terminal end, which requires NS4A as a cofactor, and an ATP-ase-dependent helicase function at the carboxyl terminus. NS4A is a tightly associated but non-covalent cofactor of the serine protease. 
         [0009]    The NS3.4A protease is responsible for cleaving four sites on the viral polyprotein. The NS3-NS4A cleavage is autocatalytic, occurring in cis. The remaining three hydrolyses, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B all occur in trans. NS3 is a serine protease which is structurally classified as a chymotrypsin-like protease. While the NS serine protease possesses proteolytic activity by itself, the HCV protease enzyme is not an efficient enzyme in terms of catalyzing polyprotein cleavage. It has been shown that a central hydrophobic region of the NS4A protein is required for this enhancement. The complex formation of the NS3 protein with NS4A seems necessary to the processing events, enhancing the proteolytic efficacy at all of the sites. 
         [0010]    A general strategy for the development of antiviral agents is to inactivate virally encoded enzymes, including NS3, that are essential for the replication of the virus. Current efforts directed toward the discovery of NS3 protease inhibitors were reviewed by S. Tan, A. Pause, Y. Shi, N. Sonenberg, Hepatitis C Therapeutics: Current Status and Emerging Strategies,  Nature Rev. Drug Discov.  1, 867-881 (2002). Other patent disclosures describing the synthesis of HCV protease inhibitors are: WO 2006/007700; US 2005/0261200; WO 2004/113365; WO 03/099274 (2003); US 2003/0008828; US2002/0037998 (2002); WO 00/59929 (2000); WO 00/09543 (2000); WO 99/50230 (1999); U.S. Pat. No. 5,861,297 (1999); WO 99/07733 (1999). 
       SUMMARY OF THE INVENTION 
       [0011]    The present invention relates to novel hydroxyamic peptide compounds and methods of treating a hepatitis C infection in a subject in need of such therapy with said hydroxyamic peptide compounds. The present invention further relates to pharmaceutical compositions comprising the compounds of the present invention, or pharmaceutically acceptable salts, esters, or prodrugs thereof, in combination with a pharmaceutically acceptable carrier or excipient. 
         [0012]    In one embodiment of the present invention there are disclosed compounds represented by Formulas I, or pharmaceutically acceptable salts, esters, or prodrugs thereof: 
         [0000]    
       
                 
         
             
             
         
       
     
       Wherein 
       [0000]    
       
         
           
             A is O or NH; 
             R and R′ are independently selected from the group consisting of: 
             (i) —C 1 -C 8  alkyl, —C 2 -C 8  alkenyl, or —C 2 -C 8  alkynyl containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N; substituted —C 1 -C 8  alkyl, substituted —C 2 -C 8  alkenyl, or substituted —C 2 -C 8  alkynyl containing 0, 1, 2, or 3 heteroatoms selected from O, S or N; —C 3 -C 12  cycloalkyl, or substituted —C 3 -C 12  cycloalkyl; —C 4 -C 12  alkylcycloalkyl, or substituted —C 4 -C 12  alkylcycloalkyl; —C 3 -C 12  cycloalkenyl, or substituted —C 3 -C 12  cycloalkenyl; —C 4 -C 12  alkylcycloalkenyl, or substituted —C 4 -C 12  alkylcycloalkenyl; 
             (ii) aryl; substituted aryl; heteroaryl; substituted heteroaryl; 
             (iii) heterocycloalkyl or substituted heterocycloalkyl; 
             (iv) hydrogen; deuterium; 
             L 1  is absent, and R 101  is selected from H or R 1 ; 
             or L 1  is selected from —(C═O)—, —(C═NH)—, —SO 2 —, or —SO—; and R 101  is selected from OR 1 , —NHR 1 , or —N(R 1 )R 2 ; 
             R 1  is selected from the group consisting of: 
             (i) aryl; substituted aryl; heteroaryl; substituted heteroaryl; 
             (ii) heterocycloalkyl or substituted heterocycloalkyl; 
             (iii) —C 1 -C 8  alkyl, —C 2 -C 8  alkenyl, or —C 2 -C 8  alkynyl containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N; substituted —C 1 -C 8  alkyl, substituted —C 2 -C 8  alkenyl, or substituted —C 2 -C 8  alkynyl containing 0, 1, 2, or 3 heteroatoms selected from O, S or N; —C 3 -C 12  cycloalkyl, or substituted —C 3 -C 12  cycloalkyl; —C 3 -C 12  cycloalkenyl, or substituted —C 3 -C 12  cycloalkenyl; the representative substitutents include, but are not limited to: hydroxyl, halo, —O—C 1 -C 6  alkyl, —S—C 1 -C 6  alkyl, —SO—C 1 -C 6  alkyl, —SO 2 —C 1 -C 6  alkyl, —O-aryl or substituted —O-aryl, —S-aryl, or substituted —S-aryl, —SO-aryl or substituted —SO-aryl, —SO 2 -aryl or substituted —SO 2 -aryl. 
             R 2  is selected from the group consisting of: 
             (i) aryl; substituted aryl; heteroaryl; substituted heteroaryl; 
             (ii) heterocycloalkyl or substituted heterocycloalkyl; 
             (iii) —C 1 -C 8  alkyl, —C 2 -C 8  alkenyl, or —C 2 -C 8  alkynyl containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N; substituted —C 1 -C 8  alkyl, substituted —C 2 -C 8  alkenyl, or substituted —C 2 -C 8  alkynyl containing 0, 1, 2, or 3 heteroatoms selected from O, S or N; —C 3 -C 12  cycloalkyl, or substituted —C 3 -C 12  cycloalkyl; —C 3 -C 12  cycloalkenyl, or substituted —C 3 -C 12  cycloalkenyl; 
             alternatively, R 1  and R 2  taken together with the atom to which they are attached form cyclic moiety consisting of: substituted or unsubstituted cycloalkyl, cycloalkenyl, or heterocylic; substituted or unsubstituted cycloalkenyl, or heterocylic; 
             L 2  is absent, and R 102  is selected from H or R 1 ; 
             or L 2  is selected from —(C═O)—, —(C═NH)—, —SO 2 —, or —SO—; and R 102  is selected from OR 1 , —NHR 1 , or —N(R 1 )R 2 ; wherein R 1  and R 2  are as previously defined; 
             X is absent or is selected from the group consisting of: 
             (1) oxygen; 
             (2) sulfur; 
             (3) NH or NR 1 ; where R 1  is as previously defined above; 
             Y is absent or is selected from the group consisting of: 
             (i) —C 1 -C 6  alkyl containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N, optionally substituted with one or more substituent selected from halogen, aryl, substituted aryl, heteroaryl, or substituted heteroaryl; 
             (ii) —C 2 -C 6  alkenyl containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N, optionally substituted with one or more substituent selected from halogen, aryl, substituted aryl, heteroaryl, or substituted heteroaryl; 
             (iii) —C 2 -C 6  alkynyl containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N, optionally substituted with one or more substituent selected from halogen, aryl, substituted aryl, heteroaryl, or substituted heteroaryl; 
             (iv) —C 3 -C 12  cycloalkyl, substituted —C 3 -C 12  cycloalkyl, heterocycloalkyl, substituted heterocycloalkyl; 
             (v) —(C═O)N(R 1 )—, —(C═NH)N(R 1 )—, —(C═O)O—, —S(O) 2  N(R 1 )—, —(C═O)—, —(C═NH)—, —S(O) 2 —; where R 1  is as previously defined above; 
             Z is selected from aryl, substituted aryl, heteroaryl, substituted heteroaryl; 
             Alternatively, Y and Z taken together form the group selected from: 
           
         
       
     
         [0000]    
       
                 
         
             
             
         
       
       
         
           
             
               
                 U is selected from O, S, or NH; 
                 R 301 , R 302 , R 303  and R 304  are each independently selected from H or substitutents as defined in the section of Definitions; 
                 p is 0 or 1; 
               
             
             G is selected from —OH, —NHS(O) 2 —R 3 , —NH(SO 2 )NR 4 R 5 ; 
             R 3  is selected from: 
             (i) aryl; substituted aryl; heteroaryl; substituted heteroaryl; 
             (ii) heterocycloalkyl or substituted heterocycloalkyl; 
             (iii) —C 1 -C 8  alkyl, —C 2 -C 8  alkenyl, or —C 2 -C 8  alkynyl containing 0, 1, 2, or 3 heteroatoms selected from O, S or N, substituted —C 1 -C 8  alkyl, substituted —C 2 -C 8  alkenyl, or substituted —C 2 -C 8  alkynyl containing 0, 1, 2, or 3 heteroatoms selected from O, S or N; —C 3 -C 12  cycloalkyl, or substituted —C 3 -C 12  cycloalkyl; —C 3 -C 12  cycloalkenyl, or substituted —C 3 -C 12  cycloalkenyl; 
             R 4  and R 5  are independently selected from: 
             (i) hydrogen; 
             (ii) aryl; substituted aryl; heteroaryl; substituted heteroaryl; 
             (iii) heterocycloalkyl or substituted heterocycloalkyl; 
             (iv) —C 1 -C 8  alkyl, —C 2 -C 8  alkenyl, or —C 2 -C 8  alkynyl containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N; substituted —C 1 -C 8  alkyl, substituted —C 2 -C 8  alkenyl, or substituted —C 2 -C 8  alkynyl containing 0, 1, 2, or 3 heteroatoms selected from O, S or N; —C 3 -C 12  cycloalkyl, or substituted —C 3 -C 12  cycloalkyl; —C 3 -C 12  cycloalkenyl, or substituted —C 3 -C 12  cycloalkenyl;
           alternatively, R 4  and R 5  taken together with the atom to which they are attached form cyclic moiety consisting of: substituted or unsubstituted cycloalkyl, cycloalkenyl, or heterocylic; substituted or unsubstituted cycloalkenyl, or heterocylic;   
         
             m=0, 1, or 2; 
             m′=1 or 2. 
           
