APICIDIN-DERIVED CYCLIC TETRAPEPTIDES

Abstract: Cyclic tetrapeptide compounds derived from apicidin therapeutically inhibit histone deacetylase activity and are represented by Formula (I).

Description: TITLE OF THE INVENTION APICIDIN-DERIVED CYCLIC TETRAPEPTEDES BACKGROUND OF THE INVENTION Field of the invention The present invention relates to anti-protozoal agents. In particular, the present invention relates to cyclic tetrapeptide compounds derived from apicidin that therapeutically inhibit histone deacetylase activity by protozoa. Related background Parasitic protozoa are responsible for a wide variety of infections in man and animals. Many of the diseases are life threatening to the host and cause considerable economic loss in animal husbandry. Malaria remains a significant health threat to humans despite massive international attempts to eradicate the disease. Trypanosomiasis such as i) Chagas disease caused by Trypanosoma cruzi and ii) African sleeping sickness caused by T. brucei are not uncommon in Africa and South America. Furthermore; opportunistic infections, caused by Pneumocystis carinii, Toxoplasma gondii, and Crypto sporidium sp., in immunocompromised hosts are becoming increasingly significant in developed countries. A protozoal infection of great economic importance is coccidiosis, a widespread disease of domesticated animals produced by infections by protozoa of the genus Eimeria. Some of the most significant of Eimeria species are those in poultry, namely E. tenella, E. acervulina, E. necatrix, E. praecox, E. mitis, E. brunetti and E. maxima. Coccidiosis can cause high levels of morbidity and mortality in poultry, resulting in extreme economic losses. In some protozoal diseases, such as Chagas disease, there is no satisfactory treatment. In other protozoal diseases, drug-resistant strains of the protozoa may develop or have developed. Accordingly, there exists a continued need to identify new and effective anti-protozoal drugs. However, antiparasitic drug discovery has been, for the most part, a random and laborious process - through biological screening of natural products and synthetic compounds against a panel of parasites. Drug discovery can be greatly facilitated and made more directed if a specific target of antiprotozoal drugs can be identified, and incorporated into the screening process. Histone deacetylase ("HDA") and histone acetyltransferase ("HAT") together control the net level of acetylation of histones. Inhibition of the action of HDA results in the accumulation of hyperacetylated histones, which in turn is implicated in a variety of cellular responses, including altered gene expression, cell differentiation and cell-cycle arrest. Recently, trichostatin A and trapoxin A have been reported as reversible and irreversible inhibitors, respectively, of mammalian HDA (see e.g., Yoshida et al., BioAssays, 17(5), 423-430 (1995)). Trichostatin A has also been reported to inhibit partially purified yeast HDA (Sanchez del Pino et al., Biochem. J., 303, 723-729 (1994)). Trichostatin A is an antifungal antibiotic and has been shown i) to have anti-trichomonal activity as well as cell differentiating activity in murine erythroleukemia cells, and ii) the ability to induce phenotypic reversion in ^^-transformed fibroblast cells (see e.g., U.S. Patent No. 4,218,478; Yoshida et al., BioAssays, 17(5), 423-430 (1995); and references cited therein). Trapoxin A, a cyclic tetrapeptide, induces morphological reversion of v-szs-transformed NTH3T3 cells (Yoshida and Sugita, Jap. J. Cancer Res., 83(4), 324-328 (1992). HDA inhibition as a target for cancer research is described in Saito et al., Proc. Natl Acad. Sci. USA, 96, 4592-4597(1999); Bernardi et al., Amino Acids 6, 315-318 (1994); and R.E. Shute et al., J. Med. Chem. 30, 71-78 (1987). U.S. Patent No. 5,620,953 describes novel cyclic tetrapeptides, including apicidin. Apicidin [cycZø(N-O-methyl-L-Tιp-L-Ile-D-Pip-L-2-amino-8- oxo-decanoyl)] is a broad-spectrum an ti protozoal, antifungal and antineoplastic agent isolated from the fermentation culture of Fusarium fungus. The structure of apicidin is shown below: Nevertheless, there remains a need to develop novel antiprotozoic compounds. The present inventors have found that a number of cyclic tetrapeptides derived from apicidin, structurally related to trapoxin A, are inhibitors of histone deacetylase and possess antiprotozoal activity. SUMMARY OF THE INVENTION The present invention relates to novel cyclic tetrapeptides and pharmaceutical compositions containing the tetrapeptides. The invention also concerns a method for treating protozoal infections by administering to a host suffering from protozoal infection a therapeutically effective amount of a compound that inhibits histone deacetylase. Additionally, the invention relates to the use of known cyclic tetrapeptides to inhibit histone deacetylase activity and effective as antiprotozoal agents. This invention relates i) to new antiprotozoal, antifungal and antineoplastic agents related to apicidin, ii) to processes for preparation of such novel agents, iii) to compositions containing such novel agents, iv) to the use of such novel agents in the treatment of parasitic infections, including malaria, in human and animals and v) the use of such novel agents in treating cancer. In treating cancer the compounds of this invention can be used as cytostatic compounds, as agents in treating abnormal cell differentiation or proliferation, as agents against tumor growth, or as antimitotic agents for cancer chemotherapy. DETAILED DESCRIPTION OF THE INVENTION In one aspect, according to one embodiment, the present invention relates to a novel cyclic tetrapeptide represented by Formula I shown below: or a pharmaceutically acceptable salt thereof wherein X is (1) -CH2-, (2) -C(O)-, (3) -CH(OR a )-, (4) =CH- or (5) not present; n is (1) one, or (2) two; Rl is (1) R7, (2) C(O)R 7 , (3) CN, (4) CO2R b , (5) C(O)N(OR b )R c , (6) C(O)NR R d , (7) NHCO2R b , (8) NHC(O)NR R d , (9) (Co-C4alkyl)OR a , (10) (Co-C4alkyl)OCO2R b , (11) (Co-C4alkyl)OC(O)NR c R d , (12) C(O)NR c NR c R d , (13) C(O)NR c SO2R b , (14) OS(O)niR7, (15) NR b S(O)niR7, wherein ni is from 0 to 2, (16) a 3- to 8-membered heterocycle containing 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2-C5alkenyl, Ci- C5perfluoroalkyl, NRcRd, 0 χo, thiono, ORa, S(O) n iR a (where ni = 0, 1 or 2), C(O)Ra, C(O)NRCR d , cyano, (Cfj- C6alkyl)aryl, CO2R b , or halogen, and each group may be saturated, partly unsaturated or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an R c substituent, (17) a benzene ring fused to a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups each independently is Cι-C5alkyl, C2- Csalkenyl, Ci-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd 5 cyano, CO2R b or halogen, each group may be saturated, partly unsaturated, or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, and wherein the benzene/heterocycle fused ring is attached at any site to X or to the tetrapeptide, or (18) a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms fused to a second 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, each heterocyclic ring independently optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NR c R d , cyano, CO2R b or halogen, wherein each heterocycle may be saturated, partly unsaturated or fully unsaturated, and wherein each heteroatom independently is oxygen, sulfur, or nitrogen, and the nitrogen optionally has an Rc substituent; R2 is (1) optionally substituted C2-Ci2alkyl, (2) optionally substituted C2-Ci2alkenyl, (3) optionally substituted C2-Ci2alkynyl, or (4) (CH2)nii-O-(CH2)mii wherein nii, mii = 0 to 7, wherein the optional substituents on the alkyl, alkenyl, and alkynyl are 1 to 8 groups and each group independently is (a) CO 2 R a , (b) C(O)R b , (c) C(O)N(OR b )R c , (d) C(O)NR c R d , (e) C(O)NR c NR c R d ( ) C(O)NR c SO2R7, (g) C3-C8cycloalkyl, (h) C2-C5alkenyl, 0) cyano, 10 (j) =NOR a , (k) =NNR b R c , (1) =NNR b S(O)niR7, (m) N(OR b )C(O)NR b R , (n) N(OR b )C(O)R7, 15 (o) NHC(O)N(OR b )R c , (P) NR c CO2R b , (q) NR c C(O)NR c R d , (r) NR C(S)NR R d , (s) NR c C(O)R7, 20 (t) NR b S(O)niR7, (u) NR c CH2CO2R a , (v) NR C C(S)R7, 00 NR c C(O)CH2OH, (y) NR c C(O)CH2SH, 25 (z) NR c CH2CO2R a , (aa) NR c CH2CH(OH)R7, (bb) NR c P(O)(OR a )R7, (cc) NYlγ , wherein γl and γ2 are independently H or Ci-Cioalkyl, 30 ( dd ) NO 2 , (ee) N(OR b )C(O)R b > (ff) C l -C i oalkanoylamino, (gg) OR a , (hh) OS(O) ni R 7 , (ϋ) oxo, (jj) OCO2R b , (kk) OC(O)NR c R d , GO P(O)(OR ) , (mm) P(O)(OR a )R7, (nn) SC(O)R 7 , (oo) S(O)niR7, (PP) SR7, (qq) S(O)niNRCR d , (rr) NR CH2CO2R a , (ss) diazo, (tt) C1-C5 perfluoroalkyl, (uu) B(O)(OR a )OR a , (w) halogen, (ww) aryl(C()-C5alkyl), wherein the aryl is optionally substituted with 1 to 3 groups, wherein each group independently is R', or (xx) a 3- to 8-membered heterocycle containing from 1 to 4 heteroatoms, each heteroatom independently is oxygen, sulfur or nitrogen, wherein the heterocycle is optionally substituted by 1 to 3 groups, wherein each group independently is Rf, and the heterocycle may be saturated or partly unsaturated; R3 each independently is (1) hydrogen, (2) halogen, (3) OR a , (4) Cι-C4alkyl, or R5 is (1) isopropyl, or (2) sec-butyl; R6 each independently is (1) o, (2) S, or (3) H; R7 is (1) hydrogen, (2) optionally substituted C2-C 1 fjalkyl , (3) optionally substituted C2-Cιoalkenyl, (4) optionally substituted C2-Cιoalkynyl, (5) optionally substituted C3-Cscycloalkyl, (6) optionally substituted C5-C8cycloalkenyl, (7) optionally substituted aryl, wherein the optional substituents on the alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl and aryl are 1 to 4 groups, and each group independently is (a) Ci-Csalkyl, (b) Xi-Ci-Cioalkyl, wherein X 1 is O or S(O) m , (c) C3-C8cycloalkyl, (d) hydroxy, (e) halogen, (f) cyano, (g) carboxy, (h) NYlγ2, wherein γl and γ2 are independently H or Ci-Cioalkyl, (i) nitro, (j) Cι-Cιoalkanoylamino, (k) aroyl amino wherein the aroyl is optionally substituted with 1 to 3 groups wherein each group independently is Rfl, wherein R*l is defined by any of the definitions below for R* except for (14), (26), (27), and (32), (1) oxo, (m) aryl C()-C5alkyl wherein the aryl is optionally substituted with 1 to 3 groups, wherein each group independently is R fl , (n) Cι-C5perfluoroalkyl, (o) N(OR b )C(O)R7' , wherein R7' is any of the above definitions of R7 from (1) to (7)(n), and below of R7 from (8) to (12), or (p) NR c C(O)R7', (8) a 5- to 10-membered heterocycle containing from 1 to 4 heteroatoms, each heteroatom independently is oxygen, sulfur or nitrogen and the heterocycle is optionally substituted by 1 to 3 groups, each group independently is R* 1 , and the heterocycle may be saturated . or partly unsaturated, (9) a benzene ring fused to a 5- to 10-membered heterocyclic ring containing from 1 to 4 heteroatoms, each heteroatom independently is oxygen, sulfur or nitrogen and the heterocycle is optionally substituted by 1 to 3 groups, each group independently is Rfl, and the heterocycle may be saturated or partly unsaturated, (10) a 5- to 10-membered heterocyclic ring containing from 1 to 4 heteroatoms fused to a second 5- to 10-membered heterocyclic ring containing from 1 to 4 heteroatoms, each heteroatom in either heterocyclic ring independently is oxygen, sulfur or nitrogen and the second heterocyclic ring is optionally substituted by 1 to 3 groups, each group independently is R^l, and each heterocycle independently may be saturated or partly unsaturated, (11) a benzene ring fused to a C3-Cscycloalkyl ring, wherein the cycloalkyl is optionally substituted by 1 to 3 groups each independently being Rfl, and the cycloalkyl ring may be saturated or partly unsaturated, or (12) a 5- to 10-membered heterocyclic ring containing from 1 to 4 heteroatoms, each heteroatom independently is oxygen, sulfur or nitrogen, the heterocyclic ring is fused to a C3-C8cycloalkyl ring, wherein the cycloalkyl ring is optionally substituted by 1 to 3 groups each independently being R*l, and the cycloalkyl ring may be saturated or partly unsaturated, R a is (1) hydrogen, (2) optionally substituted Ci-CiQalkyl, (3) optionally substituted C3-Cιoalkenyl, (4) optionally substituted C3-Cιoalkynyl, (5) optionally substituted Cι-Cιoalkanoyl, (6) optionally substituted C3-Cιoalkenoyl, (7) optionally substituted C3-Cιoalkynoyl, (8) optionally substituted aroyl, (9) optionally substituted aryl, (10) optionally substituted C3-C7cycloalkanoyl, (11) optionally substituted C5-C7cycloalkenoyl, (12) optionally substituted Ci-Cioalkylsulfonyl, (13) optionally substituted C3-Cscycloalkyl, (14) optionally substituted C5-C8cycloalkenyl, wherein the optional substituents on the Ci-Cioalkyl, C3-Cιoalkenyl, C3-Cιoalkynyl, Cι-Cιoalkanoyl, C3-Cιoalkenoyl, C3-Cιoalkynoyl, aroyl, aryl, C3-C7cycloalkanoyl, C5-C7cycloalkenoyl, Ci- Cioalkylsulfonyl, C3-C8cycloalkyl and Cs-Cscycloalkenyl are from 1 to 10 groups, wherein each group independently is hydroxy, Ci- C6alkoxy, C3-C7cycloalkyl, aryl Cι-C3alkoxy, NRXRx, CO2R b , CONR c R d > or halogen, (15) Cι-C5perfluoroalkyl, (16) arylsulfonyl optionally substituted with 1 to 3 groups, wherein each group independently is Cι-C5alkyl, Ci- C5perfluoroalkyl, nitro, halogen or cyano, (17) a 5- or 6-membered heterocycle containing 1 to 4 heteroatoms, wherein each heteroatom is oxygen, sulfur or nitrogen, wherein the heterocycle is optionally substituted by 1 to 4 groups, wherein each group independently is Cι-C5alkyl, Cι-C5alkenyl, Ci- C5perfluoroalkyl, amino, C(O)NR c R d , cyano, CO2R b or halogen, and wherein the heterocycle may be saturated or partly unsaturated, or (18) OP(O)(OR b )2; R b is (1) H, (2) optionally substituted aryl, (3) optionally substituted Ci-CiQalkyl, (4) optionally substituted C3-Cιoalkenyl, (5) optionally substituted C3-Cιoalkynyl, (6) optionally substituted C3-Ci5cycloalkyl, (7) optionally substituted C5-Cιocycloalkenyl, or (8) optionally substituted 5- to 10-membered heterocycle containing 1 to 4 heteroatoms, wherein each heteroatom independently is oxygen, sulfur, or nitrogen, wherein the optional substituents on the aryl, Cι-Cιoalkyl, C3- Cioalkenyl, C3-Cιoalkynyl 1, C3-Ci5cycloalkyl, C5-Cιocycloalkenyl, or 5- to 10-membered heterocycle are from 1 to 10 groups, wherein each group independently is (a) hydroxy, ( b ) Ci-C6alkyl, (c) oxo, (d) SO2NR X R X , (e) aryl Cι-C6alkoxy, ( ) hydroxy Cι-C6alkyl, (g) Cl-Ci2alkoxy, (h) hydroxy Ci-Cβalkoxy, (I) amino Cι-C6alkoxy, (j) cyano, (k) mercapto, (1) (Ci-C6alkyl)-S(O)ni-(C 0 -C6alkyl), (m) C3-C7cycloalkyl optionally substituted with 1 to herei n each group independently is R e , (n) C5-C7cycloalkenyl, (0) halogen, (P) Cι-C5alkanoyloxy, (q) C(O)NR X R x , (r) CO2R 1 , (s) formyl, (t) -NR X R X , ( ) 5 to 9-membered heterocycle, which may be saturated or partially unsaturated, containing from 1 to 4 heteroatoms, wherein each heteroatom independently is oxygen, sulfur or nitrogen, and the heterocycle is optionally substituted with 1 to 5 groups, wherein each group independently is R e , (v) optionally substituted aryl, wherein the optional substituents are 1,2-methylenedioxy or 1 to 5 groups, wherein each group independently is R e , (x) optionally substituted aryl Cι-C3alkoxy, wherein the optional substituents are 1,2-methylenedioxy or 1 to 5 groups, wherein each group independently is R e , or (y) Ci-C5perfluoroalkyl; R c and R d are independently selected from R b ; or R c and R d together with the N to which they are attached form a 3- to 10-membered ring containing 0 to 2 additional heteroatoms, each additional heteroatom independently being oxygen, nitrogen, or (O) n i substituted sulfur, wherein the ring is optionally substituted with 1 to 3 groups, wherein each group independently is Rg, hydroxy, thioxo, or oxo; R e is (1) halogen, (2) Ci-C7alkyl, (3) Ci-C3perfluoroalkyl, (4) -S(O) m Ri, (5) cyano, (6) nitro, (7) RiO(CH 2 ) v -, (9) RiOCO(CH2)v, (10) optionally substituted aryl wherein the optional substituents are from 1 to 3 groups, wherein each group independently is halogen, Cι-C6alkyl, Cι-C6alkoxy, or hydroxy, (11) SO2NR X R X , (12) CO2R x , or (13) NR R X ; R f is (1) Ci-C4alkyl, (2) X^Ci-C^alkyl, wherein X 1 is O or S(O)mi, (3) C2-C4alkenyl, (4) C2-C4 alkynyl, (5) Cι-C3perfluoroalkyl, (6) Nγ3γ4 ; wherein γ3 and γ are each independently hydrogen, Cι-C5alkyl, or SO2R b , (7) hydroxy, (8) halogen, (9) Cι-C5alkanoyl amino, (10) (Co-C4alkyl)CO2R a , (H) (Co-C4alkyl)C(O)NR b R , ( 12 ) (Co-C4alkyl)NY 5 Y 6 wherein Y 5 and Y 6 together with the N to which they are attached form a 3- to 7-membered ring containing 0 to 2 additional heteroatoms, wherein the additional heteroatoms independently are oxygen, nitrogen, or (O)mi substituted sulfur, wherein the ring is optionally substituted with 1 to 3 groups, wherein each group independently is R e or oxo, (13) (Co-C4alkyl)NO2, (14) (Co-C 4 alkyl)C(O)R 7 , (15) (Co-C4alkyl)CN, (16) oxo, (17) (Co-C4alkyl)C(O)N(OR b )R c , (18) (Co-C4alkyl)C(O)NR c R d , (19) (Co-C4alkyl)NHC(O)OR b , (20) (Co-C4alkyl)NHC(O)NR R d , (21) (Co-C4alkyl)OR a , (22) (Co-C4alkyl)OCO2R b , (23) (Co-C4alkyl)OC(O)NR c R d , (24) (Co-C4alkyl)C(O)NR c NRCR d (25) (Co-C4alkyl)C(O)NR SO2R b , (26) (Co-C4alkyl)OS(O)niR7, (27) (Co-C 4 alkyl)NR b S(O)niR7, (28) Co-C4alkyl halogen, (29) (Co-C 4 alkyl) SR a , (30) P(O)(OR ) 2 , (31) Co-C4alkyl azide, (32) Co-C4aryl substituted with from 1 to 4 groups, wherein each group independently is S(O)2R7, or (33) Co-C4aryl where the aryl group is optionally substituted from 1 to 4 groups, wherein each group independently is CO2R b , C(O)NR c R d , NO2, halogen, OC(O)R a , OR a or Cι-C4alkyl; Rg and R n together with the N to which they are attached form a 3- to 7-membered ring containing 0 to 2 additional heteroatoms, wherein each additional heteroatom independently is oxygen, nitrogen, or (O)mi substituted sulfur, and the ring is optionally substituted with 1 to 3 groups, wherein each group independently is R e or oxo; or Rg and R n are each independently (1) hydrogen, (2) Ci-Cβalkyl optionally substituted with hydroxy, amino, or CO2R 1 , (3) aryl optionally substituted with halogen, 1,2- methylenedioxy, Cι-C7alkoxy, Cι-C7alkyl, or Cι-C3perfluoroalkyl, (4) aryl Cι-C6alkyl, wherein the aryl is optionally substituted with Cl-C3perfluoroalkyl or 1,2-methylenedioxy, (5) Cι-C5alkoxycarbonyl, (6) Cι-C5alkanoyl, (7) Ci-C5alkanoyl Cι-C6alkyl, (8) arylCi-C5 alkoxycarbonyl, (9) aminocarbonyl, (10) (Cι-C5monoalkyl)aminocarbonyl, (11) (Cι-C5dialkyl)aminocarbonyl, or (12) CO2R b ; R 1 is (1) hydrogen, (2) Cι-C3perfluoroalkyl, (3) Ci-C6alkyl, or (4) optionally substituted aryl Cø-Cόalkyl, wherein the aryl optional substituents are from 1 to 3 groups, wherein each group independently is halogen, Cι-C6alkyl, Cι-C6alkoxy, or hydroxy; R is a Cι-C4alkyl; ni is 0 to 2; V IS 0 to 3; and excluding apicidin, N-desmethoxy apicidin and compounds represented by the following chemical Formula HA and Formula OB: ΠA ΠB Within this embodiment, the novel cyclic tetrapeptide of this invention includes a genus of compounds represented by Formula I or a pharmaceutically acceptable salt thereof wherein: X is (1) -CH2-, (2) -C(O)-, (3) -CH(OR a )-, (4) =CH- or (5) not present; and Rl is (1) R7, (2) C(O)R 7 , (3) CN, (4) CO2R b , (5) C(O)N(OR b )R c , (6) C(O)NR c R d , (7) NHCO2R b , (8) NHC(O)NR R d , (9) (Co-C4alkyl)OR a , (10) (Co-C4alkyl)OCO2R b , (11) (Co-C4alkyl)OC(O)NR c R d , (12) C(O)NR c NR c R d (13) C(O)NR c SO2R b , (13) OS(O)niR7, (14) NR b S(O) n iR7, wherein ni is from 0 to 2, (15) a 3- to 8-membered heterocycle containing 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups, each group independently is Ci-C5alkyl, C2-C5alkenyl, Ci- C5perfluoroalkyl, NRCRd, 0 χo, thiono, ORa, S(O) n iR a (where ni = 0, 1 or 2), C(O)Ra, C(O)NRCRd C yano, (Co- C6alkyl)aryl, CO2R b , or halogen, and each group may be saturated, partly unsaturated or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, (16) a benzene ring fused to a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups each independently is Cι-C5alkyl, C2- Csalkenyl, Ci-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd ; cyano, CO2R b or halogen, each group may be saturated, partly unsaturated, or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an R c substituent, and wherein the benzene/heterocycle fused ring is attached at any site to X or to the tetrapeptide, or (17) a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms fused to a second 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, each heterocyclic ring independently optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NR R d , cyano, CO2R b or halogen, wherein each heterocycle may be saturated, partly unsaturated or fully unsaturated, and wherein each heteroatom independently is oxygen, sulfur, or nitrogen, and the nitrogen optionally has an Rc substituent. Within this genus there is a class of compounds represented by Formula I or a pharmaceutically acceptable salt thereof wherein: X is (1) -CH2-, (2) -C(O)- (3) -CH(OR a )-, (4) =CH- or (5) not present; Rl is (1) R 7 , (2) C(O)R 7 , (3) CN, (4) CO2R b (5) C(O)N(OR b )R c , (6) C(O)NRCR d , (7) NHCO2R b (8) NHC(O)NR c R d , (9) (Co-C4alkyl)OR a , (10) (Co-C4alkyl)OCO2R b , (11) (Co-C4alkyl)OC(O)NR C R d (12) C(O)NR c NR c R d , (13) C(O)NR c SO2R b , (14) OS(O)niR7, (15) NR b S(O)niR7, wherein ni is from 0 to 2, (16) a 3- to 8-membered heterocycle containing 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2-C5alkenyl, Ci- C5perfluoroalkyl, NRCRd, 0 χo, thiono, OR a , S(O) n iR a (where ni = 0, 1 or 2), C(O)R a , C(O)NRCRd cy ano, (Co C6alkyl)aryl, CO2R b , or halogen, and each group may be saturated, partly unsaturated or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, (17) a benzene ring fused to a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups each independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd ; cyano, CO2R b or halogen, each group may be saturated, partly unsaturated, or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, and wherein the benzene/heterocycle fused ring is attached at any site to X or to the tetrapeptide, or (18) a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms fused to a second 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, each heterocyclic ring independently optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd, cyano, CO2R b or halogen, wherein each heterocycle may be saturated, partly unsaturated or fully unsaturated, and wherein each heteroatom independently is oxygen, sulfur, or nitrogen, and the nitrogen optionally has an Rc substituent; and R2 is (1) optionally substituted C2-Ci2alkyl, (2) optionally substituted C2-Ci2alkenyl, (3) optionally substituted C2-Ci2alkynyl, or (4) (CH2)nii-O-(CH2)mii wherein nii, mii = 0 to 7, wherein the optional substituents on the C2-Ci2alkyl, C2-Ci2alkenyl, and C2-Ci2alkynyl are 1 to 8 groups and each group independently is (a) CO2R a , (b) C(O)R b , (c) C(O)N(OR b )R c , ( d ) C(O)NR c R d (e) C(O)NRCNRCR d , ( ) C(O)NR c SO2R7, (g) C3-C8cycloalkyl, (h) C2-C5alkenyl, (i) cyano, (j) =NOR a , (k) =NNR b R c , (1) =NNR b S(O)niR7, ( ) N(OR b )C(O)NR R c , (n) N(OR b )C(O)R7, 10 (o) NHC(O)N(OR b )R c , (P) NR c CO2R b , (q) NR c C(O)NR R d , (r) NR c C(S)NRCR d , (s) NR c C(O)R7, 15 (t) NR b S(O)niR7, ( ) NR c CH2CO2R a , (v) NR C C(S)R7, (x) NR c C(O)CH2OH, (y) NR c C(O)CH2SH, 20 (z) NR c CH2CO2R a , (aa) NR c CH2CH(OH)R7, (bb) NR C P(O)(OR a )R7, (cc) NY γ2, wherein γl and γ2 are independently H or Ci-Cioalkyl, 25 ( dd ) NO 2 , (ee) N(OR b )C(O)R b ' (ff) Ci-Cioalkanoylamino, (gg) OR a , (hh) OS(O) ni R 7 , 30 (ϋ) oxo, (jj) OCO2R b , (kk) OC(O)NRCR d , (11) P(O)(OR ) 2 , (mm) P(O)(OR a )R7, (nn) SC(O)R 7 , (oo) S(O)niR7, (PP) SR 7 , (qq) S(O)niNRCR d , (rr) NR c CH2CO2R a , (ss) diazo, (tt) C1-C5 perfluoroalkyl, (uu) B(O)(OR a )OR a , (vv) halogen, (ww) aryl(Co-C5alkyl), wherein the aryl is optionally substituted with 1 to 3 groups, wherein each group independently is R*, or (xx) a 3- to 8-membered heterocycle containing from 1 to 4 heteroatoms, each heteroatom independently is oxygen, sulfur or nitrogen, wherein the heterocycle is optionally substituted by 1 to 3 groups, wherein each group independently is Rf, and the heterocycle may be saturated or partly unsaturated. Within the above class of compounds, there is a subclass of compounds represented by Formula I or a pharmaceutically acceptable salt thereof wherein n is 1 or 2. Within this genus there is another class of compounds represented by Formula I or a pharmaceutically acceptable salt thereof wherein: X is (1) -CH2- (2) -C(O)-, or (3) not present; and Ri is (1) R7, (2) C(O)R 7 , (3) CN, (4) CO2R b , (5) C(O)N(OR b )R , (6) C(O)NR c R d , (7) NHCO2R b (8) NHC(O)NRCR d , (9) (Co-C4alkyl)OR a , (10) (Co-C4alkyl)OCO2R b , (11) (Co-C4alkyl)OC(O)NRCR d , (12) C(O)NR c NRCR d , (13) C(O)NR c SO2R b , (14) OS(O)niR7, (15) NR b S(O)niR7, wherein ni is from 0 to 2, (16) a 3- to 8-membered heterocycle containing 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2-C5alkenyl, Ci- C5perfluoroalkyl, NRCRd, 0 χo, thiono, ORa, S(O) n iR a (where ni = 0, 1 or 2), C(O)Ra, C(O)NRCRd, cyano, (Co- C6alkyl)aryl, CO2R b , or halogen, and each group may be saturated, partly unsaturated or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, (17) a benzene ring fused to a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups each independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd ; cyano, CO2R or halogen, each group may be saturated, partly unsaturated, or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an R substituent, and wherein the benzene/heterocycle fused ring is attached at any site to X or to the tetrapeptide, or (18) a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms fused to a second 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, each heterocyclic ring independently optionally substituted by 1 to 4 groups, each group independently is Ci-C5alkyl, C2- C5alkenyl, Ci-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd, cyano, CO2R b or halogen, wherein each heterocycle may be saturated, partly unsaturated or fully unsaturated, and wherein each heteroatom independently is oxygen, sulfur, or nitrogen, and the nitrogen optionally has an Rc substituent. Within the above class of compounds, there is a subclass of compounds represented by Formula I or a pharmaceutically acceptable salt thereof wherein n is 1 or 2. Within this genus there is yet another class of compounds represented by Formula I or a pharmaceutically acceptable salt thereof wherein: X is (1) -CH2-, (2) -C(O)-, or (3) not present; and Rl is (1) R 7 , (2) C(O)R 7 , (3) CO2R b , (4) C(O)N(OR b )R , (5) C(O)NR c R d , (6) a 3- to 8-membered heterocycle containing 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2-C5alkenyl, Ci- C5perfluoroalkyl, NRCRd 0 χo, thiono, ORa, S(O) n iRa (where ni = 0, 1 or 2), C(O)Ra, C(O)NRCRd, cyano, (Co- C(5alkyl)aryl, CO2R b , or halogen, and each group may be saturated, partly unsaturated or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, (7) a benzene ring fused to a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups each independently is Cι-C5alkyl, C2- Csalkenyl, Ci-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd ; cyano, CO2R b or halogen, each group may be saturated, partly unsaturated, or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, and wherein the benzene/heterocycle fused ring is attached at any site to X or to the tetrapeptide, or (8) a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms fused to a second 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, each heterocyclic ring independently optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2- C5alkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd, cyano, CO2R b or halogen, wherein each heterocycle may be saturated, partly unsaturated or fully unsaturated, and wherein each heteroatom independently is oxygen, sulfur, or nitrogen, and the nitrogen optionally has an Rc substituent. Within the above class of compounds, there is a subclass of compounds represented by Formula I or a pharmaceutically acceptable salt thereof wherein n is 1 or 2. Within this genus there is yet another class of compounds represented by Formula I or a pharmaceutically acceptable salt thereof wherein: X is (1) -CH2- (2) -C(O)-, or (3) not present; Ri is (1) R7, (2) C(O)R 7 , (3) CO2R b , (4) C(O)N(OR b )R c , (5) C(O)NRCR d (6) a 3- to 8-membered heterocycle containing 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups, each group independently is Ci-C5alkyl, C2-C5alkenyl, Ci- C5perfluoroalkyl, NRCRd, 0 χo, thiono, ORa, S(O) n iR a (where ni = 0, 1 or 2), C(O)R a , C(O)NRCRd C yano, (Co- C6alkyl)aryl, CO2R b , or halogen, and each group may be saturated, partly unsaturated or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, (7) a benzene ring fused to a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups each independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd, cyano, CO2R b or halogen, each group may be saturated, partly unsaturated, or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, and wherein the benzene/heterocycle fused ring is attached at any site to X or to the tetrapeptide, or (8) a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms fused to a second 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, each heterocyclic ring independently optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2- C5alkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd, cyano, CO2R b or halogen, wherein each heterocycle may be saturated, partly unsaturated or fully unsaturated, and wherein each heteroatom independently is oxygen, sulfur, or nitrogen, and the nitrogen optionally has an Rc substituent;and R2 is (1) optionally substituted C2-Ci2alkyl, (2) optionally substituted C2-C 12alkenyl , (3) optionally substituted C2-Ci2alkynyl, or (4) (CH2)nii-O-(CH2)mii wherein nii, mii = 0 to 7, wherein the optional substituents on the C2-Ci2alkyl, C2-Ci2alkenyl, and C2-Ci2alkynyl are 1 to 5 groups and each group independently is (a) CO2R a , (b) C(O)R b , (c) C(O)N(OR b )R c , (d) C(O)NRCR d , (e) C(O)NRCNRCR d , (f) C(O)NR c SO2R7> (g) C3-C8cycloalkyl, (h) C2-C5alkenyl, (i) cyano, 0 ) =NOR a , 00 =NNR b R c , 0) =NNR b S(O)niR7, (m) N(OR b )C(O)NR b R c , (n) N(OR b )C(O)R7, (o) NHC(O)N(OR b )R c , (P) NR c CO2R b , (q) NR C(O)NRCR d , (0 NR c C(S)NRCR d , (s) NR c C(O)R7, (t) NR b S(O)niR7, (u) NR c CH2CO2R a , (v) NR C C(S)R7, (x) NR C(O)CH2θH, (y) NR c C(O)CH2SH, (z) NR c CH2CO2R a , (aa) NR c CH2CH(OH)R7, (cc) Nγlγ2, wherein γ and γ2 are independently H or methyl, (dd) NO 2 , (ee) N(OR b )C(O)R b > (ff) Cι-C3alkanoylamino, (gg) OR a , (hh) OS(O)niR7, (ii) oxo, (jj) OCO 