3-DESCLADINOSE 6-O-SUBSTITUDED ERYTHROMYCIN DERIVATIVES

Abstract: Novel multicyclic erythromycin compounds and pharmaceutically acceptable salts and esters thereof having antibacterial activity having a formula selected from the group consisting of (I), (II), (III), (IV) and (V), compositions comprising a therapeutically eff ective amount of a compound of the invention in combination with a pharmaceutically acceptable carrier, as well as a method for treating bacterial infections by administering to a mammal a pharmaceutical composition containing a therapeutically effective amount of a compound of formulas (I)-(V).

Description: 3-DESCLADINOSE 6-O-SUBSΗTUTED ERYTHROMYCIN DERIVATIVES Technical Field This invention relates to novel semi- synthetic macrolides having antibacterial activity, to pharmaceutical compositions comprising these compounds, and to a medical method of treatment. More particularly, the invention relates to 3- descladinose 6-O-substituted erythromycin derivatives and methods for preparing them, compositions containing these compounds, and a method of treating bacterial infections with such compositions. Background of the Invention Erythromycins A through D, represented by formula (E), (E) are well-known and potent antibacterial agents, used widely to treat and prevent bacterial infection. As with other antibacterial agents, however, bacterial strains having resistance or insufficient susceptibility to erythromycin have been identified. Also, erythromycin A has only weak activity against Gram-negative bacteria. Therefore, there is a continuing need to identify new erythromycin derivative compounds which possess improved antibacterial activity, which have less potential for developing resistance, which possess the desired Gram-negative activity, or which possess unexpected selectivity against target microorganisms. Consequently, numerous investigators have prepared chemical derivatives of erythromycin in an attempt to obtain analogs having modified or improved profiles of antibiotic activity. Morimoto et al. describes the preparation of 6-O-methyl erythromycin A in J. Antibiotics 37:187 (1984). Morimoto et al. further discloses 6-O-alkyl erythromycin A derivatives in J. Antibiotics, 43: 286 (1990) and in European Patent Application 272,110, published June 22, 1988. European Patent Application 215,355, published March 28, 1987, discloses 6-O-loweralkyl erythromycins as stimulants of gastrointestinal contractile motion. United States Patent 5,444,051 discloses 6-O-substituted-3-oxoerythromycin A derivatives in which the substituents are selected from alkyl, -CONH2, -CONHC(O) alkyl and - CONHSO2alkyl. PCT application WO 97/10251, published March 20, 1997, discloses 6-O- methyl 3-descladinose erythromycin derivatives, and PCT application WO 97/17356, published May 15, 1997, discloses 3-deoxy-3-descladinose erythromycin derivatives. . PCT appUcation WO 92/09614, published June 11, 1992, discloses tricyclic 6-O-methyl erythromycin A derivatives. Certain intermediates to the present invention are disclosed in U.S. Patent AppUcation Serial Number 08/888,350. European Patent Application 596802, published May 11, 1994, discloses bicyclic 6-O- methyl-3-oxo erythromycin A derivatives. U. S. Patent 5.523,399, published June 4, 1996 discloses 6-O-methyl 3-descladinose 3-O-carbamoyl erythromycin derivatives. Summary of the Invention. The present invention provides a novel class of 3-descladinose 6-O-substituted erythromycin derivatives which possess antibacterial activity. In one aspect of the present invention are compounds, or pharmaceuticaUy acceptable salts and esters thereof, having a formula selected from the group consisting of (I) or a pharmaceuticaUy acceptable salt, ester or prodrug thereof, wherein Y and Z taken together define a group X, wherein X is selected from the group consisting of (1) =O, (2) =N-OH, (3) =N-O-R 1 where R 1 is selected from the group consisting of (a) unsubstituted Ci-C 12- alkyl, (b) Cι-Ci2-alkyl substituted with aryl, (c) Cι-Ci2-alkyl substituted with substituted aryl, (d) Cι-Ci2-alkyl substituted with heteroaryl, (e) Cι-Ci2-alkyl substituted with substituted heteroaryl, (f) C3-Ci2-cycloalkyl, and (g) -Si-(R 2 )(R )(R 4 ) wherein R 2 , R 3 and R 4 are each independently selected from Cι-Ci2-alkyl and aryl; and (4) =N-O-C(R 5 )(R 6 )-O-R 1 where R 1 is as previously defined and R 5 and R 6 are each independently selected from the group consisting of (a) hydrogen, (b) unsubstituted Cι-Ci2-alkyl, (c) Cι-Ci2-alkyl substituted with aryl, (d) Ci-C 12- alkyl substituted with substituted aryl, (e) Cι-Ci2-alkyl substituted with heteroaryl, and (f) Cι-Ci2-alkyl substituted with substituted heteroaryl, or R 5 and R 6 taken together with the atom to which they are attached form a C3-Ci2-cycloalkyl ring; or, one of Y and Z is hydrogen and the other is selected from a group consisting of (1) hydrogen, (2) hydroxy, (3) protected hydroxy, and (4) NR 7 R 8 wherein R 7 and R 8 are independently selected from hydrogen and Ci - C6-alkyl, or R 7 and R 8 are taken with the nitrogen atom to which they are connected to form a 3- to 7-membered ring which, when the ring is a 5- to 7-membered ring, may optionaUy contain a hetero function selected from the group consisting of -O-, -NH-, -N(Cι-C6-alkyl-)-, N(aryl)-, -N(aryl-Cι-C6-alkyl-)-, -N(substituted-aryl-Cι-C6-alkyl-)-, -N(heteroaryl)-, - N(heteroaryl-Cι-C6-alkyl-)-, -N(substituted-heteroaryl-Cι-C6-alkyl-)-, and -S- or -S(O) n -, wherein n is 1 or 2, W is absent or is selected from the group consisting of -O-, -NH-CO-, -N=CH- and -NH-; R w is selected from the group consisting of (1) hydrogen, (2) Ci- -alkyl optionally substituted with one or more substituents selected from the group consisting of (a) aryl, (b) substituted-aryl, (c) heteroaryl, (d) substituted-heteroaryl, (e) hydroxy, (f) Cι-C6-alkoxy, (g) NR 7 R 8 , wherein R 7 and R 8 are as defined previously, and wherein M is selected from the group consisting of: (i) -C(O)-NH-, (ii) -NH-C(O)-, (tii) -NH-, (iv) -N=, (v) -N(CH 3 )-, (vi) -NH-C(O)-O- (vii) -NH-C(O)-NH- (vni) -O-C(O)-NH- (ix) -O-C(O)-O- (x) -O-, (xi) -S(O) n -, wherein n is 0, 1 or 2, (xn) -C(O)-O-, (xUi) -O-C(O)-, and (xiv) -C(O)-, and R 9 is selected from the group consisting of: (i) Cι-C6-alkyl, optionally substituted with a substituent selected from the group consisting of (aa) aryl, (bb) substituted-aryl, (cc) heteroaryl, and (dd) substituted-heteroaryl, (ii) aryl, (iii) substituted-aryl, (iv) heteroaryl, (v) substituted-heteroaryl, and (vi) heterocycloalkyl, (3) C3-C7-cycloalkyl, (4) aryl, (5) substituted-aryl, (6) heteroaryl, and (7) substituted-heteroi RP is hydrogen or a hydroxy protecting group; R is selected from the group consisting of (1) methyl substituted with a moiety selected from the group consisting of (a) CN, (b) F, (c) -CO2R 10 wherein R 10 is Cι-C3-alkyl or aryl substituted Cι-C3-alkyl, or heteroaryl substituted Cι-C3-alkyl, (d) S(O) n R 10 where n is OA or 2 and R 10 is as previously defined, (e) NHC(O)R 10 where R 10 is as previously defined, (f) NHC(O)NR ! ! R 12 wherein R 1 J and R 12 are independently selected from hydrogen, Cι-C3-alkyl, Cι-C3-alkyl substituted with aryl, substituted aryl, heteroaryl, substituted heteroaryl, (g) aryl, (h) substituted aryl, (i) heteroaryl, and (j) substituted heteroaryl, (2) C2-Cιo-alkyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) hydroxy, (c) Cι-C3-alkoxy, (d) Cι-C3-alkoxy-Cι-C3-alkoxy, (e) oxo, ( ) -N3, (g) -CHO, (h) O-SO2-(substituted Ci-Cβ-alkyl), (i) -NR 13 R 14 wherein R 13 and R 14 are selected from the group consisting of (i) hydrogen, (n) Cι-Ci2-alkyl, (in) substituted Cι-Ci2-aUcyl, (iv) Cι-Ci2-alkenyl, (v) substituted Cι-Ci2-alkenyl, (vi) Cι-Ci2-alkynyl, (vii) substituted Cι-Ci2-alkynyl, (viii) aryl, (ix) C3-C8-cycloaU_yl, (x) substituted C3-C8-cycloalkyl, (xi) substituted aryl, (xn) heterocycloalkyl, (xiti) substituted heterocycloalkyl, (xiv) Cι-Ci2-aUcyl substituted with aryl, (xv) Cι-Ci2-alkyl substituted with substituted aryl, (xvi) Cι-Ci2-alkyl substituted with heterocycloalkyl, (xvii) Cj-C 12- alkyl substituted with substituted heterocycloalkyl, (xviii) Cι-Ci2-alkyl substituted with C3-Cg-cycloalkyl, (xix) Cι-Ci2-alkyl substituted with substituted C3-C8-cycloalkyl, (xx) heteroaryl, (xxi) substituted heteroaryl, (xxii) Cι-Ci2-alkyl substituted with heteroaryl, and (xxiti) Cι-Ci2-aUcyl substituted with substituted heteroaryl, or R 13 and R 14 are taken together with the atom to which they are attached form a 3-10 membered heterocycloalkyl ring which may be substituted with one or more substituents independently selected from the group consisting of (i) halogen, (ii) hydroxy, (tii) Cι-C3-alkoxy, (iv) Cι-C3-alkoxy-Cι-C3-alkoxy, (v) oxo, (vi) Cι-C 3 -alkyl, (vii) halo-Cι-C3-alkyl, and (vu) Cι-C3-alkoxy-Cι-C3-alkyl, (j) -CO2R 10 wherein R 10 is as previously defined, (k) -C(O)NR u R 12 wherein R 11 and R 12 are as previously defined, (1) =N-O-R 10 wherein R 10 is as previously defined, (m) -ON, (n) O-S(O) n R 10 wherein n is 0. 1 or 2 and R 10 is as previously defined, (o) aryl, (p) substituted aryl, (q) heteroaryl, (r) substituted heteroaryl, (s) C3-C8-cycloalkyl, (t) substituted C3-C8-cycloalkyl, (u) Cι-Ci2-alkyl substituted with heteroaryl, (v) heterocycloalkyl, (w) substituted heterocycloalkyl, (x) NHC(O)R 10 where R 10 is as previously defined, (y) NHC(O)NR π R 12 wherein R 11 and R 12 are as previously defined, (z) =N-NR 13 R 14 wherein R 13 and R 14 are as previously defined, (aa) =N-R 9 wherein R 9 is as previously defined, (bb) =N-NHC(O)R 10 wherein R 10 is as previously defined, and (cc) =N-NHC(O)NR 1 J R 12 wherein R 11 and R 12 are as previously defined; (3) C3-alkenyl substituted with a moiety selected from the group consisting of (a) halogen, (b) -CHO, (c) -CO2R 10 where R 10 is as previously defined, (d) -C(O)-R 9 where R 9 is as previously defined, (e) -C^NR^R 12 wherein R 11 and R 12 are as previously defined, (f) -C≡N, (g) aryl, (h) substituted aryl, (i) heteroaryl, (j) substituted heteroaryl, (k) C 3 -C7-cycloalkyl, and (1) Cι-Ci2-alkyl substituted with heteroaryl, (4) C -Cιo-alkenyl; (5) C4-C 10- alkenyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) Cι-C3-alkoxy, (c) oxo, ( ) -CHO, (e) -CO2R 10 where R 10 is as previously defined, ( ) -C(O)NR 11 R 12 wherein R 11 and R 12 are as previously defined, (g) -NR 13 R 14 wherein R 13 and R 14 are as previously defined, (h) =N-O-R 10 where R 10 is as previously defined, (i) -C≡N, (j) O-S(O) n R 10 where n is 0, 1 or 2 and R 10 is as previously defined, ( ) aryl, (1) substituted aryl, (m) heteroaryl, (n) substituted heteroaryl, (o) C3-C7-cycloalkyl, (P) Cι-Ci2-alkyl substituted with heteroaryl, (q) NHC(O)R 10 where R 10 is as previously defined, (r) NHC(O)NR π R 12 wherein R 11 and R 12 are as previously defined, (s) =N-NR 13 R 14 wherein R 13 and R 14 are as previously defined, (t) =N-R 9 wherein R 9 is as previously defined, (u) =N-NHC(O)R 10 where R 10 is as previously defined, and (v) =N-NHC(O)NR n R 12 wherein R 11 and R 12 are