         
       
     
     
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0060]    A first embodiment of the invention is a compound represented by Formula I as described above, or a pharmaceutically acceptable salt, ester or prodrug thereof, alone or in combination with a pharmaceutically acceptable carrier or excipient. 
         [0061]    A second embodiment of the invention is a compound represented by Formula II, or a pharmaceutically acceptable salt, ester or prodrug thereof, alone or in combination with a pharmaceutically acceptable carrier or excipient. 
         [0062]    Representative subgenera of the invention include, but are not limited to: 
         [0063]    A compound of Formula II: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0064]    wherein R 101 , L 1 , R 102 , L 2 , R, X, Y, Z and G are as previously defined. 
         [0065]    A compound of Formula III: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0066]    wherein R 301 , R 302 , R 303  and R 304  are each independently selected from H or substitutents as defined in the section of Definitions; R 401  is selected from H, aryl, substituted aryl, heteroaryl, substituted heteroaryl or substitutents as defined in the section of Definitions; wherein R 101 , L 1 , R 102 , L 2 , R and G are as previously defined. 
         [0067]    A compound of Formula IV: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0068]    wherein R 301 , R 302 , R 303  and R 304  are each independently selected from H or substitutents as defined in the section of Definitions; R 401  is selected from H, aryl, substituted aryl, heteroaryl, substituted heteroaryl or substitutents as defined in the section of Definitions; wherein R 101 , L 1 , R 102 , L 2 , R and G are as previously defined. 
         [0069]    A compound of Formula V: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0070]    wherein R 301 , R 302 , R 303  and R 304  are each independently selected from H or substitutents as defined in the section of Definitions; wherein R 101 , L 1 , R 102 , L 2 , R and G are as previously defined. 
         [0071]    Representative compounds of the invention include, but are not limited to, the following compounds (Table 1) according to Formula VI: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    Wherein R 501 , R 502 , R, Q and G are delineated for each example in Table 1: 
         [0000]    
       
         
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 1 
               
               
                   
                   
               
               
                   
                 Example# 
                 R 501   
                 R 502   
                 R 
                 Q 
                 G 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 1. 
                 H 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 2. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 3 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 4 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 5. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 6. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 7. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 8. 
                 H 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 9. 
                 H 
                 H 
                 tert-Butyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 10. 
                 H 
                 H 
                 Ethyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 11. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 12. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 13. 
                 H 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 14. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 15. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 16. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 17. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 18. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 19. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 20. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 21. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 22. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 23. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 24. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 25. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 26. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 27. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 28. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 29. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 30. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 31. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 32. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 33. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 34. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 35. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 36. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 37. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 38. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 39. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 40. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 41. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 42. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 43. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 44. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 45. 
                 H 
                 H 
                 tert-Butyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 46. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 47. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 48. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 49 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 50. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 51. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 52. 
                 H 
                 H 
                 Ethyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 53. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 Ethyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 54. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 55. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 56. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 57. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 58. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 59. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 60. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 61. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 62. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 63. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 64. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 65. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 66. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 67. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 68. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 69. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 70. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 71. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 72. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 73. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 74. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 75. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 76. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 77. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 78. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 79. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 80. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 81. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 82. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 83. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 84. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 85. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 86. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 87. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 88. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 89. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 90. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 91. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 92. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 93. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 94. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 95. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 96. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 97. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 98. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 99. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 100. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 101. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 102. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 103. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 104. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 105. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 106. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 107. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 108. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 109. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 110. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 111. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 112. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 113. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 114. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 115. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 116. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 117. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 118. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 119. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 120. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 121. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 122. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 123. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 124. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 125. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 126. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 127. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 128. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 129. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 130. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 131. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 132. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 133. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 134. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 135. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 136. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 137. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 138. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 Ethyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 139. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 140. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 141. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 142. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 143. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 144. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 145. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 146. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 147. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 148. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 149. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 150. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 151. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 152. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 153. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 154. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 155. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 156. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 157. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 158. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 159. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 160. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 161. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 162. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 163. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 164. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 165. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 166. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 167. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 168. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 169. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 170. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 171. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 172. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 173. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 174. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 175. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 176. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 177. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 178. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 179. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 180. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 181. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 182. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 183. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 184. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 185. 
                 H 
                 H 
                 tert-Butyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 186. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 187. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 188. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 189. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 190. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 191. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 192. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 193. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 194. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 195. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 196. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 197. 
                 H 
                 H 
                 Ethyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 198. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 Ethyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 199. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 200. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 201. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 202. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 203. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 204. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 205. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 206. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 207. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 208. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 209. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 210. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 211. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 212. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 213. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 214. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 215. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 216. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 217. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 218. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 219. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 220. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 221. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 222. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 223. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 224. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 225. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 226. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 227. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 228. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 229. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 230. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 231. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 232. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 233. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 234. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 235. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 236. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 237. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 238. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 239. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 240. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 241. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 242. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 243. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 244. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 245. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 246. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 247. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 248. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 249. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 250. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 251. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 252. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 253. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 254. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 255. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 256. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 257. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 258. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 259. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 260. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 261. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 262. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 263. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 264. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 265. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 266. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 267. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 268. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 269. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 270. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 271. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 272. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 273. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
                   
               
               
                   
                 274. 
                 H 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 275. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 276. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 277. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 278. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 279. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 280. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 281. 
                 H 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 282. 
                 H 
                 H 
                 tert-Butyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 283. 
                 H 
                 H 
                 Ethyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 284. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 285. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                   
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 286. 
                 H 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 287. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 288. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 289. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 290. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 291. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 292. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 293. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 294. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 295. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 296. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 297. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 298. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 299. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 300. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 301. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 302. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 303. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 304. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 305. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 306. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 307. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 308. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 309. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 310. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 311. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 312. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 313. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 314. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 315. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 316. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 317. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 318. 
                 H 
                 H 
                 tert-Butyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 319. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 320. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 321. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 322. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 323. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 324. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 325. 
                 H 
                 H 
                 Ethyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 326. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 Ethyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 327. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 328. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 329. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 330. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 331. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 332. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 333. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 334. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 335. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 336. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 337. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 338. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 339. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 340. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 341. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 342. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 343. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 344. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 345. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 346. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 347. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 348. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 349. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 350. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 351. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 352. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 353. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 354. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 355. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 356. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 357. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 358. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 359. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 360. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 361. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 362. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 363. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Proply 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 364. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 365. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 366. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 367. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 368. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 369. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 370. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 371. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 372. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 373. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 374. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 375. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 376. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 377. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 378. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 379. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 380. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 381. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 382. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 383. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 384. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 385. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 386. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 387. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 388. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 389. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 390. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 391. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 392. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 393. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 394. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 395. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 396. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 397. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 398. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 399. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 400. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 401. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 402. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 403. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 404. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 405. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 406. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 407. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 408. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 409. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 410. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 411. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 Ethyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 412. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 413. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 414. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 415. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 416. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 417. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 418. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 419. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 420. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 421. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 422. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 423. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 424. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 425. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 426. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 427. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 428. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 429. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 430. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 431. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 432. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 433. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 434. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 435. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 436. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 437. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 438. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 439. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 440. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 441. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 442. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 443. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 444. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 445. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 446. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 447. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 448. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 449. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 450. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 451. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 452. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 453. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 454. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 455. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 456. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 457. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 458. 
                 H 
                 H 
                 tert-Butyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 459. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 460. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 461. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 462. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 463. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 464. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 465. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 466. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 467. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 468. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 469. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 470. 
                 H 
                 H 
                 Ethyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 471. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 Ethyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 472. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 473. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 474. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 475. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 476. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 477. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 478. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 479. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 480. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 481. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 482. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 483. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 484. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 485. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 486. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 487. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 488. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 489. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 490. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 491. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 492. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 493. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 494. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 495. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 496. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 497. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 498. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 499. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 500. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 501. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 502. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 503. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 504. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 505. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 506. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 507. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 508. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 509. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 510. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 511. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 512. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 513. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 514. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 515. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 516. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 517. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 518. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 519. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 520. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 521. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 522. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 523. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 524. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 525. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 526. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 527. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 528. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 529. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 530. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 531. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 532. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 533. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 534. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 535. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 536. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 537. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 538. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 539. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 540. 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 541. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 542. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 543. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 544. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 545. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
               
                   
                 546. 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 iso- Propyl 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OH 
               
               
                   
                   
               
             
          
         
       