2 R b , (kk) OC(O)NR c R d , (11) P(O)(OR ) 2 , (mm) P(O)(OR a )R7, (nn) SC(O)R 7 , (oo) S(O) ni R 7 , (pp) SR 7 , (qq) S(O)niNR C R d , (rr) NR CH2CO2R a , (ss) diazo, (tt) C1-C5 perfluoroalkyl, (uu) B(O)(OR a )OR a , (vv) halogen, (ww) aryl(Co-C5alkyl), wherein the aryl is optionally substituted with 1 to 3 groups, wherein each group independently is R*, or (xx) a 3- to 6-membered heterocycle containing from 1 to 4 heteroatoms, each heteroatom independently is oxygen, sulfur or nitrogen, wherein the heterocycle is optionally substituted by 1 to 3 groups, wherein each group independently is Rf, and the heterocycle may be saturated or partly unsaturated. Within the above class of compounds, there is a subclass of compounds represented by Formula I or a pharmaceutically acceptable salt thereof wherein n is 1 or 2. Within this embodiment there is a second genus of compounds represented by Formula I or a pharmaceutically acceptable salt thereof wherein: R3 each independently is (1) hydrogen, (2) halogen, (3) OR a , (4) Cι-C4alkyl, or R a is (1) hydrogen, (2) optionally substituted Cι-C6alkyl, (3) optionally substituted C3-C6alkenyl, (4) optionally substituted C2-C4alkanoyl, (5) optionally substituted C3-C4alkenoyl, (6) optionally substituted aroyl, (7) optionally substituted aryl, (8) optionally substituted C5-C6cycloalkanoyl, (9) optionally substituted Cι-C4alkylsulfonyl, (10) optionally substituted C5-C6cycloalkyl, (11) optionally substituted C5-C6cycloalkenyl, wherein the optional substituents on the Cι-C6alkyl, C3-C6alkenyl, C2-C4alkanoyl, C3-C4alkenoyl, aroyl, aryl, C5-C6cycloalkanoyl, Ci- C4alkylsulfonyl, C5-C6cycloalkyl and C5-C6cycloalkenyl are from 1 to 10 groups, wherein each group independently is hydroxy, methoxy, aryl methoxy, NRXRx, CO2R b CONR c R d > or halogen, (12) CF 3 , (13) arylsulfonyl optionally substituted with 1 to 3 groups, wherein each group independently is methyl, CF3, nitro, halogen or cyano, or (14) a 5- or 6-membered heterocycle containing 1 to 3 heteroatoms, wherein each heteroatom is oxygen, sulfur or nitrogen, wherein the heterocycle is optionally substituted by 1 to 3 groups, wherein each group independently is methyl, CF3, NMe2, C(O)NR c R d , cyano, CO2R b or halogen, and wherein the heterocycle may be saturated or partly unsaturated. Within this second genus is a class of compounds represented by Formula I or a pharmaceutically acceptable salt thereof wherein: R3 each independently is (I) hydrogen, (2) halogen, (3) OR a , (4) Cι-C4alkyl, or R a is (1) hydrogen, (2) optionally substituted Cι-C6alkyl, (6) optionally substituted C3-C6alkenyl, (7) optionally substituted C2-C4alkanoyl, (5) optionally substituted C3-C4alkenoyl, (6) optionally substituted aroyl, (7) optionally substituted aryl, (8) optionally substituted C5-C6cycloalkanoyl, (9) optionally substituted Cι-C4alkylsulfonyl, (10) optionally substituted C5-C6cycloalkyl, (I I) optionally substituted C5-C6cycloalkenyl, wherein the optional substituents on the Ci-Cβalkyl, C3-C6alkenyl, C2-C4alkanoyl, C3-C4alkenoyl, aroyl, aryl, Cs-Cβcycloalkanoyl, Ci- C4alkylsulfonyl, C5-C6cycloalkyl and Cs-Cβcycloalkenyl are from 1 to 10 groups, wherein each group independently is hydroxy, methoxy, aryl methoxy, NRXRx, CO2R b , CONR c R d > or halogen, (12) CF3, (13) arylsulfonyl optionally substituted with 1 to 3 groups, wherein each group independently is methyl, CF3, nitro, halogen or cyano, or (14) a 5- or 6-membered heterocycle containing 1 to 3 heteroatoms, wherein each heteroatom is oxygen, sulfur or nitrogen, wherein the heterocycle is optionally substituted by 1 to 3 groups, wherein each group independently is methyl, CF3, NMe2, C(O)NR c R , cyano, CO2R b or halogen, and wherein the heterocycle may be saturated or partly unsaturated. X is (1) -CH2- (2) -C(O)-, (3) =CH- or (4) not present; and Rl is (1) R 7> (2) C(O)R 7 , (3) CN, (4) CO2R b , (5) C(O)N(OR b )R c , (6) C(O)NR c R d , (7) NHCO2R b , (8) NHC(O)NRCR d , (9) (Co-C4alkyl)OR a , (10) (Co-C4alkyl)OCO2R b (11) (Co-C4alkyl)OC(O)NRCR d , (12) C(O)NR c NR c R d , (13) C(O)NR c SO2R b , (14) OS(O)niR7, (15) NR b S(O)niR7, wherein ni is from 0 to 2, (16) a 3- to 8-membered heterocycle containing 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2-C5alkenyl, Ci- C5perfluoroalkyl, NRCRd, 0 χo, thiono, ORa S(O) n iRa (where ni = 0, 1 or 2), C(O)Ra, C(O)NRCRd cyano, (Co- C6alkyl)aryl, CO2R b , or halogen, and each group may be saturated, partly unsaturated or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an R c substituent, (17) a benzene ring fused to a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups each independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd 5 cyano, CO2R b or halogen, each group may be saturated, partly unsaturated, or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an R c substituent, and wherein the benzene/heterocycle fused ring is attached at any site to X or to the tetrapeptide, or (18) a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms fused to a second 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, each heterocyclic ring independently optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd ; cyano, CO2R b or halogen, wherein each heterocycle may be saturated, partly unsaturated or fully unsaturated, and wherein each heteroatom independently is oxygen, sulfur, or nitrogen, and the nitrogen optionally has an Rc substituent. Within the above class of compounds, there is a subclass of compounds represented by Formula I or a pharmaceutically acceptable salt thereof wherein n is 1 or 2. Within this second genus is a class of compounds represented by Formula I or a pharmaceutically acceptable salt thereof wherein: R3 each independently is (1) hydrogen, (2) halogen, (3) OR a , (4) Cι-C4alkyl, or (5) Ci-C4aryl; ); R a is (1) hydrogen, (2) optionally substituted Cι-C6alkyl, (3) optionally substituted C3-C6alkenyl, (4) optionally substituted C2-C4alkanoyl, (5) optionally substituted C3-C4alkenoyl, (6) optionally substituted aroyl, (7) optionally substituted aryl, (8) optionally substituted C5-C6cycloalkanoyl, (9) optionally substituted Ci-C4alkylsulfonyl, (10) optionally substituted C5-C6cycloalkyl, (11) optionally substituted C5-C6cycloalkenyl, wherein the optional substituents on the Ci-Cβalky], C3-C6alkenyl, C2-C4alkanoyl, C3-C4alkenoyl, aroyl, aryl, C5-C6cycloalkanoyl, Ci- C4alkylsulfonyl, C5-C6cycloalkyl and C5-C6cycloalkenyl are from 1 to 10 groups, wherein each group independently is hydroxy, methoxy, aryl methoxy, NRXRx, CO2R b , CONR c R<± or halogen, (12) CF 3 , (13) arylsulfonyl optionally substituted with 1 to 3 groups, wherein each group independently is methyl, CF3, nitro, halogen or cyano, or (14) a 5- or 6-membered heterocycle containing 1 to 3 heteroatoms, wherein each heteroatom is oxygen, sulfur or nitrogen, wherein the heterocycle is optionally substituted by 1 to 3 groups, wherein each group independently is methyl, CF3, NMe2, C(O)NR c R d , cyano, CO2R b or halogen, and wherein the heterocycle may be saturated or partly unsaturated; X is (1) -CH2- (2) -C(O)-, (3) =CH- or (4) not present; and Rl is (1) R7, (2) C(O)R 7 , (9) CO2R b (10) C(O)N(OR b )R c , (11) C(O)NR c R d , (12) a 3- to 8-membered heterocycle containing 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2-C5alkenyl, Ci- C5perfluoroalkyl, NRCRd, oxo, thiono, ORa, S(O) n iR a (where ni = 0, 1 or 2), C(O)R a , C(O)NRCR d , cyano, (Co- Cβalky aryl, CO2R b , or halogen, and each group may be saturated, partly unsaturated or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, (13) a benzene ring fused to a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups each independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd ; cyano, CO2R b or halogen, each group may be saturated, partly unsaturated, or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, and wherein the benzene/heterocycle fused ring is attached at any site to X or to the tetrapeptide, or (14) a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms fused to a second 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, each heterocyclic ring independently optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2- C5alkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd, cyano, CO2R b or halogen, wherein each heterocycle may be saturated, partly unsaturated or fully unsaturated, and wherein each heteroatom independently is oxygen, sulfur, or nitrogen, and the nitrogen optionally has an R substituent. Within the above class of compounds, there is a subclass of compounds represented by Formula I or a pharmaceutically acceptable salt thereof wherein n is 1 or 2. Within this embodiment there is a third genus of compounds represented by Formula I or a pharmaceutically acceptable salt thereof wherein: R6 each independently is (1) O, (2) S, or (3) H; X is (1) -CH2-, (2) -C(O)-, (3) =CH-, or (4) not present; and Rl is (1) R 7> (2) C(O)R 7 , (3) CN, (4) CO2R b (5) C(O)N(OR b )R c , (6) C(O)NR c R d , (7) NHCO2R b , (8) NHC(O)NRCR d , (9) (Co-C4alkyl)OR a , (10) (Co-C4alkyl)OCO2R b , (11) (Co-C4alkyl)OC(O)NR c R d , (12) C(O)NR c NRCR d (13) C(O)NR c SO2R b , (14) OS(O) ni R 7 , (15) NR b S(O)niR7, wherein ni is from 0 to 2, (16) a 3- to 8-membered heterocycle containing 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2-C5alkenyl, Ci- C5perfluoroalkyl, NRCRd, 0 χo, thiono, ORa, S(O) n iR (where ni = 0, 1 or 2), C(O)R a , C(O)NRCRd, cyano, (Co- C6alkyl)aryl, CO2R b , or halogen, and each group may be saturated, partly unsaturated or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, (17) a benzene ring fused to a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups each independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd, cyano, CO2R b or halogen, each group may be saturated, partly unsaturated, or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, and wherein the benzene/heterocycle fused ring is attached at any site to X or to the tetrapeptide, or (18) a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms fused to a second 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, each heterocyclic ring independently optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd 7 cyano, CO2R b or halogen, wherein each heterocycle may be saturated, partly unsaturated or fully unsaturated, and wherein each heteroatom independently is oxygen, sulfur, or nitrogen, and the nitrogen optionally has an R substituent. Within this third genus is a class of compounds represented by Formula I or a pharmaceutically acceptable salt thereof wherein n is 1 or 2. Within this third genus is a class of compounds represented by Formula I or a pharmaceutically acceptable salt thereof wherein: R3 each independently is (1) hydrogen, (2) halogen, (3) OR a , (4) Cι-C4alkyl, or (5) Cι-C4aryl; R6 each independently is (1) O, (2) S, or (3) H; X is (1) -CH2-, (2) -C(O)-, (3) =CH- or (4) not present; and Rl is (1) R7, (2) C(O)R 7 , (3) CN, (4) CO2R b , (5) C(O)N(OR b )R c , (6) C(O)NRCR d , (7) NHCO2R b (8) NHC(O)NR c R d , (9) (Co-C4alkyl)OR a , (10) (Co-C4alkyl)OCO2R b , (11) (Co-C4alkyl)OC(O)NRCR d , (12) C(O)NRC NR c R d ? (13) C(O)NR c SO2R b , (14) OS(O)niR7, (15) NR b S(O)niR7, wherein ni is from 0 to 2, (16) a 3- to 8-membered heterocycle containing 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups, each group independently is Ci-Csalkyl, C2-C5alkenyl, Ci- C5perfluoroalkyl, NRCRd, 0 χo, thiono, ORa, S(O) n iR a (where ni = 0, 1 or 2), C(O)Ra, C(O)NRcRd, cyano, (Co- C6alkyl)aryl, CO2R b , or halogen, and each group may be saturated, partly unsaturated or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an R c substituent, (17) a benzene ring fused to a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups each independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd j cyano, CO2R b or halogen, each group may be saturated, partly unsaturated, or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, and wherein the benzene/heterocycle fused ring is attached at any site to X or to the tetrapeptide, or (18) a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms fused to a second 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, each heterocyclic ring independently optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd, cyano, CO2R b or halogen, wherein each heterocycle may be saturated, partly unsaturated or fully unsaturated, and wherein each heteroatom independently is oxygen, sulfur, or nitrogen, and the nitrogen optionally has an Rc substituent. Within the above class of compounds, there is a subclass of compounds represented by Formula I or a pharmaceutically acceptable salt thereof wherein n is 1 or 2. In one aspect, the present invention provides a novel cyclic tetrapeptide represented by Formula I, wherein X is preferably -CH2-. In another aspect, the present invention provides a novel cyclic tetrapeptide represented by Formula I, wherein X is preferably -C(O)-. In still another aspect, the present invention provides a novel cyclic tetrapeptide represented by Formula I, wherein X is preferably not present. In yet another aspect, the present invention provides a novel cyclic tetrapeptide represented by Formula I, wherein R is preferably a 3- to 8-membered heterocycle containing 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2-C5alkenyl, Cι-C5perfluoroalkyl, NRCRd, oxo, thiono, OR a , S(O) n jR a (where ni = 0, 1 or 2), C(O)R a , C(O)NRCRd ; cyano, (Co-C6alkyl)aryl, CO2R b , or halogen, and each group may be saturated, partly unsaturated or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent. In another aspect, the present invention provides a novel cyclic tetrapeptide represented by Formula I, wherein Ri is preferably a benzene ring fused to a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups each independently is Cι-C5alkyl, C2-C5alkenyl, Ci- C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd ) cyano, CO2R b or halogen, each group may be saturated, partly unsaturated, or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an R c substituent, and wherein the benzene/heterocycle fused ring is attached at any site to X or to the tetrapeptide In another aspect, the present invention provides a novel cyclic tetrapeptide represented by Formula I, wherein Ri is preferably a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms fused to a second 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, each heterocyclic ring independently optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd 5 cyano, CO2R b or halogen, wherein each heterocycle may be saturated, partly unsaturated or fully unsaturated, and wherein each heteroatom independently is oxygen, sulfur, or nitrogen, and the nitrogen optionally has an R c substituent. In another aspect, the present invention provides a novel cyclic tetrapeptide represented by Formula I, wherein the compound is Example 2, 3a, 3b, 3d, 10, 11, 12d, 12e, 17, or 18: In another aspect, the present invention provides a novel cyclic tetrapeptide represented by Formula I, wherein the compound is Example 22a, 22b, 23a, 23b, 145, 146c, 146d, 146e, 146f, or 147: In yet another aspect, the present invention provides a novel cyclic tetrapeptide represented by Formula I, wherein the compound is Example 21a, 21b, 24a, 24b, 26, 27, 28, 29, 30, 32, 37, 39, 43, 44, 46, 51, 56a, 63, 64, or 67: In another aspect, the present invention provides a novel cyclic tetrapeptide represented by Formula I, wherein the compound is Example 69, 70, 72, 73, 74a. 74b, 74c, 74d, 74e, 74f, 74g, 74h, 74i, 74j, 75, 79, 91, 93, 97, 98, 129a, or 129b: In yet another aspect, the present invention provides a novel cyclic tetrapeptide represented by Formula I, wherein the compound is Example 132a, 133, 135, 138, 139a, 139b, 139c, 139d, 139e, 139f, 139g, 139h, 139i, 139j, 140, 141, 142, 144b, 144d, 144f, 158, 159, 160, 162a, or 162b. In still another aspect, the present invention provides a novel cyclic tetrapeptide represented by Formula I, wherein the compound is Example 102, 103, 108a, or 108b. In another aspect, the present invention provides a novel cyclic tetrapeptide represented by Formula I, wherein the compound is Example 109 or 110. In another aspect, the present invention provides a novel cyclic tetrapeptide represented by Formula I, wherein the compound is Example 168. In another aspect, the present invention provides a novel cyclic tetrapeptide represented by Formula I, wherein the compound is Example 156, 157a, 157b, 157c, or 157d. In another aspect, the present invention provides a novel cyclic tetrapeptide represented by Formula I, wherein the compound is In another aspect, the present invention provides a novel cyclic tetrapeptide represented by Formula I, wherein the compound is In another aspect, the present invention provides a novel cyclic tetrapeptide represented by Formula I, wherein the compound is Example 153 or 154. In another aspect, the present invention provides a method for the treatment of protozoal infections comprising the step of administering to a host suffering from a protozoal infection a therapeutically effective amount of the novel compounds of the invention which inhibits histone deacetylase. A therapeutically effective amount is that safe amount sufficient to inhibit histone deacetylase activity of the causative protozoa to control and overcome the infection. The present invention also provides a method for the prevention of protozoal infections comprising the step of administering to a host an effective preventative amount of the novel compounds of the invention, which inhibits histone deacetylase. An effective preventative amount is that safe amount sufficient to inhibit the infection of the host. In yet another aspect, the present invention provides a composition useful for the treatment or prevention of protozoal diseases which comprises an inert carrier and an effective amount of a compound of formula I. As used herein, "alkyl" as well as other groups having the prefix "alk" such as, for example, alkoxy, alkanoyl, alkenyl, alkynyl and the like, means carbon chains which may be linear or branched or combinations thereof. Examples of alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, sec- and tert-butyl, pentyl, hexyl, heptyl and the like. "Alkenyl", "alkynyl" and other like terms include carbon chains containing at least one unsaturated C-C bond. The term "cycloalkyl" means carbocycles containing no heteroatoms, and includes mono-, bi- and tricyclic saturated carbocycles, as well as fused ring systems. Such fused ring systems can include one ring that is partially or fully unsaturated such as a benzene ring to form fused ring systems such as benzofused carbocycles. Cycloalkyl includes such fused ring systems as spirofused ring systems. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, decahydronaphthalene, adamantane, indanyl, indenyl, fluorenyl, 1,2,3,4- tetrahydronaphalene and the like. Similarly, "cycloalkenyl" means carbocycles containing no heteroatoms and at least one non-aromatic C-C double bond, and include mono-, bi- and tricyclic partially saturated carbocycles, as well as benzofused cycloalkenes. Examples of cycloalkenyl include cyclohexenyl, indenyl, and the like. The term "halogen" includes fluorine, chlorine, bromine and iodine atoms. The term "heterocycle", unless otherwise specified, means cyclic systems such as those described above for cycloalkyl and cycloalkenyl in which at least one atom is a sulfur, oxygen or nitrogen atom in a group of atoms that form the backbone of a ring. Such heterocycles include mono- or bicyclic compounds that are saturated or partly unsaturated, as well as benzo- or heteroaromatic ring fused saturated heterocycles or partly unsaturated heterocycles, and containing from 1 to 4 heteroatoms independently selected from oxygen, sulfur and nitrogen. Examples of saturated heterocycles include morpholine, thiomorpholine, piperidine, piperazine, tetrahydropyran, tetrahydrofuran, dioxane, tetrahydrothiophene, oxazolidine, pyrrolidine; examples of partly unsaturated heterocycles include dihydropyran, dihydropyridazine, dihydrofuran, dihydrooxazole, dihydropyrazole, dihydropyridine, dihydropyridazine and the like. Examples of benzo- or heteroaromatic ring fused heterocycle include 2,3-dihydrobenzofuranyl, benzopyranyl, tetrahydroquinoline, tetrahydroisoquinoline, benzomorpholinyl, 1,4-benzodioxanyl, 2,3-dihydrofuro(2,3- b)pyridyl and the like. The term "aryl" is intended to include mono- and bicyclic aromatic and heteroaromatic rings containing from 0 to 5 heteroatoms independently selected from nitrogen, oxygen and sulfur. The term "aryl" is also meant to include benzofused cycloalkyl, benzofused cycloalkenyl, and benzofused heterocyclic groups. Examples of "aryl" groups include phenyl, pyrrolyl, isoxazolyl, pyrazinyl, pyridinyl, oxazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, furanyl, triazinyl, thienyl, pyrimidinyl, pyridazinyl, pyrazinyl, naphthyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furo(2,3-B)pyridyl, 2,3-dihydrofuro(2,3-b)pyridyl, benzoxazinyl, benzothiophenyl, quinolinyl, indolyl, 2,3-dihydrobenzofuranyl, benzopyranyl, 1,4- benzodioxanyl, indanyl, indenyl, fluorenyl, 1,2,3,4-tetrahydronaphthalene and the like. Aroyl means arylcarbonyl in which aryl is as defined above. Examples of NR c Rd or NR§R n forming a 3- to 10- membered ring containing 0 to 2 additional heteroatoms selected from O, S(O) m and N are aziridine, azetidine, pyrrolidine, piperidine, thiomorpholine, morpholine, piperazine, octahydroindole, tetrahydroisoquinoline and the like. The term "Co" means that the carbon is not present. Thus, "C0-C5" means that there are from none to five carbons present - that is, five, four, three, two, one, or no carbons present. The term "optionally substituted" is intended to include both substituted and unsubstituted. Thus, for example, optionally substituted aryl could represent a pentafluorophenyl or a phenyl ring. Compounds described herein contain one or more asymmetric centers and may thus give rise to diastereomers and optical isomers. The present invention includes all such possible diastereomers as well as their racemic mixtures, their substantially pure resolved enantiomers, all possible geometric isomers, and pharmaceutically acceptable salts thereof. The above Formula I is shown without a definitive stereochemistry at certain positions. The present invention includes all stereoisomers of Formula I. Further, mixtures of stereoisomers as well as isolated specific stereoisomers are also included. During the the course of the synthetic procedures used to prepare such compounds, or in using racemization or epimerization procedures known to those skilled in the art, the products of such procedures can be a mixture of stereoisomers. The term "pharmaceutically acceptable salts" refers to salts prepared from pharmaceutically acceptable non-toxic bases or acids. When the compound of the present invention is acidic, its corresponding salt can be conveniently prepared from pharmaceutically acceptable non-toxic bases, including inorganic bases and organic bases. Salts derived from such inorganic bases include aluminum, ammonium, calcium, copper (ic and ous), ferric, ferrous, lithium, magnesium, manganese (ic and ous), potassium, sodium, zinc and the like salts. Particularly preferred are the ammonium, calcium, magnesium, potassium and sodium salts. Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, and tertiary amines, as well as cyclic amines and substituted amines such as naturally occurring and synthesized substituted amines. Other pharmaceutically acceptable organic non-toxic bases from which salts can be formed include ion exchange resins such as, for example, arginine, betaine, caffeine, choline, N,N -dibenzylethylenediamine, diethylamine, 2-diethylaminoethanol, 2- dimethylaminoethanol, ethanolamine, ethylenediamine, N-ethylmorpholine, N- ethylpiperidine, glucamine, glucosamine, histidine, hydrabamine, isopropylamine, lysine, methylglucamine, morpholine, piperazine, piperidine, polyamine resins, procaine, purines, theobromine, triethylamine, trimethylamine, tripropylamine, tromethamine and the like. When the compound of the present invention is basic, its corresponding salt can be conveniently prepared from pharmaceutically acceptable non-toxic acids, including inorganic and organic acids. Such acids include, for example, acetic, benzenesulfonic, benzoic, camphorsulfonic, citric, ethanesulfonic, fumaric, gluconic, glutamic, hydrobromic, hydrochloric, isethionic, lactic, maleic, malic, mandelic, methanesulfonic, mucic, nitric, pamoic, pantothenic, phosphoric, succinic, sulfuric, tartaric, p-toluenesulfonic acid and the like. Particularly preferred are citric, hydrobromic, hydrochloric, maleic, phosphoric, sulfuric, and tartaric acids. The concept of the inhibition of histone deacetylase as a target for antiprotozoal compounds is described in pending U.S. Patent Applications 09/296,834, filed April 22, 1999, and 08/716,978, filed September 20, 1996. Known compounds that may be histone deacetylase inhibitors and therefore useful in the treatment of protozoal diseases include, for example, trichostatin A, trapoxin A and B, HC -toxin, chlamydocin, Cly-2, WF-3161, Tan-1746, apicidin, and analogs thereof. Trapoxin A is described in Itazaki et al., J. Antibiot. 43, 1524-1532(1990); HC-Toxin is described in Liesch et al., Tetrahedron 38 ^ 45-48(1982); chlamydocin is described in Closse et al., Helv. Chim. Acta 57, 533-545(1974); Cly-2 is described in Hirota et al., Agri. Biol. Chem 37, 955-56(1973); WF-3161 is described in Umehana et al., J. Antibiot. 36, 478-483(1983); and Tan-1746 is described in Japanese Patent No. 7196686. Unlike the ethyl ketone sidechain found in apicidin, HC toxin, chlamydocin, trapoxin A and trapoxin B contain a C8 α-ketoepoxide functionality. Apicidin and analogs thereof referred to herein are described by the following chemical formula: Apicidin es include Compound n Rl R2 R3 Apicidin la 1 H OMe H lb 0 H OMe H Ic 1 H OMe OH ΠA 1 =O OMe H ΠB 1 =O H H These compounds are described in pending U.S. Patent Application Nos. 08/281,325, filed July 27, 1994 and 08/447,664, filed May 23, 1995. The compounds are produced from a strain of Fusaήum as disclosed in the applications. The compounds of the present invention have been found to be histone deacetylase inhibitors. Accordingly, they can be useful in the treatment and prevention of protozoal diseases in human and animals, including poultry. Examples of protozoal diseases against which histone deacetylase inhibitors may be used, and their respective causative pathogens, include: 1) amoebiasis (Dientamoeba sp., Entamoeba histolytica); 2) giardiasis (Giardia lamblia); 3) malaria (Plasmodium species including P. vivax, P. falciparum, P. malariae and P. ovale); 4) leishmaniasis (Leishmania species including L. donovani, L. tropica, L. mexicana, and L. braziliensis); 5) trypanosomiasis and Chagas disease (Trypanosoma species including T. brucei, T. theileri, T. rhodesiense, T. gambiense, T. evansi, T. equiperdum, T. equinum, T. congolense, T. vivax and T. cruzi); 6) toxoplasmosis (Toxoplasma gondii); 1) neosporosis (Neospora caninum); 8) babesiosis (Babesia sp. ; 9) cryptosporidiosis (Cryptosporidium sp.); 10) dysentary (Balantidium coli); 11) vaginitis (Trichomonas species including T.vaginitis, and T. foetus); 12) coccidiosis (Eimeria species including E. tenella, E. necatrix, E. acervulina, E. maxima and E. brunetti, E. mitis, E. bovis, E. melagramatis, and Isospora sp ; 13) enterohepatitis (Histomonas gallinarum); and 14) infections caused by Anaplasma sp., Besnoitia sp., Leucocytozoan sp., Microspoήdia sp., Sarcocystis sp., Theileria sp., and Pneumocystis carinii. The histone deacetylase inhibiting compounds and compositions of the present invention are preferably used in the treatment or prevention of protozoal infections caused by a member of the sub-phylum Apicomplexans. More preferably the compounds and compositions are used i) in the treatment or prevention of malaria, toxoplasmosis, cryptosporidiosis and trypanosomiasis in humans and animals, and ii) in the management of coccidiosis, particularly in poultry, either to treat coccidial infection or to prevent the occurrence of such infection. When the histone deacetylase inhibiting compounds and compositions of this invention are administered on a chronic basis, such as in the prevention of coccidiosis in poultry, the histone deacetylase inhibitor preferably is selective for protozoal histone deacetylase over the host histone deacetylase. Such a selective inhibitor would minimize adverse histone deacetylase inhibition effects to the host over the long term. Two specific examples of the method of this invention of administering an effective preventative amount of an histone deacetylase inhibitor to prevent the establishment of parasitic infections in humans and animals are 1) the prevention of Plasmodium (malaria) infection in humans in endemic areas and 2) the prevention of coccidiosis in poultry. The histone deacetylase-inhibiting compound can be conveniently administered continually in the feed or drinking water, or regularly by oral or parenteral dosing. Malaria is the number one cause of death in the world. The disease is transmitted by mosquitoes in endemic areas and can very rapidly progress to a life threatening infection. Therefore, individuals living in or visiting areas where malaria carrying mosquitoes are present routinely take prophylactic drugs to prevent infection. Thus, according to an embodiment of the present invention, a histone deacetylase inhibitor is administered orally or parenterally one or more time(s) a day, preferably each dose ranges from about O.Olmg/kg to about lOOmg/kg. The compound may be administered for the entire period during which the patient or animal is at risk of acquiring a parasitic infection. Coccidiosis is a disease that can occur in humans and animals and is caused by several genera of coccidia. The most economically important occurrence of coccidiosis is the disease in poultry. Coccidiosis in poultry is caused by protozoan parasites of the genus Eimeria. The disease can spread quite rapidly throughout flocks of birds via contaminated feces. The parasites destroy gut tissue and damage the gut lining, thereby impairing nutrient absorption. An outbreak of coccidiosis in a poultry house can cause such dramatic economic losses for poultry producers that it has become standard practice to use anticoccidial agents prophylactically in the poultry feed. Thus, according to another embodiment of this invention, a histone deacetylase inhibitor is administered in the feed or drinking water for the entire or a portion of the lifetime of domestic birds with a dose that ranges between about 0.1 ppm to