as previously defined; (6) C -C !l0-alkynyl; and (7) C3-Cιo-alkynyl substituted with one or more substituents selected from the group consisting of (a) trialkylsilyl, (b) aryl, (c) substituted aryl, (d) heteroaryl, (e) halogen, and (f) substituted heteroaryl; U is selected from the group consisting of: (1) hydrogen, (2) hydroxy, (3) protected hydroxy, (4) -O-T-R 1 , wherein T is absent or selected from the group consisting of: (a) -C(O)-, (b) -C(O)-O- (c) -CH 2 -, (d) -C(S)-S-, (e) -C(O)-N(R s )-, wherein R s is H or Cι-C 6 -alkyl, (f) -S(O) n -, wherein n is 0, 1 or 2, (g) -S(O) n -O-, wherein n is 0, 1 or 2, (h) -P(O)(OR r ) n -, wherein n is 0, 1 or 2, and R r is Cι-C6-alkyl, and (i) -SO2-N(R s )-, wherein R s is as defined previously; and R l is selected from the group consisting of: (a) C1-C6- alkyl, optionally substituted with a substituent selected from the group consisting of (i) aryl, (ii) substituted-aryl, (iii) heteroaryl, and (iv) substituted-heteroaryl, (v) heterocycloalkyl, (vi) substituted-heterocycloalkyl, (vii) hydroxy, (vtii) Cι-C6-alkoxy, (ix) NR 7 R 8 wherein R 7 and R 8 are as defined previously, (b) C3-C6-alkenyl, optionally substituted with a substituent selected from the group consisting of (i) aryl, (ii) substituted-aryl, (in) heteroaryl, and (iv) substituted-heteroaryl, (v) heterocycloalkyl, (vi) substituted-heterocycloalkyl, (vii) hydroxy, (vtii) Cι-C6-alkoxy, (ix) NR 7 R 8 wherein R 7 and R 8 are as defined previously, (c) C3-Ci2-cycloalkyl, optionally substituted with a substituent selected from the group consisting of (i) aryl, (ii) substituted-aryl, (tii) heteroaryl, and (iv) substituted-heteroaryl, (v) heterocycloalkyl, (vi) substituted-heterocycloalkyl, (vn) hydroxy, (viti) Cι-C6-alkoxy, (ix) NR 7 R 8 wherein R 7 and R 8 are as defined previously, (d) aryl, (e) substituted-aryl, (f) heteroaryl, (g) substituted-heteroaryl, and (h) heterocycloalkyl; or in compounds of formula (II) and (III) U is taken together with U' to form a double bond between the carbon atoms to which they are attached; and U' is hydrogen or in compounds of formula (II) and (III) U' is taken together with U to form a double bond between the carbon atoms to which they are attached. The present invention also provides pharmaceutical compositions which comprise a therapeuticaUy effective amount of a compound as defined above in combination with a pharmaceuticaUy acceptable carrier. The invention further relates to a method of treating bacterial infections in a host mammal in need of such treatment comprising administering to a mammal in need of such treatment a therapeuticaUy effective amount of a compound as defined above. In a further aspect of the present invention, processes are provided for the preparation of 6-O-substituted macrolide derivatives of Formula (I), (II), (III), (IV) and (V) above. Detatied Description of The Invention In a first embodiment of the invention is a compound having the formula (I) as described above. A preferred embodiment is a compound of formula (I) wherein Y and Z taken together define a group X which is =O. Representative compounds of the invention having formula (I) are those selected from the group consisting of: Compound of Formula (I): R is allyl, RP is H, X is O, U is OH; Compound of Formula (I): R is allyl, RP is benzoyl, X is O, U is OH; Compound of Formula (I): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, X is O, U is OH; Compound of Formula (I): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, X is O, U is O- acetyl; Compound of Formula (I): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, X is O, U is O-(4-methoxy)benzoyl; Compound of Formula (I): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, X is O, U is O-methanesulfonyl; and Compound of Formula (I): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, X is O, U is O-CO- NH-(2-nitrophenyl). In a second embodiment of the invention is a compound having the formula (Et) as described above. A preferred embodiment is a compound of formula (II) wherein W is absent and R is H. Representative compounds of the invention having formula (II) are those selected from the group consisting of: Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R w is H, U is OH; Compound of Formula (II): R is -CH 2 -CH=CH2-(3-quinolinyl), RP is H, W is absent, R w is H, U is O-acetyl; Compound of Formula (II): R is -CH -CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R is H, U is O-(4-nitrobenzoyl); Compound of Formula (11): R is -CH2-CH=CH -(3-quinolinyl), RP is H, W is absent, R w is H, U is O-benzoyl; Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R w is H, U is O-(3,5-diphenylpyridinecarboxyl); Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R w is H, U is O-(2-nitrobenzoyl); Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R is H, U is O-(3,4,5-trimethoxybenzoyl); Compound of Formula (II): R is -CH -CH=CH -(3-quinolinyl), RP is H, W is absent, R is H, U is O-(2-thiophenecarboxoyl); Compound of Formula (Jl): R is -CH2-CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R w is H, U is O-(2-methylbutanoyl); Compound of Formula (II): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, W is absent, R w is H, U is O-(4-bromobenzoyl); Compound of Formula (II): R is -CH 2 -CH=CH2-(3-quinolinyl), RP is H, W is absent, R w is H, U is O-(4-pyridinecarboxoyl); Compound of Formula (II): R is -CH 2 -CH=CH2-(3-quinolinyl), RP is H, W is absent, R is H, U is O-(methoxycarbonyl); Compound of Formula (II): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, W is absent, R w is H, U is O-(l,l-dimethylethoxycarbonyl); Compound of Formula (II): R is -CH 2 -CH=CH2-(3-quinolinyl), RP is H, W is absent, R w is H, U is O-(2-bromobenzoyl); Compound of Formula (II): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, W is absent, R w is H, U is O-(4-methoxybenzoyl); Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R is H, U is O-(2-furancarboxoyl); Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R w is H, U is O-butanoyl; Compound of Formula (II): R is -CH 2 -CH=CH2-(3-quinolinyl), RP is H, W is absent, R w is H, U is O-methanesulfonyl; Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R is H, U is O-(2-methylpropenoyl); Compound of Formula (II): R is -CH 2 -CH=CH2-(3-quinolinyl), RP s H, X is O, W is absent, R w is H, U is O-CO-NH-phenyl; Compound of Formula (II): R is -CH 2 -CH=CH2-(3-quinolinyl), RP s H, X is O, W is absent, R w is H, U is O-CO-NH-allyl; Compound of Formula (II): R is -CH 2 -CH=CH2-(3-quinolinyl), RP s H, X is O, W is absent, R is H, U is O-CO-NH-CH(C(O)OCH 3 )-CH(CH 3 )2; Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP s H, X is O, W is absent, R w is H, U is O-CO-NH-CH(CH 3 ) 2 ; Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP s H, X is O, W is absent, R w is H, U is O-CO-NH-cyclohexyl; Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP s H, X is O, W is absent, R is H, U is O-CO-NH-(4-fluorophenyl); Compound of Formula (II): R is -CH -CH=CH2-(3-quinolinyl), RP s H, X is O, W is absent, R w is H, U is O-CO-NH-(2-nitrophenyl); Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP s H, X is O, W is absent, R w is H, U is O-CO-NH-(4-methyl-2-nitrophenyl); Compound of Formula (II): R is -CH -CH=CH2-(3-quinolinyl), RP s H, X is O, W is absent, R w is H, U is O-CO-NH-(4-nitrophenyl); Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP s H, X is O, W is absent, R is H, U is O-CO-NH-(4-methoxyphenyl); Compounds of Formula (II): R is -CH 2 -CH=CH2-(3-quinolinyl), RP s H, W is absent, R w is H, U is O-S(O) 2 -CH=CH 2 ; Compounds of Formula (II): R is -CH 2 -CH=CH2-(3-quinolinyl), RP s H, W is absent, R w is H, U is O-S(O)2-CH 2 -CH2-N(CH 3 )2; Compounds of Formula (II): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, W is absent, R w is H, U is O-S(O)2-CH 2 -CH 2 -S-phenyl; Compounds of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R w is H, U is O-allyl; Compound of Formula (II): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, W is absent, R w is H, U is O-(4-morphotinecarbonyl); Compound of Formula (II): R is -CH2-CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R w is H, U is O-pyrroUdinylcarbonyl; Compound of Formula (II): R is -CH2-CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R w is H, U is O-(2-tetrahydropyranyl); Compound of Formula (II): R is -CH2-CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R w is H, U is O-C(=S)-SCH ; Compound of Formula (II): R is -CH2-CH=CH2, RP is H, U and U' taken together are double bond, W is absent, R w is H; Compound of Formula (II): R is -CH2-CH=CH 2 -(3-quinolinyl), RP is H, U and U' taken together are double bond, W is absent, R w is H; Compound of Formula (II): R is -CH2-CH=CH 2 -(6-nitro-3-quinolinyl), RP is H, U and U' taken together are double bond, W is absent, R w is H; Compound of Formula (II): R is -CH2-CH=CH 2 -(6-methoxy-2-naρhthyl), RP is H, U and U' taken together are double bond, W is absent, R w is H; Compound of Formula (II): R is -CH2-CH=CH 2 -(3-(5-(3-isoxazolyl)-2-furanyl)), RP is H, U and U' taken together are double bond, W is absent, R w is H; Compound of Formula (II): R is -CH2-CH=CH 2 , RP is H, W is NH, R is H, U is OH; Compound of Formula (II): R is -CH2-CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R w is H, U is H, U' is H; Compound of Formula (II): W is absent, R w is H, R is -CH 2 CH(O), RP is acetyl, U is OH; Compound of Formula (II): W is absent, R w is H, R is -CH2CH 2 NHCH 2 -phenyl, RP is acetyl, U is OH; Compound of Formula (II): W is absent, R is H, R is -CH 2 CH NHCH 2 CH 2 -phenyl, RP is acetyl, U is OH; Compound of Formula (II): W is absent, R w is H, R is -CH 2 CH2NHCH2CH 2 CH2-phenyl, RP is acetyl, U is OH; Compound of Formula (II): W is absent, R w is H, R is -CH2CH2NHCH2CH2CH2CH2- phenyl, RP is acetyl, U is OH; Compound of Formula (II): W is absent, R is H, R is -CH2CH2NHCH2CH2CH2- (3-quinolyl), RP is acetyl, U is OH; Compound of Formula (II): W is absent, R w is H, R is -CH2CH 2 NHCH2-(3-quinolyl), RP is acetyl, U is OH; Compound of Formula (II): W is absent, R w is H, R is -CH2CH=NO-(phenyl), RP is acetyl, U is OH; Compound of Formula (II): W is absent, R is H, R is -CH CH=NOCH2-(ρhenyl), RP is acetyl, U is OH; Compound of Formula (II): W is absent, R w is H, R is -CH 2 CH=NOCH 2 -(4-NO2-phenyl), RP is acetyl, U is OH; Compound of Formula (II): W is absent, R w is H, R is -CH 2 CH=NOCH 2 -(4-quinolyl), RP is acetyl, U is OH; Compound of Formula (II): W is absent, R w is H, R is -CH 2 CH=NOCH2-(2-quinolyl), RP is acetyl, U is OH; and Compound of Formula (II): W is absent, R w is H, R is -CH 2 CH=NOCH2-(3-quinolyl), RP is acetyl, U is OH. In a third embodiment of the invention is a compound having the formula (HI) as described above. Representative compounds of the invention having formula (HI) are those selected from the group consisting of: Compound of Formula (HI): R is -CH 2 -CH=CH 2 , RP is H, U is OH, U' is H; Compound of Formula (III): R is -CH2-CH=CH 2 -(3-quinolinyl), RP is H, U is OH, U' is