     
         [0072]    According to one embodiment, the pharmaceutical compositions of the present invention may further contain other anti-HCV agents. Examples of anti-HCV agents include, but are not limited to, α-interferon, β-interferon, ribavirin, and amantadine. For further details see S. Tan, A. Pause, Y. Shi, N. Sonenberg, Hepatitis C Therapeutics: Current Status and Emerging Strategies,  Nature Rev. Drug Discov.,  1, 867-881 (2002); WO 00/59929 (2000); WO 99/07733 (1999); WO 00/09543 (2000); WO 99/50230 (1999); U.S. Pat. No. 5,861,297 (1999); and US2002/0037998 (2002) which are herein incorporated by reference in their entirety. 
         [0073]    According to one embodiment, the pharmaceutical compositions of the present invention may further contain other HCV protease inhibitors. 
         [0074]    According to another embodiment, the pharmaceutical compositions of the present invention may further comprise inhibitor(s) of other targets in the HCV life cycle, including, but not limited to, helicase, polymerase, metalloprotease, and internal ribosome entry site (IRES). 
         [0075]    According to another embodiment, the present invention includes methods of treating hepatitis C infections in a subject in need of such treatment by administering to said subject an anti-HCV virally effective amount or an inhibitory amount of the pharmaceutical compositions of the present invention. 
         [0076]    An additional embodiment of the present invention includes methods of treating biological samples by contacting the biological samples with the compounds of the present invention. 
         [0077]    Yet a further aspect of the present invention is a process of making any of the compounds delineated herein employing any of the synthetic means delineated herein. 
       DEFINITIONS 
       [0078]    Listed below are definitions of various terms used to describe this invention. These definitions apply to the terms as they are used throughout this specification and claims, unless otherwise limited in specific instances, either individually or as part of a larger group. 
         [0079]    The term “C 1 -C 6  alkyl,” or “C 1 -C 8  alkyl,” as used herein, refer to saturated, straight- or branched-chain hydrocarbon radicals containing between one and six, or one and eight carbon atoms, respectively. Examples of C 1 -C 6  alkyl radicals include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, neopentyl, n-hexyl radicals; and examples of C 1 -C 8  alkyl radicals include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, neopentyl, n-hexyl, heptyl, octyl radicals. 
         [0080]    The term “C 2 -C 6  alkenyl,” or “C 2 -C 8  alkenyl,” as used herein, denote a monovalent group derived from a hydrocarbon moiety containing from two to six, or two to eight carbon atoms having at least one carbon-carbon double bond by the removal of a single hydrogen atom. Alkenyl groups include, but are not limited to, for example, ethenyl, propenyl, butenyl, 1-methyl-2-buten-1-yl, heptenyl, octenyl and the like. 
         [0081]    The term “C 2 -C 6  alkynyl,” or “C 2 -C 8  alkynyl,” as used herein, denote a monovalent group derived from a hydrocarbon moiety containing from two to six, or two to eight carbon atoms having at least one carbon-carbon triple bond by the removal of a single hydrogen atom. Representative alkynyl groups include, but are not limited to, for example, ethynyl, 1-propynyl, 1-butynyl, heptynyl, octynyl and the like. 
         [0082]    The term “C 3 -C 8 -cycloalkyl”, or “C 3 -C 12 -cycloalkyl,” as used herein, denotes a monovalent group derived from a monocyclic or polycyclic saturated carbocyclic ring compound by the removal of a single hydrogen atom, respectively. Examples of C 3 -C 8 -cycloalkyl include, but not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopentyl and cyclooctyl; and examples of C 3 -C 12 -cycloalkyl include, but not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo [2.2.1] heptyl, and bicyclo [2.2.2] octyl. 
         [0083]    The term “C 3 -C 8 -cycloalkenyl”, or “C 3 -C 12 -cycloalkenyl” as used herein, denote a monovalent group derived from a monocyclic or polycyclic carbocyclic ring compound having at least one carbon-carbon double bond by the removal of a single hydrogen atom. Examples of C 3 -C 8 -cycloalkenyl include, but not limited to, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, and the like; and examples of C 3 -C 12 -cycloalkenyl include, but not limited to, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, and the like. 
         [0084]    The term “aryl,” as used herein, refers to a mono- or bicyclic carbocyclic ring system having one or two aromatic rings including, but not limited to, phenyl, naphthyl, tetrahydronaphthyl, indanyl, idenyl and the like. 
         [0085]    The term “arylalkyl,” as used herein, refers to a C 1 -C 3  alkyl or C 1 -C 6  alkyl residue attached to an aryl ring. Examples include, but are not limited to, benzyl, phenethyl and the like. 
         [0086]    The term “heteroaryl,” as used herein, refers to a mono- or polycyclic (e.g., bi-, or tri-cyclic or more) fused or non-fused, aromatic radical or ring having from five to ten ring atoms of which one or more ring atom is selected from, for example, S, O and N; zero, one or two ring atoms are additional heteroatoms independently selected from, for example, S, O and N; and the remaining ring atoms are carbon, wherein any N or S contained within the ring may be optionally oxidized. Heteroaryl includes, but is not limited to, pyridinyl, pyrazinyl, pyrimidinyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isooxazolyl, thiadiazolyl, oxadiazolyl, thiophenyl, furanyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzooxazolyl, quinoxalinyl, and the like. 
         [0087]    The term “heteroarylalkyl,” as used herein, refers to a C 1 -C 3  alkyl or C 1 -C 6  alkyl residue attached to a heteroaryl ring. Examples include, but are not limited to, pyridinylmethyl, pyrimidinylethyl and the like. 
         [0088]    The term “heterocycloalkyl,” as used herein, refers to a non-aromatic 3-, 4-, 5-, 6- or 7-membered ring or a bi- or tri-cyclic group fused system, where (i) each ring contains between one and three heteroatoms independently selected from oxygen, sulfur and nitrogen, (ii) each 5-membered ring has 0 to 1 double bonds and each 6-membered ring has 0 to 2 double bonds, (iii) the nitrogen and sulfur heteroatoms may optionally be oxidized, (iv) the nitrogen heteroatom may optionally be quaternized, and (iv) any of the above rings may be fused to a benzene ring. Representative heterocycloalkyl groups include, but are not limited to, [1,3]dioxolane, pyrrolidinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, piperidinyl, piperazinyl, oxazolidinyl, isoxazolidinyl, morpholinyl, thiazolidinyl, isothiazolidinyl, and tetrahydrofuryl. 
         [0089]    The terms “substituted”, “substituted C 1 -C 6  alkyl,” “substituted C 1 -C 8  alkyl,” “substituted C 2 -C 6  alkenyl,” “substituted C 2 -C 8  alkenyl,” “substituted C 2 -C 6  alkynyl”, “substituted C 2 -C 8  alkynyl”, “substituted C 3 -C 12  cycloalkyl,” “substituted C 3 -C 8  cycloalkenyl,” “substituted C 3 -C 12  cycloalkenyl,” “substituted aryl”, “substituted heteroaryl,” “substituted arylalkyl”, “substituted heteroarylalkyl,” “substituted heterocycloalkyl,” as used herein, refer to CH, NH, C 1 -C 6  alkyl, C 1 -C 8  alkyl, C 2 -C 6  alkenyl, C 2 -C 8  alkenyl, C 2 -C 6  alkynyl, C 2 -C 8  alkynyl, C 3 -C 12  cycloalkyl, C 3 -C 8  cycloalkenyl, C 3 -C 12  cycloalkenyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocycloalkyl groups as previously defined, substituted by independent replacement of one, two, or three or more of the hydrogen atoms thereon with substituents including, but not limited to, —F, —Cl, —Br, —I, —OH, protected hydroxy, —NO 2 , —CN, —NH 2 , protected amino, —NH—C 1 -C 12 -alkyl, —NH—C 2 -C 12 -alkenyl, —NH—C 2 -C 12 -alkenyl, —NH—C 3 -C 12 -cycloalkyl, —NH-aryl, —NH-heteroaryl, —NH-heterocycloalkyl, -dialkylamino, —diarylamino, -diheteroarylamino, —O—C 1 -C 12 -alkyl, —O—C 2 -C 12 -alkenyl, —O—C 2 -C 12 -alkenyl, —O—C 3 -C 12 -cycloalkyl, —O-aryl, —O-heteroaryl, —O-heterocycloalkyl, —C(O)—C 1 -C 12 -alkyl, —C(O)—C 2 -C 12 -alkenyl, —C(O)—C 2 -C 12 -alkenyl, —C(O)—C 3 -C 12 -cycloalkyl, —C(O)-aryl, —C(O)-heteroaryl, —C(O)-heterocycloalkyl, —CONH 2 , —CONH—C 1 -C 12 -alkyl, —CONH—C 2 -C 12 -alkenyl, —CONH—C 2 -C 12 -alkenyl, —CONH—C 3 -C 12 -cycloalkyl, —CONH-aryl, —CONH-heteroaryl, —CONH-heterocycloalkyl, —OCO 2 —C 1 -C 12 -alkyl, —OCO 2 —C 2 -C 12 -alkenyl, —OCO 2 —C 2 -C 12 -alkenyl, —OCO 2 —C 3 -C 12 -cycloalkyl, —OCO 2 -aryl, —OCO 2 -heteroaryl, —OCO 2 -heterocycloalkyl, —OCONH 2 , —OCONH—C 1 -C 12 -alkyl, —OCONH—C 2 -C 12 -alkenyl, —OCONH—C 2 -C 12 -alkenyl, —OCONH—C 3 -C 12 -cycloalkyl, —OCONH— aryl, —OCONH-heteroaryl, —OCONH— heterocycloalkyl, —NHC(O)—C 1 -C 12 -alkyl, —NHC(O)—C 2 -C 12 -alkenyl, —NHC(O)—C 2 -C 12 -alkenyl, —NHC(O)—C 3 -C 12 -cycloalkyl, —NHC(O)-aryl, —NHC(O)-heteroaryl, —NHC(O)-heterocycloalkyl, —NHCO 2 —C 1 -C 12 -alkyl, —NHCO 2 —C 2 -C 12 -alkenyl, —NHCO 2 —C 2 -C 12 -alkenyl, —NHCO 2 —C 3 -C 12 -cycloalkyl, —NHCO 2 — aryl, —NHCO 2 -heteroaryl, —NHCO 2 — heterocycloalkyl, —NHC(O)NH 2 , —NHC(O)NH—C 1 -C 12 -alkyl, —NHC(O)NH—C 2 -C 12 -alkenyl, —NHC(O)NH—C 2 -C 12 -alkenyl, —NHC(O)NH—C 3 -C 12 -cycloalkyl, —NHC(O)NH-aryl, —NHC(O)NH-heteroaryl, —NHC(O)NH-heterocycloalkyl, NHC(S)NH 2 , —NHC(S)NH—C 1 -C 12 -alkyl, —NHC(S)NH—C 2 -C 12 -alkenyl, —NHC(S)NH—C 2 -C 12 -alkenyl, —NHC(S)NH—C 3 -C 12 -cycloalkyl, —NHC(S)NH-aryl, —NHC(S)NH-heteroaryl, —NHC(S)NH-heterocycloalkyl, —NHC(NH)NH 2 , —NHC(NH)NH—C 1 -C 12 -alkyl, —NHC(NH)NH—C 2 -C 12 -alkenyl, —NHC(NH)NH—C 2 -C 12 -alkenyl, —NHC(NH)NH—C 3 -C 12 -cycloalkyl, —NHC(NH)NH-aryl, —NHC(NH)NH-heteroaryl, —NHC(NH)NH-heterocycloalkyl, —NHC(NH)—C 1 -C 12 -alkyl, —NHC(NH)—C 2 -C 12 -alkenyl, —NHC(NH)—C 2 -C 12 -alkenyl, —NHC(NH)—C 3 -C 12 -cycloalkyl, —NHC(NH)-aryl, —NHC(NH)-heteroaryl, —NHC(NH)-heterocycloalkyl, —C(NH)NH—C 1 -C 12 -alkyl, —C(NH)NH—C 2 -C 12 -alkenyl, —C(NH)NH—C 2 -C 12 -alkenyl, —C(NH)NH—C 3 -C 12 -cycloalkyl, —C(NH)NH-aryl, —C(NH)NH-heteroaryl, —C(NH)NH-heterocycloalkyl, —S(O)—C 1 -C 12 -alkyl, —S(O)—C 2 -C 12 -alkenyl, —S(O)—C 2 -C 12 -alkenyl, —S(O)—C 3 -C 12 -cycloalkyl, —S(O)-aryl, —S(O)-heteroaryl, —S(O)-heterocycloalkyl —SO 2 NH 2 , —SO 2 NH—C 1 -C 12 -alkyl, —SO 2 NH—C 2 -C 12 -alkenyl, —SO 2 NH—C 2 -C 12 -alkenyl, —SO 2 NH—C 3 -C 12 -cycloalkyl, —SO 2 NH— aryl, —SO 2 NH— heteroaryl, —SO 2 NH-heterocycloalkyl, —NHSO 2 —C 1 -C 12 -alkyl, —NHSO 2 —C 2 -C 12 -alkenyl, —NHSO 2 —C 2 -C 12 -alkenyl, —NHSO 2 —C 3 -C 12 -cycloalkyl, —NHSO 2 -aryl, —NHSO 2 -heteroaryl, —NHSO 2 -heterocycloalkyl, —CH 2 NH 2 , —CH 2 SO 2 CH 3 , -aryl, -arylalkyl, -heteroaryl, -heteroarylalkyl, -heterocycloalkyl, —C 3 -C 12 -cycloalkyl, polyalkoxyalkyl, polyalkoxy, -methoxymethoxy, -methoxyethoxy, —SH, —S—C 1 -C 12 -alkyl, —S—C 2 -C 12 -alkenyl, —S—C 2 -C 12 -alkenyl, —S—C 3 -C 12 -cycloalkyl, —S-aryl, —S-heteroaryl, —S-heterocycloalkyl, or methylthiomethyl. It is understood that the aryls, heteroaryls, alkyls, and the like can be further substituted. 
         [0090]    In accordance with the invention, any of the aryls, substituted aryls, heteroaryls and substituted heteroaryls described herein, can be any aromatic group. Aromatic groups can be substituted or unsubstituted. 
         [0091]    It is understood that any alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl moiety described herein can also be an aliphatic group, an alicyclic group or a heterocyclic group. An “aliphatic group” is non-aromatic moiety that may contain any combination of carbon atoms, hydrogen atoms, halogen atoms, oxygen, nitrogen or other atoms, and optionally contain one or more units of unsaturation, e.g., double and/or triple bonds. An aliphatic group may be straight chained, branched or cyclic and preferably contains between about 1 and about 24 carbon atoms, more typically between about 1 and about 12 carbon atoms. In addition to aliphatic hydrocarbon groups, aliphatic groups include, for example, polyalkoxyalkyls, such as polyalkylene glycols, polyamines, and polyimines, for example. Such aliphatic groups may be further substituted. It is understood that aliphatic groups may be used in place of the alkyl, alkenyl, alkynyl, alkylene, alkenylene, and alkynylene groups described herein. 
         [0092]    The term “alicyclic,” as used herein, denotes a monovalent group derived from a monocyclic or polycyclic saturated carbocyclic ring compound by the removal of a single hydrogen atom. Examples include, but not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo [2.2.1] heptyl, and bicyclo [2.2.2] octyl. Such alicyclic groups may be further substituted. 
         [0093]    The terms “halo” and “halogen,” as used herein, refer to an atom selected from fluorine, chlorine, bromine and iodine. 
         [0094]    The compounds described herein contain one or more asymmetric centers and thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that may be defined, in terms of absolute stereochemistry, as (R)- or (S)-, or as (D)- or (L)- for amino acids. The present invention is meant to include all such possible isomers, as well as their racemic and optically pure forms. Optical isomers may be prepared from their respective optically active precursors by the procedures described above, or by resolving the racemic mixtures. The resolution can be carried out in the presence of a resolving agent, by chromatography or by repeated crystallization or by some combination of these techniques which are known to those skilled in the art. Further details regarding resolutions can be found in Jacques, et al.,  Enantiomers, Racemates, and Resolutions  (John Wiley &amp; Sons, 1981). When the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, and unless specified otherwise, it is intended that the compounds include both E and Z geometric isomers. Likewise, all tautomeric forms are also intended to be included. The configuration of any carbon-carbon double bond appearing herein is selected for convenience only and is not intended to designate a particular configuration unless the text so states; thus a carbon-carbon double bond depicted arbitrarily herein as trans may be cis, trans, or a mixture of the two in any proportion. 
         [0095]    The term “subject” as used herein refers to a mammal. A subject therefore refers to, for example, dogs, cats, horses, cows, pigs, guinea pigs, and the like. Preferably the subject is a human. When the subject is a human, the subject may be referred to herein as a patient. 
         [0096]    As used herein, the term “pharmaceutically acceptable salt” refers to those salts of the compounds formed by the process of the present invention which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, S. M. Berge, et al. describes pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 66: 1-19 (1977). The salts can be prepared in situ during the final isolation and purification of the compounds of the invention, or separately by reacting the free base function with a suitable organic acid. Examples of pharmaceutically acceptable include, but are not limited to, nontoxic acid addition salts are salts of an amino group formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid or with organic acids such as acetic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid or by using other methods used in the art such as ion exchange. Other pharmaceutically acceptable salts include, but are not limited to, adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate salts, and the like. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, alkyl having from 1 to 6 carbon atoms, sulfonate and aryl sulfonate. 