about 500ppm in the feed or water. For treatment of established parasitic infections in humans or animals, the histone deacetylase inhibitor is conveniently administered orally or parenterally when the infection is suspected or diagnosed. The treatment period varies according to the specific parasitic disease and the severity of the infection. In general the treatment is continued until the parasites are effectively eradicated and/or the symptoms of the disease are resolved. Two specific examples of the method of this invention for the treatment of protozoal infections by administering a therapeutically effective amount of a histone deacetylase inhibitor are 1) the treatment of a Cryptosporidium parvum infection in an animal or human and 2) the treatment of acute Plasmodium falciparum malaria in humans. Cryptosporidium parvum is a protozoan parasite that infects and destroys cells lining the intestinal tract of humans and animals. The infection establishes quite rapidly and has acute effects on the patient. In the case of humans, patients get severe dysentery for a period of 5-7 days. In immune compromised patients C. parvum infections can persist and can be life threatening. In animals C. parvum infection is the leading cause of death in young dairy calves. A C. parvum infection can be easily diagnosed by symptoms and examination of a stool sample. When the disease is suspected and/or diagnosed, treatment with a histone deacetylase inhibitor according to the method of this invention can be initiated. The dose preferably ranges from about O.Olmg/kg to about 500mg/kg. The histone deacetylase is administered one or more time(s) a day, orally or parenterally until the infection is eliminated. The dosing period typically is in the range of about 1-3 weeks. P. falciparum causes acute life threatening malarial infections in humans. The infection if left untreated can often result in the death of the patient. A malaria infection can be easily diagnosed by symptoms and examination of a blood sample from the patient. Treatment would be initiated following diagnosis. According to an embodiment of this invention, a histone deacetylase inhibitor is administered one or more time(s) a day, orally or parenterally, until the infection is eliminated. The dose preferably ranges from about O.Olmg kg to about 200 mg/kg. The histone deacetylase inhibiting compositions of this invention may be administered to a host in need of treatment in a manner similar to that used for other known antiprotozoal agents. For example, the compositions may be administered parenterally, orally, topically, or rectally. The dosage to be administered will vary according to the particular compound used, the infectious organism involved, the particular host, the severity of the disease, the physical condition of the host, and the selected route of administration; the appropriate dosage can be readily determined by a person skilled in the art. For the treatment of protozoal diseases in human and animals, the dosage preferably ranges from about O.Olmg/kg to about 500mg/kg. For prophylactic use in human and animals, the dosage preferably ranges from about O.Olmg/kg to about lOOmg/kg. For use as an anticoccidial agent, particularly in poultry, the compound is preferably administered in the animals' feed or drinking water. The dosage preferably ranges from about O.lppm to about 500ppm. In one aspect, the composition of the present invention comprises a histone deacetylase inhibitor and an inert carrier. The compositions include pharmaceutical compositions for human and veterinary usage, and feed compositions for the control of coccidiosis in poultry. The pharmaceutical compositions of the present invention comprise a histone deacetylase inhibitor as an active ingredient, a pharmaceutically acceptable carrier and optionally other therapeutic ingredients or adjuvants. The compositions include compositions suitable for oral, rectal, topical, and parenteral (including subcutaneous, intramuscular, and intravenous) administration, although the most suitable route in any given case will depend on the particular host, and nature and severity of the conditions for which the active ingredient is being administered. The pharmaceutical compositions may be conveniently presented in unit dosage form and prepared by any of the methods well known in the art of pharmacy. In practice, the histone deacetylase inhibitor of this invention can be combined as the active ingredient in intimate admixture with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques. The carrier may take a wide variety of forms depending on the form of preparation desired for administration, e.g., oral or parenteral (including intravenous). Thus, the pharmaceutical compositions of the present invention can be presented as discrete units suitable for oral administration such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient. Further, the compositions can be presented as a powder, as granules, as a solution, as a suspension in an aqueous liquid, as a non-aqueous liquid, as an oil-in-water emulsion or as a water-in-oil liquid emulsion. In addition to the common dosage forms set out above, the histone deacetylase inhibitors may also be administered by controlled release means and/or delivery devices. The compositions may be prepared by any of the methods of pharmacy. In general, such methods include a step of bringing into association the active ingredient with the carrier that constitutes one or more necessary ingredients. In general, the compositions are prepared by uniformly and intimately admixing the active ingredient with liquid carriers or finely divided solid carriers or both. The product can then be conveniently shaped into the desired presentation. In preparing the compositions for oral dosage form, any convenient pharmaceutical media may be employed. For example, water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents and the like may be used to form oral liquid preparations such as suspensions, elixirs and solutions; while carriers such as starches, sugars, microcrystalline cellulose, diluents, granulating agents, lubricants, binders, disintegrating agents, and the like may be used to form oral solid preparations such as powders, capsules and tablets. Because of their ease of administration, tablets and capsules are the preferred oral dosage units whereby solid pharmaceutical carriers are employed. Optionally, tablets may be coated by standard aqueous or nonaqueous techniques A tablet containing the composition of this invention may be prepared by compression or molding, optionally with one or more accessory ingredients or adjuvants. Compressed tablets may be prepared by compressing, in a suitable machine, the active ingredient in a free-flowing form such as powder or granules, optionally mixed with a binder, lubricant, inert diluent, surface active or dispersing agent. Molded tablets may be made by molding in a suitable machine, a mixture of the powdered compound moistened with an inert liquid diluent. Each tablet preferably contains from about lmg to about 500mg of the active ingredient and each cachet or capsule preferably containing from about 1 to about 500mg of the active ingredient. Pharmaceutical compositions of the present invention suitable for parenteral administration may be prepared as solutions or suspensions of the active compounds in water. A suitable surfactant can be included such as, for example, hydroxypropylcellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof in oils. Further, a preservative can be included to prevent the detrimental growth of microorganisms. Pharmaceutical compositions of the present invention suitable for injectable use include sterile aqueous solutions or dispersions. Furthermore, the compositions can be in the form of sterile powders for the extemporaneous preparation of such sterile injectable solutions or dispersions. In all cases, the final injectable form must be sterile and must be effectively fluid for easy syringability. The pharmaceutical compositions must be stable under the conditions of manufacture and storage; thus, preferably should be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g. glycerol, propylene glycol and liquid polyethylene glycol), vegetable oils, and suitable mixtures thereof. Pharmaceutical compositions of the present invention can be in a form suitable for topical use such as, for example, an aerosol, cream, ointment, lotion, dusting powder, or the like. Further, the compositions can be in a form suitable for use in transdermal devices. These formulations may be prepared, utilizing the histone deacetylase inhibiting compounds of this invention, via conventional processing methods. As an example, a cream or ointment is prepared by mixing hydrophilic material and water, together with about 5 wt% to about 10 wt% of the compound, to produce a cream or ointment having a desired consistency. Pharmaceutical compositions of this invention can be in a form suitable for rectal administration wherein the carrier is a solid. It is preferable that the mixture forms unit dose suppositories. Suitable carriers include cocoa butter and other materials commonly used in the art. The suppositories may be conveniently formed by first admixing the composition with the softened or melted carrier(s) followed by chilling and shaping in moulds. In addition to the aforementioned carrier ingredients, the pharmaceutical formulations described above may include, as appropriate, one or more additional carrier ingredients such as diluents, buffers, flavoring agents, binders, surface-active agents, thickeners, lubricants, preservatives (including anti-oxidants) and the like. Furthermore, other adjuvants can be included to render the formulation isotonic with the blood of the intended recipient. As described above, to manage coccidiosis in poultry, the histone deacetylase inhibitor of this invention can be conveniently administered as a component of a feed composition. The poultry feed preferably contains from about lppm to about lOOOppm, more preferably from about lOppm to about 150ppm of the histone deacetylase inhibitor of this invention. The optimum levels will vary with the species of Eimeria involved, and can be readily determined by one skilled in the art. It is preferred that the histone deacetylase inhibitor of this invention be added to poultry feed in the amount of from about 0.01% to about 0.1% by weight of the diet. The compositions of this invention are especially useful in controlling the pathology associated with E. tenella. The preferred concentration for similar control of intestinal-dwelling species is from about 0.01% to about 0.1% by weight of the diet. Amounts of about 0.01% to about 0.1% percent by weight are advantageous in reducing the pathogenic effects of both fecal coccidiosis and intestinal coccidiosis. In the preparation of poultry feed incorporating the compositions of the invention, the histone deacetylase inhibitor can be conveniently dispersed, for example, by i) being mechanically mixed in a finely ground form with the poultry feedstuff, or ii) being first mixed with an intermediate formulation (to form a premix) that is subsequently blended with other poultry feedstuff components. Typical components of poultry feedstuffs include molasses, fermentation residues, corn meal, ground and rolled oats, wheat shorts and middlings, alfalfa, clover and meat scraps, together with mineral supplements such as bone meal, calcium carbonate and vitamins. Compositions containing a compound described by formula I may also be prepared in powder or liquid concentrate form. In accordance with standard veterinary formulation practice, conventional water-soluble excipients, such as lactose or sucrose, may be incorporated in the powders to improve their physical properties. It is preferable that the powder compositions of this invention comprise from about 50wt% to about 100wt%, and more preferably about 60wt% to about 80wt% of the compound. These powders may either be added to animal feedstuffs, for example, by way of an intermediate premix, or added to the animal drinking water by dilution. Liquid concentrates of this invention suitably contain a water-soluble compound combination and may optionally further include a veterinary acceptable water miscible solvent. For example, a solvent such as polyethylene glycol, propylene glycol, glycerol, or glycerol formal can be mixed with up to 30% v/v of ethanol. It is preferable that the liquid concentrates of this invention comprise from about 50wt% to about 100wt%, and more preferably about 60wt% to about 80wt% of the compound. The liquid concentrates may be administered to the drinking water of animals, particularly poultry. The following examples are provided to more fully illustrate the present invention, and are not to be construed as limiting the scope of the claims in any manner. Preparation of Side Chain-Modified Apicidin Analogs Referring to Scheme I below, apicidin can be converted into alpha- substituted analog compounds 4 and 5. Scheme I Λ : Apicidin 1) Base 1) Oxidize 2) RX 2) Deprotect Oxidative Cleavage Apicidin is first enolized with an appropriate amine base including, but not limited to, LiN( Pr)2, NaN(SiMe3)2, KN(SiMe3)2, and the like at temperatures ranging from -78°C to 0°C to form an enolate. The amine base is preferably KN(SiMe3)2- Appropriate solvents for this reaction include, but are not limited to, Et2θ, dioxane, tetrahydrofuran (THF), dimethoxyethane, and the like. The solvent is preferably THF. The enolate is reacted with an appropriate electrophile RX including, but not limited to, Mel, Etl, allyl bromide, benzyl bromide, PhSeCl, PhSCl, PhSSPh, (MeO)2P(O)Cl, (CF2SO2)2O, Et3SiCl, tBu(Me)2SiCl, (nPr)3SiCl, Me3SiCl, Ph(Me)2SiCl, and the like to form a silyl enol ether. The electrophile is preferably Me3SiCl. Treatment of the thus prepared silyl enol ethers with an oxidant, including but not limited to, H2O2, tBuOOH, Me3SiOOH, AcOOH, dimethydioxirane and the like, or preferably MCPBA (meta-chloroperbenzoic acid), at temperatures from -78°C to RT (room temperature) but preferably 0°C to RT will produce the corresponding alpha-silyloxyketones, compounds 4a/5a. The silyl protecting groups can be then removed using a variety of acid or fluoride sources including, but not restricted to, HC1, H2SO4, HBF4, acetic acid, PPTS (pyridinium p- toluenesulfonate), TsOH (p-toluenesulfonyl hydroxide), HF, HF'pyridine, or Bu4NF and the like in protic or aprotic solvents including, but not limited to, CH2CI2, CHCI3, MeOH, EtOH, iPrOH, THF, Et2θ and dioxane and the like at temperatures from 0°C to 50°C to generate the alpha-hydroxyketones, compounds 4d/5d. The alpha-hydroxyketone compounds 4d/5d may be separated or used with no further separation, as desired. Compounds 4d/5d can be oxidized to the corresponding diketones, compounds 4e/5e, by treatment including, but not limited to, Swern oxidation, Dess-Martin oxidation, PCC (pyridinium chlorochromate), PDC (pyridinium dichromate), Moffat-oxidation, and the like, or most preferably TPAP/NMO (tetrapropylammonium perruthenate(VU)/4-methylmo holine N-oxide) in solvents including, but not limited to, toluene, CH2CI2, CHCI3 and the like at temperatures ranging from -78°C to RT. The alpha-hydroxyketone compounds 4d/5d can be converted into the corresponding alpha-haloketone compounds such as 4f/5f by treatment with Ph3P/CBr4, Ph3P/l2, PH3P/CCI4, Ph3P/CHCl2CHCl2, DAST (diethylaminosulfur trifluoride), morpholinyl sulfur trifluoride, and the like in solvents such as CH2CI2, CHCI3, benzene, toluene and the like at temperatures from -78°C to RT. The alpha-hydroxyketone compounds 4d/5d can be treated with an oxidizing agent including, but not restricted to, NaK>4, HIO4, Mnθ2, Amberlite® IRA-904 ion-exchange resin available from Aldrich Chemical Company, Milwaukee, Wisconsin, NaIO4, KIO4, and nBu4NIO4, or most preferably Pb(OAc)4 to yield a C7-aldehyde compound 6, and a C8-methyl ester compound 7, by an oxidative cleavage reaction. The oxidative cleavage reaction may be performed in a variety of solvents or mixtures of solvents, including water, EtOH, ϊ ' PrOH (isopropanol), tBuOH (tert-butanol), acetone, ether, THF, benzene, toluene, CH2CI2, CHCI3, and the like, or most preferably MeOH. Generally, the oxidative cleavage reaction is performed at temperatures from about -78°C to about 80°C. When utilizing MeOH, the reaction should be performed at temperatures from -20°C to RT. The oxidative cleavage reaction may be improved by the addition of a base, including but not restricted to NaHCO3, Et3N, EtN( Pr)2, lutidine and the like, or most preferably pyridine. The oxidative cleavage reaction is generally complete in from about 5 minutes to about 24 hours. Referring to Scheme II below, the phenylsulfide compounds 4c/5c or phenylselenide compounds 4b/5b, analogs of apicidin, are oxidized to the corresponding sulfoxide or selenoxide compounds (not shown) using reagents which include, but not limited to, Oxone, MCPBA, tBuOOH, AcOOH, NaIO4, dimethyldioxirane, and the like, or most preferably H2O2, in solvents or mixtures of solvents, including, but not limited to toluene, CHCI3, MeOH, water, or most preferably CH2CI2 and at temperatures ranging from -20°C to 50°C. Scheme II 8 1) Dihydroxylate 2) Oxidative cleavage 10 Although the Scheme II shows only compounds 4b/5b as the starting compounds, the same scheme applies just as well to using compounds 4c/5c as starting compounds. The sulfoxides and selenoxides are thermally eliminated to generate the corresponding enone compounds 8 and 9 in solvents including, but not limited to, CH2CI2, CHCI3, MeOH, or most preferably toluene, at temperatures ranging from RT to 110°C. Enone compounds 8 and 9 can be epoxidized (not shown) with appropriate epoxidizing agents including, but not limited to, dimethyldioxirane, H2O2, tBuOOH, AcOOH, and the like, or most preferably MCPBA, in solvents or mixtures of solvents including, but not limited to, toluene, CHCI3, MeOH, or most preferably CH2CI2, at temperatures ranging from -20°C to RT. Enone compounds 8 and 9 also may be dihydroxylated with OSO4 under conditions known to those skilled in the art to form the corresponding diols. Osmium tetroxide may be used either stoichiometrically or catalytically in the presence of an oxidant including, but not restricted to, morpholine N-oxide, trimethylamine N-oxide, hydrogen peroxide, tert-butyl hydroperoxide and the like. The dihydroxylation reactions are performed in a variety of solvents or mixtures of solvents. The solvents include both protic and aprotic solvents such as water, MeOH, EtOH, tert-butanol, ether, THF, benzene, pyridine, acetone, and the like. The dihydroxylation reactions are performed at from -78 °C to 80°C and are complete in from 5 minutes to 24 hours. The diol products thus obtained can be oxidatively cleaved as described previously for compounds 6 and 7 to yield a C6-aldehyde compound 10 and a C8 methyl ester compound 7 from compounds 8 and 9, respectively. Referring to Scheme m below, apicidin's sidechain C8-ketone group can be a starting point for analog synthesis. Scheme III NΛ WW* Λ Apicidiiv 11a: OH 11 b: OH, R 1 1 11 c: OC(O)R 11 c or OC(S)R 11 c 11 d: OSO 2 R 1 1 d 11e: H 1 h 11j: epoxide 11 k: SR-nk Rllb, Rile Rlld, Rllfl, Rllf2. Rllg, RHh, Rllil, Rlli2, and Rllk are each independently an alkyl or aryl group which optionally is substituted. By Scheme HI, the sidechain C8-ketone group can be reduced using reagents known to those skilled in the art, including, but not limited to LiBI j., IJAIH4, DIBAL-H (diisobutylaluminum hydride), K-Selectride® (potassium tή-sec- butylborohydride) available from Aldrich Chemical Company, Milwaukee, Wisconsin, L-Selectride® (lithium tri-sec-butylborohydride) available from Aldrich, Alpine-Borane® (B-isopinocampheyl-9-borabicyclo[3.3.1]-nonane) available from Aldrich, and the like or most preferably NaBH j. to yield the C8 alcohol compound 11a. These reduction reactions may be performed in protic or aprotic solvents including, but not limited to, THF, ether, dimethyl ether, dioxane, EtOH, CH2CI2, EtOAc, CHCI3, benzene, toluene, or most preferably MeOH, and at temperatures from -78°C to RT. Apicidin 's sidechain C8-ketone group can also be treated with RMgBr, RMgCl, RMgl, RLi, R2CuLi, RCeCl2Li and the like to generate substituted alcohol compounds lib. In these RLi, RLiX, or RMgX type reactants, R is an alkyl or aryl group, and the alkyl and aryl groups are optionally substituted. These substitution reactions may be performed in solvents or mixtures of solvents, including but not limited to, Et2θ, dioxane, HMPA (hexamethylphosphoramide), DMSO, NMP (1- methyl-2-pyrrolidinone), dimethoxyethane, and the like, or most preferably THF, at temperatures from -78 °C to RT, and are complete in from 5 minutes to 12 hours. The C8-alcohol compound 11a generated above can be alkylated, acylated or sulfonylated using known methods for acylation, sulfonylation and alkylation of alcohols to generate apicidin derivative compounds lie or lid. Thus, acylation may be accomplished using reagents such as acid anhydrides, acid chlorides, chloroformates, carbamoyl chlorides, ClC(S)OPh(F5), thiocarbonyldimidazole, isocyanates, and the like, and amine bases according to general procedures known to those skilled in the art. Sulfonylations may be carried out using sulfonyl chlorides or sulfonic anhydrides. Alkylations may be carried out using alkyl halides or trichloroacetimi dates. Suitable solvents for these reactions include benzene, toluene, CHCI3, CH2CICH2CI, and the like, or most preferably CH2CI2, and may be performed from temperatures of -40°C to 80°C. The hydroxyl group at C8 of compound 11a can be eliminated using Burgess reagent, Martin's sulfurane reagent or by treating compound lid with a base to generate a mixture of C6, C7- and C7, C8-olefin isomers. Suitable bases include, but are not limited to, Et3N, EtN(z ' Pr)2, NaOMe, KOtBu, and the like or most preferably DBU in solvents such as CH2CI2, CHCI3, toluene, benzene, MeOH, EtOH, pyridine and the like and at temperatures from 0°C to 110°C. The C8-hydroxyl group of compound 11a can also be eliminated by reduction via the intermediary compound lie wherein R is OPh, OPh(F5), Set, and the like, or most preferably N-1-imidazolyl. Intermediary compound lie is treated with i) a radical initiator such as oxygen/Et3B, AIBN (2,2'-azobisisobutyronitrile), benzoyl peroxide and the like, and ii) a hydride source, including, but not limited to, Et3SiH, Me3SnH, Ph3SnH, Ph3AsH, nBu3SnCl/NaBH4, and the like, or most preferably «Bu3SnH in solvents including but not limited to CH2CI2, CHCI3, benzene, MeOH, EtOH, or most preferably toluene, and the like, at temperatures from -78°C to 110°C, to form compound lie. Apicidin can be treated with mono- or disubstituted amines, a hydride source, and a proton source to generate compound llf. Suitable solvents include, but are not restricted to, benzene, toluene, EtOH, PrOH and the like, or more preferably, MeOH. Suitable proton sources include, but are not limited to, TsOH, HC1, HCO2H, PPTS and the like, or most preferably HOAc. The intermediate imine may be reduced in situ as it is formed or after azeotropic removal of water using a Dean-Stark trap. Suitable reducing agents include, but are not limited to, LiAlH4, NaBH4, LiBEL)., H2/(10% Pd/C) and the like, or most preferably NaBH3CN. Oxime compound llg and hydrazone compound llh are prepared by treating apicidin with hydrazine in a solvent with a proton source. For example, apicidin can be treated with mono- or disubstituted amines, and a proton source. Suitable solvents include, but are not restricted to, benzene, toluene, EtOH, iPrOH and the like, or more preferably, MeOH. Suitable proton sources include, but are not limited to, TsOH, HC1, HCO2H, PPTS and the like, or most preferably HOAc. Apicidin is treated with stabilized Wittig reagents, unstabilized Wittig reagents or Horner-Emmons reagents to generate the unsaturated product, compound Hi. Suitable reagents include, but are not limited to, Ph3P=CH2, Ph3P=CHMe, Ph3P=CH(nPr), (MeO)2P(O)CH2CO2Me, Ph3P=CH2C(O)Me and the like. These olefination reactions may be performed in solvents including, but not limited to, DMF (N,N-dimethylformamide), MeOH, CH2CI2, toluene, Et2θ, MeCΝ, THF and the like and may be performed at from -78°C to 110°C. The C8 ketone of apicidin may be converted into an epoxide (compound llj) by treated with CH2=Ν2 or Me3SiCH=N2 in MeOH, or Me3S(O)I in a solvent such as tBuOH, dimethoxyethane, THF, DMF, DMSO, or more preferably HMPA and a strong base such a tBuOK, nBuLi, or more preferably NaH at temperatures from -78°C to 50°C. Treatment of compound lid with an appropriate sulfur containing nucleophile permitted the introduction of sulfur at C8 to form compound Ilk. Suitable nucleophiles include NaSMe, KSAc, HSPh Et3N, HSCH2CH2OH/EtN( Pr)2 and the like. These reactions proceed readily in polar solvents such as MeOH, EtOH, DMF, DMSO, HMPA, NMP and the like at temperatures from 0°C to 50°C. Referring to Scheme IV below, a Beckmann rearrangement to form compounds 12a and 12b can be induced by treatment of compound llg with an acylating agent, including but not limited to, POCI3, SOCI2, MeSO2Cl and the like or more preferably TsCl and an amine base at temperatures from 0°C to 50°C. Suitable amine bases include Et3N, EtN(iPr)2, lutidine, DBU (l,8-diazabicyclo[5.4.0]undec-7- ene) and the like, or most preferably pyridine. Pyridine also may serve as a solvent for this reaction or alternatively MeCN, benzene, toluene, dioxane and the like may be used. Scheme IV Beckmann Rearrangement 11g 12a 12b Referring to Scheme V below, the C7-aldehyde compound 6 could be oxidized to the corresponding C7 methyl ester compound 13 by treating with suitable oxidants including NaOCl/HOAc/MeOH, tBuOCl/MeOH/pyridine, and the like, or most preferably PDC/DMF/MeOH under conditions known in the art. The C7 methyl ester compound 13 can further serve as the starting material for additional derivatives. Similarly, the C6-aldehyde compound 10 can be oxidized to its corresponding C6 methyl ester (not shown). Scheme V Referring to Scheme VI below, the methyl ester compounds 7 and 13 can be converted into a series of esters, amides and ketones. Scheme VI wwvw 1) Saponify 5 (CH 2 ) n CO 2 Me 2) Amide or ester formation 3) RMgBr (optional) 7: n = 2 13: n = 1 14a: OR-| 4a 3 ^^5^(CH 2 ) n C(O)R 12 14b: NR 14b1 R-| 4 2 14c: H 14 (n = 1 or 2) 14d: alkyl group 14e: aryl group Rl4a > Rl4bL and Rl4b2 > is each independently an alkyl or aryl group, which optionally is substituted. Saponification could be accomplished by treating compound 7 with reagents including, but not limited to, NaOH, KOH, Me3SiOOK, LiOOH and the like, or more preferably LiOH. Solvents, or mixtures of solvents, include MeOH, EtOH, tBuOH, DMF, DMSO, HMPA, Et2θ, THF, water and the like. The reaction proceeds at temperatures from 0°C to 100°C. Amide and ester formation may be accomplished by reacting the C8-carboxylic acid (compound 14a) thus prepared using standard ester- and amide-forming reagents known to those skilled in the art. The esterification reaction is carried out using at least one equivalent of an alcohol, HOR. Although preferably ten to one hundred equivalents of alcohol are used, the esterification also may be carried out using the alcohol as solvent. Esterification reagents include, but are not restricted to, dicyclohexylcarbodiimide, l-(3-dimethylaminopropyl)-3- ethylcarbodiimide hydrochloride (EDC » HC1), diisopropylcarbodiimide, benzotriazol- l-yloxy-tris(dimethylamino)phosphonium hexafluorphosphate (BOP), bis(2-oxo-3- oxazolidinyl)phosphinic chloride (BOP-C1), benzotriazole-1-yl-oxy-tris-pyrrolidino- phosphonium hexafluorophosphate (PyBOP), chloro-tris-pyrrolidino-phosphonium hexafluorophosphate (PyClOP), bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBrOP), diphenylphosphoryl azide (DPP A), 2-(lH- benzotriazole-l-yl)-l,l,3,3-tetramethyluronium hexafluorophosphate (HBTU), O- benzotriazol-l-yl-N,N,N',N'-bis(pentamethylene)uronium hexafluorophosphate and 2- chloro-1-methylpyridinium iodide. The ester-forming reactions may be facilitated by the optional addition of N-hydroxybenzotriazole, N-hydroxy-7-aza-benzotriazole, 4- (N,N-dimethylamino)pyridine or 4-pyrrolidinopyridine. The ester-forming reaction is generally performed using at least one equivalent (although several equivalents may be employed) of amine bases such as triethylamine, diisopropylethylamine, pyridine and the like. The carboxyl group may be activated for ester bond formation via its corresponding acid chloride or mixed anhydride, using conditions known to those skilled in the art. The ester-forming reaction is carried out in an aprotic solvent such as, for example, methylene chloride, tetrahydrofuran, diethyl ether, dimethylformamide, N-methylpyrrolidine, and the like, at temperatures ranging from - 20°C to 60°C, and is complete in about 15 minutes to about 24 hours. Amides (where Rl2 is NRi4 lRl4b2) are prepared as described for esters (vida supra) from the corresponding carboxylic acids using and an appropriate amine, HNRi4blRl4b2- The amide compound 14b (in which NRi4blRl4b2 is N(OMe)Me) can be treated with nucleophilic agents to yield the corresponding aldehyde (compound 14c) and ketones (compounds 14d and 14e). Suitable nucleophiles include, but are not limited to, hydride reagents, RLi or RMgX and the like as described above for the preparation of compounds 11a and lib. In addition, the aldehyde and ketone products 14c, 14b and 14e can be further reacted with hydride reagents, RLi or RMgX, to generate the corresponding alcohol adducts as described previously. Referring to Scheme VII below, the aldehyde compounds 6, 10 and 14c serve as starting material for the preparation of a variety of derivatives. Scheme VII VΛVΛV 1) Reduce 5 ^ (CH 2 ) n CHO 2) Sulfonylate 3) Nucleophile 14c: ri = 2 — 6: n = 1 lϋ- n = 0 15d: NR 15d1 R 15d2 15 (n = 1, 2 or 3) 15e: P(O)(OR 15e ) 2 Rl5a> Rl5b> Rl5dl> Rl5d2> and Ri5e, are each independently an alkyl or aryl group which optionally is substituted. Reduction of the side chain aldehyde group in compounds 6, 10 and 14c with hydride reagents produced compound 15a (where Rl5a = H). The side chain alcohol thus obtained can then be sulfonylated, as described above in Scheme in. The sulfonyl group can then be displaced with an appropriate sulfur, nitrogen or phosphorous nucleophile to form compounds 15b, 15c and 15e respectively. Suitable nucleophiles include NaSMe, KSAc, NaN3, (PhCH2θ)2P(O)H, (P(OCH2Ph)3, (MeO)2P(O)H, P(OMe)3 and the like. Further, the side chain azide compound 15c can be reduced using conditions known to those skilled in the art including, but not restricted