H; Compound of Formula (III): W is absent, R w is H, R is -CH CH(O), RP is H, U is OH; Compound of Formula (III): W is absent, R is H, R is -CH2CH 2 NHCH2-phenyl, RP is H, U is OH; and Compound of Formula (HI): W is absent, R w is H, R is -CH 2 CH=NO(phenyl), RP is H, U is OH. In a fourth embodiment of the invention is a compound having the formula (IV) as described above. Representative compounds of the invention having formula (IV) are those selected from the group consisting of: Compound of Formula (IV): R is -CH 2 -CH=CH 2 , RP is acetyl, U is OH; Compound of Formula (IV): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP is acetyl, U is OH. Compound of Formula (IV): R is -CH2-CH=CH 2 -(3-quinolinyl), RP is H, U is O-C(O)- phenyl; Compound of Formula (IV): R is -CH2-CH=CH -(3-quinolinyl), RP is H, U is O-C(O)-(2- nitrophenyl); Compound of Formula (IV): W is absent, R w is H, R is -CH 2 CH(O), RP is H, U is OH; Compound of Formula (IV): W is absent, R w is H, R is -CH2CH2NHCH 2 -phenyl, RP is H, U is OH; and Compound of Formula (IV): W is absent, R is H, R is -CH 2 CH=NO(phenyl), RP is H, U is OH. In a fifth embodiment of the invention is a compound having the formula (V) as described above. Representative compounds of the invention having formula (V) are those selected from the group consisting of: Compound of Formula (V): R is -CH2-CH=CH 2 , RP is H, U is OH; Compound of Formula (V): R is -CH2-CH=CH 2 , RP is H, U is O-acetyl; Compound of Formula (V): R is -CH2-CH=CH , RP is H, U is H, U' is H; Compound of Formula (V): W is absent, Rw is H, R is -CH2CH(O), RP is H, U is OH; Compound of Formula (V): W is absent, R is H, R is -CH2CH2NHCH2-phenyl, RP is H, U is OH; and Compound of Formula (V): W is absent, R is H, R is -CH2CH=NO(phenyl), RP is H, U is OH. The compounds of the present invention include both those in which the group at the 3- position is the natural (3S) isomer and those in which the group at the 3-position is non-natural (3R) isomer. One aspect of the invention is a process for preparing a compound of formula (I) wherein Y and Z taken together define a group X which is =O, having the formula (LA) (IA) wherein RP, R and U are as defined above, the method comprising: (a) treating hydrolyticaUy with acid a compound having the formula wherein R is as defined previously, to give a compound having the formula which is a compound of formula (IA) wherein RP is H and U is hydroxy; (b) optionally treating the compound of Step (a) with a hydroxy protecting reagent to give a compound having the formula which is a compound of formula (IA) wherein Rp is a hydroxy-protecting group and U is hydroxy, optionaUy foUowed by converting the compound having the natural (3S) isomeric configuration into the compound having the non-natural (3R) isomeric configuration by oxidation of the 3-hydroxyl group and selective reduction of the 3-oxo group to give the non- natural (3R) isomer; (c) optionaUy treating the compound of formula (IA) wherein Rp is a hydroxy-protecting group and U is hydroxy (the compound from Step (b)) with an excess of NaH in an aprotic solvent followed by reaction of the intermediate anion with CS2 and CH3I to form a xanthate intermediate which is then treated with Bu3SnH under an inert atmosphere in the presence of a catalytic amount of a suitable radical initiator to afford the desired 3-deoxy compound having the formula which is a compound of formula (IA) wherein U is hydrogen; (d) optionaUy treating the compound of formula (IA) wherein Rp is a hydroxy-protecting group and U is hydroxy (the compound from Step (b)) with a hydroxy-protecting reagent to give a compound of formula (IA) wherein Rp is a hydroxy-protecting group and U is a protected hydroxyl group; (e) optionaUy treating the compound of formula (IA) wherein Rp is a hydroxy-protecting group and U is hydroxy (the compound from Step (b)) with base and a reagent L-T-R 1 , wherein T and R l are as previously defined, and L is a suitable reactive leaving group to give compound having the formula (f) optionally deprotecting, and isolating the desired compound of formula (IA). In the process for preparing compounds of formula (I), in step (e) the reagent L-T-R 1 is selected from the group consisting of: (e-i) halogen-C(O)-Rt; (e-ii) O-(C(O)-R t ) 2 ; (e-iii) O-(C(O)-O-R t )2; (e-iv) halogen-CH2-R . (e-v) alkali metal hydride followed by CS2 then followed by halogen-R 1 ; (e-vi) O=C=N-Rt; (e-vii) carbonyl diimidazole foUowed by N(R S )H-R l ; (e-viiii) Cl-S(O) n -O-R t ; (e-ix) Cl-P(O)(OR r ) n - . (e-x) Cl-SO 2 -N(RS)-Rt; Alternately, in the process for preparing compounds of formula (I), in step (e) the reagent L-T-R 1 in the presence of base is replaced with 3,4-dihydro-2H-pyran in the presence of a acid catalyst. Another aspect of the invention is a process for preparing a compound of formula (II) wherein RP, R , U, U', W and R w are as defined above, the method comprising: (a) optionaUy treating hydrolyticaUy with acid a compound having the formula \_ wherein R is as defined above and Rp is a hydroxy protecting group to give a compound having the formula & wherein U is hydroxy and U' is hydrogen (b) optionaUy treating a compound from Step (a) with an excess of sodium hexamethyldisilazide or a hydride base in the presence of carbonyldumidazole in an aprotic solvent to give a compound having the formula wherein U and U' are taken together to form a double bond; (c) optionally treating a compound from Step (b) with aqueous ammonia to give the desired compound of formula (II) where U and U' are taken together to form a double bond, W is absent and R w is H; (d) optionally treating a compound from Step (b) with a substituted amine compound of the formula H2N-W-R W , wherein W is absent and R w is not H but is otherwise as previously defined, to give the desired compound of formula (II) where U and U' are taken together to form a double bond, W is absent and R w is not H; (e) optionaUy treating a compound from Step (b) with a hydroxylamine compound of the formula H 2 N-W-R W , wherein W is -O- and R w is as previously defined, to give the desired compound of formula (II) where U and U' are taken together to form a double bond, W is -O- and R w is as previously defined; (f) optionally treating a compound from Step (b) with an unsubstituted hydrazine to give the desired compound of formula (II) where U and U' are taken together to form a double bond, W is -NH- and R is H; (g) optionaUy treating a compound from Step (b) with a substituted hydrazine compound of the formula H2N-NH-R W wherein R w is not hydrogen but otherwise is as previously defined to give the desired compound of formula (II) where U and U' are taken together to form a double bond, W is -NH-R W and R w is not H; (h) optionally treating a compound of formula j_4 as defined above with a strong base selected from the group consisting of (i) sodium hexamethyldisUazide and (ii) an alkali metal hydride base in the presence of carbonyldumidazole in an aprotic solvent to give a compound having the formula (i) optionally treating a compound from Step (h) with aqueous ammonia to give a compound having the formula (16A) wherein W is absent, R w is H and U is 4"-fιydroxy protected cladinose; (j) optionally treating the compound from step (i), wherein W is absent and R w is H and U is 4"-hydroxy protected cladinose, with an alkylating agent selected from the group consisting of R w -halogen to give a compound of formula (16A) wherein W is absent, U is 4"-hydroxy protected cladinose, and R is as defined above; (k) optionaUy treating a compound from Step (h) with a substituted amine compound of the formula H2N-W-R W , wherein W is absent and R w is as previously defined except not H, to give to give a compound having of formula (16A) wherein W is absent, U is 4"-hydroxy protected cladinose, and R is as previously defined except not H; (1) optionally treating a compound from Step (h) with a hydroxylamine compound of the formula H 2 N-W-R W , wherein W is -O- and R w is as previously defined, to give to give a compound of formula (16A) wherein W is -O-, U is 4"-hydroxy protected cladinose, and R w is as previously defined; (m) optionally treating a compound from Step (h) with an unsubstituted hydrazine to give to give a compound of formula (16A) wherein W is -NH-, U is 4"-hydroxy protected cladinose, and R w is H; (n) optionaUy treating the compound from step (m) wherein W is -NH-, U is 4"-hydroxy protected cladinose, and R w is H with an acylating agent selected from the group consisting of R -C(O)-halogen or (R -C(O)) 2 -O to give a compound of formula ( 16A) wherein W is -NH- CO-, U is 4"-hydroxy protected cladinose, and R w is as defined above; (o) optionaUy treating the compound from step (m) wherein W is -NH-, U is 4"-hydroxy protected cladinose, and R w is H with an aldehyde R w -CHO, wherein R w as defined above to give a compound of formula (16A) wherein W is -N=CH-, U is 4"-hydroxy protected cladinose, and R w is as defined above; (p) optionaUy treating a compound from Step (h) with a substituted hydrazine compound of the formula H2N-NH-R W , wherein R w is as defined above except not hydrogen, to give to give a compound of formula (16A) wherein W is -NH-, U is 4"-hydroxy protected cladinose, and R w is as defined above except not hydrogen; (q) optionaUy treating hydrolyticaUy with acid a compound selected from the group consisting of the compounds of Step (i), Step (j), Step (k), Step (1), Step (m), Step (n), Step (o), and Step (p) to give the desired compound of formula (II) wherein U is OH, optionally followed by converting the compound having the natural (3S) isomeric configuration into the compound having the non-natural (3R) isomeric configuration by oxidation of the 3-hydroxyl group and selective reduction of the 3-oxo group to give the non-natural (3R) isomer; (r) optionally treating a compound of formula (II) wherein RP is a hydroxy protecting group and U is hydroxy (a compound from Step (q)) with an excess of NaH in an aprotic solvent followed by reaction of the intermediate anion with CS2 and CH3I to form a xanthate intermediate which is then treated with Bu3SnH under an inert atmosphere in the presence of a catalytic amount of a suitable radical initiator to give the desired compound of formula (II) wherein U is hydrogen; (s) optionally treating a compound of formula (II) wherein RP is a hydroxy protecting group and U is hydroxy (a compound from Step (q) with base and a reagent L-T-R 1 , wherein T and R l are as previously defined, and L is a suitable reactive leaving group to give the desired compound of formula (II) wherein U is O-T-R 1 ; and (t) optionally deprotecting, and isolating the desired compound of formula (II). In the process for preparing compounds of formula (II), in step (s) the reagent L-T-R 1 is selected from the group consisting of: (e-i) halogen-C(O)-Rt; (e-ii) O-(C(O)-Rt) 2 ; (e-iii) O-(C(O)-O-R t ) 2 ; (e-iv) halogen-CH 2 -R . (e-v) alkali metal hydride followed by CS2 then followed by halogen-R 