         [0097]    As used herein, the term “pharmaceutically acceptable ester” refers to esters of the compounds formed by the process of the present invention which hydrolyze in vivo and include those that break down readily in the human body to leave the parent compound or a salt thereof. Suitable ester groups include, for example, those derived from pharmaceutically acceptable aliphatic carboxylic acids, particularly alkanoic, alkenoic, cycloalkanoic and alkanedioic acids, in which each alkyl or alkenyl moiety advantageously has not more than 6 carbon atoms. Examples of particular esters include, but are not limited to, formates, acetates, propionates, butyrates, acrylates and ethylsuccinates. 
         [0098]    The term “pharmaceutically acceptable prodrugs” as used herein refers to those prodrugs of the compounds formed by the process of the present invention which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals with undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit/risk ratio, and effective for their intended use, as well as the zwitterionic forms, where possible, of the compounds of the present invention. “Prodrug”, as used herein means a compound which is convertible in vivo by metabolic means (e.g. by hydrolysis) to afford any compound delineated by the formulae of the instant invention. Various forms of prodrugs are known in the art, for example, as discussed in Bundgaard, (ed.), Design of Prodrugs, Elsevier (1985); Widder, et al. (ed.), Methods in Enzymology, vol. 4, Academic Press (1985); Krogsgaard-Larsen, et al., (ed). “Design and Application of Prodrugs, Textbook of Drug Design and Development, Chapter 5, 113-191 (1991); Bundgaard, et al., Journal of Drug Deliver Reviews, 8: 1-38 (1992); Bundgaard, J. of Pharmaceutical Sciences, 77:285 et seq. (1988); Higuchi and Stella (eds.) Prodrugs as Novel Drug Delivery Systems, American Chemical Society (1975); and Bernard Testa &amp; Joachim Mayer, “Hydrolysis In Drug And Prodrug Metabolism: Chemistry, Biochemistry And Enzymology,” John Wiley and Sons, Ltd. (2002). 
         [0099]    Combinations of substituents and variables envisioned by this invention are only those that result in the formation of stable compounds. The term “stable”, as used herein, refers to compounds which possess stability sufficient to allow manufacture and which maintains the integrity of the compound for a sufficient period of time to be useful for the purposes detailed herein (e.g., therapeutic or prophylactic administration to a subject). 
         [0100]    The synthesized compounds can be separated from a reaction mixture and further purified by a method such as column chromatography, high pressure liquid chromatography, or recrystallization. As can be appreciated by the skilled artisan, further methods of synthesizing the compounds of the formulae herein will be evident to those of ordinary skill in the art. Additionally, the various synthetic steps may be performed in an alternate sequence or order to give the desired compounds. In addition, the solvents, temperatures, reaction durations, etc. delineated herein are for purposes of illustration only and one of ordinary skill in the art will recognize that variation of the reaction conditions can produce the desired bridged macrocyclic products of the present invention. Synthetic chemistry transformations and protecting group methodologies (protection and deprotection) useful in synthesizing the compounds described herein are known in the art and include, for example, those such as described in R. Larock,  Comprehensive Organic Transformations , VCH Publishers (1989); T. W. Greene and P. G. M. Wuts,  Protective Groups in Organic Synthesis,  2d. Ed., John Wiley and Sons (1991); L. Fieser and M. Fieser,  Fieser and Fieser&#39;s Reagents for Organic Synthesis , John Wiley and Sons (1994); and L. Paquette, ed.,  Encyclopedia of Reagents for Organic Synthesis , John Wiley and Sons (1995). 
         [0101]    The compounds of this invention may be modified by appending various functionalities via any synthetic means delineated herein to enhance selective biological properties. Such modifications are known in the art and include those which increase biological penetration into a given biological system (e.g., blood, lymphatic system, central nervous system), increase oral availability, increase solubility to allow administration by injection, alter metabolism and alter rate of excretion. 
       Pharmaceutical Compositions 
       [0102]    The pharmaceutical compositions of the present invention comprise a therapeutically effective amount of a compound of the present invention formulated together with one or more pharmaceutically acceptable carriers. As used herein, the term “pharmaceutically acceptable carrier” means a non-toxic, inert solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type. Some examples of materials which can serve as pharmaceutically acceptable carriers are sugars such as lactose, glucose and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil; safflower oil; sesame oil; olive oil; corn oil and soybean oil; glycols; such a propylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer&#39;s solution; ethyl alcohol, and phosphate buffer solutions, as well as other non-toxic compatible lubricants such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, releasing agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the composition, according to the judgment of the formulator. The pharmaceutical compositions of this invention can be administered to humans and other animals orally, rectally, parenterally, intracisternally, intravaginally, intraperitoneally, topically (as by powders, ointments, or drops), buccally, or as an oral or nasal spray. 
         [0103]    Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents. 
         [0104]    Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution, suspension or emulsion in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer&#39;s solution, U.S.P. and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid are used in the preparation of injectables. 
         [0105]    The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use. 
         [0106]    In order to prolong the effect of a drug, it is often desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle. Injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycolide. Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions which are compatible with body tissues. 
         [0107]    Compositions for rectal or vaginal administration are preferably suppositories which can be prepared by mixing the compounds of this invention with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol or a suppository wax which are solid at ambient temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound. 
         [0108]    Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. 
         [0109]    The active compounds can also be in micro-encapsulated form with one or more excipients as noted above. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings, release controlling coatings and other coatings well known in the pharmaceutical formulating art. In such solid dosage forms the active compound may be admixed with at least one inert diluent such as sucrose, lactose or starch. Such dosage forms may also comprise, as is normal practice, additional substances other than inert diluents, e.g., tableting lubricants and other tableting aids such a magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions which can be used include polymeric substances and waxes. 
         [0110]    Dosage forms for topical or transdermal administration of a compound of this invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or patches. The active component is admixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives or buffers as may be required. Ophthalmic formulation, ear drops, eye ointments, powders and solutions are also contemplated as being within the scope of this invention. 
         [0111]    The ointments, pastes, creams and gels may contain, in addition to an active compound of this invention, excipients such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof. 
         [0112]    Powders and sprays can contain, in addition to the compounds of this invention, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances. Sprays can additionally contain customary propellants such as chlorofluorohydrocarbons. 
         [0113]    Transdermal patches have the added advantage of providing controlled delivery of a compound to the body. Such dosage forms can be made by dissolving or dispensing the compound in the proper medium. Absorption enhancers can also be used to increase the flux of the compound across the skin. The rate can be controlled by either providing a rate controlling membrane or by dispersing the compound in a polymer matrix or gel. 
       Antiviral Activity 
       [0114]    An inhibitory amount or dose of the compounds of the present invention may range from about 0.1 mg/Kg to about 500 mg/Kg, alternatively from about 1 to about 50 mg/Kg. Inhibitory amounts or doses will also vary depending on route of administration, as well as the possibility of co-usage with other agents. 
         [0115]    According to the methods of treatment of the present invention, viral infections are treated or prevented in a subject such as a human or lower mammal by administering to the subject an anti-hepatitis C virally effective amount or an inhibitory amount of a compound of the present invention, in such amounts and for such time as is necessary to achieve the desired result. An additional method of the present invention is the treatment of biological samples with an inhibitory amount of a compound of composition of the present invention in such amounts and for such time as is necessary to achieve the desired result. 
         [0116]    The term “anti-hepatitis C virally effective amount” of a compound of the invention, as used herein, mean a sufficient amount of the compound so as to decrease the viral load in a biological sample or in a subject. As well understood in the medical arts, an anti-hepatitis C virally effective amount of a compound of this invention will be at a reasonable benefit/risk ratio applicable to any medical treatment. 
         [0117]    The term “inhibitory amount” of a compound of the present invention means a sufficient amount to decrease the hepatitis C viral load in a biological sample or a subject. It is understood that when said inhibitory amount of a compound of the present invention is administered to a subject it will be at a reasonable benefit/risk ratio applicable to any medical treatment as determined by a physician. The term “biological sample(s),” as used herein, means a substance of biological origin intended for administration to a subject. Examples of biological samples include, but are not limited to, blood and components thereof such as plasma, platelets, subpopulations of blood cells and the like; organs such as kidney, liver, heart, lung, and the like; sperm and ova; bone marrow and components thereof, or stem cells. Thus, another embodiment of the present invention is a method of treating a biological sample by contacting said biological sample with an inhibitory amount of a compound or pharmaceutical composition of the present invention. 
         [0118]    Upon improvement of a subject&#39;s condition, a maintenance dose of a compound, composition or combination of this invention may be administered, if necessary. Subsequently, the dosage or frequency of administration, or both, may be reduced, as a function of the symptoms, to a level at which the improved condition is retained when the symptoms have been alleviated to the desired level, treatment should cease. The subject may, however, require intermittent treatment on a long-term basis upon any recurrence of disease symptoms. 
         [0119]    It will be understood, however, that the total daily usage of the compounds and compositions of the present invention will be decided by the attending physician within the scope of sound medical judgment. The specific inhibitory dose for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; the activity of the specific compound employed; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed; and like factors well known in the medical arts. 
         [0120]    The total daily inhibitory dose of the compounds of this invention administered to a subject in single or in divided doses can be in amounts, for example, from 0.01 to 50 mg/kg body weight or more usually from 0.1 to 25 mg/kg body weight. Single dose compositions may contain such amounts or submultiples thereof to make up the daily dose. In general, treatment regimens according to the present invention comprise administration to a patient in need of such treatment from about 10 mg to about 1000 mg of the compound(s) of this invention per day in single or multiple doses. 
         [0121]    In yet another embodiment, the compounds of the invention may be used for the treatment of HCV in humans in monotherapy mode or in a combination therapy (e.g., dual combination, triple combination etc.) mode such as, for example, in combination with antiviral and/or immunomodulatory agents. Examples of such antiviral and/or immunomodulatory agents include Ribavirin (from Schering-Plough Corporation, Madison, N.J.) and Levovirin (from ICN Pharmaceuticals, Costa Mesa, Calif.), VP 50406 (from Viropharma, Incorporated, Exton, Pa.), ISIS14803 (from ISIS Pharmaceuticals, Carlsbad, Calif.), Heptazyme™ (from Ribozyme Pharmaceuticals, Boulder, Colo.), VX 497, and Teleprevir (VX-950) (both from Vertex Pharmaceuticals, Cambridge, Mass.), Thymosin™ (from SciClone Pharmaceuticals, San Mateo, Calif.), Maxamine™ (Maxim Pharmaceuticals, San Diego, Calif.), mycophenolate mofetil (from Hoffman-LaRoche, Nutley, N.J.), interferon (such as, for example, interferon-alpha, PEG-interferon alpha conjugates) and the like. “PEG-interferon alpha conjugates” are interferon alpha molecules covalently attached to a PEG molecule. Illustrative PEG-interferon alpha conjugates include interferon alpha-2a (Roferon™, from Hoffman La-Roche, Nutley, N.J.) in the form of pegylated interferon alpha-2a (e.g., as sold under the trade name Pegasys™), interferon alpha-2b (Intron™, from Schering-Plough Corporation) in the form of pegylated interferon alpha-2b (e.g., as sold under the trade name PEG-Intron™), interferon alpha-2c (BILB 1941, BILN 2061 and Berofor Alpha™, (all from Boehringer Ingelheim, Ingelheim, Germany), consensus interferon as defined by determination of a consensus sequence of naturally occurring interferon alphas (Infergen™, from Amgen, Thousand Oaks, Calif.). Other suitable anti-HCV agents for use in combination with the present invention include but are not limited to: Yeast-core-NS3 vaccine, Envelope Vaccine, A-837093 (Abbott Pharmaceuticals), AG0121541 (Pfizer), GS9132 (Gilead); HCV-796 (Viropharma), ITMN-191 (Intermune), JTK 003/109 (Japan Tobacco Inc.), Lamivudine (EPIVIR) (Glaxo Smith Kline), MK-608 (Merck), R803 (Rigel), ZADAXIN (SciClone Pharmaceuticals); Valopicitabine (Idenix), VGX-410C (Viralgenomix), R1626 (Hoffman La-Roche), and SCH-503034 (Schering Plough Corporation). 
         [0122]    Unless otherwise defined, all technical and scientific terms used herein are accorded the meaning commonly known to one with ordinary skill in the art. All publications, patents, published patent applications, and other references mentioned herein are hereby incorporated by reference in their entirety. 
       ABBREVIATIONS 
       [0123]    Abbreviations which have been used in the descriptions of the schemes and the examples that follow are:
       ACN for acetonitrile;   BML for 2-mercaptoethanol;   BOP for benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate;   COD for cyclooctadiene;   DAST for diethylaminosulfur trifluoride;   DABCYL for 6-(N-4′-carboxy-4-(dimethylamino)azobenzene)-aminohexyl-1-O-(2-cyanoethyl)-(N,N-diisopropyl)-phosphoramidite;   DCM for dichloromethane;   DIAD for diisopropyl azodicarboxylate;   DIBAL-H for diisobutylaluminum hydride;   DIPEA for diisopropyl ethylamine;   DMAP for N,N-dimethylaminopyridine;   DME for ethylene glycol dimethyl ether;   DMEM for Dulbecco&#39;s Modified Eagles Media;   DMF for N,N-dimethyl formamide;   DMSO for dimethylsulfoxide;   DUPHOS for       
 