to, H2/10% Pd/C, HSAc/MeOH, SnCl2, Ph3P/H2θ and the like to form a side chain amine compound (not shown). The amine compound thus obtained can be acylated, alkylated or sulfonylated as described above. Alternatively, reductive amination of the aldehyde compounds 6, 10 and 14c with a suitable amine as described above will generate the amine compound 15d. Referring to Scheme VIII below, the side chain of compounds 6, 10 or 14c can be extended by reacting the aldehyde with stabilized Wittig reagents, unstabilized Wittig reagents or Horner-Emmons reagents to form compound 16a. Scheme Vm WWN Λ 1 ) Wittig ^ (CH 2 )nCHO 2) Reduction 3) Saponification 14c: n = 2 6: n = 1 10: n = 0 Rl6a> Rl6b> Rl6dL Rl6d2, and Rl6e are each independently an alkyl or aryl group, which optionally is substituted. The side chain unsaturation of compound 16a can be reduced by catalytic hydrogenation using conditions known to those skilled in the art. Suitable catalysts include 5% Pd/C, 10% Pd/C, Pd(OH)2, Ptθ2, RhCl3, RuCl2(PPh3)3, and the like. The hydrogenation reactions may be performed in solvents or mixtures of solvents including CH2CI2, CHCI3, toluene, MeOH, EtOH, EtOAc, acetone, THF, Et2θ, dimethoxyethane, DMF, DMSO, and the like. The reductions may be run at from one to 10 atmospheres of hydrogen pressure and the reactions are complete in from 5min to 24h. For apicidin analog compounds 16a or 16b in which Ri6a or Rl6b represents an ester moiety, the ester may be saponified and the carboxylic acid thus obtained may be converted into other esters or amides as described previously. Referring to Scheme IX below, the N-methoxy group of apicidin may be removed by hydrogenation as described previously and the liberated indole nitrogen compound thus generated may be N-alkylated, acylated or sulfonylated using known methods for acylation, sulfonylation and alkylation of indoles to generate apicidin derivative compound 17. Scheme DC Apicidin 1) Hydrogenation 2) Alkylation Rl7 is an alkyl or aryl group, which optionally is substituted. Thus, acylation may be accomplished using reagents such as acid anhydrides, acid chlorides, chloroformates, carbamoyl chlorides, isocyanates and the like according to general procedures known to those skilled in the art. Sulfonylations may be carried out using sulfonyl chlorides or sulfonic anhydrides. Alkylations may be carried out using alkyl halides. Suitable bases for these acylation, sulfonylation and alkylation reactions include KH, nBuLi, tBuLi, LiN( Pr)2, NaN(SiMe3)2, KN(SiMe3)2 and the like or more preferably NaH. Suitable solvents, or mixtures of solvents for these reactions include benzene, toluene, CHCI3, CH2CICH2CI, CH2CI2, DMSO, HMPA, NMP and the like or most preferably DMF and may be performed from temperatures of -40°C to 80°C. When the newly incorporated R17 group contains an ester moiety, the apicidin derivative compound 17 can be saponified to the corresponding carboxylic acid and converted into a series of amides using conditions described previously. When the newly incorporated R17 group contains an alcohol function, the apicidin derivative compound 17, can be acylated, alkylated, phosphorylated or sulfonylated as described previously. Alternatively, this alcohol function may be converted into a leaving group such as a sulfonate or halide and displaced with appropriate sulfur, nitrogen or phosphorus nucleophiles as described previously Referring to Scheme X below, apicidin's tryptophan may be allylically oxidized to generate beta-oxo apicidin analog compound 18 using conditions known to those skilled in the art. . (What is Rl8?) Scheme X Apicidin 1) Hydrogenation 2) Oxidation 3) Alkylation Rl8 is an alkyl or aryl group, which optionally is substituted. Suitable oxidants include but are not restricted to tBuOOH, Seθ2, Crθ3, Na2CrO4, PCC, and the like, or more preferably DDQ (2,3-dichloro-5,6- dicyano-l,4-benzoquinone). Appropriate solvents, or mixtures of solvents, include DMF, toluene, benzene, CH2CI2, CHCI3, HOAc, pyridine, THF, MeOH, EtOH, water, and the like, or more preferably MeCN. These reactions are performed at from -20°C to 50°C and are complete in from 5min to 24h. The stereochemistry of the beta-oxo-tryptophan attachment of compound 18 may be changed by treatment with bases such as pyridine, EtN(ιPr)2, NaH, KH, DBU, lutidine, or most preferably Et3N. The epimerization reaction proceeds at from 0°C to 50°C in solvents including CHCI3, CH2CICH2CI, MeOH, EtOH, DMF, DMSO, NMP, and the like, or most preferably CH2CI2. The nitrogen of the beta-oxo-tryptophan may be alkylated, acylated, sulfonylated or phosphorylated as described previously. The beta-oxo carbonyl of compound 18 may be selectively reduced using a hydride source under radical conditions. Suitable hydride sources include Me3SnH, «Bu3SnCl/NaBH4, Ph3SnH, Ph3AsH, and the like, or most preferably nBu3SnH, in the presence of radical initiators. Suitable radical initiators include, for example, benzoyl peroxide, Et3B/O2, and the like, or most preferably AIBN. Suitable solvents for the carbonyl reduction include MeOH, EtOH, water, benzene, or most preferably toluene. The reaction proceeds at temperatures from 0°C to 110°C. Referring to Scheme XI below, the indole of apicidin may be subjected to oxidative degradation to prepare carboxylic acid compound 19a (where R2 = OH) using conditions known to those skilled in the art. Scheme XI Apicidin 1 ) Oxidative degradation 2) Esterify 3) Amide formation 4) Carbonyl reduction 5) Nucleophilic attack 6) Carbonyl oxidation 19 R.19. = 19a: CHiC(0)R 19a 19b: C(0)R 19b 19c: CH 2 CH 2 OR 19c 19d: CH 2 OR 19d Rl9a» Rl9b> Rl9c, and Rl9d are each independently an alkyl or aryl group, which optionally is substituted. Suitable oxidants include, but are not restricted to, KMnθ4, KMnO4/NaIO4, NaIO4/RuO4, and the like, or most preferably Na >4/RuCl3. Suitable solvents, or mixtures of solvents include CHCI3, CH2CICH2CI, MeCN, MeOH, EtOH, tBuOH, and the like, or most preferably CH2CI2. The reaction proceeds at temperatures from 0°C to 50°C. This carboxylic acid may be converted into esters or amides as described previously. Alternatively, a methyl ester may be prepared first (eg. compound 19a, wherein R 19a is OMe) and reacted with LiN(OMe)Me, Me2AlN(OMe)Me, or most preferably BrMgN(OMe)Me, to produce a Weinreb amide compound 19a, in which Rl9a i N(OMe)Me. Suitable solvents for this reaction include Et2θ, dimethoxyethane, dioxane, and the like, or most preferably THF. The reactions are performed at from -78°C to 50°C and are complete in from 30min to 12h. Reduction of the sidechain C8-ketone group of compound 19a to the corresponding alcohol proceeds as described previously. The Weinreb amide thus directly generated can then be reacted with hydride reagents, RLi, or RMgX as described previously to prepare the corresponding aldehyde or ketones (eg. 19a where Rl9a is H, alkyl or aryl group). At this point, the side chain C8-alcohol may be oxidized back to regenerate the C8-ketone as described previously. When Rl9a is OH in compound 19a, the carboxylic acid may be reduced using BH3 to form an alcohol compound 19c (where Rl9c is H). This alcohol may be acylated, sulfonylated or phosphorylated as described previously. Treatment of the alcohol compound 19c with Ar3Bi reagents will generate the corresponding aryl ether compound 19c in which Ri9c is an aryl group. Both the alpha- and beta-stereoisomers at the tetrapeptide are accessible as described previously. Substitution of beta-oxo apicidin derivative compound 18 for apicidin in Scheme XI above results in the formation of the truncated apicidin analog compounds 19b and 19d. Referring to Scheme XII, the 2,3-indole bond in Apicidin can be cleaved oxidatively to form compound 20 using conditions known to those skilled in the art. Scheme XH Apicidin Oxidative cleavage 20 Cyclize 21 R20 and R21 are each independently an alkyl or aryl group which optionally is substituted. Suitable oxidants include KMnθ4, NaIO4, Pb(OAc)4, and the like, or more preferably ozone. This reaction may be run in solvents such as CHCI3, CH2CICH2CI, and the like, or more preferably CH2CI2, at temperatures from -78°C to RT and the reaction is complete in from lmin to 2h. Treatment of compound 20 with a base induces Aldol cyclization to form a quinolone compound 21. Suitable bases for this reaction include Et3N, EtN( Pr)2, pyridine, DBU, NaOMe, NaOEt, NaHCO3 ? an d the like, or more preferably KOtBu. The Aldol cyclization may be performed in solvents, or mixtures of solvents including CH2CI2, CHCI3, MeOH, EtOH, DMF, THF, Et2θ, DMSO, water, and the like, or more preferably tBuOH. The reaction is complete in from lOmin to 12h at 0°C to RT. Substitution of N- substituted-N-desmethoxy-apicidin derivatives (Compound 17) for apicidin in Scheme XII leads to the formation of N-substituted quinolone derivatives. Referring to Scheme XHI below, the quinolone compound 21 can be treated with sulfonylating agents as described previously to form compound 22 wherein R22 i a sulfonate moiety Scheme XHI R22 and R23 are each independently an alkyl or aryl group, which optionally is substituted. During this reaction, some inversion of stereochemistry at the tetrapeptide ring juncture occurs. When R22 of compound 22 is OSO2CF3, the triflate can be displaced with suitable nucleophiles, such as halogen, sulfur nucleophiles or nitrogen nucleophiles including, but not limited to, NaBr, NaCl, KI, NaN3, NaSMe, KSAc, pyridine and the like. The resulting compounds are not shown. Suitable solvents for the displacement reaction include, but are not limited to, CH2CI2, CHCI3, DMF, DMSO, HMPA, NMP, and the like. The reactions proceed at temperatures from 0°C to 80°C. For apicidin derivative compound 22 in which R22 is N-l -pyridinium, the pyridinium group may be reduced using catalytic hydrogenation as described previously. Further, the C8-ketone group of apicidin derivative compound 21 may be reduced first. The thus formed quinolone carbonyl can then be reacted with nucleophiles such as hydride reagents, RLi or RMgX as described previously. The apicidin derivative compound 23 can be prepared by reoxidation of the C8-alcohol as described previously. Referring to Scheme XTV below, apicidin may be brominated at the indole C2 position following removal of the N-methoxy group using conditions known to those skilled in the art to form compound 24 where R24 is Br. Scheme XTV Apicidin 1 ) Hydrogenation 2) Bromination 3) Palladium coupling Suitable brominating agents include, but are not limited to, Br2, Hg(OAc)2/Br2, CBr4, CuBr2, HOBr, Br2/HOAc/NaOAc, and the like, or most preferably N-bromosuccinamide. The bromination reaction can be facilitated by a radical initiator such as benzoyl peroxide, Et3B/O2 or AIBN. The 2-bromo-indole thus obtained can be further reacted with a palladium catalyst, a base and ArX to induce an aryl coupling reaction. Suitable palladium catalysts include, but are not limited to, Pd(OAc)2, Pd(OAc)/PPh3, PdCl2(PPh3)2, Pd(dba)2/PPh3, and the like, or most preferably Pd(PPh3)4. Suitable bases for this reaction include, but are not limited to, KOtBu, CsCO3, or most preferably NaHCO3. Suitable solvents, or mixtures of solvent for this coupling reaction include toluene, DMF, MeCN, NMP, DMSO, H2O, EtOH, or most preferably dioxane/water. Suitable ArX groups include, but are not limited to, PhB(OH)2, 2-napthylboronic acid, (4-Me)PhB(OH)2, (4-F)PhOTf, and the like. The reactions are complete in from 30min to 48h at temperatures from RT to 110°C. Synthesis of Side Chain Modified Apicidin Derivatives In the Examples, and elsewhere herein, all percentages are by weight unless specifically stated otherwise. Further, all ratios of compounds are by volume unless specifically stated otherwise. Room temperature (RT) means a temperature from about 18°C to about 25°C. If no temperature is specified, then the conditions are understood to be room temperature. In certain steps that describe using an ingredient without specifying an amount, one of ordinary skill would understand the desired result and can determine the amount without difficulty. In general, the purities of the pure Examples were better than about 95% pure. EXAMPLE 1 Example 1 was prepared by the following procedure. At room temperature, 27mg of Me3S(O)I was added to a mixture of i) 5.6mg of 60% NaH and ii) 0.35mL HMPA. The resulting solution was allowed to stand for 5min. Then, a mixture of 12mg apicidin in 96μL DMF was added to form a reacting mixture. After 48 hours, the reaction was quenched with water, extracted with EtOAc and dried in Na2SO4 to produce 8mg Example 1. Example 1 was thus obtained without requiring further purification and was characterized by H NMR and MS [m/z: 638 (M +1)]. EXAMPLE 2 Example 2 was prepared by the following procedure. At room temperature, 60mg HCl » H2NOH and 181μL Et3N was added to 20mg apicidin in lOmL CH2C12- The resulting solution was aged for 12h. The volatiles were then removed under reduced pressure. Example 2 was obtained following preparative RP- HPLC (reversed phase high performance liquid chromatography), without workup, using a gradient elution characterized by 1:3 MeCN:H2θ to 100% MeCN, with a 60min linear ramp. The pure Example 2 thus obtained was characterized by H NMR and MS [m z: 639.3 (M + +l)]. EXAMPLES 3A-3M Examples 3a-3m were prepared following the general procedure described in Scheme HI for compound 1 If, 1 lg, and 1 lh, and for Ex.2. Examples 3a- 3m are described by the following chemical formula and were characterized by NMR and mass spectroscopy: Table 1 EXAMPLES 4A AND 4B Ex. 4a Ex. 4b Examples 4a and 4b were prepared by the following procedure. At 0°C, 4.5mg of p-toluenesulfonyl chloride was added to 3mg of Example 2 (the C8- ketoxime of apicidin) in 0.5mL pyridine to form a solution. The solution was maintained at 0°C for lOmin, then warmed to RT and aged for 50min. Then lmL each of saturated brine and saturated NaHCO3(aq) were added. Next, the solution was extracted with EtOAc and dried with Na2SO4. A mixture of pure Examples 4a and 4b was obtained following preparative RP-HPLC using gradient elution (1:3 MeCN:H2θ isocratic for lOmin, then a 75min linear ramp to 100% MeCN). The pure mixture thus obtained was characterized by H NMR and MS [m z: 639.2 (M +1)]. EXAMPLE 5 Example 5 was prepared by the following procedure. At room temperature (RT), 114mg of Ph3PCH3 + Br " was added to i) 16.8mg of a 60% dispersion of NaH in oil, ii) 2mL DMF, and iii) 0.2mL HMPA to form a mixture. After the mixture ceased foaming, a solution of 20mg apicidin in lmL DMF was added. The resulting solution was aged for 4 hours. Preparative RP-HPLC without workup using gradient elution (1:3 MeCN:H2θ isocratic for lOmin, then a 75min linear ramp to 100% MeCN yielded 14mg of pure Example 5 which was characterized by l H NMR and MS [m z: 622.3 (M + +l)]. EXAMPLES 6A-6D Ex. 6a Example 6a was prepared by the following procedure. At 0°C, 0.12mL of l.OM (4-Cl)PhMgBr in Et2θ was dropwise added to 15mg apicidin in a mixture of 1.75mL THF and 0.25mL pyridine. After lh at 0°C, an additional 0.12mL of l.OM (4-Cl)PhMgBr in Et2θ was added. The resulting solution was aged for lh at 0°C and then lh at RT. The reaction was quenched by the addition of saturated NH4Cl(aq) to the solution. The quenched mixture was extracted with EtOAc and dried with Na2SO4. Preparative RP-HPLC using gradient elution (1:3 MeCN:H2θ isocratic for lOmin, then a 75min linear ramp to 100% MeCN) yielded 8mg of pure Example 6a, which was characterized by H NMR and MS [m/z: 736.3 (M + +l)]. Examples 6b, 6c, and 6d are described by the chemical structure shown below. The specific substituents are tabulated in Table 2. Examples 6b, 6c, and 6d were prepared following the general procedure described in Scheme HI for compound lib under conditions similar to those described above for Ex. 6a Table 2 EXAMPLE 7 cyc/ø(N-O-Methyl-L-Trp-L-Ile-D-Pip-L-2-amino-8-hydroxy-decanoyl) Example 7 was made by first adding 18mg NaBH4 to 300mg apicidin in 12mL MeOH at 0°C. Next, the ice bath was removed immediately and the solution was stirred at RT for 4 hours. Acetone was added to quench the reaction and the solvents were removed under reduced pressure at ambient temperature. The residue was dissolved in CH2CI2, poured into saturated NaHCO3, extracted with 1:9 iPrOH:CH2θ2 and dried with Na2SO4. The pure product was obtained following flash chromatography on silica gel using 1:1 acetone:hexanes as eluant. The pure Example 7 was characterized by H NMR. TLC: Rf = 0.32 (1:1 acetone:hexanes). EXAMPLE 8 Example 8 was prepared following the general procedure of Example 7 but using N-desmethoxy-apicidin as the starting material. Example 8 was characterized by H NMR and MS [m/z: 596 (M + +l)]. EXAMPLE 9 Example 9 was prepared by the following process. At room temperature, 57mg of thiocarbonylimidazole was added to 40mg of cyclo(N-0- methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-8-hydroxy-decanoyl) in 1.6mL CH2O2. The resulting solution was heated to 75°C for 2 hours. Next, lmg of DMAP (4- dimethylaminopyridine) was added and the solution aged for lh at 75°C and 48h at RT. The solvent then was removed under reduced pressure. 59mg of the pure intermediary product 8-OC(S)imidazolyl-apicidin (also known as cyc/o(N-O-methyl- L-Tφ-L-Ile-D-Pip-L-2-amino-8-imidazoylylthionooxy-decanoyl) was obtained by PTLC (2 x 1500μm plate) using 1:3:96 NH4OH:MeOH:CHCl3 as eluant and was characterized by H NMR and MS [m z: 736 (M + +l)]. To the above prepared 59mg of intermediary product 8- OC(S)imidazolyl-apicidin in 1.6mL toluene was added 2.6mg AIBN and 53μL «Bu3SnH. The solution was then degassed and heated to 80°C for lh, concentrated under reduced pressure, and partitioned between MeCN and hexanes. The hexanes layer was discarded. The volatiles were removed under reduced pressure and pure Example 9 product was obtained following RP-HPLC using gradient elution (4:6 to 1:0 MeCN:H2θ). Example 9 was characterized by H NMR and MS [m/z: 610 (M + +l)]. EXAMPLE 10 (4-Me) Example 10 was made by adding lOmg DMAP to lOOmg cyclo N-0- methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-8-hydroxy-decanoyl) in 2mL pyridine at RT. Next, 94mg tosic anhydride was added. After 3d at RT, the solution was poured into saturated NaHCO3, extracted with CH2CI2 and dried with Na2SO4. Pure Example 10 was obtained following flash chromatography on silica gel using gradient elution (1:1:98 then 1:2:97 then 1:3:96 NH4OH:MeOH:CHCl3 as eluant). Example 10 was characterized by H NMR. TLC: Rf = 0.36 (1:3:96 NH4OH:MeOH:CHCl3). EXAMPLE 11 The procedure to form Example 11 was as follows. At room temperature, 50mg NaBH4 was added to lOOmg apicidin in lOmL 1:1 THF:MeOH. After 30min at RT, the solution was poured into brine, extracted with CH2CI2 and dried with Na2SO4. To the residue thus obtained was added 2mL pyridine, followed by addition of lOmg DMAP and 10 drops of Ac2θ. After another 15min at RT, the solution was heated to 80°C for lOmin. without noting any reaction. An additional 5 drops of fresh Ac2θ (from an unopened bottle) were added and the solution stirred at RT for 24 hours. The solvents were removed under reduced pressure and the residue was lyophilized from dioxane. Preparative RP-HPLC using gradient elution (3:7 to 6:4 MeCN:H2θ) yielded 69mg of pure Example 11 product, which was characterized by *H NMR and MS [m/z: 668.6 (M + +l)]. HPLC: t/j = 4.95min (6:4 MeCN:H2θ, 1.5mL/min, Zorbax™ RX-8 available from Rainin Co. EXAMPLES 12A-12E Following the general procedure described in Scheme HI, compounds 1 lc and 1 Id, and similarly to the procedure for Examples 10 and 11, the following Examples 12a-12f were prepared and characterized by NMR and mass spectroscopy: EXAMPLE 13 To form Example 13, 0.16mL (Me3Si)2NH and 235mg ZnCl2 was added to lOOmg apicidin in 5mL EtOAc at RT. The solution was heated to 55°C for 12 hours. The solution was then cooled to 0°C and 12mg NaBE ). was added. After lh, the solution was warmed to RT and aged an additional 2h. The solution was poured into 1:1 brine:saturated NaHCO3, extracted with CH2CI2 and dried with Na2SO4. Pure Example 13 product was obtained following preparative RP-HPLC using gradient elution (3:7 to 6:4 MeCN:H2θ) and was characterized by H NMR and MS [m/z: 625.3 (M + +l)]. TLC: 0.22min (1:9:90 NH4OH:MeOH:CHCl3). EXAMPLE 14 To form Example 14, 2 drops Ac2θ and a catalytic amount of DMAP was added to 14mg 8-amino-8-desoxo apicidin in 2mL pyridine at 0°C. The solution was stirred at 0°C for 30min and at RT for another 30min. Next, lmL methanol was added and the solution was then concentrated under reduced pressure. Pure Example 14 was obtained following preparative RP-HPLC purification (gradient elution using 25:75 MeCN:H2θ for lOmin, then a 70min ramp to 100% MeCN) and was characterized by H NMR and MS [m z: 667.4 (M + +l)]. TLC: Rf = 0.67 (1:9:90 NH4OH:MeOH:CHCl3). HPLC: tR = 4.60min, 1:1 MeCN:H2θ, 1.5mL/min, Zorbax™ RX-8). EXAMPLE 15 Example 15 was made by first adding to 60mg apicidin in 0.5mL MeOH at RT i) lmL pyridine, ii) 40μL ethanolamine, iii) 60μL glacial HOAc (pH 5.0), and iv) powdered 4A sieves. The solution was cooled to 0°C and 7.9mg NaCNBH3 was added. After 2h, the solution was warmed to RT and aged for 12h. The solution was then filtered through Celite filter agent (available from Aldrich Chemical Company, Milwaukee, Wisconsin) using 1:1 CH2Cl2:MeOH as eluant, reduced in volume in vacuo, poured into saturated NaHCO3, extracted with CH2CI2 and dried with Na2SO4. Following preparative RP-HPLC using 1:1 MeCN:H2θ to 100% MeCN gradient elution, 4.2mg pure Example 15 was obtained. The product thus obtained was characterized by H NMR and MS [m/z: 669 (M +1)]. EXAMPLE 16 Example 16 was prepared similarly to Example 15. At room temperature, to 60mg apicidin in 0.5mL MeOH was added i) 2mL pyridine, ii) 0.5mL propylamine, iii) lmL glacial HOAc (pH ~ 4.5), and iv) powdered 4A sieves. The solution was cooled to 0°C and 60mg NaCNBH3 was added. After 2h, the solution was warmed to RT and aged for 12h. The solution was filtered through Celite using 1:1 CH2θ2:MeOH as eluant, reduced in volume in vacuo, poured into saturated NaHCO3, extracted with CH2CI2 and dried with Na2SO4. Pure Example 16 was obtained following PTLC on silica gel (1 x 1500μm plate) using 2:18:80 NH4OH:MeOH:CHCl3 as eluant. The pure Example 16 product thus obtained was characterized by H NMR and MS [m/z: 667 (M + +l)]. EXAMPLE 17 To form Example 17, 32mg KSAc was added to lδ.lmg of the Example 10 C8-tosylate compound in 3mL 95% EtOH. The solution was heated to 70°C for 3 hours. The solution was then cooled to RT and saturated NH4Cl(aq) was added. Next, the solution was extracted with EtOAc and dried with Na2SO4. The solution then was filtered, evaporated to dryness. PTLC on silica gel (1 x lOOOμm plate) using 3:7 acetone:hexanes as eluant yielded 3.4mg of pure Example 17 product that was characterized by H NMR. EXAMPLE 18 To form Example 18, 3.4mg of the Example 17 C8-thioacetate compound was placed at RT in 0.2mL NaOMe 2M solution in MeOH) and aged for 3h. The solution was poured into saturated NH4θ(aq), extracted with CH2CI2, and dried with Na2SO4. The solution was filtered, concentrated to dryness, and pure Example 18 was obtained following RP-HPLC. Example 18 thus obtained was characterized by H NMR. EXAMPLES 19A AND 19B Ex. 19a Ex. 19b Examples 19a and 19b were prepared by the following procedure. 50mg apicidin was heated in 5mL THF at 50°C until the resulting solution became homogenous. The solution was then cooled to -78°C and immediately 800μL 0.5M potassium hexamethyldisilazane in toluene was added. After 5min, 40L TMSC1 as a solution in lmL THF was added. After lOmin at - 78°C the reaction was stopped by the addition of 5mL saturated NaHCO3. Next, the solution was extracted, first with EtOAc, followed by CH2CI2 and dried with Na2SO4. The crude mixture of Example 19a and Example 19b was used with no further purification in the next reaction. The crude yield was 74mg (145%). The mixture was characterized by H NMR. TLC: Rf = 0.52 (1:2 acetone:hexanes). EXAMPLES 20A AND 20B Ex. 20a Ex. 20b To form Examples 20a and 20b, 74mg of the crude -1:1 mixture Example 19a, cyc/o(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-8-trimethylsiloxy-7- ene- decanoyl), and Example 19b, cycZσ(N-O-Methyl-L-Tφ-L-Ile-D-Pip-L-2-amino- 8-trimethylsiloxy-8-ene-decanoyl), was placed in 5mL CH2CI2 at RT to which was added 200mg solid NaHCO3. To this solution was added 20mg 85% MCPBA. After 5min, the reaction was quenched with 1:1 saturated Na2S2θ3 saturated NaHCO3, extracted with CH2CI2, and dried with Na2SO4. This yielded a 43mg pure mixture of Example 20a, cycZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-8-oxo-7- trimethylsiloxy-decanoyl), and Example 20b, cycZø(N-O-Methyl-L-Tφ-L-Ile-D-Pip- L-2-amino-8-oxo-9-trimethylsiloxy-decanoyl) following flash chromatography on silica gel using 4:1 hexanes: acetone as eluant. The mixture was characterized by H NMR. TLC: Rf = 0.33 (1:2 acetone:hexanes). EXAMPLES 21A AND 21B Ex. 21a Ex. 21b Example 21a and Example 21b were prepared by the following procedure. To 43mg of a 1:1 mixture of Example 20a, cycZø(N-O-methyl-L-Tφ-L- Ile-D-Pip-L-2-amino-8-oxo-7-trimethylsiloxy-decanoyl), and Example 20b, cyclo(N- O-Methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-8-oxo-9-trimethylsiloxy-decanoyl), in 4mL THF at RT was added 120μL 1M nBu4NF in THF. After 20min at RT, the solvent was evaporated under reduced pressure and the crude mixture purified by RP-HPLC without workup using 6:4 MeCN:H2θ. The resulting pure mixture of Examples 21a and 21b was characterized by H NMR and MS [m/z: 657.2 (M + +NH4)]. TLC: Rf = 0.14 (1:2 acetone exanes). EXAMPLES 22A AND 22B Ex. 22a Ex. 22b Following the general procedure of Examples 19-21, a 95% pure mixture of Examples 22a and 22b was prepared and characterized by H NMR. EXAMPLES 23A AND 23B Ex. 23a Ex. 23b Following the general procedure of Examples 19-21, a 95% pure mixture of Example 23a and 23b was prepared and characterized by H NMR. EXAMPLES 24A AND 24B Ex. 24a Ex. 24b Examples 24a and 24b were prepared by adding lOmL pyridine to lOmg -1:1 mixture of Examples 21a and 21b in 3mL MeOH at 0 °C, followed by the addition of lOmg Pb(OAc)4. After lOmin, the solution was quenched with 2mL Na2S2θ3, diluted with about 2mL brine, extracted with CH2CI2 and dried with Na2SO4. Following preparative TLC on silica gel (500μm plate) using 1:2 acetone: hexanes as eluant, separated pure products were obtained. Example 24a, c cZø(N-O-Methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-7-oxo- heptanoyl) (5.5mg) was characterized by *H NMR and MS [m/z: 582.2 (M+1)]. TLC: Rf = 0.16 (1:2 acetone:hexanes). Example 24b, cycZø(N-O-Methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-7- carboxymethyl --hheeppttaannooyyll)) ((66..55mmgg)) wwaass cchhaarraacctteeririzzeedd bbyy H NMR and MS [m z: 626.3 (M + +l)]. TLC: Rf = 0.23 (1:2 acetone:hexanes). EXAMPLES 25A-25D Examples 25a-25d were prepared by following the general procedure of Example 24b. Starting with Examples 21a and 21b, and using an appropriate alcohol as solvent, the following derivatives were prepared and analyzed by NMR and mass spectroscopy: Table 4 EXAMPLE 26 Example 26 was prepared by the following procedure. To 41mg cycZo(N-O-methyl-L-Tφ-L-Ue-D-Pip-L-2-amino-7-carbomethoxy-heptanoyl) in 4mL 3:1:1 THF:MeOH:H2θ at 0°C was added lOOμL IM LiOH. The solution was stirred for lh and then additional 300μL IM LiOH was added. After 12h, 33mg pure Example 26 product was obtained following preparative RP-HPLC without workup using gradient elution (column equilibrated in 5:95 MeCN:H2θ, using 25:75 MeCN:H2θ for 40min followed by a 20min ramp to 100% MeCN, flow rate lOm min). Example 26 was characterized by H NMR and MS [m z: 629.2 (M + +NH4)]. HPLC: tR = 1.98min 45:55 MeCN:H2θ, 1.5mI7min, Zorbax™ RX-8). EXAMPLE 27 Example 27 was prepared by the following procedure. To 15mg cycZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-7-carboxy-heptanoyl), lithium salt in 3mL DMF at RT was added 5.4mg H2NOSi(Me)2tBu and 7mg EDC-HC1. After 2h at RT, 15mg additional H2NOSi(Me)2tBu (15mg) and 14mg EDC-HC1 were added and the solution allowed to stir overnight. The reaction was quenched by the addition of 5 drops glacial HOAc and lmL MeOH. The solution was poured into brine, extracted with CH2CI2, and dried with Na2SO4. The crude product was chromatographed on silica gel using gradient elution (1:3:96 NH4OH:MeOH:CHCl3 to 1:4:95 NH4OH:MeOH:CHCl3, to 1:9:90 NH4OH:MeOH:CHCl3). To remove some contaminating EDU present in the chromatographed material, the product was dissolved in 2mL CHCI3 and 2mL 10% aq. HOAc. After 5min, the aqueous layer was decanted and the washing repeated twice more to yield 5.5mg pure Example 27 product. The pure Example 27 stained positive (puφle-orange) for a hydroxamic acid using Fe^ CI3 stain. The product was characterized by H NMR and MS [m/z: 627.3 (M + +l)]. TLC: Rf = 0.26 (then 1:9:90 NH4OH:MeOH:CHCl3). EXAMPLE 28 Example 28 was prepared by the following procedure. To 30mg cycZo(N-O-methyl-L-Tφ-L-Ηe-D-Pip-L-2-amino-7-carboxy-heptanoyl) lithium salt in lmL DMF at RT was added 47mg HCl*HN(OMe)Me, 2mg DMAP, 7mg HOBT (1- hydroxybenzotriazole hydrate) and 90μL DIEA (Et2Nz ' Pr) followed by 12mg EDCI (l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride). After 36h, the solution was poured into brine, acidified to pH~4.0 with 2N HC1, extracted with CH2CI2 and dried with Na2SO4. Following flash chromatography on silica gel using 1:3:96 NH4OH:MeOH:CHCl3 as eluant, 29.6mg purified Example 28 was obtained and was characterized by X H NMR and MS [m/z: 655.3 (M + +l)]. TLC: Rf = 0.39 (1:3:96 NH4OH:MeOH:CHCl3). HPLC: tR = 3.90min (62:38 MeCN:H2θ, 1.5mI7min, Zorbax™ RX-8). EXAMPLE 29 Example 29 was prepared by the following procedure. To 150mg c cZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-7-carboxy-heptanoyl) in 14mL CH2CI2 at 0°C was added 78mg HCl-H2NOCH2Ph, 0.13mL DIEA, 33mg HOBT, 2mg DMAP, and 108mg BOP. After lh at 0°C and 12h at RT, the solution was poured into saturated NaHCO3, extracted with CH2CI2 and dried with Na2SO4. Following preparative TLC on silica gel (5 x lOOOμm plates) using 5:95 MeOH:CHCl3 as eluant, 137mg pure Example 29 was obtained and was characterized by ! H NMR. TLC: Rf = 0.62 (5:95 MeOH:CHCl3). HPLC: tR = 7.46min (45:55 MeCN:H2θ, 1.5mL/min, Zorbax™ RX-8). EXAMPLE 30 Example 30 was prepared by the following procedure. To 130mg cycZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-7-(N-benzyloxy-carboxamido)- heptanoyl) in 5mL MeOH at RT was added 5% Pd/C and an H2 atmosphere (balloon pressure) was established. After 12h, lOmg Pd(OH)2 was added and the reaction continued for an additional 2h. The catalyst was removed by filtration through Celite using MeOH as eluant and the solution concentrated under reduced pressure. Pure Example 30 product was obtained following RP-HPLC purification using gradient elution (5:95 MeCN:H2θ for 5min then 55min ramp to 50:50 MeCN:H2θ). The pure Example 30 was characterized by l H NMR and MS [m/z: 597.5 (M + +l)]. TLC: Rf = 0.11 (1:9:90 NH4OH:MeOH:CHCl3). HPLC: tR = 10.65min (2min ramp from 5:95 MeCN:H2θ to 1:1 MeCN:H2θ, l.OmL/min, Zorbax™ RX-8). EXAMPLE 31 Example 31 was prepared by the following procedure. To lOmg cycZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-7-(N-O-methyl-N-methyl- carboxamido)-heptanoyl) in 2mL THF at 0°C was added 150μL IM CH2=CHMgBr in Et2θ. After 15min at 0°C, the solution was cooled to -78°C and quenched by addition of lmL saturated NH4CI. The solution was poured into brine and extracted with CH2CI2 and dried with Na2SO4. The product was partially purified on a silica gel pipette plug using 1:2 acetone:hexanes as eluant. Following preparative TLC on silica gel (1 x 250μm plate) using 1:3:96 NH4OH:MeOH:CHCl3 as eluant, 2.1mg pure Example 31 was obtained and was characterized by H NMR and MS [m/z: 596.3 (M + +l)]. TLC: Rf = 0.57 (1:3:96 NH4OH:MeOH:CHCl3). EXAMPLE 32 Example 32 was prepared by the following procedure. To 7mg cyc/o(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-7-(N-methoxy-N-methyl- carboxamido)-heptanoyl) in lmL THF at 0°C was added 55μL IM MeMgBr in Et2θ. After lOmin, an additional 55μL IM MeMgBr in Et2θ was added. The solution was poured into saturated NH4CI, extracted with CH2CI2 and dried with Na2SO4. 