1 ; (e-vi) O=C=N-R t ; (e-vii) carbonyl diimidazole foUowed by N(R S )H-R l ; (e-viiii) Cl-S(O) n -O-R t ; (e-ix) Cl-P(O)(OR r )n-R t ; (e-x) Cl-SO2-N(R s )-R t ; Alternately, in the process for preparing compounds of formula (II), in step (s) the reagent L-T-R 1 in the presence of base is replaced with 3,4-dihydro-2H-pyran in the presence of a acid catalyst. Another aspect of the invention is a process for preparing a compound of formula (HI) wherein RP is R, U and U' are as described above, the method comprising: (a) optionaUy treating hydrolyticaUy with acid a compound having the formula 14 wherein R is as defined above and RP is a hydroxy protecting group to give a compound having the formula 8 wherein U is hydroxy and U' is hydrogen, optionally followed by converting the compound having the natural (3S) isomeric configuration into the compound having the non-natural (3R) isomeric configuration by oxidation of the 3-hydroxyl group and selective reduction of the 3- oxo group to give the non-natural (3R) isomer; (b) treating a compound selected from the group consisting of compound J and compound wherein U is hydroxy and U' is hydrogen with a base selected from the group consisting of sodium hexamethyldisilazide and a metal hydride base in the presence of carbonyldumidazole in an aprotic solvent to give a compound selected from the group consisting of compounds 15A and 15B, respectively 15A. wherein U is -O-4"-acetyl-cladinose and U' is H, or 15B. wherein U and U' are taken together to form a double bond; (c) treating a compound selected from the group 15A and 15B of step (b) with ethylenediamine to give a bicychc carbamate compound selected from the group consisting of compounds 21A, wherein U is O-4"-acetylcladinose, and 21B. wherein U and U' form a double bond, respectively, 21A, wherein U is O-4"-acetylcladιnose, 21B, wherein U and U' from a double bond, (d) treating the a compound selected from the group 21A and 21B of step (c) with dilute acid to give a compound selected from the group consisting of compounds 22A and 22B, respectively, 22 A, U is O-4"-acetylcladιnose, and 22B, U and U' form a double bond, (e) hydrolyticaUy removing the cladinose moiety from a compound (22A) from step (d) by treatment with acid, reprotecting the 2' hydroxyl group by treatment with a hydroxy protecting reagent, optionally followed by converting the compound having the natural (3S) isomeπc configuration into the compound having the non-natural (3R) isomeric configuration by oxidation of the 3-hydroxyl group and selective reduction of the 3-oxo group to give the non- natural (3R) isomer, to give a compound having the formula (23P), which is a compound of formula (HI) wherein RP is H, U is hydroxy and U' is hydrogen; (f) optionaUy treating the 3-hydroxy group of the product compound from step (e) having the formula (III) wherein R is as defined previously and RP is H, U is hydroxy and U' is hydrogen with base and a reagent L-T-R 1 , wherein L is a leaving group and T and R l are as defined previously, to give a compound of formula (III) wherein RP is H, U is -O-T-R* and U' is hydrogen; (i) optionally treating the 3-hydroxy group of the product compound from step (e) having the formula (III) wherein R is as defined previously and RP is H, U is hydroxy and U' is hydrogen sequentially with an excess of NaH, CS2 and CH3I to form a 3-O-xanthate intermediate which is treated with Bu3SnH in the presence of a radical initiator to give the desired compound of formula (HI) wherein RP, U and U' are hydrogen; and (j) optionally deprotecting, and isolating the desired compound of formula (III). In the process for preparing compounds of formula (HI), in step (f) the reagent L-T-R 1 is selected from the group consisting of: (e-i) halogen-C(O)-Rt; (e-ii) O-(C(O)-R t ) 2 ; (e-iii) O-(C(O)-O-R t ) 2 ; (e-iv) halogen-CH 2 -R t ; (e-v) alkali metal hydride followed by CS2 then followed by halogen-R 1 ; (e-vi) O=C=N-R t ; (e-vii) carbonyl diimidazole foUowed by N(R S )H-R l ; (e-viin) Cl-S(O) n -O-R t ; (e-ix) Cl-P(O)(OR r )n-_ . (e-x) Cl-SO2-N(Rs)-Rt; Alternately, in the process for preparing compounds of formula (HI), in step (f) the reagent L-T-R 1 is in the presence of base is replaced with 3,4-dihydro-2H-pyran in the presence of a acid catalyst. Another aspect of the invention is a process for preparing a compound of formula (IV) wherein Rp, R and U are as defined above; the method comprising: (a) optionally treating a compound having the formula 14 wherein R is as defined above and Rp is a hydroxy protecting group, with carbonyldiimidazole and sodium hexamethyldisilazide for a short time at about -30 °C to give a compound having the formula 29 (b) optionally treating a compound having the formula J_4 as shown in Step (a) with an alkati metal hydride and a carbonylating agent selected from the group consisting of phosgene, diphosgene and triphosgene under anhydrous conditions with careful control of the amount of base present in order to prevent base catalyzed decarboxylation to give a compound having the formula 29 as shown in Step (a); (c) treating hydrolytically with acid a compound having the formula 29 to give a compound of formula (IV) wherein U is hydroxy and Rp is a hydroxy protecting group, optionally followed by converting the compound having the natural (3S) isomeric configuration into the compound having the non-natural (3R) isomeric configuration by oxidation of the 3-hydroxyl group and selective reduction of the 3-oxo group to give the non-natural (3R) isomer; (d) optionally treating a compound of formula (IV) wherein U is hydroxy and RP is a hydroxy protecting group (a compound from Step (c)) with an excess of NaH in an aprotic solvent followed by reaction of the intermediate anion with CS and CH3I to form a xanthate intermediate which is then treated with B_3SnH under an inert atmosphere in the presence of a catalytic amount of a suitable radical initiator to give the desired compound of formula (IV) wherein U is hydrogen and RP is a hydroxy protecting group; (e) optionally treating a compound of formula (IV) wherein U is hydroxy and RP is a hydroxy protecting group (a compound from Step (c)) with base and a reagent L-T-R 1 , wherein T and R l are as previously defined, and L is a suitable reactive leaving group to give the desired compound of formula (IV) wherein U is O-T-R 1 and RP is a hydroxy protecting group; (f) optionally deprotecting, and isolating the desired compound of formula (IV). In the process for preparing compounds of formula (IV), in step (e) the reagent L-T-R 1 is selected from the group consisting of: (e-i) halogen-C(O)-R l ; (e-ii) O-(C(O)-R t ) 2 ; (e-iii) O-(C(O)-O-R t ) 2 ; (e-iv) halogen-CH2-R t ; (e-v) alkali metal hydride followed by CS2 then followed by halogen-R 1 ; (e-vi) O=C=N-R , (e-vii) carbonyl diimidazole foUowed by N(R S )H-R l ; (e-viiii) Cl-S(O)n-O-R l ; (e-ix) Cl-P(O)(OR r )n-R t ; (e-x) Cl-SO 2 -N(R s )-R t ; Alternately, in the process for preparing compounds of formula (IV), in step (e) the reagent L-T-R 1 is in the presence of base is replaced with 3,4-dihydro-2H-pyran in the presence of a acid catalyst. Another aspect of the invention is a process for preparing a compound of formula (V) wherein Rp, R and U are as defined above, the method comprising: (a) treating a compound having the formula .14 wherein R is as defined above and Rp is a hydroxy protecting group, with a reagent selected from the group consisting of (i) formaldehyde in the presence of an acid and (ii) chloroiodomethane in the presence of base, to give a compound having the formula 33 (b) treating hydrolytically with acid a compound from Step (a) having the formula 33. to give a compound of formula (V) wherein U is hydroxy and Rp is a hydroxy protecting group, optionally foUowed by converting the compound having the natural (3S) isomeric configuration into the compound having the non-natural (3R) isomeric configuration by oxidation of the 3- hydroxyl group and selective reduction of the 3-oxo group to give the non-natural (3R) isomer; (c) optionaUy treating a compound of formula (V) wherein U is hydroxy and RP is a hydroxy protecting group (a compound from Step (b)) with an excess of NaH in an aprotic solvent followed by reaction of the intermediate anion with CS2 and CH3I to form a xanthate intermediate which is then treated with Bu3SnH under an inert atmosphere in the presence of a catalytic amount of a suitable radical initiator to give the desired compound of formula (V) wherein U is hydrogen and RP is a hydroxy protecting group; (d) optionaUy treating a compound of formula (IV) wherein U is hydroxy and RP is a hydroxy protecting group (a compound from Step (b)) with base and a reagent L-T-R 1 , wherein T and R t are as previously defined, and L is a suitable reactive leaving group to give the desired compound of formula (V) wherein U is O-T-R 1 and RP is a hydroxy protecting group; (e) optionally deprotecting, and isolating the desired compound of formula (V). In the process for preparing compounds of formula (V), in step (d) the reagent L-T-R 1 is selected from the group consisting of: (e-i) halogen-C(O)-R l ; (e-ii) O-(C(O)-R t ) 2 ; (e-iii) O-(C(O)-O-R t )2; (e-iv) halogen-CH 2 -R . (e-v) alkali metal hydride followed by CS 2 then followed by halogen-R 1 ; (e-vi) O=C=N-R t ; (e-vii) carbonyl diimidazole foUowed by N(R S )H-R l ; (e-viπi) Cl-S On-O-R 1 ; (e-ix) Cl-P(O)(OR r ) n -R . (e-x) Cl-SO 2 -N(Rs)-R . Alternately, in the process for preparing compounds of formula (V), in step (d) the reagent L-T-R 1 in the presence of base is replaced with 3,4-dihydro-2H-pyran in the presence of a acid catalyst. Definitions As used throughout this specification and the appended claims, the foUowing terms have the meanings specified. The terms "Cι-C3-alkyl", "Cι-C6-alkyl", and "Cι-Ci2-alkyl" as used herein refer to saturated, straight- or branched-chain hydrocarbon radicals derived from a hydrocarbon moiety containing between one and three, one and six, and one and twelve carbon atoms, respectively, by removal of a single hydrogen atom. Examples of Cι-C3-alkyl radicals include methyl, ethyl, propyl and isopropyl, examples of Cι-C6-alkyl radicals include, but are not Hmited to, methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, neopentyl and n-hexyl. Examples of Ci- Ci2-alkyl radicals include, but are not hmited to, all the foregoing examples as well as n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl and n-docecyl. The term "C1-C6- alkoxy" as used herein refers to an Cι-C6-alkyl group, as previously defined, attached to the parent molecular moiety through an oxygen atom. Examples of -C6- alkoxy, but are not hmited to, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, tert-butoxy, neo-pentoxy and n-hexoxy. The term "Cι-Ci2-alkenyl" denotes a monovalent group derived from a hydrocarbon moiety containing from two to twelve carbon atoms and having at least one carbon-carbon double bond by the removal of a single hydrogen atom. Alkenyl groups include, for