         [0000]    
       
                 
         
             
             
         
       
       
         
           
             EDANS for 5-(2-Amino-ethylamino)-naphthalene-1′-sulfonic acid; 
             EDCI or EDC for 1-(3-diethylaminopropyl)-3-ethylcarbodiimide hydrochloride; 
             EtOAc for ethyl acetate; 
             HATU for O (7-Azabenzotriazole-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate; 
             Hoveyda&#39;s Cat. for Dichloro(o-isopropoxyphenylmethylene) (tricyclohexylphosphine)ruthenium(II); 
             KHMDS is potassium bis(trimethylsilyl) amide; 
             Ms for mesyl; 
             NMM for N-4-methylmorpholine; 
             PyBrOP for Bromo-tri-pyrrolidino-phosphonium hexafluorophosphate; 
             Ph for phenyl; 
             RCM for ring-closing metathesis; 
             RT for reverse transcription; 
             RT-PCR for reverse transcription-polymerase chain reaction; 
             TEA for triethyl amine; 
             TFA for trifluoroacetic acid; 
             THF for tetrahydrofuran; 
             TLC for thin layer chromatography; 
             TPP or PPh 3  for triphenylphosphine; 
             tBOC or Boc for tert-butyloxy carbonyl; and 
             Xantphos for 4,5-Bis-diphenylphosphanyl-9,9-dimethyl-9H-xanthene. 
           
         
       
     
       Synthetic Methods 
       [0160]    The compounds and processes of the present invention will be better understood in connection with the following synthetic schemes that illustrate the methods by which the compounds of the invention may be prepared. 
         [0161]    The present oxime hydroxyamic peptide HCV protease inhibitors were prepared by the coupling reaction of the P 1 -P 2  core intermediate such as 1-9 (Scheme 1) with hydroxyamic acids (Scheme 2). 
         [0000]    
       
                 
         
             
             
         
       
       
                 
         
             
             
         
       
     
         [0162]    Commercially available Boc-hydroxyproline 1-1 reacted with 1-2 under Mitsunobu conditions gave compound I-3. For further details on the Mitsunobu reaction, see O. Mitsunobu,  Synthesis  1981, 1-28; D. L. Hughes,  Org. React.  29, 1-162 (1983); D. L. Hughes,  Organic Preparations and Procedures Int.  28, 127-164 (1996); and J. A. Dodge, S. A. Jones,  Recent Res. Dev. Org. Chem.  1, 273-283 (1997). The hydrolysis of 1-3 gave acid 1-4, which was coupled with 1-5 using HATU, giving the ester 1-6. The hydrolysis of 1-6 gave 1-7, which was converted to sulfonamide 1-8. The deprotection of 1-8 gave the P 1 -P 2  core intermediate 1-9. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0163]    The hydroxyamic acid 2-1 was directly coupled with the HCl salt of intermediate 1-9 using HATU to afford the novel hydroxyamic peptide HCV protease inhibitor 2-2. 
         [0164]    The hydroxyamic derivatives such as carbonate, carbamate, amide and alkyl analogs were further prepared by the reaction of oxime hydroxyamic compounds with appropriate electrophile reagents as shown in Scheme 3. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0165]    The synthesis of an example of present HCV protease inhibitors was illustrated in Scheme 4. 
         [0000]    
       
                 
         