4.3mg pure Example 32 product was obtained following preparative TLC on silica gel (1 x 500μm plate) using 4:6 acetone: hexanes as eluant. The pure Example 32 was characterized by ! H NMR and MS [m/z: 610.3 (M + +l)]. TLC: Rf = 0.22 (1:2 acetone: hexanes). HPLC: tR = 4.51 min (1:1 MeCN:H2θ, 1.5mL/min, Zorbax™ RX-8). EXAMPLES 33A-33C Following the general procedure illustrated in Example 26-34, the following derivatives were prepared: Table 5 EXAMPLE 34 Example 34 was prepared by the following procedure. To 25mg cycZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-7-oxo-heptanoyl), 1 lmg anhydrous LiCl, and 2 lmL (MeO)2P(O)CH2CO2Me in 2.5mL MeCN at RT, was added 42mL DIEA. After 2h the solution was poured into saturated NaHCO3, extracted with CH2CI2 and dried with Na2SO4. Pure Example 34 product was obtained following flash chromatography on silica gel using 1:2 acetone: hexanes as eluant. The pure Example 34 was characterized by *H NMR and MS [m/z: 638.2 (M + +l)]. TLC: Rf = 0.38 (1:2 acetone:hexanes). HPLC: tR = 5.09min, (1:1 MeCN:H2θ, 1.5mL/min, Zorbax™ RX-8). EXAMPLE 35 Example 35 was prepared by the following procedure. To 35mg cyc/o(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-7,8-dehydro-8-carbomethoxy- octanoyl) in 4mL 1:1 THF:MeOH was added 20mg Pd(OH)2 and an H2 atmosphere (balloon pressure) was established. After 12h, the catalyst was filtered off and 11.7mg pure Example 35 product was obtained following flash chromatography on silica gel using 1:2 acetone: hexanes as eluant. The pure Example 35 was characterized by H NMR. TLC: Rf = 0.21 (1:2 acetone:hexanes). HPLC: tR = 3.84min (55:45 MeCN:H2θ, 1.5mL/min, Zorbax™ RX-8). EXAMPLE 36 Example 36 was prepared by the following procedure. To 10.6mg cycZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-8-carbomethoxy-octanoyl) in lmL 3:1:1 THF:MeOH:H2θ at 0°C was added 15mL IM LiOH. The solution was stirred for lh at 0°C, 6h at RT, 3 days at 4°C and then an additional 30mL IM LiOH was added. After 8h longer, the solvents were removed using a vigorous stream of N2 and pure Example 36 product was obtained by purification without workup using preparative RP-HPLC (gradient elution using 2:8 MeCN:H2θ for lOmin followed by a 60min ramp to 100% MeCN). Pure product was characterized by H NMR and MS [m/z: 596.3 (M + +l)]. HPLC: t/? = 2.89min (3:7 MeCN:H2θ, 1.5mI7min, Zorbax™ RX-8). EXAMPLE 37 Example 37 was prepared by the following procedure. To 25mg cyc/o(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-7-oxo-heptanoyl) in 1.25mL DMF at RT was added 0.25mL MeOH followed by 67.5mg PDC. The solution was stirred for 3.5h and then filtered through 1" silica gel, with 0.5" Celite on top of it, using MeOH as eluant. The solvents were removed under reduced pressure. Pure 9mg Example 37 product was obtained following preparative TLC on silica gel (2 x lOOOμm plates) using 5:95 MeOH:CHCl3 as eluant. The pure Example 37 was characterized by H NMR and MS [m/z: 612.3 (M + +l)]. TLC: Rf = 0.24 (1:2 acetone:hexanes). HPLC: tR = 9.41min (45:55 MeCN:H2θ, 1.5mL/min, Zorbax™ RX-8). EXAMPLE 38 Example 38 was prepared by following the general procedure of Example 15, and Scheme IH, utilizing methyl glycinate in place of ethylamine, and was characterized by H NMR and MS [m z: 655.0 (M + +l)]. EXAMPLE 39 Example 39 was prepared by following the general procedure of Example 36 and starting with the methyl ester of Example 38, and was characterized by *H NMR and MS [m z: 641.4 (M + +l)]. EXAMPLE 40 Example 40 was prepared by following the general procedure of Example 7, utilizing Example 32 as the starting material, and was characterized by H NMR and MS [m/z: 598.3 (M + +l)]. EXAMPLE 41 Example 41 was prepared by following the general procedure of Example 7 to convert the C7-aldehyde of Example 23 and was characterized by H NMR and MS [m/z: 584.2 (M + +l)]. EXAMPLE 42 Example 42 was prepared by the following two methods. Method A Following the general procedure of Example 7, the C6-aldehyde of Example 58a was converted into Example 42 by adding 2.1mg NaBH4 to 64mg cycZø(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-6-oxo-hexanoyl) in lmL 1:1 THF:EtOH at 0°C. After lh, the resulting solution was poured into saturated NH4CI, extracted exhaustively with CH2CI2 and 3:7 ZPrOH:CHCl3 (lx). The organic layer was dried with Na2SO4. Pure Example 42 was obtained following PTLC on silica gel (1 x 500μm plate) using 1:1 acetone:hexanes as eluant. Example 42 was characterized by ! H NMR and MS [m/z: 570 (M + +l)]. Method B 7.3mg of a -1:1 mixture of 6,7- and 9,10-enones of apicidin, Example 55a and 55b, was placed in lmL CH2CI2 at -78°C. Ozone was bubbled through the solution until a blue color persisted. A vigorous stream of nitrogen was then used to remove the excess ozone. To this solution was added 3.6mg NaBH4 in 120μL 1:1 EtOH:H2θ, the cooling bath was removed and the solution was aged overnight. The solution was poured into saturated NH4Cl(aq), extracted with CH2CI2 and dried with Na2SO4. Pure Example 42 was obtained following PTLC purification on silica gel (1 x 500μm plate) using 1:1 acetone:hexanes as eluant. EXAMPLE 43 Example 43 was prepared by the following procedure. To 32mg Example 41, cycZø(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-7-hydroxy-heptanoyl), in 2.5mL CH2CI2 at 0°C, was added 27μL DIEA, a catalytic amount of DMAP, and 36mg toluene sulfonic anhydride. After lh at 0°C and 12h at RT, the solution was poured into saturated NaHCO3, extracted with CH2CI2 and dried with Na2SO4. Following preparative TLC on silica gel (2 x lOOOμm plates) using 1:3:96 NH4OH:MeOH:CHCl3 as eluant. 20mg pure Example 43 product was obtained and was characterized by X H NMR and MS [m/z: 755.5 (M + +NH4)]. TLC: Rf = 0.58 (1:3:96 NH4OH:MeOH:CHCl3). EXAMPLE 44 Example 44 was prepared from Example 42 cycZo(N-O-methyl-L-Tφ- L-Ile-D-Pip-L-2-amino-6-hydroxy-hexanoyl) by following the general procedure of Example 43, and was characterized by H NMR and MS [m/z: ??? (M + +NH4)]. EXAMPLE 45 Example 45 was prepared by the following procedure. To 9μL (MeO)2P(O)H in 350μL THF was added 2.5mg 95% NaH at RT via syringe and the solution heated to reflux for 20min. The solution was then cooled to RT and 25mg cycZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-7-(/? ra-toluenesulfonyl)-heptanoyl) was added as a solution in 350μL THF, heated to reflux for 2h, cooled to RT and stirred for 12h. The solution was poured into saturated NaHCO3, extracted CH2CI2 and dried with Na2SO4. Pure 4.1mg Example 45 product was obtained following PTLC (1 x lOOOμm plate) on silica gel using 1:3:96 NH4OH:MeOH:CHCl3 as eluant. The pure product was characterized by H NMR and MS [m/z: 676 (M + +l)]. EXAMPLE 46 Example 46 was prepared by the following procedure. To 5mg c cZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-7-(pαra-toluenesulfonyl)-heptanoyl) in lmL DMF at RT was added 5mg NaSMe. After 2h, the solution was poured into brine, extracted with CH2CI2 and dried with Na2SO4. The pure Example 46 product was obtained following preparative TLC on silica gel (1 x 500μm plate) using 1:2 acetone:hexanes as eluant. The pure product was characterized by H NMR and MS [m/z: 614.5 (M + +l)]. TLC: Rf = 0.33 (1:2 acetone:hexanes). EXAMPLE 47 Example 47 was prepared by the following procedure. To 5mg cycZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-7-(pαrα-toluenesulfonyl)-heptanoyl) in lmL DMF at RT was added 5mg NaSAc. After 2h, the solution was poured into brine, extracted with CH2CI2 and dried with Na2SO4. Pure Example 47 product was obtained following preparative TLC on silica gel (1 x 500μm plate) using 1:2 acetone:hexanes as eluant. The pure product was characterized by H NMR and MS [m/z: 642.5 (M + +l)]. TLC: Rf = 0.22 (1:2 acetone:hexanes). EXAMPLE 48 Example 48 was prepared by starting with Example 22b and following the general procedure described for Example 7. Example 22b' s C8 ketone group was converted to a hydroxyl to form Example 48, which was characterized by H NMR. EXAMPLE 49 Example 49 was prepared by the following procedure. A solution of 63μL dibenzyl phosphonate in lmL THF was added via syringe to 7mg 95% NaH and the solution heated to reflux for 20min. The mixture was cooled to RT and 70mg cycZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-7-(pαra-toluenesulfonyl)-octanoyl) was added as a solution in lmL THF. The resultant white, heterogeneous solution was heated to reflux for 2h followed by 12h at RT. The solution was added to water, extracted with CH2CI2 and dried with Na2SO4. Pure 26mg Example 49 was obtained following PTLC on silica gel (1 x 1500μm plate) using 1:3:96 NH4OH:MeOH:CHCl3 as eluant. The product was characterized by H NMR and MS [m/z: 828 (M + +l)]. EXAMPLE 50 Example 50 was prepared by the following procedure. To llmg c cZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-7-dibenzylphosphono-octanoyl), in 2mL /PrOH containing 44μL H2O and 1.3mg KHCO3 at RT was added lmg 10% Pd/C. An atmosphere of H2 was established (balloon pressure). After 12h, the catalyst was removed by filtration through Celite using 1:1 MeOH:H2θ as eluant. The solution was concentrated in vacuo and the residue was washed with CHCI3 followed by EtOAc. The remaining glassy material was lyophilized from water to yyiieelldd 33mmgg product. The product was characterized by H NMR and MS [m/z: 738 (M + +l)]. EXAMPLE 51 Example 51 was prepared by the following procedure. To 2mg c^cZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-7-dibenzylphosphono-octanoyl) in 0.35mL iPrOH was added 8μL water, 0.25mg KHCO3 and 0.5mg 10% Pd/C and a balloon atmosphere of hydrogen was established. After 7h at RT, the catalyst was removed via filtration through Celite and washed with water. 3mg of pure Example 51 product was characterized by H NMR and MS [m/z: 648 (M + +l)]. EXAMPLES 52A AND 52B Ex. 52a Ex. 52b Examples 52a and 52b were prepared by the following procedure. To 3mg -1:1 c cZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-7-hydroxy-8-oxo- decanoyl) and cycZø(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-9- hydroxy -8-oxo- decanoyl) 3mg) in 0.25mL CH2CI2 at -78°C was added powdered, activated 4A sieves followed by 1.5μL Et2NSF3. The solution was warmed to -10°C over lh and then quenched by the addition of saturated NaHCO3. The solution was extracted with CH2CI2 and dried with Na2SO4. A pure mixture of approximately 1:1 Example 52a and 52b was obtained following PTLC on silica gel (1 x 500μm plate) using 1:3:96 NH4OH:MeOH:CHCl3 as eluant. 2.5mg of the mixture were characterized by H NMR and MS [m/z: 641 (M + +l)]. EXAMPLES 53A AND 53B Ex. 53a Ex. 53b Examples 53a and 53b were prepared by the following procedure. To 6mg -1:1 cyc/o(N-O-methyl-L-Tφ-L-Ηe-D-Pip-L-2-arnino-7-hydroxy-8-oxo- decanoyl) and c cZø(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-9-hydroxy-8-oxo- decanoyl), Examples 20a and 20b, at RT was added powdered, activated 4A sieves followed by 3mg N-methylmoφholine-N-oxide and 0.3mg TPAP. After lh, the mixture was diluted with CH2CI2 and filtered through Celite using CH2CI2 as eluant. The filtrate was extracted with 10% NaHSO3(aq), washed with water, and dried with Na2SO4. Pure products were obtained following PTLC (1 x 500 μm plate) separation using 1:3:96 NH4OH:MeOH:CHCl3 as eluant. 3.5mg of each pure Example 53a and 53b were characterized by H NMR and MS [m/z: 637 (M + +l)]. I l l - EXAMPLES 54A AND 54B Ex. 54a Ex. 54b Examples 54a and 54b were prepared by the following procedure. To 2g apicidin in 32mL THF at 0°C was added 14mL 0.5M potassium hexamethyldisilazane solution in toluene. The solution was aged at 0°C for 30min. Next, 25. g solid PhSeCl was added and the solution was warmed to RT for 2h. The reaction was quenched by the addition of saturated NaHCO3(aq), was extracted with CH2CI2, dried with Na2SO4 and filtered through 8 x 14 cm plug of silica gel using gradient elution (hexanes to 1:1 EtOAc:hexanes to 1:1 acetone:hexanes). The product was used in the preparation of Examples 55a and 55b with no further purification. The 2.3g mixture thus obtained was characterized by H NMR and MS [m/z: 780.3 (M + +l)]. TLC: Rf = 0.60 (1:3:96 NH4OH:MeOH:CHCl3). EXAMPLES 55A AND 55B Ex. 55a Ex. 55b Examples 55a and 55b were prepared by the following procedure. To 2.2g -1:1 cycZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-8-oxo-7-phenylselenyl- decanoyl) and cZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-8-oxo-9- phenylselenyl-decanoyl) in 40mL THF at 0°C was added 7.3mL 30% H2O2. The solution was warmed to 50°C and after lOmin was cooled to 0°C, quenched with saturated Na2S2θ3, extracted with CH2CI2 and dried with Na2SO4 Following purification on silica gel using 4:6 acetone:hexanes as eluant, a 230mg pure mixture of Examples 55a and 55b was characterized by H NMR and MS [m/z: 622.3 (M + +l)]. TLC:. Rf = 0.38 (1:3:96 NH4OH:MeOH:CHCl3). EXAMPLES 56A AND 56B Ex. 56a Ex. 56b Examples 56a and 56b were prepared by the following procedure. To 5.6mg -1:1 cycZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-8-oxo-6,7-dehydro- decanoyl) and cycZσ(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-8-oxo-9, 10-dehydro- decanoyl) in 0.225mL THF at RT was added 0.8mL PhCH2N(Me)3 (40% solution in MeOH) followed by 1.5mL 70% t-BuOOH(aq). After 4.5h, EtOAc and minimal water were added and the aqueous phase thoroughly extracted with EtOAc. The organic layer was washed with cold IN HCl (lx), quickly washed again with saturated NaHCO3, and then dried with Na2SO4. Pure products were separated by PTLC (1 x 500μm plate) using 4:6 acetone:hexanes as eluant. The pure examples 56a and 56b were characterized by H NMR. The procedure yielded 1.4mg cycZo(N-O-Methyl-L- Tφ-L-Ile-D-Pip-L-2-amino-6,7-oxiranyl-decanoyl); MS [m/z: 638 (M+1)]; TLC: Rf = 0.4 (4:6 acetone:hexanes). The procedure yielded 2mg cycZo(N-O-Methyl-L-Tφ-L- Ile-D-Pip-L-2-amino-9,10-oxiranyl-decanoyl); MS [m/z: 638 (M+1)]; TLC: Rf = 0.3 (4:6 acetone:hexanes). EXAMPLES 57A AND 57B Ex. 57a Ex. 57b Example 57a and 57b were prepared by the following procedure. To 115mg -1:1 cycZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-8-oxo-6,7-dehydro- decanoyl) and cyc/ø(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-8-oxo-9, 10-dehydro- decanoyl) in 4mL 8:1 acetone:water at 0°C was added 45mg trimethylamine-N-oxide followed by 0.77mL 0.024M Osθ4(aq). The solution was warmed to RT for 3h and then aged at 4°C for 12h. The brown homogenous solution was quenched at 0°C by the addition of 2mL 10% NaHSO3(aq). After lOmin, brine was added and the solution thoroughly extracted with 3:7 ZPrOH:CHCl3 (9x) and dried with Na2SO4. The solvent was removed in vacuo to yield 230mg crude product (121mg theoretical) which was used with no additional purification. A small aliquot of the regioisomeric diols were separated by PTLC on silica gel (1 x lOOOμm plate) using 1:1 acetone:hexanes as eluant and the products were characterized by H NMR and MS. cycZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-8-oxo-6,7-dihydroxy-decanoyl): MS [m/z: 656 (M + +1)]; TLC: Rf = 0.5 (4:6 acetone:hexanes). cycZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-8-oxo-9,10-dihydroxy-decanoyl): MS [m/z: 656 (M + +l)]; TLC: Rf = 0.25 (4:6 acetone:hexanes). EXAMPLES 58A AND 58B Ex. 58a Ex. 58b Examples 58a and 58b were prepared by the following procedure. To 121mg -1 :1 cyc/o(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-8-oxo-6,7-dihydroxy- decanoyl) and cycZø(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-8-oxo-9, 10- dihydroxy-decanoyl) in 6mL MeOH at 0°C was added 75mL pyridine followed by 184mg Pb(OAc)4. After 40min, the solution was poured into saturated Na2S2θ3, extracted with CH2CI2 and dried with Na2SO4. Pure separated Examples 58a and 58b were obtained following PTLC (3 x 1500μm plate) on silica gel using 1:3:96 N NHH44OOHH::MeOH:CHCl3 as eluant. The pure products were characterized by H NMR and MS. Example 58a, cycZo(N-O-Methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-6-oxo- hexanoyl): Yield: 30mg. MS [m/z: 568 (M + +l)]; TLC: Rf = 0.45 (1:1 acetone : hexanes) . Example 58b, cycZo(N-O-Methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-7- carboxymethyl-heptanoyl): Yield: 20mg. EXAMPLE 59 Example 59 was prepared by the following procedure. To 4mg cyc/o(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-6-hydroxy-hexanoyl) in 0.14mg CH2CI2 and lmL pyridine at 0°C was added lmL ethyl chloroformate. The solution was warmed to RT, aged for 3h and the solvents removed in vacuo. 1.3mg pure Example 59 was obtained following PTLC (1 x 500μm plate) on silica gel using 4:6 acetone±exanes as eluant. The pure product was characterized by H NMR and MS [m/z: 659 (M + +NH4)]. EXAMPLE 60 Example 60 was prepared by the following procedure. 7.5mg of the Example 64 C6-alcohol was placed in about lmL CH2CI2 at 0°C to which was added 3.2mg (4-NO2)PhOC(O)Cl followed by 1.3μL pyridine. After 2h at 0°C, the volatiles were removed under reduced pressure without workup and 9mg pure Example 60 product was obtained following PTLC on silica gel (1 x 500μm plate) using 1:1 acetone:hexanes as eluant. The pure Example 60 thus prepared was characterized by X H NMR and MS [m/z: 735 (M + +l)]. EXAMPLE 61 Example 61 was prepared by the following procedure. Anhydrous ammonia was bubbled into 2mL dioxane at 0°C to generate a -0.5 M solution. This solution was added to 6mg solid cycZø(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-6- αra-nitrophenoxycarbonyloxy-hexanoyl) at 0°C. The ice bath was removed and the solution aged at RT for 2h. The solution was concentrated under reduced pressure and 1.7mg pure Example 61 was obtained following PTLC (1 x 500μm plate) using 1:9:90 NH4OH:MeOH:CHCl3 as eluant, and was characterized by H NMR and MS [m z: 613 (M + +l)]. EXAMPLE 62 Example 62 was prepared by the following procedure. To 4mg Ph3P in 0.2mL THF at 0°C was added 2.4mL DEAD (diethyl azodicarboxylate) and aged for 30min. To this resulting solution was added about 4mg solid cycZo(N-O-methyl- L-Tφ-L-Ile-D-Pip-L-2-amino-6-hydroxy-hexanoyl) at 0°C. After lh at 0°C, the solution was warmed to RT for lh. Solvent was removed under reduced pressure. 2mg of pure Example 62 product was obtained following PTLC (1 x 250μm plate) using 1:1 acetone:hexanes as eluant and was characterized by H NMR and MS [m/z: 628 (M + +l)]. EXAMPLE 63 Example 63 was prepared by the following procedure. To 1.5mg cycZo(N-O-methyl-L-Tφ-L-Ue-D-Pip-L-2-amino-6-acetylthio-hexanoyl) in 0.2mL MeOH at 0°C was added 0.3mL 25 wt % NaOMe in MeOH. After 5h, water was added to quench the reaction. The solution was extracted with CH2CI2 and dried with Na2SO4. 0.5mg pure Example 63 product was obtained following PTLC (1 x 250μm plate) using 1:1 acetone:hexanes as eluant. Example 63 was characterized by H NMR and MS [m z: 588 (M + +l)]. EXAMPLE 64 Following the general procedure of Example 63, the C7 thiol was prepared from the corresponding thioacetate of Example 47. Example 64 was characterized by ! H NMR and MS [m/z: 599 (M + +l)]. EXAMPLE 65 Example 65 was prepared by the following procedure. To 1.6mg c cZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-6-hydroxy-hexanoyl) in 0.28mL CH2CI2 at 0°C was added 0.2mg DMAP followed by 2mg TsCl. After 16h, the solution was aged at RT for 16h. The solvent was removed under reduced pressure. Following PTLC (1 x 250μm plate) using 1:3:96 NH4OH:MeOH:CHCl3 as eluant, 0.3mg pure Example 65 was obtained. The pure product was characterized by H NMR and MS [m z: 724 (M + +l)]. EXAMPLE 66 Example 66 was prepared by the following procedure. To 4mg cycZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-6-hydroxy-hexanoyl) in 0.35mL CH2CI2 at 0°C was added i) 3.7mg PPh3 ; ii) lmg imidazole and iii) 3.2mg Zn(N3)2*(pyridine)2 followed by iv) 2.2μL DEAD. The solution was warmed to RT for 12h. Following PTLC (1 x 500μm plate) using 1:3:96 NH4OH:MeOH:CHCl3 as eluant, 2mg pure Example 66 was obtained. Example 66 was characterized by H NMR and MS [m/z: 595 (M + +l)]. EXAMPLE 67 Example 67 was prepared by the following procedure. To lmg cycZo(N-O-methyl-L-Tφ-L-Ile-D-Pip-L-2-amino-6-azido-hexanoyl) at 0°C in O.lmL THF was added O.lmL thiolacetic acid. After lh, the solution was warmed to RT for lh. The solvents were then removed with a vigorous stream of nitrogen. The residue was dissolved in 0.2mL neat thiolacetic acid, aged for 4h and then concentrated with a vigorous stream of nitrogen. Pure Example 67 product was obtained following PTLC (1 x 250μm plate) using 1:3:96 NH4OH:MeOH:CHCl3 as eluant. The pure product (0.7mg) was characterized by H NMR and MS [m/z: 611 (M + +l)]. EXAMPLE 68 Example 68 was prepared by the following procedure. 40mg Pd(OH)2 was added to 500mg apicidin in 40mL 1 : 1 THF:MeOH. An H2 atmosphere was established (balloon pressure). After 12h, the palladium catalyst was removed by filtration through Celite using MeOH as eluant. Following flash chromatography on silica gel using 4:6 acetone:hexanes as eluant, 467mg pure Example 68 product was obtained and was characterized by H NMR. TLC: Rf = 0.18 (1:2 acetone:hexanes). HPLC: tR = 7.54min (1:1 MeCN:H2θ, 1.5mL/min, Zorbax™ RX-8). EXAMPLE 69 Example 69 was prepared by the following methods: Method C To 30mg N-desmethoxy apicidin in 500μL DMF at RT was added 4 drops Mel followed by the addition of 1 lmg tBuOK. The solution was stirred for 2h at RT, 12h at 4°C and then for another 4h at RT. The solution was then heated at 60°C for 1.5h and cooled back to RT. An additional 20mg tBuOK was added and the solution stirred for lh. The solution was then poured into 3mL of 1:2 saturated NaHCO3: saturated brine, extracted with CH2CI2 and dried with Na2SO4. Following preparative TLC on silica gel (2 x 1500μm plates) using 1:2 acetone:hexanes as eluant, 19mg pure Example 69 was obtained and was characterized by H NMR and MS [m z: 625.3 (M + +NH4)]. TLC: Rf = 0.31 (1:2 acetone:hexanes). HPLC: tR = 3.90min (62:38 MeCN:H2θ, 1.5mL/min, Zorbax™ RX-8). Method D 1.3mg 60% NaH was added to 20mg N-desmethoxy apicidin in 0.35mL DMF at RT). After 30min, 4μL Mel was added and the solution stirred for lOh. The solution was then poured into saturated NH4CI, extracted with CH2CI2 and dried with Na2SO4. Following preparative TLC on silica gel (1 x 500 μm plate) using 1:1 acetone:hexanes as eluant, and further purification by preparative RP-HPLC using a linear gradient (1:1 to 1:0 MeCN:H2θ), 5mg pure Example 69 was obtained which was characterized by H NMR and MS [m/z: 608.5 (M + +l)]. EXAMPLE 70 Example 70 was prepared by the following procedure. At RT, 467mg N-Desmethoxy apicidin was placed in 16mL DMF to which was added 63mg 60% NaH. After lOmin, 206μL BrCH2CO2Me and 87 lmg «Bu4NI were added and the solution heated to 80°C. After 15min, the solution was poured into water, extracted with CH2CI2 and dried with Na2SO4. Following flash chromatography on silica gel using 1:1 acetone:hexanes as eluant, 401mg pure Example 70 was obtained which was characterized by *H NMR and MS [m/z: 666 (M + +l)]. TLC: Rf = 0.46 (1:1 acetone:hexanes). HPLC: tR = 7.21min 1:1 MeCN:H2θ, l.OmlJmin, Zorbax™ RX- 8). EXAMPLE 71 Example 71 was prepared by the following procedure. At 0 °C, 0.65mg HOBT, 1.6mg NaHCO3, 0.5mg 5-aminotetrazole and lmg EDCI was added to 3.5mg N-desmethoxy-N-(para-carboxyphenylmethyl) apicidin in DMF. After 12h, the solution was poured into saturated NHCI4, extracted with CH2CI2 and dried with Na2SO4 Following RP-HPLC using gradient elution (4:6 to 1:0 MeCN:water), 1.6mg pure Example 71 was obtained which was characterized by H NMR and MS [m/z: 795 (M + +l)]. EXAMPLE 72 Example 72 was prepared by the following procedure. At RT, 3.4mg 60% NaH was added to 50mg N-desmethoxy apicidin in 0.2mL DMF and 0.2mL HMPA. After gas evolution ceased, 35μL (PhO)2P(O)Cl was added. After 24h, the solution was poured into water, extracted with EtOAc and dried with Na2SO4. Following preparative chromatotron TLC (lOOOμm plate) using 1:2 acetone:hexanes as eluant, 16mg pure Example 72 was obtained which was characterized by H NMR and MS [m/z: 826 (M + +l)]. EXAMPLE 73 Example 73 was prepared by the following procedure. At RT, 7mL Et3N, and lmg DMAP was added to lOmg N-desmethoxy apicidin in 0.17mL CH2CI2. Then 3.9μL MeSO2Cl was added. After 20h, the solution was poured into water, extracted with EtOAc and dried with Na2SO4- Following preparative RP- HPLC using a linear gradient (4:6 to 1:0 MeCN:H2θ), 0.6mg pure Example 73 was obtained (Rf= 0.4, 4:6 acetone:hexanes) which was characterized by H NMR and MS [m/z: 672 (M + τ + . 1)]. EXAMPLES 74A-74J Following the general procedure of Examples 69-72, utilizing an appropriate electrophile (R-X) readily determined by one in the art, the following compounds were prepared: Table 6 EXAMPLE 75 Example 75 was prepared by the following procedure. At RT, 0. lmL pyridine was added to 9mg N-desmethoxy-N-(pαrα-aminophenoxycarbonyl) apicidin in 0.22mL DMF, followed by the addition of 22μL HOCH2CH2NMe2- After 15h, the solution was poured into saturated NaHCO3, extracted with CH2CI2 and dried with Na2SO4. Following preparative chromatotron TLC (lOOOμm plate) using 1:2 acetone:hexanes as eluant, pure Example 75 was obtained which was characterized by X H NMR and MS [m/z: 709 (M + +l)]. EXAMPLE 76 Example 76 was prepared by the following procedure. At 0°C, 7.8μL IN LiOH was added to 3.8mg N-desmethoxy-N-Qoαra-carboxymethylphenyl methyl) apicidin in 0.13mL of a 3:1:1 mixture of THF:MeOH:H2θ. After 2h at 0°C and 17h at RT, the volatiles were then removed with a vigorous stream of nitrogen. The aqueous layer was then extracted with EtOAc and the aqueous layer acidified to pH~4 with 2N HCl. The aqueous layer was further extracted with 5 aliquots of a 3:7 mixture of z ' PrOH:CHCl3 and finally dried with Na2SO4. Following RP-HPLC using a linear gradient (2:8 to 1:0 MeCN:H2θ), 2.5mg pure Example 76 was obtained which was characterized by *H NMR and MS [m/z: 728 (M + +l)]. EXAMPLE 77 Example 77 was prepared by the following procedure. At -10°C, 6.5μL IM LiOH was added to a solution of 3.3mg N-desmethoxy-N-(pαrα- acetoxyphenylcarbonyl) apicidin in 0.1 lmL of a 3: 1 : 1 mixture of THF:MeOH:H2θ. After lh, the volatiles were removed with nitrogen. Then, about 2mL each of water and EtOAc was added. The resulting solution was carefully neutralized to pH~7 with 2N HCl. The solution was extracted with EtOAc and dried with Na2SO4. Following PTLC (1 x 500μm plate) using 6:4 acetone:hexanes as eluant, 1.7mg pure Example 77 was obtained which was characterized by H NMR and MS [m/z: 714 (M +1)]. EXAMPLE 78 Example 78 was prepared by the following procedure. At RT, 0.5mg 10% Pd C catalyst was added to 2mg N-desmethoxy-N-(pαr -nitrophenoxycarbonyl)- apicidin in 0.2mL CH2CI2 and an atmosphere of hydrogen established (balloon pressure). After 6.5h, the catalyst was removed by filtration through Celite using 1 : 1 MeOH:CH2θ2 as eluant. Without any further purification, the resulting 1.8mg Example 78 was characterized by l U NMR and MS [m/z: 729 (M + +l)]. EXAMPLE 79 Example 79 was prepared by the following procedure. At 0°C, 200μL IM LiOH was added to 89mg N-desmethoxy-N-carbomethoxymethyl apicidin in 3.5mL of a 1:1:1 mixture of THF:MeOH:H2θ. After 45min at 0°C, the slightly cloudy solution was warmed to RT and became homogenous. After an additional 20min, the MeOH and THF were removed using a vigorous stream of N2- Then, 2mL Ethyl acetate was added to the solution and removed to dispose of residual organic soluble material. The solution was acidified to pH~4.0 using 2N HCl, 3mL brine was added to the aqueous layer, and then extracted with a 1:4 mixture of ZPrOH:CHCl3. The organic layer was dried with Na2SO4 to yield 5 lmg pure Example 79, which was characterized by l H NMR and MS [m z: 652.5 (M + +l)]. HPLC: tR = 1.21 min (1:1 MeCN:H2θ, 1.5mIVmin, Zorbax™ RX-8). EXAMPLE 80 Example 80 was prepared by the following procedure. At RT, 2.6mL TEA was added to 6mg N-desmethoxy-N-(6-amino-hexylaminocarbonylmethyl)- apicidin in lmL CH2CI2. Next, 4mg NBD-Cl was added and the vial was wrapped with foil. After 3h at RT, pure Example 80 was obtained by flash chromatography on silica gel without workup using 1:1 hexanes: acetone as eluant. The pure product was characterized by H NMR. TLC: Rf = 0.19 (1:1 acetone: hexanes). EXAMPLE 81 Example 81 was prepared by the following procedure. At 0 °C, 19mg EDCI was added to 50mg N-desmethoxy-N-carboxymethyl apicidin, 29mg CBZ- HN(CH2)6NH2, lOmg HOBT and 19μL DIEA in 5mL CH2CI2. After 15min at 0°C and lh at RT, 3mg DMAP was added. After an additional 2 hours, the CH2CI2 was removed using a vigorous stream of N2 and 2mL DMF was added. After 2h, the solution was poured into 20μL 2:1 H2θ:brine, acidified to pH~3.0 with 2N HCl and extracted with 5 15mL aliquots of CH2CI2. The organic layer was dried with Na2SO4. Without further purification, 54mg pure Example 81 was obtained which was characterized by l H NMR and MS [m/z: 884.6 (M + +l)]. TLC: Rf = 0.72 (1:9:90 NH4OH:MeOH:CHCl3). HPLC: tR = 5.38min (6:4 MeCN:H2θ, 1.5mL/min, Zorbax™ RX-8). EXAMPLE 82 Example 82 was prepared by the following procedure. At 0°C, 1.2mg HOBT was added to 5.7mg N-desmethoxy-N-carboxymethyl