example, ethenyl, propenyl, butenyl, l-methyl-2-buten-l-yl, and the like. The term "Cι-Ci2-alkynyl" as used herein refers to a monovalent group derived from a hydrocarbon containing from two to twelve carbon atoms and having at least one carbon- carbon triple bond by the removal of a single hydrogen atom. Representative alkynyl groups include ethynyl, 2-propynyl (propargyl), 1-propynyl and the like. The term "alkylene" denotes a divalent group derived from a straight or branched chain saturated hydrocarbon by the removal of two hydrogen atoms, for example methylene, 1 ,2- ethylene, 1,1-ethylene, 1,3-propylene, 2,2-dimethylpropylene, and the like. The term "Cι-C3-alkylamino" as used herein refers to one or two Cι-C3-alkyl groups, as previously defined, attached to the parent molecular moiety through a nitrogen atom. Examples of Cι-C3-alkylamino include, but are not limited to methylamino, dimethylamino, ethylamino, diethylamino, and propylamino. The term "oxo" denotes a group wherein two hydrogen atoms on a single carbon atom in an alkyl group as defined above are replaced with a single oxygen atom (i.e. a carbonyl group). The term "aprotic solvent" as used herein refers to a solvent that is relatively inert to proton activity, i.e., not acting as a proton-donor. Examples include, but are not limited to, hydrocarbons, such as hexane and toluene, for example, halogenated hydrocarbons, such as, for example, methylene chloride, ethylene chloride, chloroform, and the like, heteroaryl compounds, such as, for example, tetrahydrofuran and N-methylpyrrolidinone, and ethers such as diethyl ether, bis-methoxymethyl ether. Such compounds are weU known to those skilled in the art, and it wiU be obvious to those skilled in the art that individual solvents or mixtures thereof may be preferred for specific compounds and reaction conditions, depending upon such factors as the solubiUty of reagents, reactivity of reagents and preferred temperature ranges, for example. Further discussions of aprotic solvents may be found in organic chemistry textbooks or in speciaUzed monographs, for example: Organic Solvents Physical Properties and Methods of Purification. 4th ed., edited by John A. Riddick et al., Vol. II, in the Techniques of Chemistry Series, John WUey & Sons, NY, 1986. The term "aryl" as used herein refers to a mono- or bicycUc carbocyclic ring system having one or two aromatic rings including, but not limited to, phenyl, naphthyl, tetrahydronaphthyl, indanyl, indenyl and the like. Aryl groups (including bicycUc aryl groups) can be unsubstituted or substituted with one, two or three substituents independently selected from loweralkyl, substituted loweralkyl, haloalkyl, alkoxy, thioalkoxy, amino, alkylamino, dialkylamino, acylamino, cyano, hydroxy, halo, mercapto, nitro, carboxaldehyde, carboxy, alkoxycarbonyl and carboxamide. In addition, substituted aryl groups include tetrafluorophenyl and pentafluorophenyl. The term "C3-Ci2-cycloalkyl" denotes a monovalent group derived from a monocyctic or bicycUc saturated carbocycUc ring compound by the removal of a single hydrogen atom. Examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo[2.2.1]heptyl, and bicyclo[2.2.2]octyl. The terms "halo" and "halogen" as used herein refer to an atom selected from fluorine, chlorine, bromine and iodine. The term "alkylamino" refers to a group having the structure -NHR' wherein R' is alkyl, as previously defined, Examples of alkylamino include methylamino, ethylamino, iso- propylamino and the like. The term "dialkylamino" refers to a group having the structure -NR'R" wherein R' and R" are independently selected from alkyl, as previously defined. Additionally, R' and R" taken together may optionaUy be -(CH2)k- where k is an integer of from 2 to 6. Examples of dialkylamino include, dimethylamino, diethylaminocarbonyl, methylethylamino, piperidino, and the like. The term "haloalkyl" denotes an alkyl group, as defined above, having one, two, or three halogen atoms attached thereto and is exemplified by such groups as chloromethyl, bromoethyl, trifluoromethyl, and the like. The term "alkoxycarbonyl" represents an ester group; i.e. an alkoxy group, attached to the parent molecular moiety through a carbonyl group such as methoxycarbonyl, ethoxycarbonyl, and the like. The term "thioalkoxy" refers to an alkyl group as previously defined attached to the parent molecular moiety through a sulfur atom. The term "carboxaldehyde" as used herein refers to a group of formula -CHO. The term "carboxy" as used herein refers to a group of formula -CO2H. The term "carboxamide" as used herein refers to a group of formula -CONHR'R" wherein R' and R" are independently selected from hydrogen or alkyl, or R' and R" taken together may optionally be -(CH2)k- where k is an integer of from 2 to 6. The term "heteroaryl", as used herein, refers to a cyclic aromatic radical having from five to ten ring atoms of which one ring atom is selected from S, O and N; zero, one or two ring atoms are additional heteroatoms independently selected from S, O and N; and the remaining ring atoms are carbon, the radical being joined to the rest of the molecule via any of the ring atoms, such as, for example, pyridyl, pyrazinyl, pyrimidinyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, thiadiazolyl, oxadiazolyl, thiophenyl, furanyl, quinolinyl, isoquinolinyl, and the like. The term "heterocycloalkyl" as used herein, refers to a non-aromatic partially unsaturated or fuUy saturated 3- to 10-membered ring system, which includes single rings of 3 to 8 atoms in size and bi- or tri-cyclic ring systems which may include aromatic six-membered aryl or heteroaryl rings fused to a non-aromatic ring. These heterocycloalkyl rings include those having from one to three heteroatoms independently selected from oxygen, sulfur and nitrogen, in which the nitrogen and sulfur heteroatoms may optionally be oxidized and the nitrogen heteroatom may optionally be quaternized. Representative heterocycles include, but are not hmited to, pyrrolidinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, piperidinyl, piperazinyl, oxazoUdinyl, isoxazolidinyl, morpholinyl, thiazolidinyl, isothiazolidinyl, and tetrahydrofuryl. Specific heterocycloalkyl rings considered useful in preparing compounds of the invention include: 3-methyl-4-(3-methylphenyl)piperazine, 3-methylpiperidine, 4-(bis-(4- fluorophenyl)methyl)piperazine, 4-(diphenylmethyl)piperazine, 4-(ethoxycarbonyl)piperazine, 4-(ethoxycarbonylmethyl)piperazine, 4-(phenylmethyl)piperazine, 4-( 1 -phenylethyl)piperazine, 4-( 1 , 1 -dimethylethoxycarbonyl)piperazine, 4-(2-(bis-(2-propenyl)amino)ethyl)piperazine, 4- (2-(diethylamino)ethyl)piperazine, 4-(2-chlorophenyl)piperazine, 4-(2-cyanophenyl)piperazine, 4-(2-ethoxyphenyl)piperazine, 4-(2-ethylphenyl)piperazine, 4-(2-fluorophenyl)piperazine, 4- (2-hydroxyethyl)piperazine, 4-(2-methoxyethyl)piperazine, 4-(2-methoxyphenyl)piperazine, 4- (2-methylphenyl)piperazine, 4-(2-methylthiophenyl)piperazine, 4-(2-nitrophenyl)piperazine, 4- (2-nitrophenyl)piperazine, 4-(2-phenylethyl)piperazine, 4-(2-pyridyl)piperazine, 4-(2- pyrimidinyDpiperazine, 4-(2,3-dimethylphenyl)piperazine, 4-(2,4-difluorophenyl)piperazine, 4-(2,4-dimethoxyphenyl)piperazine, 4-(2,4-dimethylphenyl)piperazine, 4-(2,5- dimethylphenyι)piperazine, 4-(2,6-dimethylphenyl)piperazine, 4-(3-chlorophenyl)piperazine, 4-(3-methylphenyl)piperazine, 4-(3-trifluoromethylphenyl)piperazine, 4-(3,4- dichlorophenyl)piperazine, 4-(3,4-dimethoxyphenyl)piperazine, 4-(3,4- dimethylphenyl)piperazine, 4-(3,4-methylenedioxyphenyl)piperazine, 4-(3,4,5- trimethoxyphenyl)piperazine, 4-(3,5-dichlorophenyl)piperazine, 4-(3,5- dimethoxyphenyl)piperazine, 4-(4-(phenylmethoxy)phenyl)piperazine, 4-(4-( 1,1- dimethylethyl)phenylmethyl)piperazine, 4-(4-chloro-3-trifluoromethylphenyl)piperazine, 4-(4- chlorophenyl)-3-methylpiperazine, 4-(4-chlorophenyl)piperazine, 4-(4- chlorophenyl)piperazine, 4-(4-chlorophenylmethyl)piperazine, 4-(4-fluorophenyl)piperazine, 4-(4-methoxyphenyl)piperazine, 4-(4-methylphenyl)piperazine, 4-(4-nitrophenyl)piperazine, 4- (4-trifluoromethylphenyl)piperazine, 4-cyclohexylpiperazine, 4-ethylpiperazine, 4-hydroxy-4- (4-chlorophenyl)methylpiperidine, 4-hydroxy-4-phenylpiperidine, 4-hydroxypyrroUdine, 4- methylpiperazine, 4-phenylpiperazine, 4-piperidinylpiperazine, 4-((2- furanyl)carbonyl)piperazine, 4-((l,3-dioxolan-5-yl)methyl)piperazine, 6-fluoro- 1,2,3,4- tetrahydro-2-methylquinoline, 1,4-diazacycloheptane, 2,3-dihydroindolyl, 3,3- dimethylpiperidine, 4,4-ethylenedioxypiperidine, 1,2,3,4-tetrahydroisoquinoline, 1,2,3,4- tetrahydroquinohne, azacyclooctane, decahydroquinoUne, piperazine, piperidine, pyrroUdine, thiomorpholine, and triazole. The term "heteroarylalkyl" as used herein, refers to a heteroaryl group as defined above attached to the parent molecular moiety through an alkylene group wherein the alkylene group is of one to four carbon atoms. "Hydroxy-protecting group", as used herein, refers to an easily removable group which is known in the art to protect a hydroxyl group against undesirable reaction during synthetic procedures and to be selectively removable. The use of hydroxy-protecting groups is well known in the art for protecting groups against undesirable reactions during a synthetic procedure and many such protecting groups are known, cf., for example, T.H. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis, 2nd edition, John Wiley & Sons, New York (1991). Examples of hydroxy-protecting groups include, but are not hmited to, methylthiomethyl, tert-dimethylsilyl, tert-butyldiphenylsUyl, ethers such as methoxymethyl, and esters including acetyl benzoyl, and the like. The term "ketone protecting group", as used herein, refers to an eashy removable group which is known in the art to protect a ketone group against undesirable reactions during synthetic procedures and to be selectively removable. The use of ketone-protecting groups is weU known in the art for protecting groups against undesirable reactions during a synthetic procedure and many such protecting groups are known, cf, for example, T.H. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis, 2nd edition, John Wiley & Sons, New York (1991). Examples of ketone-protecting groups include, but are not hmited to, ketals, oximes, O-substituted oximes for example O-benzyl oxime, O-phenylthiomethyl oxime, 1- isopropoxycyclohexyl oxime, and the like. A the term "protected-hydroxy" refers to a hydroxy group protected with a hydroxy protecting group, as defined above, including benzoyl, acetyl, trimethylsUyl, triethylsilyl, methoxymethyl groups, for example. The term "protogenic organic solvent" as used herein refers to a solvent that tends to provide protons, such as an alcohol, for example, methanol, ethanol, propanol, isopropanol, butanol, t-butanol, and the like. Such solvents are weU known to those skilled in the art, and it will be obvious to those skilled in the art that individual solvents or mixtures thereof may be preferred for specific compounds and reaction conditions, depending upon such factors as the solubtiity of reagents, reactivity of reagents and preferred temperature ranges, for example. Further discussions of protogenic solvents may be found in organic chemistry textbooks or in specialized monographs, for example: Organic Solvents Physical Properties and Methods of Purification. 