             
             
         
       
       
                 
         
             
             
         
       
     
         [0166]    The corresponding carboxylic acid derivatives as HCV protease inhibitors can be prepared in a similar fashion, as shown in Scheme 5. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0167]    Alternatively, the present HCV protease inhibitors represented by formula 6-6 were made via the synthetic route shown in Scheme 6. Alcohol 6-1 was coupled with N-hydroxyphthalimide under Mitsunobu conditions to give compound 6-2, which was deprotected to yield hydroxyamine 6-3. Compound 6-3 reacted with halide 6-4 to give hydroxyamino acid 6-5, which was coupled with the intermediate 1-9 to give the desired target compound 6-6. 
         [0000]    
       
                 
         
             
             
         
       
     
         [0168]    All references cited herein, whether in print, electronic, computer readable storage media or other form, are expressly incorporated by reference in their entirety, including but not limited to, abstracts, articles, journals, publications, texts, treatises, internet web sites, databases, patents, and patent publications. 
       EXAMPLES 
       [0169]    The compounds and processes of the present invention will be better understood in connection with the following examples, which are intended as an illustration only and not to limit the scope of the invention. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art and such changes and modifications including, without limitation, those relating to the chemical structures, substituents, derivatives, formulations and/or methods of the invention may be made without departing from the spirit of the invention and the scope of the appended claims 
       Example 1 
       [0170]    Compound of Formula VI, wherein R 501 ═H, R 502 ═H, R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
       Step 1A. 
       [0171]    
       
                 
         
             
             
         
       
     
         [0172]    To a mixture of Boc cis-L-hydroxyproline methyl ester 1-1 (1.073 g, 4.37 mmol), 3-(thiophen-2-yl)-1H-quinoxalin-2-one 1-2 (0.999 g, 4.38 mmol)) and triphenylphosphine (2.29 g, 8.74 mmol) in THF at 0° C. was added dropwise DIAD (1.72 ml, 8.7 mmol). The resulting mixture was held at 0° C. for 15 min. before being warmed to room temperature. After 18 hours, the mixture was concentrated under vacuum and the residue was purified by chromatography (Hexane/EtOAC=1:0 to 8:2) to give 1-3 (2.28 g). 
       Step 1B. 
       [0173]    
       
                 
         
             
             
         
       
     
         [0174]    To a solution of compound 1-3 (2.05 g, 4.5 mmol) in THF/MeOH (20 ml-10 ml) was added aqueous lithium hydroxide (1M, 10 ml, 10 mmol). The mixture was stirred at room temperature for 20 hours. Most organic solvents were evaporated in vacuo, and the resulting residue was diluted with water and acidified to pH 5 to 6. The mixture was extracted with EtOAc three times. The combined organic extracts were dried (MgSO 4 ), filtered and concentrated in vacuo to afford 1-4 (176 g). 
       Step 1C. 
       [0175]    
       
                 
         
             
             
         
       
     
         [0176]    To a solution of 1-4 (1.7 g, 3.85 mmol), (1R,2S)-1-Amino-2-vinyl-cyclopropanecarboxylic acid ethyl ester HCl salt 1-5 (0.74 g, 3.86 mmol) and DIPEA (2 ml, 11.6 mmol) in DMF (25 ml) at 0° C. was added in portions HATU (1.75 g, 4.6 mmol). The mixture was stirred at rt for 18 h, diluted with EtOAc and washed with half-sat.-aq. NaCl four times. The organic phase was dried over anhydrous MgSO 4 , filtered, and then concentrated in vacuo. The residue was purified by silica gel chromatography (Hexane/EtOAC=9:1 to 7:3) to afford compound 1-6 (1.1 g). 
       Step 1D. 
       [0177]    
       
                 
         
             
             
         
       
     
         [0178]    To a solution of compound I-6 (0.21 g, 0.363 mmol) in THF/MeOH (6 ml-3 ml) was added aqueous lithium hydroxide (1M, 3 ml, 3 mmol). The mixture was stirred at room temperature for 20 hours. Most organic solvents were evaporated in vacuo, and the resulting residue was diluted with water and acidified to pH 5 to 6. The mixture was extracted with EtOAc three times. The combined organic extracts were dried (MgSO 4 ), filtered and concentrated in vacuo to afford 1-7 (0.205 g). MS (ESI): m/e 551.23 (M+H). 
       Step 1E. 
       [0179]    
       
                 
         
             
             
         
       
     
         [0180]    Compound I-7 (175 mg, 0.317 mmol) and carbonyldiimidazole (80 mg, 0.476 mmol) were dissolved in 3 ml of anhydrous DMF and the resulting solution was stirred at 40° C. for 1 hour. Cyclopropylsulfonamide (77 mg, 0.634 mmol) was added to the reaction followed by DBU (71 ul, 0.476 mmol). The reaction mixture was stirred at 40° C. for 20 hour. The reaction mixture was diluted with ethyl acetate and washed with half-saturated-aqueous NaCl solution three times. The organic layer was dried over anhydrous (MgSO4) and concentrated in vacuo. The residue was purified by silica gel chromatography (Hexans/EtOAc=1:1 to 1:2) to give 1-8 (96 mg). MS (ESI): m/e 654.26 (M+H). 
       Step 1F. 
       [0181]    
       
                 
         
             
             
         
       
     
         [0182]    Compound 1-8 (77 mg, 0.118 mmol) was treated with 4N HCl in 1,4-dioxane (2 ml, 8 mmol.). The mixture was stirred at room temperature for an hour, concentrated to dryness to affored HCl salt of 1-9 (˜100%). MS (ESI): m/e 554.20 (M+H). 
       Step 1G. 
       [0183]    
       
                 
         
             
             
         
       
     
         [0184]    A solution of valine benzyl ester HCl salt 4-1 (4 g, 16.4 mmol) and 4-methoxybenzaldehyde (2.1 ml, 17.22 mmol) in MeOH (20 ml) was treated with sodium carbonate (2.6 g, 24.6 mmol). The mixture was stirred at room temperature for 18 h, filtered, washed with MeOH. The residue was taken into ether (˜10 ml), filtered, washed with ether (˜5 ml). The combined filtrates were concentrated to dryness to give 4-2 (100%). MS (ESI): 326.21 (M+H). 
       Step 1H. 
       [0185]    
       
                 
         
             
             
         
       
     
         [0186]    To a mixture of 4-2 (16.4 mmol) and dichloromethane (10 ml) at −15° C. was added slowly a solution of mCPBA (4.8 g, 21.4 mmol). The resulting mixture was stirred, and the bath temperature allowed to rise gradually to rt overnight. The reaction mixture was diluted with EtOAc, washed with aqueous NaHCO3 (3×), brine, dried (MgSO4) and concentrated to dryness to give 4-3 (5.53 g). 
       Step 1I. 
       [0187]    
       
                 
         
             
             
         
       
     
         [0188]    A mixture of 4-3 (˜8.2 mmol), hydroxylamine HCl salt (1.14 g, 16.4 mmol) and MeOH (20 ml) was stirred at rt for 24 h, concentrated to remove methanol. The residue was partitioned into ether-water. The aqueous phase was further extracted with ether (3×). The combined organic layers were washed with aqueous sodium bicarbonate, 1N NaOH (3×), brine, dried (MgSO4) and concentrated to dryness to give 4-4 (1.36 g). MS (ESI): 224.1 (M+H). 
       Step 1J. 
       [0189]    
       
                 
         
             
             
         
       
     
         [0190]    A mixture of 4-4 (112 mg), Pd—C (10%, 8 mg) and MeOH (10 ml) was hydrogenated under atmospheric pressure for 1 h, filtered through celite, washed with MeOH, concentrated to dryness to give 4-5 (60 mg). MS (ESI): 133.96 (M+H), 175.05 (M+CH3CN). 
       Step 1K. 
       [0191]    
       
                 
         
             
             
         
       
     
         [0192]    To a solution of 4-5 (0.03 mmol), oxim core intermediate 1-9 (0.03 mmol) and DIPEA (0.026 ml, 0.15 mmolmmol) in DMF (1 ml) at 0° C. was added HATU (16 mg, 0.042 mmol). The mixture was stirred at room temperature for 18 h, subjected to preparative HPLC to afford the title compound (8 mg). MS (ESI): m/e 669.26 (M+H). 
       Example 2 
       [0193]    Compound of Formula VI, wherein 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R 502 ═H, R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    
       
                 
         
             
             
         
       
     
         [0194]    To a solution of compound example 1 (2 mg, 0.003 mmol) and triethylamine (15 eq.) in dichloromethane (0.5 ml) at 0° C. was added cyclopentyl chloroformate (1.1M in toluene, 0.024 ml). The resulting mixture was then stirred at rt for 0.5 to 2 h, diluted with EtOAc, washed with brine (2×), dried (MgSO4) and concentrated to dryness to give the title compound (2 mg). The sample can be further purified by preparative HPLC. MS (ESI): m/z 781.39 (M+H). 
       Example 3 
       [0195]    Compound of Formula VI, wherein 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R 502 ═H, R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0196]    The title compound was prepared by using the same procedure as described in example 2. MS (ESI): m/z 769.38 (M+H). 
       Example 4 
       [0197]    Compound of Formula VI, wherein 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R 502 ═H, R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0198]    The title compound was prepared by using the same procedure as described in example 2. MS (ESI): m/z 780.35 (M+H). 
       Example 5 
       [0199]    Compound of Formula VI, wherein 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R 501 ═H, R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    
       
                 
         
             
             
         
       
     
         [0200]    To a solution of compound example 1 (4 mg, 0.006 mmol) in pyridine (0.5 ml) at 0° C. was added TMSCl (0.02 ml). The resulting mixture was stirred at rt for 0.5 h, then treated with cyclopentyl chloroformate (1.1M in toluene, 0.045 ml). The resulting mixture was stirred at rt for 2 h, subjected to preparative HPLC to afford the title compound (1 mg). MS (ESI): m/z 781.39 (M+H). 
       Example 6 
       [0201]    Compound of Formula VI wherein 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R 501 ═H, R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0202]    The title compound was prepared by using the same procedure as described in example 5 MS (ESI): m/z 791.37 (M+Na). 
       Example 7 
       [0203]    Compound of Formula VI, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0204]    The title compound was prepared by using the same procedure as described in example 2. MS (ESI): m/z 768.34 (M+H). 
       Example 8 
       [0205]    Compound of Formula VI, wherein R 501 ═H, R 502 ═H, R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
       Step 8A. 
       [0206]    
       
                 
         