apicidin in O.lmL DMF, 2.9mg NaHCO3, and 1.2mg EtSCH2CH2NH2 « HCl. This was followed by the addition of 1.8mg EDCI. The solution was warmed to RT and aged for 16h. The aged solution was poured into saturated NaHCO3, extracted with EtOAc and dried with Na2SO4. Following RP-HPLC using gradient elution (4:6 to 1:0 MeCN:H2θ), 3.3mg pure Example 82 was obtained which was characterized by H NMR and MS [m/z: 739 (M + +l)]. EXAMPLE 83 Example 83 was prepared by the following procedure. At RT, lOmg 5% Pd/C catalyst was added to 54mg N-desmethoxy-N-[6-(benzyloxycarbonylamino)- hexylaminocarbonylmethyl]-apicidin in 3mL DMF and a H2 atmosphere (balloon pressure) was established. After 2h, an additional 40mg 5% Pd/C catalyst was added and the solution stirred overnight. The catalyst was then filtered off and the solvents were removed under reduced pressure. Following flash chromatography on silica gel using gradient elution (using first neat CHCI3, then three subsequent elutions of 1:3:96, then 1:4:95 and then 1:9:90 NH4OH:MeOH:CHCl3 as eluant), pure Example 83 was obtained which was characterized by H NMR and MS [m z: 750.4 (M + +l)]. TLC: Rf = 0.12 (1:9:90 NH4OH:MeOH:CHCl3). EXAMPLE 84 Example 84 was prepared by the following procedure. At RT, 3.2mg NHS-SS-Biotin was added to 4mg N-desmethoxy-N-(6- aminohexylaminocarbonylmethyl)-apicidin in 0.5mL CH2CI2 followed by 2μL DIEA. The solution was stirred for lh at RT, followed by 12h at 4°C and 2h at RT. Additional 3.2mg NHS-SS-Biotin and 2μL DIEA were added followed by lOOμL DMF. After an additional 1 hour, the solution was loaded directly onto a silica gel pipette column using gradient elution (1:3:96 to 1:9:90 NH4OH:MeOH:CHCl3 as eluant) to yield 4mg pure Example 84 which was characterized by H NMR. TLC: Rf = 0.26 (1:9:90 NH4OH:MeOH:CHCl3). EXAMPLE 85 Example 85 was prepared by the following procedure. At RT, 0.5mg HOBT, 2.6mg Fmoc-Phe(4-Bz)-OH (Fmoc = 9-fluorenylmethyl oxycarbonyl) and lmg EDCI was added to 2mg N-desmethoxy-N-(6-aminohexylaminocarbonylmethyl)- apicidin in 0.5mL CH2CI2. Then, 3μL DIEA was added. After 2h at RT, the crude was purified without workup on a pipette flash column with silica gel using gradient elution (1:1 acetone:hexanes followed by 5:95 MeOH:CHCl3). The partially purified Example 85 was characterized by *H NMR. TLC: Rf = 0.26 (1:9:90 NH4OH:MeOH:CHCl3). TLC: Rf = 0.53 (5:95 MeOH:CHCl3). EXAMPLE 86 Example 86 was prepared by the following procedure. At RT, 0.2mL piperidine was added to 15mg of the Fmoc -protected Example 85 compound in 2mL CH2CI2. After 3h at RT, the volatiles were removed under reduced pressure to produce Example 86. This material was used with no additional purification in Example 87. EXAMPLE 87 Example 87 was prepared by adding 5μL Et3N to 2mg of the crude product of Example 86 in 0.2mL CH2CI2 at 0 °C followed by 2μL MeSO2Cl. After 30min, the reaction was quenched by the addition of 3 drops of a 1:9:90 mixture of NH4OH:MeOH:CHCl3. Following flash chromatography on silica gel using 1:3:96 NH4OH:MeOH:CHCl3 as eluant, pure Example 87 was obtained without workup which was characterized by H NMR. EXAMPLE 88 Example 88 was prepared by the following procedure. First, 6mg HOBT, lOmg (4-Bz)PhCO2H, 23μL DIEA, and 19.6mg BOP were added to 250μL CH2CI2 at RT to generate (4-Bz)PhCO(OBT). Then, 20μL of freshly prepared (4- Bz)PhCO(OBT) solution was added to lmg N-desmethoxy-N-(6- aminohexylaminocarbonylmethyl)-apicidin in 200μL CH2CI2 in a vial. The vial was wrapped in foil and allowed to stir at RT overnight. Partially purified product was obtained following preparative TLC on silica gel (1 x 250μm plate) using 1:9:90 NH4OH:MeOH:CHCl3 as eluant. Following preparative TLC on silica gel (1 x 250μm plate) using 1:3:96 NH4OH:MeOH:CHCl3 as eluant, pure Example 88 was obtained which was characterized by l H NMR. TLC: Rf = 0.27 (1:3:96 NH4OH:MeOH:CHCl3). EXAMPLE 89 Example 89 was prepared by the following procedure. At RT, 3mg HOBT, 6μL Et3N, and 4. lmg (4-Bz)PhCH=CHCO2H was added to 9mg N- desmethoxy-N-(6-aminohexylaminocarbonylmethyl)-apicidin in lmL CH2CI2 followed by 13mg BOP. After 4h, the crude was purified without workup by flash chromatography on silica gel using 1:3:96 NH4OH:MeOH:CHCl3. This yielded 13.4mg pure Example 89, which was characterized by H NMR. TLC: Rf = 0.29 (1:3:96 NH4OH:MeOH:CHCl3). HPLC: TR = 4.90min (7:3 MeCN:H2θ, 1.5mIJmin, Zorbax™ RX-8). EXAMPLE 90 Example 90 was prepared by the following procedure. At RT, 3mg 5% Pd/C catalyst was added to 4mg Example 89 in 1 : 1 MeOH:CH2θ2 and a deuterium gas atmosphere was established (balloon pressure). After lh, the solution was purified on a silica gel pipette column using 1:9:90 NH4OH:MeOH:CHCl3 as eluant to yield 2.9mg pure Example 90, which was characterized by H NMR. TLC: Rf = 0.34 (1:3:96 NH4OH:MeOH:CHCl3). HPLC: tR = 4.66min (7:3 MeCN:H2θ, 1.5mL/min, Zorbax™ RX-8). EXAMPLE 91 Example 91 was prepared by the following procedure. To 9mg of the silyl ether Example 74d in 0.2mL pyridine at 0°C was added 0.2mL HF»pyridine solution (prepared from 25g HF « pyridine, lOmL pyridine and 25mL THF). After 1.5h, the reaction was quenched by the addition of saturated NaHCO3, extracted with CH2CI2 and the combined organic layers were dried with Na2SO4- The 7.4mg of alcohol thus obtained was used in Example 92 below with no additional purification and was characterized by H NMR and MS [m/z: 638 (M + +l)]. EXAMPLE 92 Example 92 was prepared by adding to 7.4mg of the Example 91 alcohol in 4mL CH2CI2 at RT 422mg 1,2,4-triazolyle followed by 610μL (PhCH2θ)2PNEt2. After aging the solution for 3h, the volatiles were removed in vacuo to form a yellow residue. Then, 7mL THF was added to the yellow residue to form a solution, which was cooled to -40°C. To this solution was added 4.6mL 30% H2O2 and warmed to RT. After aging for 30min, the reaction was quenched by the addition of 10% Na2S2θ3(aq), diluted with saturated NaHCO3(aq) and water, extracted with CH2CI2 and dried with Na2SO4. Following chromatotron purification (lOOOμm plate) using 1:2 acetone exanes as eluant, 255mg pure Example 92 was obtained which was characterized by H NMR and MS [m/z: 898 (M +1)]. EXAMPLE 93 Example 93 was prepared by adding 27mg KHCO3 and 25mg 10% Pd/C catalyst at RT to 245mg of Example 92 in 40mL z ' PrOH and lmL water. An atmosphere of hydrogen (balloon pressure) was established for 12h. After the catalyst was removed by filtration through Celite using 1 : 1 MeOH:H2θ as eluant, the volatiles were removed under reduced pressure. No further purification was required and yielded 214mg Example 93, which was characterized by H NMR and MS [m/z: 718 (M + +l)]. EXAMPLE 94 Example 94 was prepared by the following procedure. At 0°C, 2mg DMAP was added to 20mg apicidin alcohol in 2mL CH2CI2 followed by the addition of 26mg Ts2θ. After lOmin the solution was warmed to RT for 3h. Then, lOmg TsCl was added and the solution aged for 16h. The solvent was removed under reduced pressure and lmg pure Example 94 was obtained following centrifugal TLC (4:6 acetone:hexanes to 1:9:90 NH4OH:MeOH:CHCl3) as eluant. The product was characterized by l H NMR and MS [m/z: 792 (M + +l)]. EXAMPLE 95 Example 95 was prepared by the following procedure. At 0°C, 247mg Ph3P and 217mg Zn(N3)3 « pyridine was added to 300mg N-desmethoxy-N-(2- hydroxyethyl)-apicidin in 25mL CH2CI2, followed by the addition of 150μL DEAD. The solution was then warmed to RT. After aging for 12h, the volatiles were removed under reduced pressure. Following chromatotron TLC on silica gel (2mm plate) using 1:3:96 NH4OH:MeOH:CHCl3 as eluant, 31 lmg pure Example 95 (Rf= 0.32, 1:9:90 NH4OH:MeOH:CHCl3) was obtained which was characterized by H NMR and MS [m/z: 663 (M + +l)]. EXAMPLE 96 Example 96 was prepared by the following procedure. At RT, 60mg 10% Pd/C catalyst was added to 31 lmg N-desmethoxy-N-(2-azidoethyl) apicidin in CH2CI2 and an atmosphere of hydrogen was established (balloon pressure). After 8h, the catalyst was filtered through Celite using 3:7 /PrOH:CHCl3 as eluant to yield the desired product. Following chromatotron PTLC (1 x 2000μm plate) using 1:3:96 NH4OH:MeOH:CHCl3 as eluant, pure Example 96 (200mg, Rf= 0.21 (1:3:96 NH4OH:MeOH:CHCl3) was obtained which was characterized by H NMR and MS [m/z: 637 (M + +l)]. EXAMPLE 97 Example 97 was prepared by the following procedure. At 0°C, 9μL Et3N was added to lOmg N-desmethoxy-N-(2-aminoethyl) apicidin in 0.5mL CH2CI2 followed by the addition of 3.6μL MeSO2Cl. The solution was warmed to RT and stirred for 30min. The solution was quenched by the addition of saturated NaHCO3, extracted with CH2CI2 and dried with Na2SO4. Following PTLC (1 x 250μm plate) on silica gel using 1:1 acetone:hexanes as eluant, 9mg pure Example 97 was obtained which was characterized by X H NMR and MS [m/z: 732.7 (M+ NH4)]. TLC: Rf = 0.26 (1:1 acetone:hexanes). HPLC: tR = 4.7 min (1:1 MeCN:H2θ, 1.5 ml/min, Zorbax™ RX-C8). EXAMPLE 98 Example 98 was prepared by the following procedure. At RT, 7 μL NaN(TMS)2 (IM in THF) was added to 4mg N-desmethoxy-N-2- methanesulfonamidoethyl apicidin in 0.28mL THF followed by the addition of 1.5μL Mel. After 16h, the solution was quenched by the addition of water, extracted with CH2CI2 and dried with Na2SO4. Following PTLC (1 x 250μm plate) on silica gel using 1:3:96 NH4OH:MeOH:CHCl3 as eluant, 2.2mg pure Example 98 was obtained which was characterized by l U NMR and MS [m z; 746.6 (M + +NH4)]. TLC: Rf = 0.42 (1:3:96 NH4OH:MeOH:CHCl3). EXAMPLE 99 Example 99 was prepared by the following procedure. At RT, 5mg HOBT, 7μL TEA and 18.4mg Fmoc-Phe(4-Bz)-OH was added to 16mg N- desmethoxy-N-(2-aminoethyl)-apicidin in lmL CH2CI2 followed by the addition of 16mg BOP. After 3h at RT, the solution was purified by flash chromatography on silica gel using 1:3:96 NH4OH:MeOH:CHCl3 as eluant to yield pure Example 99, which was characterized by H NMR. TLC: Rf = 0.50 (1:3:96 NH4OH:MeOH:CHCl3). EXAMPLE 100 Example 100 was prepared by adding 50μL piperidine to 15mg of the Fmoc-protected amine of Example 99 at RT in 2mL CH2CI2. After 2h at RT, the solution was concentrated under reduced pressure and lyophilized from dioxane to remove residual piperidine. The crude deprotected amine product was dissolved in 2mL CH2CI2 at 0°C and 5.6μL Et3N was added followed by 62μL MeSO2Cl (0.26M in CH2CI2). After lh, the reaction was quenched by the addition of saturated NaHCO3(aq), extracted with CH2CI2 and dried with Na2SO4. Following PTLC on silica gel (1 x lOOOμm plate) using 1:4:95 NH4OH:MeOH:CHCl3 as eluant, pure Example 100 was obtained which was characterized by H NMR and MS [m/z: 1080 (M + +l)]. EXAMPLE 101 Example 101 was prepared by the following procedure. At RT, 8mg NaBELj. was added to 20mg N-desmethoxy-N-(2-aminoethyl) apicidin in 2mL MeOH. After 2h at RT, acetone was added to the solution to quench the reaction and the solution was poured into saturated NaHCO3, extracted with CH2CI2 and dried with Na2SO4. Following flash chromatography on silica gel using 1:9:90 NH4OH:MeOH:CHCl3 as eluant, pure Example 101 was obtained which was characterized by *H NMR. TLC: Rf= 0.28 (1:9:90 NH4OH:MeOH:CHCl3). EXAMPLE 102 Example 102 was prepared by the following procedure. At RT, 16. lmg DDQ was added to 20mg N-desmethoxy apicidin in l.lmL 9:1 MeCN:H2θ to form a dark puφle solution, which became blood-red over 30 min. The solution was aged at 0°C for 12h. The solution was purified without workup by RP-HPLC using 4:6 MeCN:H2θ as eluant. This yielded 15mg of Example 102 which was characterized by H NMR and MS [m/z: 608 (M + +l)]. EXAMPLE 103 Example 103 was prepared by the following procedure. At RT, 1.5μL Et3N was added to 6mg c c/o(beta-oxo-L-Tφ-L-Ile-D-Pip-L-2-amino-8-oxo- decanoyl) in 0.5mL CH2CI2. After lOmin, the solution was purified without workup by RP-HPLC using 1:1 MeCN:H2θ as eluant. This yielded 3mg pure Example 103, which was characterized by H NMR and MS [m/z: 608 (M + +l)]. EXAMPLES 104A AND 104B Ex. 104a Ex. 104b Examples 104a and 104b were prepared by the following procedure. At RT, 0.14mL BrCH2CH2CH2CH2Cl, 0.5g «Bu4NI and 25mg 95% NaH were added to 300mg beta-oxo-N-desmethoxy apicidin in 0.5mL DMF containing 0.25mL HMPA. The solution was degassed with bubbling N2 for 4min and then heated to 100°C for 90min. The solution was then cooled to RT, poured into saturated brine/saturated NaHCO3, extracted with CH2CI2 and dried with Na2SO4. Following PTLC (2 x 1500μm plates) on silica gel using 1:3:96 NH3:MeOH:CHCl3 as eluant, a pure mixture of Example 104a and Example 104b was obtained. The pure products were characterized by H NMR and MS [m/z: 698.5 (M+1) for each isomer]. The yield was 150mg D-Tφ isomer and 120mg L-Tφ isomer. TLC: Rf = 0.42 for D-Tφ isomer and 0.25 for L-Tφ isomer (2:3 acetone:hexanes). EXAMPLES 105 A AND 105B Ex. 105a Ex. 105b Examples 105a and 105b were prepared by adding 0.12mL BrCH2CH2CH2Cl, 0.5g Bu4NI and 25mg 95% NaH at RT to 300mg beta-oxo-N- desmethoxy apicidin in 0.5mL DMF containing 0.25mL HMPA. The solution was degassed with bubbling N2 for 4min and then heated to 100°C for 90min. The solution was cooled to RT, poured into 1:1 saturated brine:saturated NaHCO3, extracted with CH2CI2 and dried with Na2SO4. Following PTLC (2 x 1500μm plates) on silica gel using 1:3:96 NH3:MeOH:CHCl3 as eluant, a pure mixture of Examples 105a and 105b were obtained which were characterized by H NMR and MS [m/z: 684.5 (M + +l) for each isomer]. Yield: 120mg D-Tφ isomer and 80mg L- Tφ isomer. TLC: Rf = 0.55 for D-Tφ isomer and 0.27 for L-Tφ isomer (2:3 acetone:hexanes). EXAMPLES 106A AND 106B Ex. 106a Ex. 106b Examples 106a and 106b were prepared by adding 516mg Nal to 120mg cycZo(N-(4-chloro-n-butyl)-beta-oxo-D-Tφ-L-Ile-D-Pip-L-2-amino-8-oxo- decanoyl) in 2.2mL anhydrous MeCN. The resulting solution was heated to 60°C for 12h. The solution was cooled to RT and diluted with 1:1 brine: saturated NaHCO3, extracted with CH2CI2 and dried with Na2SO4. This yielded lOOmg of a mixture of Example 106a and 106b which was characterized by H NMR and MS [m z: 790.5 (M +1) for each isomer] without purification. TLC: Rf = 0.58 for D-Tφ isomer and 0.41 for L-Tφ isomer (1:3:96 NH4:MeOH:CHCl3) EXAMPLES 107A AND 107B Ex. 107a Ex. 107b Examples 107a and 107b were prepared by adding 350mg Nal to 80mg c cZo(N-(4-chloro-n-propyl)-beta-oxo-D-Tφ-L-Ue-D-Pip-L-2-amino-8-oxo-decanoyl) in 1.5mL anhydrous MeCN. The resulting solution was heated to 60°C for 12h. The solution was cooled to RT, diluted with 1:1 brine:saturated NaHCO3, extracted with CH2CI2 and dried with Na2SO4. This yielded 70mg of a mixture of Example 107a and Example 107b which were characterized by H NMR and MS [m/z: 776.5 (M +1) for each isomer] without purification. TLC: Rf = 0.53 for D-Tφ isomer and 0.42 for L-Tφ isomer (1:3:96 NH4OH:MeOH:CHCl3). EXAMPLES 108A AND 108B Examples 108a and 108b were prepared by adding 30mg MgBr2'Et2O, and 30μL nBu3SnH to 40mg of an -1:1 mixture of cycZo(N-(3-iodo-n-propyl)-beta- oxo-D-Tφ-L-Ile-D-Pip-L-2-amino-8-oxo-decanoyl) and cycZo(N-(3-iodo-n-propyl)- beta-oxo-L-Tφ-L-Ile-D-Pip-L-2-amino-8-oxo-decanoyl) in 0.5mL CH2O2. The resulting solution was cooled to -78°C. Next, lOOμL Et3B was added followed by 500μL oxygen gas via syringe over 2h. The reaction was quenched by the addition of 1:1 brine:saturated NaHCO3 at -78°C. The solution was then warmed to RT, partitioned with CH2CI2 and the organic layer dried with Na2SO4. The solution was concentrated under reduced pressure and the residue partitioned between hexanes:MeCN (1:3). The MeCN layer was washed (3x) with hexanes and the MeCN layer concentrated under reduced pressure. Pure products were obtained following PTLC (1 x lOOOμm plate) on silica gel using 1:3:96 NH4OH:MeOH:CHCl3 as eluant. Pure products were characterized by H NMR and MS [m/z: 650.6 (M +1) for each isomer]. Yield: 14mg D-Tφ isomer and 14mg L-Tφ isomer. TLC: Rf = 0.69 for D- Tφ isomer and 0.51 for L-Tφ isomer (1:3:96 NH4OH:MeOH:CHCl3). EXAMPLE 109 Example 109 was prepared by the following procedure. At RT, 5mg 2,2'-azobisisobutyronitrile and 38μL «Bu3SnH were added to a 22mg mixture of cyc/o(N-(3-iodo-n-propyl)-beta-oxo-D-(and L, ~l:l)-Tφ-L-Ile-D-Pip-L-2-amino-8- oxo-decanoyl) in 0.6mL toluene. Nitrogen was bubbled through the solution for 5min and it was then heated to 100°C for 2h. The solution was cooled to RT, concentrated under reduced pressure and the residue partitioned between hexanes:MeCN (1:3). The MeCN layer was washed (3x) with hexanes and the MeCN layer concentrated under reduced pressure. Following PTLC on silica gel using 4:6 acetone:hexanes as eluant, lOmg pure Example 109 was obtained which was characterized by H NMR and MS [m/z: 652.7 (M + +l)]. TLC: Rf = 0.50 and 0.43 (mixture of beta-hydroxy isomers) (1:3:96 NH4OH:MeOH:CHCl3). EXAMPLE 110 Example 110 was prepared by the following procedure. At RT, 6mg 2,2'-azobisisobutyronitrile and 52μL «Bu3SnH was added to 31mg of a -1:1 mixture of cycZo(N-(4-iodo-n-butyl)-beta-oxo-D-Tφ-L-Ile-D-Pip-L-2-amino-8-oxo-decanoyl) and c cZo(N-(4-iodo-n-butyl)-beta-oxo-L-Tφ-L-Ile-D-Pip-L-2-amino-8-oxo- decanoyl) in 0.8mL toluene. Nitrogen was bubbled through the solution for 5min and it was then heated to 100°C for 2h. The solution was cooled to RT, concentrated under reduced pressure and the residue partitioned between hexanes:MeCN (1:3). The MeCN layer was washed (3x) with hexanes and the MeCN layer concentrated under reduced pressure. Example 110 was characterized by H NMR without purification. TLC: Rf = 0.66 (1:3:96 NH OH:MeOH:CHCl3). EXAMPLES 111 A AND 11 IB Ex. Ilia Ex. 111b Examples I l ia and 11 lb were prepared by adding lmg NaBH4 to 3mg beta-oxo-N-desmethoxy apicidin in 0.25mL EtOH at 0°C. After 2.5h at RT and lOh at 0°C, the solution was poured into saturated NH4CI, extracted with 3:1 EtOAc:/PrOH and dried with Na2SO4. Following RP-HPLC using gradient elution (2:3 to 1:1 MeCN:H2θ), a mixture of pure Example I l ia and 111b were obtained which was characterized by H NMR and MS [m/z: 594 (M -H2O) for both isomers]. TLC: Rf = 0.50 for D-Tφ isomer and 0.28 for L-Tφ isomer (1:9:90 NH4OH:MeOH:CHCl3). HPLC: tR = 3.9min for D-Tφ isomer and 3.5min for L-Tφ isomer (1:1 MeCH:H2θ, 1.5mL/min, Zorbax™ RX-C8). EXAMPLES 112A AND 112B Ex. 112a Ex.ll2b Examples 112a and 112b were prepared by adding 5.8mg CeCl3 » 6H2O to lOmg c c/ø(beta-oxo-L-Tφ-L-Ile-D-Pip-L-2-amino-8-oxo-decanoyl) at RT in 0.2mL MeOH. After 5min, the solution was cooled to 0°C and 0.6mg NaBH4 was added. The solution was poured into saturated NH4CI, extracted with EtOAc and dried with Na2SO4- Following RP-HPLC using 1:1 MeCN:H2θ as eluant, a pure mixture of 0.7mg Example 112a and 1.3mg Example 112b was obtained which was characterized by H NMR and MS [m/z: 609 (M + +l) for each isomer]. EXAMPLES 113 A AND 113B Ex. 113a Ex. 113b Examples 113a and 113b were prepared by adding 14mg DMAP and 0.533mL Ac2θ to 700mg cycZo(beta-oxo-L-Tφ-L-Ile-D-Pip-L-2-amino-8-hydroxy- decanoyl) in 115mL dichloroethane at RT. After 8h, the mixture was poured into saturated NH4CI, extracted with CH2CI2 and dried with Na2SO4. Following preparative chromatotron (4μm plate) on silica gel using 2:8 to 4:6 acetone:hexanes gradient elution as eluant, 8mg of a mixture of Examples 113a and 113b was obtained. Pure epimeric products were characterized by H NMR and MS. D-Tφ isomer: yield: 140mg; TLC: Rf = 0.71 (1:1 acetone: hexanes); MS [m/z: 694.4 (M + +l)]. L- Tφ isomer: yield: l lOmg; TLC: Rf = 0.57 (1:1 acetone:hexanes); MS [m/z: 694.5 (M + +l)]. EXAMPLE 114 Example 114 was prepared by the following procedure. At RT, 28.5mg N-bromosuccinamide and 1.2mg benzoyl peroxide was added to lOOmg apicidin in 5.3mL CCI4. Nitrogen then was bubbled through the solution for 5min. The solution was refluxed for 15min and then cooled to RT. Following PTLC on silica gel (3 x lOOOμm plates) using 1:3:96 NH4OH:MeOH:CHCl3 (one development) followed by 4:6 acetone:hexanes (two developments) as eluant, 62mg pure Example 114 was obtained which was characterized by H NMR and MS [m/z: 704 (M + +l)]. RP-HPLC: tR = 5.02 min (apicidin: tR = 4.82min), 6:4 MeCN:H2θ, 1.5mL/min. EXAMPLES 115A AND 115B Ex. 115a Ex. 115b Example 115a (mobile product A) and Example 115b (polar product B) were prepared by the following methods E and F. Method E At 0°C, lOmg Example 114 was added to 4mg AgBF4 in 250μL 3:1 DMSO:CH2Cl2- After aging for lOmin (at this point, TLC showed the disappearance of the starting bromide), lOμL Et3N was added and the solution aged for an additional hour. The reaction was quenched by the addition of water. The mixture was then extracted with CH2CI2 and dried with Na2SO4. Following PTLC on silica gel (1 x 250μm plate) using 1:1 acetone:hexanes as eluant, a pure mixture of Examples 115a and 115b was obtained which were characterized by H NMR and MS [m/z: 640 (M + +l) for both isomers]. TLC: Rf= 0.48 Example 115a (mobile product A) and 0.41 Example 115b (polar product B), 1:1 acetone:hexanes. Method F At RT, 12mg NaHCO3 was added to 43mg apicidin in CH2CI2, followed by 18mg 85% MCPBA. The resulting solution was vigorously stirred for 12h. The solution was then poured into saturated NaHCO3(aq), extracted with CH2CI2 and dried with Na2SO4. Following PTLC on silica gel (1 x 250μm plate) using 1:1 acetone:hexanes, pure Example 115a was obtained which was identical in all respects to Example 115a, mobile product A, from Method E above. EXAMPLE 116 Example 116 was prepared by following the general procedure of Example 115a, method E. Starting with lOmg of Example 114, 4mg of Example 116 was prepared which was characterized by H NMR and MS [m/z: 718.6 (M +1)]. EXAMPLE 117 Example 117 was prepared by adding 4μL Ac2θ to 5.4mg of Example 115b at RT in 375μL CICH2CH2CI, followed by the addition of 0.3mg DMAP. After 1.5h, the volatiles were removed under a stream of nitrogen. Following PTLC on silica gel (1 x 250μm plate) using 1:1 acetone:hexanes as eluant, 6mg pure Example 117 which was characterized by H NMR and MS [m/z: 762 (M + +l)]. EXAMPLE 118 Example 118 was prepared by the following procedure. To 5mg of Example 117 at RT in lmL CH2CI2 was added lmg Pd(OH)2 and a hydrogen atmosphere was established (balloon pressure). After aging for 2h, the solution was filtered and concentrated under reduced pressure. Following flash chromatography on silica gel using 1:9:90 NH4:MeOH:CHCl3, 3.5mg pure Example 118 was obtained which was characterized by H NMR and MS [m/z: 652 (M + +l)]. EXAMPLE 119 Example 119 was prepared by the following procedure. To 25mg beta- oxo-N-desmethoxy-apicidin at RT in 1.5mL MeOH was added 15μL pyridine followed by the addition of 126mg Pb(OAc)4. After aging for 48h, the solution was cooled to 0°C and saturated Na2S2θ3(aq) was added. The solution was poured into saturated NH4Cl(aq):brine (1:1), extracted with ? ' PrOH:CHCl3 (3:7) and dried with Na2SO4. The solution was filtered and concentrated under reduced pressure. Following flash chromatography on silica gel using 1:9:90 NH4:MeOH:CHCl3, 36mg pure Example 119 was obtained which was characterized by H NMR and MS [m/z: 638 (M + +l)]. EXAMPLE 120 Example 120 was prepared by the following procedure. To 8 lmg of Example 114 in 6mL THF:H2θ at RT was added 141mg basic AI2O3 and 191mg Ag2CO3. The solution was warmed to 50°C for 5h, then cooled to RT. The mixture was partitioned between water and CH2CI2, the layers separated, the organic layer dried with Na2SO4 and then filtered through Celite. Following PTLC (1 x 500μm plate) using 1:3:96 NH4OH:MeOH:CHCl3 as eluant, pure Example 120 was obtained which was characterized by H NMR and MS [m/z: 640.5 (M + +l)]. EXAMPLE 121 Example 121 was prepared by following the general procedure of Example 120, and utilizing the dibromide Example 126 as the starting material. The product thus obtained was characterized by H NMR and MS [m/z: 720 (M + +l)]. EXAMPLE 122 Example 122 was prepared by the following procedure. To 200μL CH2CI2 at -78°C was added 6μL oxallyl chloride (2M solution in CH2CI2) followed by the addition of 2μL DMSO. After 5min, 3.3mg of Example 120 (as a solution in 50μL CH2CI2) was added to the DMSO/oxallyl chloride solution. After aging for 15min, 14μL Et3N was added and the solution was warmed to 0°C. The reaction was then quenched by the addition of water, extracted with CH2CI2 and dried with Na2SO4. Following PTLC on silica gel (1 x 500μm plate) using 1:3:96 NH4OH:MeOH:CHCl3 as eluant, pure Example 122 was obtained which was characterized by ! H NMR and MS [m z: 658 (M + +l)]. EXAMPLE 123 Example 123 was prepared by mixing 28mg of Example 126 in 1.5mL DMF at RT with 13mg NaSMe. The mixture was then warmed to 50°C. After lh, the solution was poured into water, extracted with CH2CI2 and dried with Na2SO4. Following PTLC purification on silica gel (1 x 250μm plate) using 4:6 acetone:hexanes as eluant (two developments). Pure Example 123 was obtained which was characterized by X H NMR and MS [m/z: 748 (M + +l)]. EXAMPLE 124 Example 124 was prepared by adding 5.4mg KSAc to llmg of Example 114 in 260μL DMF at 0°C. After aging the solution for 48h, it was warmed to RT and aged an additional 20h. The solution was poured into water, extracted with CH2CI2 and dried with Na2SO4. Following PTLC on silica gel using 4:6 acetone:hexanes as eluant, the product thus obtained was characterized by H NMR and MS [m/z: 622 (M + +1)]. EXAMPLE 125 Example 125 was prepared by adding 5mg DDQ to 5mg of Example 115a (mobile product A) at RT in 200μL THF. The resulting solution was warmed to 65°C. After aging for 20h, an additional 5mg DDQ was added. After an additional 6h, the volatiles were removed at ambient temperature under reduced pressure. Methylene chloride was added, the solution was filtered and the filtrate was loaded onto a preparative TLC plate (1 x 250μm plate, silica gel). Following PTLC purification using 4:6 acetone:hexanes as eluant, the pure Example 125 thus obtained was characterized by *H NMR and MS [m/z: 608.6 (M + +l)]. EXAMPLE 126 Example 126 was prepared by the following procedure. At RT, 86mg N-bromosuccinamide was added to lOOmg apicidin in 5.3mL CCI4, followed by the addition of 1.2mg benzoyl peroxide. The resulting solution was purged with vigorous nitrogen bubbling for 5min. The solution was heated to reflux for 45min and then cooled to RT. The volatiles were removed under reduced pressure and pure Example 126 was obtained following PTLC purification on silica gel (1500μm plate) using 1:3:96 NH4OH:MeOH:CHCl3 as eluant. The dibromide Example 126 product thus obtained was characterized by H NMR and MS [m z: 780 (M + +l)]. TLC: Rf= 0.49 (1:3:96 NH4OH:MeOH:CHCl3). HPLC: tR = 10.02min, lmlJmin, 6:4 MeCN:H2θ, Zorbax™ RX-8). EXAMPLES 127 A AND 127B Mobile product A Polar product B Ex. 127a Ex. 127b Examples 127a and 127b were prepared by adding 0.32mL DMF, and 0.32mL 1:1 saturated NaHCO3:H20 to lOmg of Example 126, followed by the addition of 4.5mg Na2S2θ4. The milky white solution thus formed was aged at RT for 24h. Then, 2mL Acetonitrile was added, and the solids were removed by filtration. This yielded lmg pure Example 127a (mobile product A) and 4mg pure Example 127b (polar product B) following RP-HPLC using 1:1 MeCN:H2θ as eluant. Both products were characterized by H NMR and MS. Example 127a, mobile product A: MS: [m/z: 704 (M + +l)]; TLC: Rf = 0.75 (1:1 acetone:hexanes); HPLC: tR = 8min, 2mL/min, 1:1 MeCN:H2θ, Zorbax™ RX-8). Example 127b, polar product B: MS: [m/z: 702 (M + +l)]; TLC: Rf= 0.60 (1:1 acetone:hexanes); HPLC: tR = 7min, 2mL/min, 1:1 MeCN:H2θ, Zorbax™ RX-8). EXAMPLE 128 Example 128 was prepared by the following procedure. At 0°C, 6mg N-bromosuccinamide was added to 13mg apicidin in lmL CH2CI2 and 0.5mL MeOH. After 4min, lmL saturated Na2SO3(aq) was added, followed by lmL brine. The solution was extracted with EtOAc and dried with Na2SO4. Partially purified product was obtained following PTLC on silica gel (1 x 1500μm plate) using 1:2 acetone:hexanes as eluant. Pure Example 128 was subsequently obtained following flash chromatography on silica gel using 1:2 acetone:hexanes as eluant. The Example 128 thus obtained was characterized by H NMR and MS [m/z: 670.4 (M + +l)]. EXAMPLES 129A AND 129B Ex. 129a Ex. 129b Examples 129a and 129b were prepared by the following procedure. To lOmg N-desmethoxy apicidin at RT in O.lmL DMF was added 3μL 37% formaldehyde(aq) and 3μL pyrrolidine. After 48h, the reaction was quenched with saturated NaHCO3, extracted with EtOAc and dried with Na2SO4. Pure 2mg of the pyrrolidino Example 129a (Rf= 0.2) and 2mg of the hydroxymethyl Example 129b (Rf= 0.1) was obtained following PTLC (1:3:96 NH4OH:MeOH:CHCl3, Rf= 0.2) as eluant. The pure products were characterized by H NMR and MS [m/z: 624 (M +1) for the pyrrolidino Example 129a and 677 (M+1) for the hydroxymethyl Example 129b]. EXAMPLE 130 Example 130 was prepared by the following procedure. To 5mg N- desmethoxy-N-hydroxymethyl apicidin in 0.16mL pyridine at RT was added 0.63mL acetyl chloride and one crystal of DMAP. After 12h, the reaction was quenched with saturated NH4CI, extracted with EtOAc and dried with Na2SO4. Following RP- HPLC using a linear gradient of 4:6 to 1:0 MeCN:H2θ as eluant, pure Example 130 was obtained which was characterized by H NMR and MS [m/z: 666 (M +1)]. EXAMPLE 131 Example 131 was prepared by the following procedure. To 9mg N- desmethoxy-N-hydroxymethyl apicidin in CH2CI2 at 0°C was added 13μL EtN0 ' Pr)2 followed by the addition of 43μL (PhCH2θ)2P(O)Cl. After 30min at 0°C, 0.4mg DMAP was added and the solution was aged for 1.5h at 0°C, followed by 2.5h at RT. The reaction was quenched by the addition of water, extracted with CH2CI2 and dried with Na2SO4. Following preparative RP-HPLC using a linear gradient of 4:6 JE 1:0 MeCN:H2θ as eluant, 0.3mg pure Example 131 was obtained which was characterized by l K NMR and MS [m/z: 884 (M+1)]. EXAMPLES 132A AND 132B Ex. 132a Ex. 132b Examples 132a and 132b were prepared by the following methods G, H and I. Method G To lOOmg apicidin in 4mL MeCN and 3mL CH2CI2 at RT was added 800mg NaIO4 in lOmL water, followed by the addition of lOmg RUCI3. The solution was then aged overnight. The solution was poured into brine, acidified with glacial acetic acid and filtered to remove particulates. The solids were rinsed with CH2CI2 and the solution was extracted with CH2CI2. The combined organic layers were dried with Na2SO4, filtered, and concentrated under reduced pressure. Pure 52mg carboxylic acid Example 132a was obtained following preparative RP-HPLC using gradient elution (1:4 to 1:1 MeCN:H2θ, 50min linear ramp). Example 132a obtained was characterized by H NMR and MS [m/z: 523.2 (M + +l)]. Also obtained from this reaction was the nitrophenylketone apicidin analog, Example 132b, which was characterized by *H NMR and MS [m/z: 628.2 (M + +l)]. Method H To a solution containing 0.3mg