4th ed., edited by John A. Riddick et al., Vol. π, in the Techniques of Chemistry Series, John Wiley & Sons, NY, 1986. The term "substituted aryl" as used herein refers to an aryl group as defined herein substituted by independent replacement of one, two or three of the hydrogen atoms thereon with Cl, Br, F, I, OH, CN, Cι-C3-alkyl, Cι-C6-alkoxy, Cι-C6-alkoxy substituted with aryl, haloalkyl, thioalkoxy, amino, alkylamino, dialkylamino, mercapto, nitro, carboxaldehyde, carboxy, aUcoxycarbonyl and carboxamide. In addition, any one substitutent may be an aryl, heteroaryl, or heterocycloalkyl group. Also, substituted aryl groups include tetrafluorophenyl and pentafluorophenyl. The term "substituted heteroaryl" as used herein refers to a heteroaryl group as defined herein substituted by independent replacement of one, two or three of the hydrogen atoms thereon with Cl, Br, F, I, OH, CN, Cι-C3-alkyl, Cι-C6-alkoxy, Cι-C6-alkoxy substituted with aryl, haloalkyl, thioalkoxy, amino, alkylamino, dialkylamino, mercapto, nitro, carboxaldehyde, carboxy, alkoxycarbonyl and carboxamide. In addition, any one substitutent may be an aryl, heteroaryl, or heterocycloalkyl group. The term "substituted heterocycloalkyl" as used herein, refers to a heterocycloalkyl group, as defined above, substituted by independent replacement of one, two or three of the hydrogen atoms thereon with Cl, Br, F, I, OH, CN, Cι-C3-alkyl, Cι-C6-alkoxy, -C6- alkoxy substituted with aryl, haloalkyl, thioalkoxy, amino, alkylamino, dialkylamino, mercapto, nitro, carboxaldehyde, carboxy, alkoxycarbonyl and carboxamide. In addition, any one substitutent may be an aryl, heteroaryl, or heterocycloalkyl group. Numerous asymmetric centers may exist in the compounds of the present invention. Except where otherwise noted, the present invention contemplates the various stereoisomers and mixtures thereof. Accordingly, whenever a bond is represented by a wavy line, it is intended that a mixture of stereo-orientations or an individual isomer of assigned or unassigned orientation may be present. As used herein, the term "pharmaceuticaUy acceptable salt" refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well known in the art For example, S. M. Berge, et al. describe pharmaceutically acceptable salts in detail in Pharmaceutical Sciences. 66: 1-19 (1977), incorporated herein by reference. The salts can be prepared in situ during the final isolation and purification of the compounds of the invention, or separately by reacting the free base function with a suitable organic acid. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid or by using other methods used in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate salts, and the like. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceuticaUy acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as hahde, hydroxide, carboxylate, sulfate, phosphate, nitrate, loweralkyl sulfonate and aryl sulfonate. As used herein, the term "pharmaceuticaUy acceptable ester" refers to esters which hydrolyze in vivo and include those that break down readUy in the human body to leave the parent compound or a salt thereof. Suitable ester groups include, for example, those derived from pharmaceutically acceptable aliphatic carboxyhc acids, particularly aUcanoic, alkenoic, cycloalkanoic and alkanedioic acids, in which each alkyl or alkenyl moiety advantageously has not more than 6 carbon atoms. Examples of particular esters includes formates, acetates, propionates, butyrates, acrylates and ethylsuccinates. The term "pharmaceutically acceptable prodrugs" as used herein refers to those prodrugs of the compounds of the present invention which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals with undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit/risk ratio, and effective for their intended use, as well as the zwitterionic forms, where possible, of the compounds of the invention. The term "prodrug" refers to compounds that are rapidly transformed in vivo to yield the parent compound of the above formula, for example by hydrolysis in blood. A thorough discussion is provided in T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems. Vol. 14 of the A.C.S. Symposium Series, and in Edward B. Roche, ed., Bioreversible Carriers in Drug Design. American Pharmaceutical Association and Pergamon Press, 1987, both of which are incorporated herein by reference. Antibacterial Activity Representative compounds of the present invention were assayed in vitro for antibacterial activity as foUows: Twelve petri dishes containing successive aqueous dilutions of the test compound mixed with 10 mL of sterihzed Brain Heart Infusion (BHI) agar (Difco 0418-01-5) were prepared. Each plate was inoculated with 1:100 (or 1:10 for slow-growing strains, such as Micrococcus and Streptococcus) dilutions of up to 32 different microorganisms, using a Steers replicator block. The inoculated plates were incubated at 35- 37 °C for 20 to 24 hours. In addition, a control plate, using BHI agar containing no test compound, was prepared and incubated at the beginning and end of each test. An additional plate containing a compound having known susceptibility patterns for the organisms being tested and belonging to the same antibiotic class as the test compound was also prepared and incubated as a further control, as well as to provide test-to-test comparability. Erythromycin A was used for this purpose. After incubation, each plate was visually inspected. The minimum inhibitory concentration (MIC) was defined as the lowest concentration of drug yielding no growth, a slight haze, or sparsely isolated colonies on the inoculum spot as compared to the growth control. The results of this assay, shown below in Table 2 demonstrate the antibacterial activity of the compounds of the invention. Table 1 Antibacterial Activity (MIC's) of Selected Compounds Microorganism Organism Ery. A code Staphylococcus aureus ATCC 6538P AA 0.2 Staphylococcus aureus A5177 BB 3.1 Staphylococcus aureus A-5278 CC >100 Staphylococcus aureus CMX 642A DD 0.39 Staphylococcus aureus NCTC10649M EE 0.39 Staphylococcus aureus CMX 553 FF 0.39 Staphylococcus aureus 1775 GG > 100 Staphylococcus epidermidis 3519 HH 0.39 Enterococcus faecium ATCC 8043 II 0.05 Streptococcus bovis A-5169 JJ 0.02 Streptococcus agalactiae CMX 508 KK 0.05 Streptococcus pyogenes EES61 LL 0.05 Streptococcus pyogenes 930 MM > 100 Streptococcus pyogenes PIU 2548 NN 6.2 Micrococcus luteus ATCC 9341 OO 0.05 Micrococcus luteus ATCC 4698 PP 0.2 Escherichia coU JUHL QQ > 100 Escherichia coli SS RR 0.78 Escherichia coU DC-2 S S > 100 Candida albicans CCH 442 TT >100 Mycobacterium smegmatis ATCC 1 14 U U 3.1 Nocardia Asteroides ATCC9970 W 0.1 Haemophilis Influenzae DILL AMP R WW 4 Streptococcus Pheumoniae ATCC6303 XX 0.06 Streptococcus Pheumoniae GYR 1 171 YY 0.06 Streptococcus Pheumoniae 5979 ZZ >128 Streptococcus Pheumoniae 5649 ZZA 16 * missing data is indicated by "-" Table 1 , continued Antibacterial Activity (MIC's) of Selected Compounds Organism Example Example Example Example Example Example Example code 3 4 5 6 7 8 9 0.2 100 25 25 1.56 0.78 0.78 AA BB 3.1 > 100 25 12.5 3.1 0.78 0.78 CC >100 >100 25 > 100 >100 > 100 >100 0.2 DD >100 25 25 1.56 1.56 1.56 EE 0.39 100 25 25 3.1 0.78 0.78 FF 0.2 100 12.5 25 3.1 0.78 0.78 GG >100 >100 25 >100 >100 > 100 >100 HH 0.2 100 12.5 12.5 1.56 1.56 1.56 π 0.1 100 25 6.2 0.78 0.39 0.39 0.02 JJ 3.1 1.56 0.78 0.39 0.02 0.05 KK 0.02 12.5 3.1 1.56 0.1 0.1 0.1 0.02 LL 3.1 3.1 0.39 0.1 0.01 0.01 MM 1.56 >100 6.2 >100 12.5 50 100 NN 0.39 6.2 3.1 3.1 0.78 0.39 0.39 OO 0.05 3.1 1.56 0.78 0.39 0.1 0.05 PP 0.1 6.2 3.1 3.1 0.39 0.2 0.39 50 > 100 >100 >100 >100 >100 > 100 QQ RR 1.56 6.2 > 100 3.1 25 0.78 0.39 SS 100 > 100 >100 >100 >100 >100 , 100 TT >100 >100 25 > 100 >100 > 100 >100 UU 0.1 3.1 3.1 3.1 0.39 6.2 0.78 w 0.05 3.1 6.2 3.1 6.2 0.2 0.39 ww 2 128 >128 >128 >128 16 4 XX 0.03 16 4 8 1 0.12_ 5 0.25 1 32 128 32 16 2 1 YY ZZ 16 >128 8 >128 16 32 64 ZZA 1 16 8 8 2 0.5 0.5 * missing data is indicated by "- Table 1 [. continued Antibacterial Activitv (MIC's) of Selected Compounds Organism Example Example Example Example Example Example Example code 10 11 12 13 14 15 16 AA 0.39 0.78 > 100 0.39 3.1 0.78 0.39 BB 0.39 0.78 >100 0.39 6.2 0.78 0.2 CC >100 >100 >100 >100 >100 >100 50 DD 0.39 0.78 >100 0.39 3.1 0.78 0.39 EE 0.78 0.78 0.39 3.1 0.78 0.39 FF 0.78 0.78 >100 0.39 3.1 0.78 0.2 GG >100 100 >100 50 >100 > 100 25 HH 0.78 0.78 >100 0.39 3.1 0.78 0.39 π 0.39 0.39 >100 0.2 0.78 0.39 0.1 JJ 0.1 0.1 50 0.05 0.2 0.05 0.02 KK 0.1 0.1 50 0.01 0.2 0.02 0.05 LL 0.2 0.1 12.5 0.01 0.1 0.02 0.05 MM 25 25 50 6.2 25 25 6.2 NN 0.78 0.39 > 100 0.39 1.56 0.39 0.39 OO 0.2 0.1 50 0.1 0.78 0.2 0.1 PP 0.39 0.78 >100 0.39 1.56 0.78 0.39 > 100 >100 >100 > 100 >100 >100 >100 QQ RR 12.5 12.5 >100 6.2 25 6.2 6.2 SS > 100 >100 >100 >100 >100 >100 >100 TT > 100 > 100 >100 >100 > 100 >100 50 UU 0.78 0.78 100 0.39 3.1 3.1 0.39 w 1.56 1.56 >100 1.56 6.2 6.2 0.39 ww 16 >128 >128 4 >128 64 8 XX 0.03 0.25 4 0.125 0.5 0.25 0.125 YY 8 32 >128 4 16 16 4 zz 32 32 8 16 32 64 16 ZZA 1 1 4 0.5 2 1 1 missing data is indicated by "-" Table 1 , continued Antibacterial Activitv (MIC's) of Selected Compounds Organism Example Example Example Example Example Example Example code 17 18 19 21 22 23 24 AA 0.78 0.39 1.56 0.78 1.56 0.78 0.78 BB 1.56 0.39 1.56 0.78 1.56 0.39 0.78 CC > 100 > 100 >100 50 >100 >100 50 DD 1.56 0.39 3.1 0.78 1.56 0.78 1.56 EE 1.56 0.39 1.56 0.78 1.56 0.78 1.56 FF 1.56 0.39 1.56 0.78 1.56 0.78 0.78 GG 25 > 100 >100 50 >100 >100 25 HH 1.56 0.39 1.56 0.78 1.56 0.78 0.78 π 0.39 0.39 0.78 0.39 0.78 0.1 0.39 JJ 0.05 0.1 0.1 0.2 0.39 0.05 0.2 KK 0.05 0.1 0.39 0.2 0.39 0.1 0.39 0.2 0.1 LL 0.1 0.2 0.39 0.05 0.2 6.2 MM >100 > 100 6.2 12.5 100 12.5 NN 0.78 0.39 0.39 0.39 1.56 0.39 0.39 0.39 0.1 OO 0.1 0.2 0.39 0.05 0.2 PP 0.78 0.39 0.39 0.78 1.56 0.39 0.39 >100 >100 >100 >100 > 100 >100 >100 QQ RR >100 6.2 1.56 6.2 12.5 3.1 3.1 SS >100 >100 >100 >100 > 100 > 100 >100 TT >100 > 100 > 100 >100 >100 >100 25 UU 1.56 0.78 1.56 0.78 3.1 0.39 0.39 w 6.2 0.39 0.39 3.1 3.1 0.78 1.56 ww 64 16 32 >128 64 32 16 0.5 0.25 XX 0.25 0.25 0.25 0.25 0.25 YY 16 8 8 8 16 16 8 zz 16 >128 > 128 16 32 64 16 2 1 ZZA 1 1 2 0.5 1 * missing data is indicated by "-" Table 1 , continued Antibacterial Activitv (MIC's) of Selected Compounds Organism Example Example Example Example Example Example Example code 25 26 27 28 29 30 31 AA 0.39 0.78 0.39 0.39 0.2 0.39 0.39 BB 0.39 0.78 0.39 - - 0.2 0.39 CC >100 > 100 50 > 100 >100 >100 50 0.2 0.39 0.39 DD 0.39 0.78 0.39 0.39 EE 0.39 0.78 0.78 0.39 0.2 0.39 FF 0.39 0.78 0.39 0.39 0.39 0.2 0.39 GG >100 100 25 >100 >100 > 100 