             
             
         
       
     
         [0207]    To a solution of compound 8A-1 (0.312 g, 0.587 mmol, prepared by the procedures described in WO 05095403) in THF/MeOH (8 ml-4 ml) was added aqueous lithium hydroxide (1M, 4 ml, 4 mmol). The mixture was stirred at room temperature for 20 hours. Most organic solvents were evaporated in vacuo, and the resulting residue was diluted with water and acidified to pH 5 to 6. The mixture was extracted with EtOAc three times. The combined organic extracts were dried (MgSO 4 ), filtered and concentrated in vacuo to afford 8A (0.273 g). 
       Step 8B. 
       [0208]    
       
                 
         
             
             
         
       
     
         [0209]    Compound 8A (265 mg, 0.526 mmol) and carbonyldiimidazole (195 mg, 1.16 mmol) were dissolved in 6 ml of anhydrous DMF and the resulting solution was stirred at 40° C. for 1 hour. Cyclopropylsulfonamide (130 mg, 1.07 mmol) was added to the reaction followed by DBU (0.150 ml, 1.0 mmol). The reaction mixture was stirred at 40° C. for 20 hour. The reaction mixture was diluted with ethyl acetate and washed with half-saturated-aqueous NaCl solution three times. The organic layer was dried over anhydrous (MgSO4) and concentrated to dryness to give compound 8B (˜100%) 
       Step 8C. 
       [0210]    
       
                 
         
             
             
         
       
     
         [0211]    A mixture of compound 8B (0.21 mmol) and dichloromethane (0.5 ml) was treated with 4N HCl in 1,4-dioxane (3 ml, 12 mmol.). The mixture was stirred at room temperature for an hour, concentrated to dryness to afford 8C (˜100%). MS (ESI): m/z 507.26 (M+H). 
       Step 8D. 
       [0212]    
       
                 
         
             
             
         
       
     
         [0213]    To a solution of 4-5 (0.06 mmol), oxim core intermediate 8c (0.06 mmol) and DIPEA (0.07 ml, 0.4 mmolmmol) in DMF (2 ml) at 0° C. was added HATU (28 mg, 0.074 mmol). The mixture was stirred at room temperature for 18 h, subjected to preparative HPLC to afford the title compound (10 mg). MS (ESI): m/e 669.26 (M+H). 
       Example 9 
       [0214]    Compound of Formula VI, wherein R 501 ═H, R 502 ═H, R=tert-Butyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0215]    The title compound was prepared by using the same procedure as described in example 8. MS (ESI): m/z 636.37 (M+H). 
       Example 10 
       [0216]    Compound of Formula VI, wherein R 501 ═H, R 502 ═H, R=Ethyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0217]    The title compound was prepared by using the same procedure as described in example 8. MS (ESI): m/z 608.28 (M+H). 
       Example 11 
       [0218]    Compound of Formula VI, wherein 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R 502 ═H, R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0219]    The title compound was prepared from example 8 by using the same procedure as described in example 2. MS (ESI): m/z (M+H). 
       Example 12 
       [0220]    Compound of Formula VI, wherein 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R 502 ═H, R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0221]    The title compound was prepared from example 8 by using the same procedure as described in example 2. MS (ESI): m/z (M+H). 
       Example 13 
       [0222]    Compound of Formula VI, wherein R 501 ═H, R 502 ═H, R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
       Step 13A. 
       [0223]    
       
                 
         
             
             
         
       
     
         [0224]    To a solution of 13A-1 (0.6 g, 1.628 mmol) and Et3N (0.34 ml, 2.44 mmol) in dichloromethane (5 ml) at 0° C. was added slowly MsCl (0.14 ml, 1.8 mmol). The resulting mixture was stirred at room temperature for 1-2 h, diluted with EtOAc, washed with brine, dried (MgSO4) and concentrated in vacuo to dryness to give crude 1-2 which was directly used in next step. 
       Step 13B. 
       [0225]    
       
                 
         
             
             
         
       
     
         [0226]    A mixture of 13A (1.6 mmol), cesium carbonate (1.45 g, 4.45 mmol), 13B-1 (0.548 g, 1.56 mmol) and NMP (10 ml) was stirred at 50° C. for 19 h, cooled to rt, diluted with ETOAc, washed with brine (5×), dried (MgSO4) and concentrated. The residue was purified by silica gel chromatography (Hexane/Acetoen=5:1 to 1:1) to afford 13B (0.602 g). MS (ESI): 666.36 (M+H). 
       Step 13C. 
       [0227]    
       
                 
         
             
             
         
       
     
         [0228]    To a solution of compound 13B (0.595 g, 0.587 mmol in THF/MeOH (12 ml-6 ml) was added aqueous lithium hydroxide (1M, 6 ml, 6 mmol). The mixture was stirred at room temperature for 20 hours. Most organic solvents were evaporated in vacuo, and the resulting residue was diluted with water and acidified to pH 5 to 6. The mixture was extracted with EtOAc three times. The combined organic extracts were dried (MgSO 4 ), filtered and concentrated in vacuo to afford 13 (0.465 g). MS (ESI): m/z 638.33 (M+H). 
       Step 13D. 
       [0229]    
       
                 
         
             
             
         
       
     
         [0230]    Compound 13C (258 mg, 0.4 mmol) and carbonyldiimidazole (100 mg, 0.616 mmol) were dissolved in 6 ml of anhydrous DMF and the resulting solution was stirred at 40° C. for 1 hour. Cyclopropylsulfonamide (100 mg, 0.82 mmol) was added to the reaction followed by DBU (0.09 ml, 0.6 mmol). The reaction mixture was stirred at 40° C. for 20 hour. The reaction mixture was diluted with ethyl acetate and washed with half-saturated-aqueous NaCl solution three times. The organic layer was dried over anhydrous (MgSO4) and concentrated to dryness. The residue was purified by silica gel chromatography (Hexane/Acetoen=1:2 to 0:1 then AcOEt/MeOH=95:5 to 85:15) to afford 13D (0.257 g). MS (ESI): 741.38 (M+H). 
       Step 13E. 
       [0231]    
       
                 
         
             
             
         
       
     
         [0232]    A mixture of compound 13D (0.275 mmol) was treated with 4N HCl in 1,4-dioxane (4 ml, 16 mmol.). The mixture was stirred at room temperature for an hour, concentrated to dryness to afford HCl salt of 13E (˜100%). MS (ESI): m/z 641.35 (M+H). 
       Step 13F. 
       [0233]    
       
                 
         
             
             
         
       
     
         [0234]    To a solution of 4-5 (0.03 mmol), intermediate 13E (0.03 mmol) and DIPEA (0.024 ml, 0.14 mmolmmol) in DMF (1 ml) at 0° C. was added HATU (15 mg, 0.04 mmol). The mixture was stirred at room temperature for 18 h, subjected to preparative HPLC to afford the title compound (5 mg). MS (ESI): m/e 756.4 (M+H). 
       Example 14 
       [0235]    Compound of Formula VI, wherein 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R 502 ═H, R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0236]    The title compound was prepared from example 13 by using the same procedure as described in example 2. MS (ESI): m/z 868.47 (M+H). 
       Example 15 
       [0237]    Compound of Formula VI wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0238]    The title compound was prepared from example 8 by using the same procedure as described in example 5. MS (ESI): m/z 706.36 (M+H) 
       Example 16 
       [0239]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0240]    The title compound was prepared by using the same procedure as described in example 9. 
         [0241]    MS (ESI): m/z 664.25 (M+H). 
       Example 17 
       [0242]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0243]    The title compound was prepared by using the same procedure as described in example 9. 
         [0244]    MS (ESI): m/z 678.26 (M+H). 
       Example 18 
       [0245]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0246]    The title compound was prepared by using the same procedure as described in example 9. 
         [0247]    MS (ESI): m/z 692.28 (M+H). 
       Example 19 
       [0248]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0249]    The title compound was prepared by using the same procedure as described in example 9. 
         [0250]    MS (ESI): m/z 692.29 (M+H). 
       Example 20 
       [0251]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0252]    The title compound was prepared by using the same procedure as described in example 9. 
         [0253]    MS (ESI): m/z 706.31 (M+H). 
       Example 21 
       [0254]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0255]    The title compound was prepared by using the same procedure as described in example 9. 
         [0256]    MS (ESI): m/z 720.33 (M+H). 
       Example 22 
       [0257]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0258]    The title compound was prepared by using the same procedure as described in example 9. 
         [0259]    MS (ESI): m/z 690.29 (M+H) 
       Example 23 
       [0260]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0261]    The title compound was prepared by using the same procedure as described in example 9. 
         [0262]    MS (ESI): m/z 704.30 (M+H). 
       Example 24 
       [0263]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0264]    The title compound was prepared by using the same procedure as described in example 9. 
         [0265]    MS (ESI): m/z 718.33 (M+H). 
       Example 25 
       [0266]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0267]    The title compound was prepared by using the same procedure as described in example 9. 
         [0268]    MS (ESI): m/z 732.34 (M+H). 
       Example 26 
       [0269]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0270]    The title compound was prepared by using the same procedure as described in example 9. 
         [0271]    MS (ESI): m/z 732.35 (M+H). 
       Example 27 
       [0272]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0273]    The title compound was prepared by using the same procedure as described in example 9. 
         [0274]    MS (ESI): m/z 746.36 (M+H). 
       Example 28 
       [0275]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0276]    The title compound was prepared by using the same procedure as described in example 9. 
         [0277]    MS (ESI): m/z 746.37 (M+H). 
       Example 29 
       [0278]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0279]    The title compound was prepared by using the same procedure as described in example 9. 
         [0280]    MS (ESI): m/z 726.31 (M+H). 
       Example 30 
       [0281]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0282]    The title compound was prepared by using the same procedure as described in example 9. 
         [0283]    MS (ESI): m/z 760.27 (M+H). 
       Example 31 
       [0284]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0285]    The title compound was prepared by using the same procedure as described in example 9. 
         [0286]    MS (ESI): m/z 744.30 (M+H). 
       Example 32 
       [0287]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0288]    The title compound was prepared by using the same procedure as described in example 9. 
         [0289]    MS (ESI): m/z 756.33 (M+H). 
       Example 33 
       [0290]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0291]    The title compound was prepared by using the same procedure as described in example 9. 
         [0292]    MS (ESI): m/z 760.28 (M+H). 
       Example 34 
       [0293]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0294]    The title compound was prepared by using the same procedure as described in example 9. 
         [0295]    MS (ESI): m/z 744.31 (M+H). 
       Example 35 
       [0296]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0297]    The title compound was prepared by using the same procedure as described in example 9. 
         [0298]    MS (ESI): m/z 756.33 (M+H). 
       Example 36 
       [0299]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0300]    The title compound was prepared by using the same procedure as described in example 9. 
         [0301]    MS (ESI): m/z 740.35 (M+H). 
       Example 37 
       [0302]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0303]    The title compound was prepared by using the same procedure as described in example 9. 
         [0304]    MS (ESI): m/z 774.31 (M+H). 
       Example 38 
       [0305]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0306]    The title compound was prepared by using the same procedure as described in example 9. 
         [0307]    MS (ESI): m/z 758.34 (M+H). 
       Example 39 
       [0308]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0309]    The title compound was prepared by using the same procedure as described in example 9. 
         [0310]    MS (ESI): m/z 770.37 (M+H). 
       Example 40 
       [0311]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0312]    The title compound was prepared by using the same procedure as described in example 9. 
         [0313]    MS (ESI): m/z 754.36 (M+H). 
       Example 41 
       [0314]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0315]    The title compound was prepared by using the same procedure as described in example 9. 
         [0316]    MS (ESI): m/z 810.35 (M+H). 
       Example 42 
       [0317]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0318]    The title compound was prepared by using the same procedure as described in example 9. 
         [0319]    MS (ESI): m/z 732.29 (M+H). 
       Example 43 
       [0320]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0321]    The title compound was prepared by using the same procedure as described in example 9. 
         [0322]    MS (ESI): m/z 716.31 (M+H). 
       Example 44 
       [0323]    Compound of Formula IV, wherein R 501 ═H, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    R=iso-Propyl, 
         [0000]    
       