RuCl3*xH2O and 50mg N-desmethoxy apicidin in 2mL 1 : 1 MeCN:CCl4 was added 324mg NaIO4 (as a solution in lmL H2O). After 45h, the resulting green solution was partitioned between 1:1 brine:saturated NH4CI and 3:7 ZPrOH:CHCl3. The organic layer then was dried with Na2SO4. The solution .was concentrated under reduced pressure to yield 60mg crude product. Method I To 9mg cycZo(L-Asp-L-Ile-D-Pip-L-2-amino-8-oxo-decanoyl), methyl ester in lmL 3:1:1 THF:MeOH:H2θ at 0 °C was added 50μL IM LiOH. After lh at 0°C, followed by 2 days at RT, the solution was filtered through a reversed-phase plug (0.5 g C-18) with MeOH as eluant, concentrated under reduced pressure, and purified without workup by RP-HPLC using gradient elution (lOmin ramp from 5:95 MeCN:H2θ to 25:75 MeCN:H2θ, then 60min ramp to 100% MeCN). EXAMPLE 133 Example 133 was prepared by adding lmL Me3SiCH=N2 (0.5M solution in hexanes) to 12mg of the carboxylic acid product of Example 132a in 4mL 2:1 MeOH:Et2θ at RT. After 20min, the solution became homogenous and 0.25mL glacial acetic acid was added. The solution was poured into brine, extracted with CH2CI2 and dried with Na2SO4. The solution was filtered and concentrated under reduced pressure. Pure Example 133 was obtained following PTLC on silica gel (1 x lOOOμm plate) using 1:1 acetone:hexanes as eluant. The methyl ester Example 133 thus obtained was characterized by H NMR and MS [m/z: 537.5 (M + +l)]. EXAMPLE 134 Example 134 was prepared by adding 9.6mg NaBF j. to 120mg of Example 133 in 7mL THF at 0°C. After aging for 3h, the reaction was quenched by the addition of saturated NH4θ(aq), extracted with CH2CI2 and dried with Na2SO4. Following PTLC using 4:6 acetone:hexanes 0.53) as eluant, 117mg of pure Example 134 was obtained which was characterized by H NMR. EXAMPLE 135 Example 135 was prepared by the following methods J and K. Method J To 50mg of Example 132a in 2mL CH2CI2 at RT was added sequentially 14μL Et3N followed by 8μL MeSO2Cl. After aging for 2h, 18mg solid HCl»HN(OMe)Me was added. After an additional hour, the volatiles were removed under reduced pressure. Following flash chromatography on silica gel using 1:2:97 NH4OH:MeOH:CHCl3 as eluant, 1.9mg pure Example 135 was obtained which was characterized by H NMR and MS. Method K To 20mg of Example 132a in lmL THF at -78°C was added 10.6mg HCl « HN(OMe)Me followed by the dropwise addition of 112μL /PrMgBr (2M solution in THF). The resulting solution was slowly allowed to warm to 4°C and was aged for 12h. The reaction was quenched by addition of lmL saturated NH4θ(aq), extracted with CH2CI2 and dried with Na2SO4. Following flash chromatography on silica gel using 1:2:97 NH4OH:MeOH:CHCl3 as eluant, l lmg pure Example 135 was obtained which was characterized by H NMR and MS. EXAMPLE 136 Example 136 was prepared from 117mg of Example 134 using Method K as described in Example 135. This resulted in 76mg of Example 136 (Rf= 0.46, 1 :9:90 NH4OH:MeOH:CHCl3) which was characterized by *H NMR and MS [m/z: 568 (M+1)]. EXAMPLE 137 Example 137 was prepared by the following procedure. To 1 lmg c cZσ(N-O-methyl-N-methyl-L-Asp-L-Ile-D-Pip-L-2-amino-8-hydroxy-decanoyl) in 0.39mL THF and 80μL HMPA at 0°C was added 388 μL n-CioH2lMgBr (IM in Et2θ). The solution was warmed immediately to RT and aged for 12h. The solution was poured into saturated NILjC aq), partitioned with THF and dried with Na2SO4. Following PTLC (1 x 500μm plate) on silica gel using 1:9:90 NH4OH:MeOH:CHCl3 as eluant, 2.5mg pure Example 137 was obtained which was characterized by H NMR and MS [m/z: 649 (M + +l)]. EXAMPLE 138 Example 138 was prepared by adding 5μL pyridine to 2mg of Example 137 in 0.35mL CH2CI2 at 23°C, followed by the addition of 7mg Dess-Martin periodinane. After 1.5h, the solution was poured into 1:1 saturated NaHCO3:10% NaHSO3, aged for lOmin, then extracted with CH2CI2, and dried with Na2SO4. Following PTLC (1 x 250μm plate) on silica gel using 1:3:96 NH4OH:MeOH:CHCl3 as eluant, 1.5mg pure Example 138 was obtained which was characterized by H NMR and MS [m/z: 647 (M + +l)]. EXAMPLES 139A-139J Following the general procedures described in Examples 137 and 138, and utilizing the appropriate starting compounds and reactants - particularly the appropriate nucleophile for the Ri group - which would be clear to one in the art, the following compounds were prepared: Table 7 EXAMPLE 140 Example 140 was prepared by the following procedure. To lOOmg cyc/o(beta-oxo-L-Tφ-L-Ηe-D-Pip-L-2-amino-8-oxo-decanoyl) at RT in 6mL 1:1:1 MeCN:CCU:H2θ was added 0.7mg RuCl3«2H2O followed by the addition of 634mg NaIO4 (as a sonicated solution in 2mL H2O). After 30h, the resulting tan-white heterogeneous solution was partitioned between 1:1 brine:saturated NH4CI and 3:7 z ' PrOH:CHCl3. The organic layer was dried with Na2SO4 and concentrated under reduced pressure to yield lOOmg of Example 140. The crude product was characterized by H NMR and MS [m/z: 526 (M + +NH4)] with no additional purification. EXAMPLE 141 Example 141 was prepared by the following procedure. To 80mg c cZσ(D-2-amino-2-carboxy-ethanoyl-L-Ile-D-Pip-L-2-amino-8-oxo-decanoyl) in 3.3mL 2:1 MeOH:Et2θ at RT was added lmL TMSCHN2 (2M in hexanes). After 1.5h, glacial HOAc was added dropwise until foaming ceased and the solution was partitioned between 1:1 brine:saturated NH4CI and CH2CI2. The organic layer was dried with Na2SO4. Following PTLC (1 x 1500μm plate) on silica gel using 3:97 HOAc:EtOAc as eluant, 28mg pure Example 141 was obtained which was characterized by l K NMR and MS [m/z: 540 (M + +NH4)]. EXAMPLE 142 Example 142 was prepared by the following procedure. To 26.5mg of Example 140 in 2mL CH2CI2 at RT was added 5 lmg HCl « HN(OMe)Me and 13mg DMAP, followed by the addition of 46mg BOP. After aging for 8h at RT, the solution was warmed to 40°C for 12h. Following removal of volatiles, 2mg pure Example 142 was obtained following PTLC on silica gel using 1 : 1 acetone:hexanes as eluant. The product was characterized by H NMR and MS [m/z: 552 (M + +l)]. EXAMPLE 143 Example 143 was prepared by starting with Example 141. First, the side chain carbonyl of Example 141 was reduced as described in Example 134. The resulting intermediate compound was then treated by the procedure described in Example 135. The pure Example 143 thus obtained was characterized by H NMR. EXAMPLES 144A-144G Following the general procedures described above in Examples 142 and 143 (procedure of Example 142 was utilized for Example 144g, while the procedure of Example 143 was utilized for the other Examples 144a- 144f), and using the appropriate materials which would be clear to one in the art, the following compounds were prepared: Table 8 EXAMPLE 145 Example 145 was prepared by the following procedure. To lOmg N- desmethoxy-N-methyl apicidin in 2.5mL CH2CI2 at -78°C was bubbled O3 until the solution turned light blue. The resulting solution was stirred for lOmin and then N2 was bubbled through the solution for 5min. Next, 250μL Dimethylsulfide was added, the solution then warmed slowly to RT and concentrated under reduced pressure. The resulting residue was dissolved in 1:1 THF:tBuOH at 0°C, followed by the addition of 3.7mg tBuOK. After 2h at 0°C, the solution was poured into 1:1 water: saturated NaHCO3, extracted with CH2CI2 and dried with Na2SO4. Following preparative TLC on silica gel (1 x 500μm plate) using 1:3:96 NH4OH:MeOH:CHCl3 as eluant, pure Example 145 was obtained which was characterized by H NMR and MS [m/z: 622.7 (M + +l)]. TLC: Rf = 0.15 (1:3:96 NH4OH:MeOH:CHCl3). EXAMPLES 146A-146F Following the general ozonalysis procedure described for Example 145, the following compounds were prepared: Table 9 EXAMPLE 147 Example 147 was prepared by the following procedure. To lOmg cycZø(L-2-amino-2-(3'-(quinol-4'-onyl))-ethanoyl-L-Ile-D-Pip-L-2-amino-8-oxo- decanoyl) in lmL CICH2CH2CI at RT was added 4mg DMAP and 19μL TEA, followed by the addition of 5μL MeSO2Cl. After 15min at RT, the solution was poured into saturated NaHCO3, extracted with CH2CI2 and dried with Na2SO4. Following preparative TLC on silica gel (1 x 500μm plate) using 1:1 acetone:hexanes as eluant, pure Example 147 was obtained which was characterized by H NMR and MS [m/z: 608.5 (M + +l)]. TLC: Rf = 0.43 (1:1 acetone:hexanes). EXAMPLES 148A AND 148B Ex. 148a Ex. 148b Examples 148a and 148b were prepared by adding 3mg NaBFLx to 20mg cycZo(L-2-amino-2-(3'-(N-O-methyl-quinol-4'-onyl))-ethanoyl-L-Ile-D-Pip-L- 2-amino-8-oxo-decanoyl) in 5mL MeOH at 0°C. Then the cooling bath was removed promptly. After 20min, acetone was added to quench the reaction and the solution was poured into saturated NaHCO3, extracted with CH2CI2 and dried with Na2SO4. Initial purification was accomplished following flash chromatography on silica gel using 1 : 1 acetone:hexanes as eluant. At this juncture, it was noted that the resulting product was approximately 1 : 1 mixture of two compounds with similar TLC Revalues (product A: 0.39 and Product B: 0.28 in 1:1 acetone:hexanes). Repurification by preparative TLC on silica gel (1 x 500μm plate) yielded two pure products which were characterized by H NMR and MS [m/z: 640.6 (M + +l) for Example 148a and 610.5 (M + +l) for Example 148b]. Example 148a: cyc/o(L-2-amino-2-(3'-(N-O-methyl-quinol-4'-onyl))- ethanoyl-L-Ile-D-Pip-L-2-amino-8-hydroxy-decanoyl); TLC: Rf = 0.55 (1:3:96 NH4OH:MeOH:CHCl3); HPLC: tR = 7.17min (1:1 MeCN:H2θ, l.OmL/min, Zorbax™ RX-8). Example 148b: cycZo(L-2-amino-2-(3'-quinol-4'-onyl)-ethanoyl-L-Ile- D-Pip-L-2-amino-8-hydroxy-decanoyl); TLC: Rf = 0.18 (1:3:96 NH4OH:MeOH:CHCl3); HPLC: tR = 5.86min (1:1 MeCN:H2θ, l.OmlJmin, Zorbax™ RX-8). EXAMPLE 149 Example 149 was prepared by the following procedure. Ozone was bubbled through 25mg apicidin in 2.5mL CH2CI2 at -78°C until the resulting solution remained pale blue. After lOmin, the solution was purged with a vigorous stream of nitrogen, followed by the addition of lmL Me2S. Then the solution was warmed to RT. The volatiles were removed under reduced pressure and pure Example 149 was obtained following PTLC on silica gel (1 x 2000μm plate) using 1:2 acetone:hexanes as eluant. The pure Example 149 thus obtained was characterized by H NMR and MS [m/z: 662.5 (M + +Li)]. EXAMPLE 150 Example 150 was prepared by the following procedure. Ozone was bubbled through a solution of 470mg N-desmethoxy-apicidin in 40mL CH2CI2 at - 78°C for about lOmin until a blue color persisted. Then the solution was purged with a vigorous stream on nitrogen, followed by the addition of lmL Dimethylsulfide. The resulting solution was allowed to warm to RT and the volatiles were removed under reduced pressure. Following flash chromatography on silica gel using gradient elution (2:3 to 1:1 acetone:hexanes), 320mg pure Example 150 was obtained which was characterized by *H NMR and MS [m/z: 626 (M + +l)]. EXAMPLE 151 Example 151 was prepared similarly to the procedure described for Example 150 utilizing beta-oxo-N-desmethoxy-apicidin as the starting material. Example 151 thus obtained was characterized by H NMR and MS [m/z: 640 (M + +l)]. EXAMPLES 152A AND 152B Ex. 152a Ex. 152b Examples 152a and 152b were prepared by adding 30μL pyridine to 43mg ycZo(L-2-amino-2-(3'-quinol-4'-onyl)-ethanoyl-L-Ile-D-Pip-L-2-amino-8-oxo- decanoyl) in 1.2mL CH2CI2. The mixture was cooled to 0 °C. To the resulting solution was added 14μL (CF3SO2)2O. After 40min, the solvent was removed in vacuo. The crude pyridinium salt thus obtained was characterized by H NMR and MS [m/z: 740 (M + +l)]. EXAMPLE 153 Example 153 was prepared by the following methods L and M. Method L To 52mg crude cycZo(L-2-amino-2-(3'-(4'-pyridium-quinolyl))- ethanoyl-L-Ile-D-Pip-L-2-amino-8-oxo-decanoyl) in 4mL CH2CI2 at RT was added lmg 20% Pd(OH)2 Degussa catalyst. A hydrogen atmosphere (balloon pressure) was established. After 12h, the catalyst was removed by filtration through Celite using acetone as eluant. Following PTLC (1 x 1000 μm plate) on silica gel using 1:3:96 NH4OH:MeOH:CHCl3 as eluant, 28mg pure Example 153 was obtained which was characterized by H NMR and MS [m/z: 675 (M + +l)]. Method M To 20mg ycZo(L-2-amino-2-(3'-quinol-4'-onyl)-ethanoyl-L-Ile-D-Pip- L-2-amino-8-oxo-decanoyl) in 0.6mL CH2CI2 at 0 °C was added 8mg 2,6-di-t-butyl- 4-methyl-pyridine followed by 7μL (CF3SO2)2O. After 3.5h, 7μL piperidine was added, the solution was aged for 2.5h and then was warmed to RT for 12h. Following PTLC without workup (1 x 500μm plate) on silica gel using 1:3:96 NH4OH:MeOH:CHCl3 as eluant, 6mg pure Example 153 was obtained which was characterized by X H NMR and MS [m/z: 675 (M + +l)]. EXAMPLE 154 Example 154 was prepared by the following procedure. At 23°C, 13mg of Example 146a was placed in 360μL DMF. Then 5.3mg 2,6-di-tert-butyl-4- methyl-pyridine was added followed by 6.9mg 2,4-dinitrobenzenesulfonyl chloride. After aging for 6h, 2.7mg LiCl was added and the solution was warmed to 60°C for 12h. The reaction was cooled to RT, quenched by the addition of water, extracted with CH2CI2 and dried with Na2SO4. Following PTLC on silica gel (1 x 500μm plate) using 1:9:90 NH4OH:MeOH:CHCl3 as eluant, 5mg pure Example 154 was obtained which was characterized by H NMR and MS [m/z: 626 (M +1)]. EXAMPLE 155 Example 155 was prepared by mixing 1.2g N-Desmethoxy-apicidin, 360mg N-bromosuccinamide and 15mg benzoyl peroxide in 70mL CCI4. The resulting mixture was heated to 80°C for 15min. The solvent was then removed under reduced pressure and the crude product was purified in two batches by RP-HPLC using 4:6 MeCN:H2θ as eluant to yield 400mg pure Example 155 which was characterized by ! H NMR and MS [m/z: 674 (M + +l)]. EXAMPLE 156 Example 156 was prepared by dissolving lOOmg c cZø(2-bromo-L-Tφ- L-Ile-D-Pip-L-2-amino-8-oxo-decanoyl) in 3mL dioxane and 3mL EtOH. Then 63mg LiCl, 270mg (3,5-diMeO)PhB(OH)2 and 1.5mL IM NaHCO3 was added. To the resulting mixture was added 17mg Pd(PPh3)4 and the resulting solution was heated in sequence to 90°C for 90min, 100°C for 15min and 80°C for 12h. The solution was poured into 1:1 saturated NaHCθ3:brine, extracted with CH2CI2 and dried with Na2SO4. Following preparative TLC on silica gel (1 x 500μm plate) using 1:3:96 NH4OH:MeOH:CHCl3 as eluant (four developments), 67 pure Example 156 was obtained which was characterized by H NMR and MS [m z: 730 (M + +l)]. EXAMPLES 157A-157D Examples 157a-157d were prepared following the procedure described in Example 156. Table 10 EXAMPLE 158 Example 158 was prepared by adding 9mg NaBH4 to lOOmg of Example 141 in 6mL THF at 0°C. After 2h, the reaction was quenched by the addition of acetone followed by the addition of saturated NaHCO3(aq), extracted with CH2CI2 and dried with Na2SO4. This yielded lOmg pure diol Example 158 (Rf= 0.37) following PTLC on silica gel using 3:7 acetone:hexanes as eluant. The product thus obtained was characterized by H NMR. EXAMPLE 159 Example 159 was prepared by the following methods N and O. Method N: To lOOmg of Example 133 in 3.5mL THF at 0°C was added 11.6mg LiBH4. After aging for 4h at 0°C, the reaction was warmed to RT. After an additional 2h, the reaction was quenched by the addition of acetone followed by the addition of saturated brine(aq), extracted with 3:7 ZPrOH:CHCl3 and dried with Na2SO4- Following PTLC on silica gel using 1:3:96 NH4OH:MeOH:CHCl3 as eluant, 60mg pure diol Example 159 was obtained which was characterized by H NMR and MS [m/z: 511 (M + +l)]. Method O To 250mg of Example 133 in 1 lmL THF at 0°C was added 2.65mL DD3AL-H (IM solution in toluene). After aging for 4h at 0°C, the reaction was quenched by the addition of acetone followed by the addition of saturated brine, extracted with 3:7 ZPrOH:CHCl3 and dried with Na2SO4. Following flash chromatography on silica gel using 1:3:96 to 1:9:90 NH4OH:MeOH:CHCl3 gradient elution, lOOmg pure diol Example 159 (Rf= 0.41, 1:9:90 NH4OH:MeOH:CHCl3) was obtained which was characterized by H NMR. EXAMPLE 160 Example 160 was prepared by the following procedure. To 27mg Ph3Bi dissolved in lmL CH2CI2 at RT was added 0.5μL CH3CO3H. After lOmin, a Ph3Bi/CH3CO3H solution resulted. To the solution, 22mg of Example 159 was added as a solution in lmL CH2CI2, followed by the addition of 3.5mg Cu(OAc)2- The resulting solution was then warmed to 60°C for 3h. After cooling to RT, the reaction was quenched by the addition of saturated NaHCO3(aq), extracted with 3:7 * ' PrOH:CHCl3 and dried with Na2SO4. Following PTLC on silica gel using 4:6 acetone: hexanes (Rf= 0.66) as eluant, 4mg pure Example 160 was obtained which was characterized by H NMR and MS [m/z: 587 (M + +l)]. EXAMPLE 161 Example 161 was prepared by oxidizing 3mg of Example 160 using Dess-Martin reagent similarly to the general procedure described in Example 138. This resulted in 2mg Example 161, which was characterized by H NMR and MS [m/z: 585 (M + +1)]. EXAMPLES 162A AND 162B Following the general procedure for Examples 160 and 161, the following Examples 162a and 162b were prepared and characterized by NMR and MS: Table 12 EXAMPLE 163 Example 163 was prepared by the following procedure. To 68mg of Example 148a in 6mL THF at RT was added 2mL PhMgBr (2M solution in THF). After aging at RT for 20h, the reaction was quenched by the addition of saturated NH4Cl(aq), extracted with CH2CI2 and dried with Na2SO4. Following PTLC on silica gel (1 x 1500μm plate) using 1:9:90 NH4OH:MeOH:CHCl3 as eluant, 18.9 mg pure intermediate compound having a side chain alcohol (Rf= 0.49, 1:9:90 NH4OH:MeOH:CHCl3) was obtained which was characterized by ! H NMR. The side chain alcohol of the intermediate was then oxidized using Dess-Martin reagent as described in Example 138. Following PTLC on silica gel (1 x 500μm plate) using 1:9:90 NH4OH:MeOH:CHCl3 as eluant, 13mg pure Example 163 was obtained (Rf= 0.66, 1:9:90 NH4OH:MeOH:CHCl3) which was characterized by H NMR and MS [m/z: 684 (M + +1)]. EXAMPLES 164 A AND 164B Following the general procedure for Example 163, the following Examples 164a and 164b were prepared: Table 13 EXAMPLE 165 Example 165 was prepared by the following procedure. To 20mg apicidin in 321μL DMF at RT was added 16μL Mel followed by the addition of 3.8mg NaH (60% suspension in mineral oil). After 20h, water was added and the solution extracted with EtOAc and dried with Na2SO4. Following PTLC on silica gel (1 x lOOOμm plate) using 1:3:96 NH4OH:MeOH:CHCl3 as eluant, 9.9mg pure Example 165 was obtained which was characterized by H NMR and MS [m/z: 666 (M + +l)]. EXAMPLES 166A-166C Examples 166a-166c were prepared similarly to the procedure described in Example 165. Apicidin was treated with benzyl bromide, in place of the methyl iodide in Example 165, to yield a mixture of mono-, di- and tri -benzyl ated derivatives. The three compounds, Examples 166a-166c, thus obtained were characterized by H NMR and MS. The regiochemistry of the mono- and di- benzylated derivatives was not established. Table 14 EXAMPLES 167A-167D Examples 167a-167d were prepared by the following procedure. To lOmg apicidin in 2mL toluene was added 13mg Lawesson's reagent. The resulting solution was heated at 80°C for 25min and then cooled to RT. The entire solution was loaded directly onto a silica gel flash chromatography column and purified by gradient elution (100 % CHCI3, one column, followed by 1:3:96 NH4OH:MeOH:CHCl3 elution) to yield two fractions: monothiono Example 167a (Fraction One - Product A, Rf= 0.83, 1:3:96 NH4OH:MeOH:CHCl3) and impure bis- and tris-thiono Examples 167b-167d (Fraction Two - Products B, C, and D, Rf= 0.68, 1:3:96 NH4OH:MeOH:CHCl3). Fraction Two was further purified by preparative RP-HPLC using gradient elution (2:3 MeCN:H2θ to 100% MeCN, 70min linear gradient). The products thus obtained were characterized by H NMR and MS. The following retention times were obtained for the four products during the preparative RP-HPLC run: tR = 34.2min (product A - Example 167a); 39.9min (product B - Example 167b); 45.6min (product C - Example 167c); 48.8min (product D - Example 167d); (2:3 MeCN:H2θ to 100% MeCN, 70min linear gradient). Table 15 EXAMPLE 168 Example 168 was prepared by adding 0.160mL BH3 » THF (IM solution in THF) to lOmg apicidin in 2mL THF at 0°C. After 30min, the resulting solution was warmed to RT and aged for 12h. At this point, after 12.5h total, the solution was heated to 60°C for 30min, then cooled to RT. Then, lmL methanol was added, followed by the addition of 0.15mL Me 2 NCH 2 CH 2 OH, and the solution was stirred for 2h. The stiπed solution was poured into saturated brine, extracted with EtOAc, and dried with Na2SO4. The volatiles were removed under reduced pressure and the crude product was filtered through a 1.5inch pad of silica gel using 1:3:96 NH 4 OH/MeOH/CHCl 3 as eluant to remove baseline contaminants. The filtered solution was concentrated under reduced pressure and pure product was obtained following preparative RP-HPLC using 1/3 MeCN/H 2 O isocratic for 20 min, followed by a 60min linear gradient to 100% MeCN. The pure Example 168 thus obtained was characterized by 1H NMR and MS [m/z: 612.4 (M + +l)]. HPLC: t R = 6.69min, 1/1 MeCN:H2θ, 1.5mL/min, Zorbax™ RX-8 column. TLC: R f = 0.50, 1:3:96 NH4OH:MeOH:CHCl3. EXAMPLES 169 AND 170 Ex. 169 Ex. 170

Claims: WHAT IS CLAIMED IS: 1. A compound having a Formula I: or a pharmaceutically acceptable salt thereof, wherein X is (1) -CH2-, (2) -C(O)-, (3) -CH(OR a )-, (4) =CH- or (5) not present; n is (1) one, or (2) two; Rl is (1) R7, (2) C(O)R 7 , (3) CN, (4) CO2R b , (5) C(O)N(OR b )R c , (6) C(O)NR c R d , (7) NHCO2R b (8) NHC(O)NR c R d , (9) (Co-C4alkyl)OR a , (10) (Co-C4alkyl)OCO2R b (11) (Co-C4alkyl)OC(O)NR Rd, (12) C(O)NR c NR c Rd, (13) C(O)NR c SO2R b , (14) OS(O)niR7, (19) NR b S(O)niR7, wherein ni is from 0 to 2, (20) a 3- to 8-membered heterocycle containing 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups, each group independently is Ci-C5alkyl, C2-C5alkenyl, Ci- C5perfluoroalkyl, NRCRd, oxo, thiono, ORa, S(O) n iR a (where ni = 0, 1 or 2), C(O)Ra, C(O)NRCRd, C yano, (Co- C6alkyl)aryl, CO2R b , or halogen, and each group may be saturated, partly unsaturated or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, (21) a benzene ring fused to a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups each independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NR c Rd, cyano, CO2R b or halogen, each group may be saturated, partly unsaturated, or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an R c substituent, and wherein the benzene/heterocycle fused ring is attached at any site to X or to the tetrapeptide, or (22) a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms fused to a second 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, each heterocyclic ring independently optionally substituted by 1 to 4 groups, each group independently is Cχ-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NR c Rd, cyano, CO2R b or halogen, wherein each heterocycle may be saturated, partly unsaturated or fully unsaturated, and wherein each heteroatom independently is oxygen, sulfur, or nitrogen, and the nitrogen optionally has an Rc substituent; R2 is (1) optionally substituted C2-Ci2alkyl, (2) optionally substituted C2-Ci2alkenyl, (3) optionally substituted C2-Cχ2alkynyl, or (4) (CH2)nii-O-(CH2)mii wherein nii, mii = 0 to 7, wherein the optional substituents on the C2-Cχ2alkyl, C2-Cχ2alkenyl, and C2-Cχ2alkynyl are 1 to 8 groups and each group independently is (a) CO2R a , (b) C(O)R b , (c) C(O)N(OR b )R c , (d) C(O)NR c Rd (e) C(O)NR c NR c R d , (f) C(O)NR c SO2R7, (g) C3-C8cycloalkyl, (h) C2-C5alkenyl, (i) cyano, (j) =NOR , (k) =NNR b R c , (1) =NNR b S(O)niR7, (m) N(OR b )C(O)NR b R c , (n) N(OR b )C(O)R7, (o) NHC(O)N(OR b )R c , (p) NR c CO2R b , (q) NR c C(O)NR c R d , (r) NRCC(S)NR c R d , (s) NR c C(O)R7, (t) NR S(O)niR7, (u) NR C CH2CO2R a , (v) NR C C(S)R7, (x) NR C(O)CH2OH, (y) NR C(O)CH2SH, (z) NR c CH2CO2R a , (aa) NR c CH2CH(OH)R7, (bb) NR c P(O)(OR a )R7, (cc) NY i γ , w erein Y*- and γ2 are independently H or Cι-Cιoalkyl, (dd) NO 2 , (ee) N(OR b )C(O)R b > (ff) C l -C 1 oalkanoylamino, (gg) OR a , (hh) OS(O) ni R 7 , (ϋ) oxo, (jj) OCO2R b , (kk) OC(O)NR c R d , (11) P(O)(OR a ) 2 , (mm) P(O)(OR a )R7, (nn) SC(O)R 7 , (oo) S(O) ni R 7 , (PP) SR 7 , (qq) S(O) ni NRCRd (rr) NR c CH2CO2R a , (ss) diazo, (tt) C1-C5 perfluoroalkyl, (uu) B(O)(OR a )OR a , (XX) halogen, (yy) aryl(Cθ-C5alkyl), wherein the aryl is optionally substituted with 1 to 3 groups, wherein each group independently is Rf, or (xx) a 3- to 8-membered heterocycle containing from 1 to 4 heteroatoms, < ϊach heteroatom independently is oxygen, sulfur or nitrogen, wherein the heterocycle is optionally substituted by 1 to 3 groups, wherein each group independently is Rf, and the heterocycle may be saturated or partly unsaturated; R3 each independently is (1) hydroger 1, (2) halogen, (3) OR a , (4) Ci-C4alkyl, or (5) Ci-C4aryl; R5 is (1) isopropyl, or (2) sec-butyl; R6 each independently is (1) O, (2) S, or (3) H; R7 is (1) hydrogen, (2) optionally substituted C2-C l oalkyl , (3) optionally substituted C2-Cιoalkenyl, (4) optionally substituted C2-Cιoalkynyl, (5) optionally substituted C3-C8cycloalkyl, (6) optionally substituted C5-Cscycloalkenyl, (7) optionally substituted aryl, wherein the optional substituents on the C2-Cιoalkyl, C2-Cιoalkenyl, C2-Cιoalkynyl, C3-Cgcycloalkyl, C5-Cscycloalkenyl and aryl are 1 to 4 groups, and each group independently is (a) Cι-C5alkyl, (b) Xi-Ci-Cioalkyl, wherein X 1 is O or S(O) n i, (c) C3-C8cycloalkyl, (d) hydroxy, (e) halogen, (f) cyano, (g) carboxy, (h) NYlγ2, wherein Y and γ2 are independently H or C1-C1 oalkyl, (i) nitro, (j) C1-C1 oalkanoylamino, (k) aroyl amino wherein the aroyl is optionally substituted with 1 to 3 groups wherein each group independently is Rf 1, wherein R* 1 is defined by any of the definitions below for Rf except for (14), (26), (27), and (32), (1) oxo, (m) aryl Co-C5alkyl wherein the aryl is optionally substituted with 1 to 3 groups, wherein each group independently is R fl , (q) Cι-C5perfluoroalkyl, (r) N(OR b )C(O)R7' , wherein R7' is any of the above definitions of R7 from (1) to (7)(n), and below of R7 from (8) to (12), or (s) NR c C(O)R7', (8) a 5- to 10-membered heterocycle containing from 1 to 4 heteroatoms, each heteroatom independently is oxygen, sulfur or nitrogen and the heterocycle is optionally substituted by 1 to 3 groups, each group independently is Rf 1, and the heterocycle may be saturated or partly unsaturated, (9) a benzene ring fused to a 5- to 10-membered heterocyclic ring containing from 1 to 4 heteroatoms, each heteroatom independently is oxygen, sulfur or nitrogen and the heterocycle is optionally substituted by 1 to 3 groups, each group independently is R l, and the heterocycle may be saturated or partly unsaturated, (10) a 5- to 10-membered heterocyclic ring containing from 1 to 4 heteroatoms fused to a second 5- to 10-membered heterocyclic ring containing from 1 to 4 heteroatoms, each heteroatom in either heterocyclic ring independently is oxygen, sulfur or nitrogen and the second heterocyclic ring is optionally substituted by 1 to 3 groups, each group independently is Rf*, and each heterocycle independently may be saturated or partly unsaturated, (11) a benzene ring fused to a C3-Cscycloalkyl ring, wherein the cycloalkyl is optionally substituted by 1 to 3 groups each independently being Rfl , and the cycloalkyl ring may be saturated or partly unsaturated, or (12) a 5- to 10-membered heterocyclic ring containing from 1 to 4 heteroatoms, each heteroatom independently is oxygen, sulfur or nitrogen, the heterocyclic ring is fused to a C3-Cscycloalkyl ring, wherein the cycloalkyl ring is optionally substituted by 1 to 3 groups each independently being Rfl, and the cycloalkyl ring may be saturated or partly unsaturated, R a is (1) hydrogen, (2) optionally substituted Cι-Cιoalkyl, (3) optionally substituted C3-Cιoalkenyl, (4) optionally substituted C3-Cιoalkynyl, (5) optionally substituted Ci-Cioalkanoyl, (6) optionally substituted C3-Cioalkenoyl, (7) optionally substituted C3-Ciθalkynoyl, (8) optionally substituted aroyl, (9) optionally substituted aryl, (10) optionally substituted C3-C7cycloalkanoyl, (11) optionally substituted C5-C7cycloalkenoyl, (12) optionally substituted Ci -Cioalkylsulfonyl, (13) optionally substituted C3-Cscycloalkyl, (14) optionally substituted C5-C8cycloalkenyl, wherein the optional substituents on the Cι-Cιoalkyl, C3-Cιoalkenyl, C3-Cιoalkynyl, Ci-Cioalkanoyl, C3-Cιoalkenoyl, C3-Cιoalkynoyl, aroyl, aryl, C3-C7cycloalkanoyl, C5-C8cycloalkenyl, Ci- Cioalkylsulfonyl, C3-C8cycloalkyl and C5-Cscycloalkenyl are from 1 to 10 groups, wherein each group independently is hydroxy, Ci- C6alkoxy, C3-C7cycloalkyl, aryl Cι-C3alkoxy, NR Rx, CO2R b , CONR c Rd, or halogen, (15) Cι-C5perfluoroalkyl, (16) arylsulfonyl optionally substituted with 1 to 3 groups, wherein each group independently is Cι-C5alkyl, Ci- C5perfluoroalkyl, nitro, halogen or cyano, (17) a 5- or 6-membered heterocycle containing 1 to 4 heteroatoms, wherein each heteroatom is oxygen, sulfur or nitrogen, wherein the heterocycle is optionally substituted by 1 to 4 groups, wherein each group independently is Cι-C5alkyl, Cι-C5alkenyl, Ci- C5perfluoroalkyl, amino, C(O)NR c Rd, cyano, CO2R b or halogen, and wherein the heterocycle may be saturated or partly unsaturated, or (18) OP(O)(OR b ) 2 ; R b i IS (1) H, (2) optionally substituted aryl, (3) optionally substituted Cι-Ciθalkyl, (4) optionally substituted C3-Cιoalkenyl, (5) optionally substituted C3-Cιoalkynyl, (6) optionally substituted C3-Ci5cycloalkyl, (7) optionally substituted C5-Cιocycloalkenyl, or (8) optionally substituted 5- to 10-membered heterocycle containing 1 to 4 heteroatoms, wherein each heteroatom independently is oxygen, sulfur, or nitrogen, wherein the optional substituents on the aryl, Cι-Cιoalkyl, C3- Cioalkenyl, C3-Cιoalkynyl, C3-Ci5cycloalkyl, C5-Ciocycloalkenyl, or 5- to 10-membered heterocycle are from 1 to 10 groups, wherein each group independently is (a) hydroxy, (b) Cι-C6alkyl, (c) oxo, (d) SO2NR x R x , (e) aryl Ci-Cβalkoxy, (f) hydroxy Cι-C6alkyl, (g) Cl-Ci2alkoxy, (h) hydroxy Ci-Cβalkoxy, (I) amino Ci-Cgalkoxy, 0 ) cyano, (k) mercapto, (1) (Ci-C6alkyl)-S(O) ni -(Co-C6alkyl), (m) C3-C7cycloalkyl optionally substituted with 1 to herei n each group independently is R e , (n) C5-C7cycloalkenyl, (0) halogen, (P) Cι-C5alkanoyloxy, (q) C(O)NR x R x , (r) CO2R 1 , (s) formyl, (t) -NR X R X , (u) 5 to 9-membered heterocycle, which may be saturated or partially unsaturated, containing from 1 to 4 heteroatoms, wherein each heteroatom independently is oxygen, sulfur or nitrogen, and the heterocycle is optionally substituted with 1 to 5 groups, wherein each group independently is R e , (vi) optionally substituted aryl, wherein the optional substituents are 1,2-methylenedioxy or 1 to 5 groups, wherein each group independently is R e , (x) optionally substituted aryl Cι-C3alkoxy, wherein the optional substituents are 1,2-methylenedioxy or 1 to 5 groups, wherein each group independently is R e , or (y) Cι-C5perfluoroalkyl; R c and Rd are independently selected from R b ; or R c and R together with the N to which they are attached form a 3- to 10-membered ring containing 0 to 2 additional heteroatoms, each additional heteroatom independently being oxygen, nitrogen, or (O) n i substituted sulfur, wherein the ring is optionally substituted with 1 to 3 groups, wherein each group independently is Rg, hydroxy, thioxo, or oxo; R e is (1) halogen, (2) Ci-C 7 alkyl, (3) Ci-C3perfluoroalkyl, (4) -S(O) m Ri, (5) cyano, (6) nitro, (7) RiO(CH 2 ) v -, (9) RiOCO(CH2) v , (10) optionally substituted aryl wherein the optional substituents are from 1 to 3 groups, wherein each group independently is halogen, Cι-C6alkyl, Cι-C6alkoxy, or hydroxy, (11) SO2NR x R x , (12) CO2R\ or (13) NR X R X ; Rf i IS (1) Cι-C4alkyl, (2) χl-Cι-C4alkyl, wherein χl is O or S(O)mi, (3) C2-C4alkenyl, (4) C2-C4 alkynyl, (5) C 1 -C3perfluoroalkyl, (6) Nγ3γ4, wherein γ and Y^ are each independently hydrog< ϊn, Cι-C5alkyl, or SO2R b , (7) hydroxy, (8) halogen, (9) Cι-C5alkanoyl amino, (18) (Q)-C4alkyl)Cθ2R a (19) (Co-C4alkyl)C(O)NR b R , (20) (Co-C4alkyl)NY 5 Y 6 wherein Y 5 and Y 6 together with the N to which they are attached form a 3- to 7-membered ring containing 0 to 2 additional heteroatoms, wherein the additional heteroatoms independently are oxygen, nitrogen, or (O)mi substituted sulfur, wherein the ring is optionally substituted with 1 to 3 groups, wherein each group independently is R e or oxo, (13) (Co-C4alkyl)NO2, (14) (Cθ-C 4 alkyl)C(O)R 7 , (15) (Co-C4alkyl)CN, (16) oxo, (17) (Co-C4alkyl)C(O)N(OR b )R c , (18) (Co-C4alkyl)C(O)NR c R d , (19) (Co-C4alkyl)NHC(O)OR b , (20) (Co-C4alkyl)NHC(O)NR c R d , (21) (Co-C4alkyl)OR a , (22) (Co-C4alkyl)OCO2R b (23) (Co-C4alkyl)OC(O)NR c R d , (24) (Co-C4alkyl)C(O)NR c NR c R d , (25) (Co-C4alkyl)C(O)NR SO2R b , (26) (Cθ-C 4 alkyl)OS(O)niR7, (27) (Co-C 4 alkyl)NR b S(O)niR7> (28) Co-C4alkyl halogen, (29) (C 0 -C 4 alkyl) SR a , (30) P(O)(OR a ) 2 , (33) Co-C4alkyl azide, (34) Co-C4aryl substituted with from 1 to 4 groups, wherein each group independently is S(O)2R7, or (33) Co-C4aryl where the aryl group is optionally substituted from 1 to 4 groups, wherein each group independently is CO2R b , C(O)NR c R d , NO2, halogen, OC(O)R a , OR a or Ci-C4alkyl; Rg and R n together with the N to which they are attached form a 3- to 7-membered ring containing 0 to 2 additional heteroatoms, wherein each additional heteroatom independently is oxygen, nitrogen, or (O) m i substituted sulfur, and the ring is optionally substituted with 1 to 3 groups, wherein each group independently is R e or oxo; or Rg and R n are each independently (1) hydrogen, (2) Ci-C6alkyl optionally substituted with hydroxy, amino, or CO2R 1 , (3) aryl optionally substituted with halogen, 1,2- methylenedioxy, Cι-C7alkoxy, Cι-C7alkyl, or Cι-C3perfluoroalkyl, (4) aryl Cι-C6alkyl, wherein the aryl is optionally substituted with Cl-C3perfluoroalkyl or 1,2-methylenedioxy, (5) Ci-Csalkoxycarbonyl, (6) Cι-C5alkanoyl, (19) Cι-C5alkanoyl Cι-C6alkyl, (20) arylCι-C5 alkoxycarbonyl, (21) aminocarbonyl, (22) (Cι-C5monoalkyl)aminocarbonyl, (23) (Cι-C5dialkyl)aminocarbonyl, or (24) CO2R b ; R 1 is (1) hydrogen, (2) Cι-C3perfluoroalkyl, (3) Cι-C6alkyl, or (4) optionally substituted aryl Co-Cβalkyl, wherein the aryl optional substituents are from 1 to 3 groups, wherein each group independently is halogen, Cι-C6alkyl, Ci-Cόalkoxy, or hydroxy; R x is a Ci-C4alkyl; m is 0 to 2; mi is 0 to 2; ni is 0 to 2; mii is 0 to 7; nii is 0 to 7; v is 0 to 3; and excluding apicidin, N-desmethoxy apicidin and compounds represented by chemical Formula HA and chemical Formula HB: ΠA ΠB 2. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein: X is (1) -CH 2 -, (2) -C(O)-, (3) -CH(OR a )-, (4) =CH- or (5) not present; and Rl is (1) R7, (2) C(O)R 7 , (3) CN, (4) CO2R b , (5) C(O)N(OR b )R c , (6) C(O)NR c R d , (7) NHCO2R b (8) NHC(O)NR c R d , (9) (Co-C4alkyl)OR a , (10) (Co-C4alkyl)OCO2R b , (11) (Co-C4alkyl)OC(O)NR c R d , (12) C(O)NR c NR c R d , (13) C(O)NR c SO2R b , (21) OS(O)niR7, (22) NR b S(O) n jR7, wherein ni is from 0 to 2, (23) a 3- to 8-membered heterocycle containing 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2-C5alkenyl, Ci- C5perfluoroalkyl, NRCRd, 0 χo, thiono, OR a , S(O) n iR a (where ni = 0, 1 or 2), C(O)R a , C(O)NRcRd, cyano, (Co- C6alkyl)aryl, CO2R b , or halogen, and each group may be saturated, partly unsaturated or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an R substituent, (24) a benzene ring fused to a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups each independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NR c Rd, cyano, CO2R b or halogen, each group may be saturated, partly unsaturated, or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, and wherein the benzene/heterocycle fused ring is attached at any site to X or to the tetrapeptide, or (25) a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms fused to a second 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, each heterocyclic ring independently optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd, cyano, CO2R b or halogen, wherein each heterocycle may be saturated, partly unsaturated or fully unsaturated, and wherein each heteroatom independently is oxygen, sulfur, or nitrogen, and the nitrogen optionally has an Rc substituent. 3. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein: X is (1) -CH2-, (2) -C(O)-, (3) -CH(OR a )-, (4) =CH- or (5) not present; Rl is (1) R7, (2) C(O)R 7 , (3) CN, (4) CO2R b , (5) C(O)N(OR b )R c , (6) C(O)NRCRd, (7) NHCO2R b (8) NHC(O)NRCRd, (9) (Co-C4alkyl)OR a , (10) (Co-C4alkyl)OCO2R b , (11) (Co-C4alkyl)OC(O)NR c R d , (12) C(O)NR c NRCRd, (25) C(O)NR c SO2R b , (26) OS(O)niR7, (27) NR b S(O)niR7, wherein ni is from 0 to 2, (28) a 3- to 8-membered heterocycle containing 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2-C5alkenyl, Ci- C5perfluoroalkyl, NRCRd 0 χo, thiono, OR a , S(O) n iR a (where ni = 0, 1 or 2), C(O)R a , C(O)NRCRd, cyano, (Cø- C6alkyl)aryl, CO2 b , or halogen, and each group may be saturated, partly unsaturated or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, (29) a benzene ring fused to a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups each independently is Ci-Csalkyl, C2- Csalkenyl, Ci-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRcRd ) cyano, CO2R b or halogen, each group may be saturated, partly unsaturated, or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an R c substituent, and wherein the benzene/heterocycle fused ring is attached at any site to X or to the tetrapeptide, or (30) a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms fused to a second 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, each heterocyclic ring independently optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd, cyano, CO2R b or halogen, wherein each heterocycle may be saturated, partly unsaturated or fully unsaturated, and wherein each heteroatom independently is oxygen, sulfur, or nitrogen, and the nitrogen optionally has an Rc substituent; and R2 is (1) optionally substituted C2-Ci2alkyl, (2) optionally substituted C2-Ci2alkenyl, (3) optionally substituted C2-Ci2alkynyl, or (4) (CH2)nii-O-(CH2)mii wherein nii, mii = 0 to 7, wherein the optional substituents on the C2-Ci2alkyl, C2-Ci2alkenyl, and C2-Ci2alkynyl are 1 to 8 groups and each group independently is (a) CO2R a (b) C(O)R b , (c) C(O)N(OR b )R c , (d) C(O)NR c Rd, (e) C(O)NR c NRCRd (f) C(O)NR c SO2R7, (g) C3-C8cycloalkyl, (h) C2-C5alkenyl, (i) cyano, (j) =NOR a , 00 =NNR b R c , (1) =NNR b S(O)niR7, (m) N(OR b )C(O)NR b R c , (n) N(OR b )C(O)R7, (o) NHC(O)N(OR b )R c , (P) NR c CO2R b , (q) NR c C(O)NRCRd, (r) NR c C(S)NR c R d , 10 (s) NR c C(O)R7, (t) NR b S(O) ni R 7 , (u) NR c CH2CO2R a , (v) NR C C(S)R7, (x) NR c C(O)CH2OH, 15 (y) NR c C(O)CH2SH, (z) NR c CH2CO2R a , (aa) NR c CH2CH(OH)R7 5 (bb) NR c P(O)(OR a )R7, (cc) Nγlγ2, wherein γl and γ2 are independently 20 H or Cι-Cι oalkyl, (dd) NO 2 , (ee) N(OR b )C(O)R b ' (ff) C i -C i oalkanoylamino, (gg) OR a , 25 (hh) OS(O)niR7, (ϋ) oxo, (jj) OCO2R b , (kk) OC(O)NRCRd, (11) P(O)(OR a ) , 30 (mm) P(O)(OR a )R7, (nn) SC(O)R 7 , (oo) S(O)niR7, (PP) SR7, (qq) S(O)niNRCRd, (rr) NR c CH2CO2R a , (ss) diazo, (tt) C1-C5 perfluoroalkyl, (uu) B(O)(OR a )OR a , (xx) halogen, (yy) aryl(Co-C5alkyl), wherein the aryl is optionally substituted with 1 to 3 groups, wherein each group independently is Rf, or (xxi) a 3- to 8-membered heterocycle containing from 1 to 4 heteroatoms, each heteroatom independently is oxygen, sulfur or nitrogen, wherein the heterocycle is optionally substituted by 1 to 3 groups, wherein each group independently is Rf, and the heterocycle may be saturated or partly unsaturated. 4. The compound according to claim 3, or a pharmaceutically acceptable salt thereof, wherein n is 1 or 2. 5. The compound according to claim 2, or a pharmaceutically acceptable salt thereof, wherein: X is (1) -CH2-, (2) -C(O)-, or (3) not present; and Ri is (1) R7, (2) C(O)R 7 , (3) CN, (4) CO2R b (5) C(O)N(OR b )R c , (6) C(O)NR c Rd (7) NHCO2R b , (8) NHC(O)NR c Rd (9) (Co-C4alkyl)OR a , (10) (Co-C4alkyl)OCO2R b , (11) (Co-C4alkyl)OC(O)NRCRd (12) C(O)NR NRCRd, (19) C(O)NR SO2R b , (20) OS(O) ni R 7 , (21) NR b S(O)niR7 ; wherein ni is from 0 to 2, (22) a 3- to 8-membered heterocycle containing 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2-C5alkenyl, Ci- C5perfluoroalkyl, NRCRd, 0 χo, thiono, OR a , S(O) n jRa (where ni = 0, 1 or 2), C(O)Ra, C(O)NRCRd, cyano, (Cø- C6alkyl)aryl, CO2R b , or halogen, and each group may be saturated, partly unsaturated or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, (23) a benzene ring fused to a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups each independently is Cι-C5alkyl, C2- C5alkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd, cyano, CO2 b or halogen, each group may be saturated, partly unsaturated, or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an R c substituent, and wherein the benzene/heterocycle fused ring is attached at any site to X or to the tetrapeptide, or (24) a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms fused to a second 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, each heterocyclic ring independently optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2- C5alkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd, cyano, CO2R b or halogen, wherein each heterocycle may be saturated, partly unsaturated or fully unsaturated, and wherein each heteroatom independently is oxygen, sulfur, or nitrogen, and the nitrogen optionally has an Rc substituent. 6. The compound according to claim 5, or a pharmaceutically acceptable salt thereof, wherein n is 1 or 2. 7. The compound according to claim 2, or a pharmaceutically acceptable salt thereof, wherein: X is (1) -CH2-, (2) -C(O)-, or (3) not present; and Rl is (1) R 7 , (2) C(O)R 7 , (15) CO2R b , (16) C(O)N(OR b )RC, (17) C(O)NRCRd (18) a 3- to 8-membered heterocycle containing 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2-C5alkenyl, Ci- C5perfluoroalkyl, NRCRd, 0 χo, thiono, ORa, S(O) n iRa (where ni = 0, 1 or 2), C(O)Ra, C(O)NRCRd, cyano, (Co- C6alkyl)aryl, CO2R b , or halogen, and each group may be saturated, partly unsaturated or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, (19) a benzene ring fused to a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups each independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd 5 cyano, CO2 b or halogen, each group may be saturated, partly unsaturated, or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, and wherein the benzene/heterocycle fused ring is attached at any site to X or to the tetrapeptide, or (20) a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms fused to a second 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, each heterocyclic ring independently optionally substituted by 1 to 4 groups, each group independently is Ci-Csalkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd ; cyano, CO2R b or halogen, wherein each heterocycle may be saturated, partly unsaturated or fully unsaturated, and wherein each heteroatom independently is oxygen, sulfur, or nitrogen, and the nitrogen optionally has an Rc substituent. 8. The compound according to claim 7, or a pharmaceutically acceptable salt thereof, wherein n is 1 or 2. 9. The compound according to claim 2, or a pharmaceutically acceptable salt thereof, wherein: X is (1) -CH2- (2) -C(O)-, or (3) not present; Rl is (1) R 7 , (9) C(O)R 7 , (10) CO2R b , (11) C(O)N(OR b )R c , (12) C(O)NR c Rd (13) a 3- to 8-membered heterocycle containing 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2-C5alkenyl, Ci- C5perfluoroalkyl, NRCRd 0 χo, thiono, ORa, S(O) n iR a (where ni = 0, 1 or 2), C(O)Ra, C(O)NRCRd, C yano, (Cø- C6alkyl)aryl, CO2R b , or halogen, and each group may be saturated, partly unsaturated or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, (14) a benzene ring fused to a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups each independently is Ci-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NR c Rd, cyano, CO2R or halogen, each group may be saturated, partly unsaturated, or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an R substituent, and wherein the benzene/heterocycle fused ring is attached at any site to X or to the tetrapeptide, or (15) a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms fused to a second 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, each heterocyclic ring independently optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2- C5alkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd, cyano, CO2R b or halogen, wherein each heterocycle may be saturated, partly unsaturated or fully unsaturated, and wherein each heteroatom independently is oxygen, sulfur, or nitrogen, and the nitrogen optionally has an R substituent;and R2 is (1) optionally substituted C2-Ci2alkyl, (2) optionally substituted C2-Ci2alkenyl, (3) optionally substituted C2-Ci2alkynyl, or (4) (CH2)nii-O-(CH2)mii wherein nii, mii = 0 to 7, wherein the optional substituents on the C2-Ci2alkyl, C2-Ci2alkenyl, and C2-Ci2alkynyl are 1 to 5 groups and each group independently is (a) CO2R a , (b) C(O)R b , (c) C(O)N(OR b )RC, (d) C(O)NRCRd (e) C(O)NR c NR c R d , (f) C(O)NR c SO2R7, (g) C3-C8cycloalkyl, (h) C2-C5 alkenyl, (i) cyano, (j) =NOR a , (1) =NNR b S(O) n iR7 ; (m) N(OR b )C(O)NR b RC, 10 (n) N(OR b )C(O)R7, (o) NHC(O)N(OR b )R , (P) NR c CO2R b , (q) NR c C(O)NRCRd, (r) NR c C(S)NRCRd, 15 (s) NR c C(O)R7, (t) NR b S(O) ni R 7 , ( ) NR c CH2CO2R a , (v) NR C C(S)R7, (x) NR c C(O)CH2OH, 20 (y) NR c C(O)CH2SH, (z) NR c CH2CO2R a , (aa) NR c CH2CH(OH)R7, (bb) NR c P(O)(OR a )R7, (cc) NYlγ2, wherein γl and γ2 are independently 25 H or methyl, (dd) NO 2 , (ee) N(OR b )C(O)R b > (ff) C 1 -C3alkanoyl amino, (gg) OR a , 30 (hh) OS(O)niR7, (ϋ) oxo, (ii ) OCO2R b , (kk) OC(O)NR c Rd, (11) P(O)(OR ) 2 , (mm) P(O)(OR a )R7, (nn) SC(O)R 7 , (oo) S(O) n iR7, (PP) SR 7 , (qq) S(O)niNRCRd, (rr) NR CH2CO2R a (ss) diazo, (tt) C1-C5 perfluoroalkyl, (uu) B(O)(OR a )OR a , (zz) halogen, (aaa) aryl(Cø-C5 alkyl), wherein the aryl is optionally substituted with 1 to 3 groups, wherein each group independently is Rf, or (xxii) a 3- to 6-membered heterocycle containing from 1 to 4 heteroatoms, each heteroatom independently is oxygen, sulfur or nitrogen, wherein the heterocycle is optionally substituted by 1 to 3 groups, wherein each group independently is Rf, and the heterocycle may be saturated or partly unsaturated. 10. The compound according to claim 9, or a pharmaceutically acceptable salt thereof, wherein n is 1 or 2. 11. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein: R3 each independently is (1) hydrogen, or (2) halogen, (3) OR a , (4) Cι-C4alkyl, or R a is (1) hydrogen, (2) optionally substituted Ci-C6alkyl, (8) optionally substituted C3-C6alkenyl, (9) optionally substituted C2-C4alkanoyl, (5) optionally substituted C3-C4alkenoyl, (6) optionally substituted aroyl, (7) optionally substituted aryl, (8) optionally substituted C5-C6cycloalkanoyl, (9) optionally substituted Cι-C4alkylsulfonyl, (10) optionally substituted C5-C6cycloalkyl, (15) optionally substituted Cs-Cβcycloalkenyl, wherein the optional substituents on the Ci-Cβalkyl, C3-C6alkenyl, C2-C4alkanoyl, C3-C4alkenoyl, aroyl, aryl, C5-C6cycloalkanoyl, Ci- C4alkylsulfonyl, C5-C6cycloalkyl and Cs-Cβcycloalkenyl are from 1 to 10 groups, wherein each group independently is hydroxy, methoxy, aryl methoxy, NR RX, CO2R b , CONR c R d , or halogen, (16) CF 3 , (17) arylsulfonyl optionally substituted with 1 to 3 groups, wherein each group independently is methyl, CF3, nitro, halogen or cyano, or (18) a 5- or 6-membered heterocycle containing 1 to 3 heteroatoms, wherein each heteroatom is oxygen, sulfur or nitrogen, wherein the heterocycle is optionally substituted by 1 to 3 groups, wherein each group independently is methyl, CF3, NMe2, C(O)NR c R d , cyano, CO2R b or halogen, and wherein the heterocycle may be saturated or partly unsaturated. 12. The compound according to claim 11, or a pharmaceutically acceptable salt thereof, wherein: R3 each independently is (1) hydrogen, (2) halogen, (3) OR (4) Ci-C4alkyl, or (5) Ci-C4aryl; ); R a is (1) hydrogen, (2) optionally substituted Cι-C6alkyl, (10) optionally substituted C3-C6alkenyl, (11) optionally substituted C2-C4alkanoyl, (5) optionally substituted C3-C4alkenoyl, (6) optionally substituted aroyl, (7) optionally substituted aryl, (8) optionally substituted C5-C6cycloalkanoyl, (9) optionally substituted Cι-C4alkylsulfonyl, (10) optionally substituted C5-C6cycloalkyl, (15) optionally substituted C5-C6cycloalkenyl, wherein the optional substituents on the Cι-C6alkyl, C3-C6alkenyl, C2-C4alkanoyl, C3-C4alkenoyl, aroyl, aryl, C5-C6cycloalkanoyl, Ci- C4alkylsulfonyl, C5-C6cycloalkyl and C5-C6cycloalkenyl are from 1 to 10 groups, wherein each group independently is hydroxy, methoxy, aryl methoxy, NRXRX, CO2R b , CONR c Rd, or halogen, (16) CF 3 , (17) arylsulfonyl optionally substituted with 1 to 3 groups, wherein each group independently is methyl, CF3, nitro, halogen or cyano, or (18) a 5- or 6-membered heterocycle containing 1 to 3 heteroatoms, wherein each heteroatom is oxygen, sulfur or nitrogen, wherein the heterocycle is optionally substituted by 1 to 3 groups, wherein each group independently is methyl, CF3, NMe2, C(O)NR c Rd cy ano, CO2R b or halogen, and wherein the heterocycle may be saturated or partly unsaturated. X is (1) -CH2- (2) -C(O)-, (5) =CH- or (6) not present; and Rl is (1) R 7> (2) C(O)R 7 , (3) CN, (4) CO2R b (5) C(O)N(OR b )R c , (6) C(O)NRCRd, (7) NHCO2R b (8) NHC(O)NRCRd, (9) (Co-C4alkyl)OR a , (10) (Co-C4alkyl)OCO2R b , (11) (Co-C4alkyl)OC(O)NRCRd, (12) C(O)NR c NRCRd (19) C(O)NR c SO2R b , (20) OS(O)niR7, (21) NR b S(O)niR7, wherein ni is from 0 to 2, (22) a 3- to 8-membered heterocycle containing 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2-C5alkenyl, Ci- C5perfluoroalkyl, NRCRd, oxo, thiono, ORa, S(O) n iRa (where ni = 0, 1 or 2), C(O)Ra, C(O)NRCRd, cyano, (Co- C6alkyl)aryl, CO2R b , or halogen, and each group may be saturated, partly unsaturated or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, (23) a benzene ring fused to a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups each independently is Cι-C5alkyl, C2- C5alkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCR.d ; cyano, CO2R b or halogen, each group may be saturated, partly unsaturated, or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an R substituent, and wherein the benzene/heterocycle fused ring is attached at any site to X or to the tetrapeptide, or (24) a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms fused to a second 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, each heterocyclic ring independently optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd, cyano, CO2R b or halogen, wherein each heterocycle may be saturated, partly unsaturated or fully unsaturated, and wherein each heteroatom independently is oxygen, sulfur, or nitrogen, and the nitrogen optionally has an Rc substituent. 13. The compound according to 12, or a pharmaceutically acceptable salt thereof, wherein n is 1 or 2. 14. The compound according to claim 11, or a pharmaceutically acceptable salt thereof, wherein: R3 each independently is (1) hydrogen, (2) halogen, (3) OR a , (4) Ci-C4alkyl, or (5) Ci-C 4 aryl; ); R a is (1) hydrogen, (5) optionally substituted Cι-C6alkyl, (6) optionally substituted C3-C6alkenyl, (7) optionally substituted C2-C4alkanoyl, (5) optionally substituted C3-C4alkenoyl, (6) optionally substituted aroyl, (7) optionally substituted aryl, (8) optionally substituted C5-C6cycloalkanoyl, (9) optionally substituted Cioalkylsulfonyl, (10) optionally substituted C5-C6cycloalkyl, (15) optionally substituted C5-C6cycloalkenyl, wherein the optional substituents on the Cι-C6alkyl, C3-C6alkenyl, C2-C4alkanoyl, C3-C4alkenoyl, aroyl, aryl, C5-C6cycloalkanoyl, Ci- C4alkylsulfonyl, C5-C6cycloalkyl and C5-C6cycloalkenyl are from 1 to 10 groups, wherein each group independently is hydroxy, methoxy, aryl methoxy, NRXRX, CO2R b , CONR R d > or halogen, (16) CF 3 , (17) arylsulfonyl optionally substituted with 1 to 3 groups, wherein each group independently is methyl, CF3, nitro, halogen or cyano, or (18) a 5- or 6-membered heterocycle containing 1 to 3 heteroatoms, wherein each heteroatom is oxygen, sulfur or nitrogen, wherein the heterocycle is optionally substituted by 1 to 3 groups, wherein each group independently is methyl, CF3, NMe2, C(O)NR c R d , cyano, CO2R b or halogen, and wherein the heterocycle may be saturated or partly unsaturated; X is (1) -CH2- (5) -C(O)-, (6) =CH- or (7) not present; and Rl is (1) R 7 , (2) C(O)R 7 , (21) CO2R b (22) C(O)N(OR b )R c , (23) C(O)NR c R d , (24) a 3- to 8-membered heterocycle containing 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2-C5alkenyl, Ci- C5perfluoroalkyl, NRCRd, oxo, thiono, ORa, S(O) n iRa (where ni = 0, 1 or 2), C(O)Ra, C(O)NRCRd, cyano, (Co- C6alkyl)aryl, CO2R b , or halogen, and each group may be saturated, partly unsaturated or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an R c substituent, (25) a benzene ring fused to a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups each independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd ; cyano, CO2R b or halogen, each group may be saturated, partly unsaturated, or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an R c substituent, and wherein the benzene/heterocycle fused ring is attached at any site to X or to the tetrapeptide, or (26) a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms fused to a second 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, each heterocyclic ring independently optionally substituted by 1 to 4 groups, each group independently is Ci-C5alkyl, C2- Csalkenyl, Ci-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRcRd, cyano, CO2R b or halogen, wherein each heterocycle may be saturated, partly unsaturated or fully unsaturated, and wherein each heteroatom independently is oxygen, sulfur, or nitrogen, and the nitrogen optionally has an R substituent. 15. The compound according to claim 14, or a pharmaceutically acceptable salt thereof, wherein n is 1 or 2. 16. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein: R6 each independently : is (1) O, (2) S, or (3) H; X is (1) -CH2- (2) -C(O)-, (5) =CH- or (6) not present; and Rl is (1) R7, (2) C(O)R 7 , (3) CN, (4) CO2R b (5) C(O)N(OR b )R c , (6) C(O)NR c Rd, (7) NHCO2R b (8) NHC(O)NRCRd, (9) (Co-C4alkyl)OR a , (10) (Co-C4alkyl)OCO2R b , (11) (Co-C4alkyl)OC(O)NRCRd (12) C(O)NR c NR c R d , (13) C(O)NR c SO2R b , (19) OS(O)niR7, (20) NR b S(O)niR7, wherein ni is from 0 to 2, (21) a 3- to 8-membered heterocycle containing 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups, each group independently is Ci-C5alkyl, C2-C5alkenyl, Ci- C5perfluoroalkyl, NRCRd, 0 χo, thiono, ORa, S(O) n iR a (where ni = 0, 1 or 2), C(O)R a , C(O)NRCRd, cyano, (Co- C6alkyl)aryl, CO2 b , or halogen, and each group may be saturated, partly unsaturated or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an R c substituent, (22) a benzene ring fused to a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups each independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NR c Rd ) cyano, CO2R b or halogen, each group may be saturated, partly unsaturated, or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, and wherein the benzene/heterocycle fused ring is attached at any site to X or to the tetrapeptide, or (23) a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms fused to a second 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, each heterocyclic ring independently optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2- Csalkenyl, Ci-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd ; cyano, CO2R b or halogen, wherein each heterocycle may be saturated, partly unsaturated or fully unsaturated, and wherein each heteroatom independently is oxygen, sulfur, or nitrogen, and the nitrogen optionally has an Rc substituent. 17. The compound according to claim 16, or a pharmaceutically acceptable salt thereof, wherein n is 1 or 2. 18. The compound according to claim 16, or a pharmaceutically acceptable salt thereof wherein: R3 each independently is (1) hydrogen, (2) halogen, (3) OR a , (4) Ci-C4alkyl, or (5) Cι-C4aryl; R6 each independently is (1) O, (2) S, or (3) H; X is (1) -CH 2 -, (2) -C(O)-, (3) =CH- or (5) not present; and Rl is (1) R 7, (2) C(O)R 7 , (3) CN, (4) CO2R b (5) C(O)N(OR b )R c , (6) C(O)NRCRd, (7) NHCO2R b (8) NHC(O)NR c Rd, (9) (Co-C4alkyl)OR a , (10) (Co-C4alkyl)OCO2R b , (11) (Co-C4alkyl)OC(O)NRCRd, (12) C(O)NR NRCRd, (19) C(O)NR SO2R b , (20) OS(O)niR7, (21) NR b S(O)niR7, wherein ni is from 0 to 2, (22) a 3- to 8-membered heterocycle containing 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2-C5alkenyl, Ci- C5perfluoroalkyl, NRCRd, oxo, thiono, OR a S(O) n iR a (where ni = 0, 1 or 2), C(O)R a , C(O)NRCRd, C yano, (Co- C6alkyl)aryl, CO2R b , or halogen, and each group may be saturated, partly unsaturated or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an Rc substituent, (23) a benzene ring fused to a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups each independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NR c Rd, cyano, CO2R or halogen, each group may be saturated, partly unsaturated, or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an R substituent, and wherein the benzene/heterocycle fused ring is attached at any site to X or to the tetrapeptide, or (24) a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms fused to a second 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, each heterocyclic ring independently optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2- Csalkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd ? cyano, CO2R b or halogen, wherein each heterocycle may be saturated, partly unsaturated or fully unsaturated, and wherein each heteroatom independently is oxygen, sulfur, or nitrogen, and the nitrogen optionally has an Rc substituent. 19. The compound according to claim 18, or a pharmaceutically acceptable salt thereof, wherein n is 1 or 2. 20. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein X is preferably -CH2-. 21. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein X is preferably -C(O)-. 22. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein X is preferably not present. 23. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein Ri is preferably a 3- to 8-membered heterocycle containing 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2-C5alkenyl, Cι-C5perfluoroalkyl, NRCRd, oxo, thiono, ORa, S(O) n iR a (where ni = 0, 1 or 2), C(O)R a , C(O)NRCRd, cyano, (Cø- C6alkyl)aryl, CO2R b , or halogen, and each group may be saturated, partly unsaturated or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an R c substituent. 24. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein Ri is preferably a benzene ring fused to a 4- to 8- membered heterocyclic ring with from 1 to 4 heteroatoms, optionally substituted by 1 to 4 groups each independently is Cι-C5alkyl, C2-C5alkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NR c Rd ) cyano, CO2R b or halogen, each group may be saturated, partly unsaturated, or fully unsaturated, wherein the heteroatoms are each independently oxygen, sulfur, or nitrogen, in which the nitrogen optionally has an R substituent, and wherein the benzene/heterocycle fused ring is attached at any site to X or to the tetrapeptide 25. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein Ri is preferably a 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms fused to a second 4- to 8-membered heterocyclic ring with from 1 to 4 heteroatoms, each heterocyclic ring independently optionally substituted by 1 to 4 groups, each group independently is Cι-C5alkyl, C2-C5alkenyl, Cι-C5perfluoroalkyl, amino, oxo, thiono, C(O)NRCRd ) cyano, CO2R b or halogen, wherein each heterocycle may be saturated, partly unsaturated or fully unsaturated, and wherein each heteroatom independently is oxygen, sulfur, or nitrogen, and the nitrogen optionally has an R c substituent. 26. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier. 27. A method for the treatment of protozoal infections comprising the step of administering, to a host in need of such treatment, a non-toxic amount of a composition according to claim 1 effective to inhibit a histone deacetylase activity of the infecting protozoa. 28. A method for the prevention of protozoal infections comprising the step of administering to a host a non-toxic effective preventative amount of a composition according to claim 1.

Inventors: COLLETTI STEVEN L, FISHER MICHAEL H, GURNETT ANNE M, MEINKE PETER T, MYERS ROBERT W, RATTRAY SANDRA J, SCHMATZ DENNIS, WYVRATT MATTHEW J, COLLETTI, STEVEN, L., FISHER, MICHAEL, H., GURNETT, ANNE, M., MEINKE, PETER, T., MYERS, ROBERT, W., RATTRAY, SANDRA, J., SCHMATZ, DENNIS, WYVRATT, MATTHEW, J.
Applicants: COLLETTI STEVEN L, FISHER MICHAEL H, GURNETT ANNE M, MEINKE PETER T, MERCK & CO INC, MYERS ROBERT W, RATTRAY SANDRA J, SCHMATZ DENNIS, WYVRATT MATTHEW J, COLLETTI, STEVEN, L., FISHER, MICHAEL, H., GURNETT, ANNE, M., MEINKE, PETER, T., MERCK & CO., INC., MYERS, ROBERT, W., RATTRAY, SANDRA, J., SCHMATZ, DENNIS, WYVRATT, MATTHEW, J.
Application year: 2000
Main classification: A61K31
IPC codes: A61K38, A61P31, A61P33, A61P35, A61P43, C07K5