50 HH 0.39 0.78 0.39 0.39 0.78 0.39 0.39 π 0.2 0.39 0.39 0.2 0.2 0.2 0.2 JJ 0.02 0.05 0.05 <=0.005 0.01 0.05 0.05 KK 0.02 0.2 0.1 0.01 0.01 0.05 0.1 LL 0.01 0.05 0.05 0.01 0.02 0.02 0.01 MM 100 25 12.5 100 50 12.5 12.5 NN 0.39 0.39 0.39 0.2 0.39 0.2 0.39 OO 0.05 0.05 0.05 0.02 0.1 0.05 0.1 PP 0.39 0.39 0.39 0.2 0.39 0.2 0.2 >100 >100 >100 50 > 100 100 100 QQ RR 0.39 1.56 3.1 0.78 6.2 1.56 6.2 SS 100 >100 >100 >100 >100 >100 >100 TT >100 >100 >100 >100 >100 >100 > 100 UU 1.56 0.39 0.78 0.78 0.39 1.56 0.39 w 0.2 0.39 0.78 0.2 0.78 0.1 0.39 ww 32 8 4 8 32 4 8 XX 0.12! > 0.25 0.25 0.125 0.03 0.03 0.125 4 YY 2 2 2 8 1 2 zz >128 32 16 >128 64 32 16 ZZA 2 1 1 0.25 0.5 0.25 0.25 * missing data is indicated by "-" Table 1.. continued Antibacterial Activity MIC's) of Selected ComDOunds Organism Example Example Example 1 Example Example Example Example code 32 33 34 35 36 37 38 0.2 0.39 0.39 0.39 0.39 6.2 3.1 AA - BB 0.39 0.39 - - 6.2 3.1 CC 25 > 100 >100 50 50 >100 >100 DD 0.39 0.39 0.39 0.39 0.39 6.2 3.1 EE 0.39 0.39 0.39 0.78 6.2 3.1 FF 0.39 0.39 0.39 0.39 0.39 6.2 3.1 25 GG >100 >100 25 50 >100 > 100 HH 0.39 0.2 0.39 0.39 0.39 6.2 3.1 π 0.39 0.39 0.39 0.39 0.39 3.1 0.78 JJ 0.1 0.1 0.2 0.2 - 0.39 0.2 KI0.1 0.01 0.2 0.2 0.1 1.56 0.39 0.1 0.2 0.1 0.39 0.2 LL 0.1 0.02 6.2 12.5 6.2 6.2 12.5 >100 > 100 MM NN 0.39 0.2 0.39 0.39 0.39 6.2 3.1 0.2 0.05 0.1 0.2 0.1 0.78 0.39 OO PP 0.39 0.2 0.39 0.78 0.39 3.1 1.56 > 100 >100 >100 >100 > 100 >100 >100 QQ RR 12.5 3.1 6.2 100 12.5 12.5 12.5 SS > 100 >100 >100 >100 >100 >100 >100 TT > 100 > 100 > 100 >100 >100 >100 >100 UU 3.1 0.39 0.39 3.1 1.56 6.2 6.2 w 1.56 0.39 0.39 3.1 1.56 3.1 1.56 ww 8 2 4 16 128 >64 XX 0.25 0.12! 5 0.125 0.25 0.12! > 1 0.5 4 2 2 4 4 16 16 YY 8 >128 >64 ZZ 16 16 8 16 ZZA 1 0.25 0.25 1 0.5 8 8 * missing data is indicated by "-" Table 1. continued Antibacterial Activitv (MIC's of Selected ComDOunds Organism Example Example Example Example Example Example Example code 39 40 41 42 43 44 46 AA 1.56 25 0.2 0.39 0.39 0.78 0.39 BB 3.1 25 3.1 0.39 0.39 1.56 0.39 CC >100 50 >100 >100 100 100 >100 DD 1.56 50 0.39 0.39 0.39 0.78 0.39 EE 1.56 12.5 0.39 0.78 0.78 0.78 0.78 FF 1.56 25 0.39 0.39 0.78 0.78 0.39 GG >100 25 >100 >100 100 25 >100 HH 1.56 25 0.2 0.39 0.39 1.56 0.39 II 0.78 6.2 0.1 0.2 0.2 0.78 0.39 JJ 0.05 1.56 0.05 0.02 0.05 0.1 0.1 KK 0.1 3.1 0.05 0.1 0.1 0.1 0.2 LL 0.1 1.56 0.02 0.1 0.02 0.1 0.1 MM 25 12.5 > 100 12.5 50 12.5 25 NN 1.56 3.1 12.5 0.2 0.39 0.39 0.39 OO 0.39 3.1 0.05 0.1 0.1 0.1 0.1 PP 1.56 6.2 0.39 0.39 0.1 0.39 0.39 >100 > 100 50 >100 100 >100 > 100 QQ RR 25 25 0.78 3.1 3.1 3.1 0.78 SS > 100 >100 >100 >100 >100 >100 >100 TT >100 25 > 100 >100 100 >100 >100 UU 0.78 1.56 6.2 0.39 0.78 0.39 0.78 w 3.1 6.2 0.1 0.2 0.78 1.56 0.39 ww 64 >128 4 8 64 8 16 XX 0.5 4 0.125 i 0.03 0.25 0.5 0.25 YY 8 32 0.5 4 4 4 2 ZZ 64 16 >128 >64 64 16 >32 ZZA 2 4 16 0.25 1 1 1 * missing data is indicated by "-" Table 1. continued Antibacterial Activity (MIC's) of Selected Compounds Organism Example Example Example Example code 47 48 49 52 AA - 3.1 12.5 >100 BB - 3.1 12.5 >100 CC - 25 >100 >100 DD 3.1 3.1 25 >100 EE 3.1 3.1 25 > 100 FF 3.1 3.1 12.5 >100 GG >100 25 >100 >100 HH 3.1 3.1 25 >100 π 0.78 0.39 3.1 25 JJ 0.2 0.39 1.56 6.2 KK 0.2 0.39 1.56 12.5 LL 0.2 0.78 0.78 12.5 MM - - >100 > 100 NN 0.78 1.56 6.2 50 OO 0.39 0.39 3.1 12.5 PP 1.56 3.1 12.5 >100 > 100 > 100 >100 >100 QQ RR 0.78 6.2 50 50 SS >100 > 100 >100 >100 TT >100 >100 >100 >100 uu 3.1 3.1 12.5 50 w 0.39 1.56 3.1 25 ww 16 >128 >128 >128 XX 0.25 0.25 2 16 YY 4 32 128 128 zz 64 16 >128 >128 ZZA 1 1 8 32 missing data is indicated by "-" Pharmaceutical Compositions The pharmaceutical compositions of the present invention comprise a therapeutically effective amount of a compound of the present invention formulated together with one or more pharmaceutically acceptable carriers. As used herein, the term "pharmaceuticaUy acceptable carrier" means a non-toxic, inert solid, semi-solid or liquid fiUer, diluent, encapsulating material or formulation auxUiary of any type. Some examples of materials which can serve as pharmaceutically acceptable carriers are sugars such as lactose, glucose and sucrose; starches such as corn starch and potato starch; ceUulose and its derivatives such as sodium carboxymethyl ceUulose, ethyl ceUulose and ceUulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oU, cottonseed oil; safflower oil; sesame oU; olive oil; corn oU and soybean oil; glycols; such a propylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic sahne; Ringer's solution; ethyl alcohol, and phosphate buffer solutions, as well as other non- toxic compatible lubricants such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, releasing agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the composition, according to the judgment of the formulator. The pharmaceutical compositions of this invention can be administered to humans and other animals orally, rectally, parenteraUy, intracisternally, intravaginally, intiaperitoneally, topically (as by powders, ointments, or drops), bucally, or as an oral or nasal spray. Liquid dosage forms for oral administration include pharmaceuticaUy acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubiUzing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oUs (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, terrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents. Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterUe injectable solution, suspension or emulsion in a nontoxic parenterally acceptable dUuent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, U.S.P. and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionaUy employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid are used in the preparation of injec tables. The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use. In order to prolong the effect of a drug, it is often desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalUne or amorphous material with poor water solubUity. The rate of absorption of the drug then depends upon its rate of dissolution which, in turn, may depend upon crystal size and crystaUine form. Alternatively, delayed absorption of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle. Injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycoUde. Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controUed. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides) Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions which are compatible with body tissues. Compositions for rectal or vaginal administration are preferably suppositories which can be prepared by mixing the compounds of this invention with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol or a suppository wax which are solid at ambient temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound. Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and siUcic acid, b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrohdinone, sucrose, and acacia, c) humectants such as glycerol, d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain sUicates, and sodium carbonate, e) solution retarding agents such as paraffin, f) absorption accelerators such as quaternary ammonium compounds, g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, h) absorbents such as kaolin and bentonite clay, and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets and piUs, the dosage form may also comprise buffering agents. Solid compositions of a simUar type may also be employed as fiUers in soft and hard- fiUed gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and sheUs such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionaUy contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentiaUy, in a certain part of the intestinal tract, optionaUy, in a delayed manner. Examples of embedding compositions which can be used include polymeric substances and waxes. Solid compositions of a similar type may also be employed as fiUers in soft and hard- fiUed gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. The active compounds can also be in micro-encapsulated form with one or more excipients as noted above. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and sheUs such as enteric coatings, release controlUng coatings and other coatings well known in the pharmaceutical formulating art. In such sohd dosage forms the active compound may be admixed with at least one inert diluent such as sucrose, lactose or starch. Such dosage forms may also comprise, as is normal practice, additional substances other than inert dUuents, e.g., tableting lubricants and other tableting aids such a magnesium stearate and microcrystalhne ceUulose. In the case of capsules, tablets and piUs, the dosage forms may also comprise buffering agents. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentiaUy, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions which can be used include polymeric substances and waxes. Dosage forms for topical or transdermal administration of a compound of this invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or patches. The active component is admixed under sterile conditions with a pharmaceuticaUy acceptable carrier and any needed preservatives or buffers as may be required. Ophthalmic formulation, ear drops, eye ointments, powders and solutions are also contemplated as being within the scope of this invention. The ointments, pastes, creams and gels may contain, in addition to an active compound of this invention, excipients such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, sUicones, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof. Powders and sprays can contain, in addition to the compounds of this invention, excipients such as lactose, talc, sihcic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances. Sprays can additionaUy contain customary propellants such as chlorofluorohydrocarbons. Transdermal patches have the added advantage of providing controUed delivery of a compound to the body. Such dosage forms can be made by dissolving or dispensing the compound in the proper medium. Absorption enhancers can also be used to increase the flux of the compound across the skin. The rate can be controUed by either providing a rate controUing membrane or by dispersing the compound in a polymer matrix or gel. According to the methods of treatment of the present invention, bacterial infections are treated or prevented in a patient such as a human or lower mammal by administering to the patient a therapeuticaUy effective amount of a compound of the invention, in such amounts and for such time as is necessary to achieve the desired result. By a "therapeutically effective amount" of a compound of the invention is meant a sufficient amount of the compound to treat bacterial infections, at a reasonable benefit/risk ratio appUcable to any medical treatment. It wiU be understood, however, that the total daily usage of the compounds and compositions of the present invention wiU be decided by the attending physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any