                 
         
             
             
         
       
     
         [0324]    The title compound was prepared by using the same procedure as described in example 9. 
         [0325]    MS (ESI): m/z 746.31 (M+H). 
         [0326]    Example 45 to Example 546 are made following the procedures described in Example 1 to 44 and the Synthetic Methods section. 
         [0327]    The compounds of the present invention exhibit potent inhibitory properties against the HCV NS3 protease. The following examples describe assays in which the compounds of the present invention can be tested for anti-HCV effects. 
       Example 547 
     NS3/NS4a Protease Enzyme Assay 
       [0328]    HCV protease activity and inhibition is assayed using an internally quenched fluorogenic substrate. A DABCYL and an EDANS group are attached to opposite ends of a short peptide. Quenching of the EDANS fluorescence by the DABCYL group is relieved upon proteolytic cleavage. Fluorescence is measured with a Molecular Devices Fluoromax (or equivalent) using an excitation wavelength of 355 nm and an emission wavelength of 485 nm. 
         [0329]    The assay is run in Corning white half-area 96-well plates (VWR 29444-312 [Corning 3693]) with full-length NS3 HCV protease 1b tethered with NS4A cofactor (final enzyme concentration 1 to 15 nM). The assay buffer is complemented with 10 μM NS4A cofactor Pep 4A (Anaspec 25336 or in-house, MW 1424.8). RET SI (Ac-Asp-Glu-Asp(EDANS)-Glu-Glu-Abu-[COO]Ala-Ser-Lys-(DABCYL)-NH 2 , AnaSpec 22991, MW 1548.6) is used as the fluorogenic peptide substrate. The assay buffer contains 50 mM Hepes at pH 7.5, 30 mM NaCl and 10 mM BME. The enzyme reaction is followed over a 30 minutes time course at room temperature in the absence and presence of inhibitors. 
         [0330]    The peptide inhibitors HCV Inh 1 (Anaspec 25345, MW 796.8) Ac-Asp-Glu-Met-Glu-Glu-Cys-OH, [−20° C.] and HCV Inh 2 (Anaspec 25346, MW 913.1) Ac-Asp-Glu-Dif-Cha-Cys-OH, are used as reference compounds. 
         [0331]    IC50 values are calculated using XLFit in ActivityBase (IDBS) using equation 205: y=A+((B−A)/(1+((C/x)̂D))). 
       Example 548 
     Cell-Based Replicon Assay 
       [0332]    Quantification of HCV replicon RNA in cell lines (HCV Cell Based Assay) Cell lines, including Huh-1-7 or Huh 9-13, harboring HCV replicons (Lohmann, et al Science 285:110-113, 1999) are seeded at 5×10 3  cells/well in 96 well plates and fed media containing DMEM (high glucose), 10% fetal calf serum, penicillin-streptomycin and non-essential amino acids. Cells are incubated in a 7.5% CO 2  incubator at 37° C. At the end of the incubation period, total RNA is extracted and purified from cells using Qiagen Rneasy 96 Kit (Catalog No. 74182). To amplify the HCV RNA so that sufficient material can be detected by an HCV specific probe (below), primers specific for HCV (below) mediate both the reverse transcription of the HCV RNA and the amplification of the cDNA by polymerase chain reaction (PCR) using the TaqMan One-Step RT-PCR Master Mix Kit (Applied Biosystems catalog no. 4309169). The nucleotide sequences of the RT-PCR primers, which are located in the NS5B region of the HCV genome, are the following: 
         [0000]    
       
         
               
               
               
             
               
               
               
               
             
               
               
               
             
               
               
               
               
             
           
               
                   
                 HCV Forward primer “RBNS5bfor” 
                   
               
             
          
           
               
                   
                 5′GCTGCGGCCTGTCGAGCT: 
                 (SEQ ID NO: 1) 
                   
               
               
                   
                   
               
             
          
           
               
                   
                 HCV Reverse primer “RBNS5Brev” 
                   
               
             
          
           
               
                   
                 5′CAAGGTCGTCTCCGCATAC. 
                 (SEQ ID NO 2) 
                   
               
             
          
         
       
     
         [0333]    Detection of the RT-PCR product is accomplished using the Applied Biosystems (ABI) Prism 7500 Sequence Detection System (SDS) that detects the fluorescence that is emitted when the probe, which is labeled with a fluorescence reporter dye and a quencher dye, is processed during the PCR reaction. The increase in the amount of fluorescence is measured during each cycle of PCR and reflects the increasing amount of RT-PCR product. Specifically, quantification is based on the threshold cycle, where the amplification plot crosses a defined fluorescence threshold. Comparison of the threshold cycles of the sample with a known standard provides a highly sensitive measure of relative template concentration in different samples (ABI User Bulletin #2 Dec. 11, 1997). The data is analyzed using the ABI SDS program version 1.7. The relative template concentration can be converted to RNA copy numbers by employing a standard curve of HCV RNA standards with known copy number (ABI User Bulletin #2 Dec. 11, 1997). 
         [0334]    The RT-PCR product was detected using the following labeled probe: 
         [0000]    
       
         
               
               
               
             
               
               
               
             
           
               
                   
                 (SEQ ID NO: 3) 
                   
               
             
          
           
               
                   
                 5′ FAM-CGAAGCTCCAGGACTGCACGATGCT-TAMRA 
                   
               
             
          
         
       
       
         
           
             FAM=Fluorescence reporter dye. 
             TAMRA:=Quencher dye. 
           
         
       
     
         [0337]    The RT reaction is performed at 48° C. for 30 minutes followed by PCR. Thermal cycler parameters used for the PCR reaction on the ABI Prism 7500 Sequence Detection System are: one cycle at 95° C., 10 minutes followed by 40 cycles each of which include one incubation at 95° C. for 15 seconds and a second incubation for 60° C. for 1 minute. 
         [0338]    To normalize the data to an internal control molecule within the cellular RNA, RT-PCR is performed on the cellular messenger RNA glyceraldehydes-3-phosphate dehydrogenase (GAPDH). The GAPDH copy number is very stable in the cell lines used. GAPDH RT-PCR is performed on the same exact RNA sample from which the HCV copy number is determined. The GAPDH primers and probes, as well as the standards with which to determine copy number, are contained in the ABI Pre-Developed TaqMan Assay Kit (catalog no. 4310884E). The ratio of HCV/GAPDH RNA is used to calculate the activity of compounds evaluated for inhibition of HCV RNA replication. 
       Activity of Compounds as Inhibitors of HCV Replication (Cell Based Assay) in Replicon Containing Huh-7 Cell Lines. 
       [0339]    The effect of a specific anti-viral compound on HCV replicon RNA levels in Huh-11-7 or 9-13 cells is determined by comparing the amount of HCV RNA normalized to GAPDH (e.g. the ratio of HCV/GAPDH) in the cells exposed to compound versus cells exposed to the 0% inhibition and the 100% inhibition controls. Specifically, cells are seeded at 5×10 3  cells/well in a 96 well plate and are incubated either with: 1) media containing 1% DMSO (0% inhibition control), 2) 100 international units, IU/ml Interferon-alpha 2b in media/1% DMSO or 3) media/1% DMSO containing a fixed concentration of compound. 96 well plates as described above are then incubated at 37° C. for 3 days (primary screening assay) or 4 days (IC50 determination). Percent inhibition is defined as: 
         [0000]      % Inhibition=[100−(( S−C 2)/ C   1   −C   2 ))]×100       where   S=the ratio of HCV RNA copy number/GAPDH RNA copy number in the sample;   C1=the ratio of HCV RNA copy number/GAPDH RNA copy number in the 0% inhibition control (media/1% DMSO); and   C2=the ratio of HCV RNA copy number/GAPDH RNA copy number in the 100% inhibition control (100 IU/ml Interferon-alpha 2b).         
         [0344]    The dose-response curve of the inhibitor is generated by adding compound in serial, three-fold dilutions over three logs to wells starting with the highest concentration of a specific compound at 10 uM and ending with the lowest concentration of 0.01 uM. Further dilution series (1 uM to 0.001 uM for example) is performed if the IC50 value is not in the linear range of the curve. IC50 is determined based on the IDBS Activity Base program using Microsoft Excel “XL Fit” in which A=100% inhibition value (100 IU/ml Interferon-alpha 2b), B=0% inhibition control value (media/1% DMSO) and C=midpoint of the curve as defined as C=(B−A/2)+A. A, B and C values are expressed as the ratio of HCV RNA/GAPDH RNA as determined for each sample in each well of a 96 well plate as described above. For each plate the average of 4-6 wells are used to define the 100% and 0% inhibition values. 
         [0345]    In the above assays, representative compounds are found to have activity. 
         [0346]    Although the invention has been described with respect to various preferred embodiments, it is not intended to be limited thereto, but rather those skilled in the art will recognize that variations and modifications may be made therein which are within the spirit of the invention and the scope of the appended claims