particular patient wiU depend upon a variety of factors including the disorder being treated and the severity of the disorder; the activity of the specific compound employed; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed; and like factors well known in the medical arts. The total daUy dose of the compounds of this invention administered to a human or other mammal in single or in divided doses can be in amounts, for example, from 0.01 to 50 mg/kg body weight or more usually from 0.1 to 25 mg/kg body weight. Single dose compositions may contain such amounts or submultiples thereof to make up the daily dose. In general, treatment regimens according to the present invention comprise administration to a patient in need of such treatment from about 10 mg to about 2000 mg of the compound(s) of this invention per day in single or multiple doses. Abbreviations Abbreviations which have been used in the descriptions of the scheme and the examples that foUow are: 9-BBN for 9-borabicyclo[3.3.1]nonane; AIBN for azobisisobutyronitrile; Bu3SnH for tributyltin hydride; CDI for carbonyldiimidazole; DBU for 1,8- diazabicyclo[5.4.0]undec-7-ene; DEAD for diethylazodicarboxylate; DMAP for 4- dimethylaminopyridine; DMF for dimethyl formamide; DPPA for diphenylphosphoryl azide; EtOAc for ethyl acetate; MeOH for methanol; NaHMDS for sodium hexamethyldisUazane; NaN (TMS)2 for sodium bis(trimethylsUyl)amide; NMMO for N-methylmorphoUne N-oxide; TEA for triethylamine; THF for tetrahydrofuran; TPP for triphenylphosphine. Preparation of the Compounds of the Invention The compounds of the present invention are prepared according to the representative methods described in Schemes 1-10 below. The groups U, U', V, W, X, Y, Z, R, R w , and RP of the compounds shown in the schemes are as defined previously for compounds of formulas (I) - (V), unless otherwise noted below. Scheme 1 Ulustrates the preparation of compounds 6, which are useful as starting materials for the preparation of compounds of formulas (I) - (V) of the invention. The preparation of protected erythromycin A is described in the following United States patents, US 4,990,602; US 4,331,803, US 4,680,368, and US 4,670,549 which are incorporated by reference. Also incorporated by reference is European Patent Application EP 260,938. In general, the C-9-carbonyl group of compound 1 is protected as an oxime, (V is =N-O-R 1 or =N-O-C(R 5 )(R 6 )-O-R 1 where R 1 is defined previously and R 5 and R 6 are each independently selected from the group consisting of (a) hydrogen, (b) unsubstituted Cι-Ci2-alkyl, (c) Ci- Ci2-alkyl substituted with aryl, and (d) Cι-Ci2-alkyl substituted with substituted aryl, or R 9 and R 10 taken together with the carbon to which they are attached form a C3-Ci2-cycloalkyl ring). An especiaUy preferred carbonyl protecting group V is O-(l-isopropoxycyclohexyl) oxime. The 2'- and 4"-hydroxy groups of 2 are protected by reaction with a suitable hydroxy protecting reagent, such as those described by T.W. Greene and P.G.M. Wuts in Protective Groups in Organic Synthesis, 2nd ed., John Wiley & Son, Inc., 1991, which is incorporated by reference. Hydroxy protecting groups include, for example, acetic anhydride, benzoic anhydride, benzyl chloroformate, hexamethyldisilazane, or a trialkylsUyl chloride in an aprotic solvent. Examples of aprotic solvents are dichloromethane, chloroform, DMF, tetrahydrofuran (THF), N-methyl pyrrolidinone, dimethylsulfoxide, diethylsulfoxide, N,N- dimethylformamide, N,N-dimethylacetamide, hexamethylphosphoric triamide, a mixture thereof or a mixture of one of these solvents with ether, tetrahydrofuran, 1 ,2-dimethoxyethane, acetonitrile, ethyl acetate, acetone and the like. Aprotic solvents do not adversely affect the reaction, and are preferably dichloromethane, chloroform, DMF, tetrahydrofuran (THF), N- methyl pyrrolidinone or a mixture thereof. Protection of 2'- and 4"-hydroxy groups of 2 may be accomplished sequentially or simultaneously to provide compound 3 where RP is a hydroxy protecting group. A preferred protecting group RP is trimethylstiyl. The 6-hydroxy group of compound 3 is then alkylated by reaction with an alkylating agent in the presence of base to give compound 4. Alkylating agents include alkyl chlorides, bromides, iodides or alkyl sulfonates. Specific examples of alkylating agents include allyl bromide, propargyl bromide, benzyl bromide, 2-fluoroethyl bromide, 4-nitrobenzyl bromide, 4-chlorobenzyl bromide, 4-methoxybenzyl bromide, α-bromo-p-tolunitrile, cinnamyl bromide, methyl 4-bromocrotonate, crotyl bromide, l-bromo-2-pentene, 3-bromo-l-propenyl phenyl sulfone, 3-bromo-l-trimethylsilyl-l-propyne, 3-bromo-2-octyne, l-bromo-2-butyne, 2-picolyl chloride, 3-picolyl chloride, 4-picolyl chloride, 4-bromomethyl quinoline, bromoacetonitrile, epichlorohydrin, bromofluoromethane, bromonitromethane, methyl bromoacetate, methoxymethyl chloride, bromoacetamide, 2-bromoacetophenone, l-bromo-2-butanone, bromo chloromethane, bromomethyl phenyl sulfone, 1,3-dibromo-l-propene, and the like. Examples of alkyl sulfonates are: allyl O-tosylate, 3-phenylpropyl-O-trifluoromethane suffonate, n-butyl -O-methanesulfonate and the like. Examples of the solvents used are aprotic solvents such as dimethylsulfoxide, diethylsulfoxide, N,N-dimethylformamide, N,N- dimethylacetamide, N-methyl-2-pyrroUdone, hexamethylphosphoric triamide, a mixture thereof or a mixture of one of these solvents with ether, tetrahydrofuran, 1,2-dimethoxyethane, acetonitrile, ethyl acetate, acetone and the like. Examples of the base which can be used include potassium hydroxide, cesium hydroxide, tetraalkylammonium hydroxide, sodium hydride, potassium hydride, potassium isopropoxide, potassium tert-butoxide, potassium isobutoxide and the like. Schemes 7-9 below describe procedures for further elaboration of the 6-position moiety of the compounds of the invention. The deprotection of the 2'- and 4"-hydroxyl groups is then carried out according to methods described in literature, for example, by Greene and Wuts (op. cit.). The conditions used for the deprotection of the 2'- and 4"-hydroxyl groups usually results in the conversion of X to =N-OH. (For example, using acetic acid in acetonitrUe and water results in the deprotection of the 2'- and 4"-hydroxyl groups and the conversion of X from =N-O-R 1 or =N-O-C(R 5 )(R 6 )-O-R 1 ,where R 1 , R 5 and R 6 are as defined previously, to =N-OH.) If this is not the case, the conversion is carried out in a separate step. The deoximation reaction can be carried out according to the methods described in the literature, for example by Greene and Wuts (op. cit.) and others. Examples of the deoximating agent are inorganic sulfur oxide compounds such as sodium hydrogen sulfite, sodium pyrosulfate, sodium thiosulfate, sodium sulfate, sodium sulfite, sodium hydrosulfite, sodium metabisulfite, sodium dithionate, potassium thiosulfate, potassium metabisulfite and the like, and inorganic nitrite salts such as sodium nitrite or potassium nitrite. Examples of the solvents used are protic solvents such as water, methanol, ethanol, propanol, isopropanol, trimethylsilanol or a mixture of one or more of the mentioned solvents and the like. The deoximation reaction is more conveniently carried out in the presence of an organic acid such as formic acid, acetic acid and trifluoroacetic acid. The amount of acid used is from about 1 to about 10 equivalents of the amount of compound 5 used. In a preferred embodiment, the deoximation is carried out using an organic acid such as formic acid in ethanol and water to give the desired product 6. Scheme 2 illustrates the conversion of intermediate 6 to compounds of formula (I) of the invention. The cladinose moiety of macrolide 6 is removed either by mtid aqueous acid hydrolysis or by enzymatic hydrolysis to give 7. Representative acids include dUute hydrochloric acid, sulfuric acid, perchloric acid, chloroacetic acid, dichloroacetic acid or trifluoroacetic acid. Suitable solvents for the reaction include methanol, ethanol, isopropanol, butanol and the like. Reaction times are typically 0.5 to 24 hours. The reaction temperature is preferably -10 to 35 °C. Compound 7 is converted to ____ which is protected at the 2'-hydroxy position, by treatment with a suitable hydroxy protecting reagent such as acetic anhydride, benzoic anhydride, benzyl chloroformate or trialkylsUyl chloride in an aprotic solvent, as defined previously, preferably dichloromethane, chloroform, DMF, tetrahydrofuran (THF), N- methyl pyrrohdinone or a mixture thereof. Preferred protecting groups are trimethylsUyl, acetyl and benzoyl. Compounds 7 and 8 are compounds of formula (I). It is possible to reverse the order of the steps for removing the cladinose and protecting the 2'-hydroxy group without affecting the yield of the process. Compound 8 is then treated with an excess of NaH at from 0 to -30°C under an inert atmosphere in an aprotic solvent such as THF, foUowed by reaction of the intermediate anion with CS2 and CH3I at about -5 to 10°C, to form the xanthate intermediate 9, which is then treated with about 1.1-1.3 equivalents of Bu3SnH under an inert atmosphere in the presence of a catalytic amount of AIBN or other suitable radical initiator, in a solvent suitable for a free radical reaction, such as benzene or toluene, for example, at reflux conditions to afford the desired 3-deoxy compound JO, which is a compound of formula (I) wherein U is hydrogen. Treatment of compound 8 with a reagent L-T-R 1 , wherein T and R l are as previously defined, and L is a suitable reactive leaving group, such as a halogen, for example, in the presence of base gives compound I L These reactions are weU known to those skUled in the art. For example, to prepare compounds H wherein T is -C(O)-, having the formula O-C(O)-R l , compound 8 is reacted with the appropriate acyl hatide having the formula halogen-C(O)-R l or an acyl anhydride having the formula O-(C(O)-R t )2 in an aprotic solvent and in the presence of a tertiary organic amine base, such as triethylamine, dimethylaminopyridine, N-methylmorpholine, N- methylpyrrohdine, or the like, or an inorganic bases such as Na2CO3, K2CO3, NaH, KH, LiH, or the like, at a temperature from about 0 °C to about 150 °C. To prepare compounds H wherein T is -C(O)-O-, having the formula O-C(O)-O-R l , compound 8_ is reacted with the appropriate carbonate compound of the formula R t -O-C(O)-O- R l under similar conditions. To prepare compounds JJ. wherein T is -CH2-, having the formula O-CH2-R 1 , compound 8 is reacted with a strong base, such as an alkali metal hydride or hexamethyldisilazane, for example, followed by reaction with the appropriate alkyl halide having the formula halogen-CH2-R l . To prepare compounds JJ. wherein T is -C(S)-S-, having the formula O-C(S)-S-R l , compound 8 is reacted with a strong base, such as an alkali metal hydride or hexamethyldisilazane, for example, followed by reaction with CS2 then the appropriate organohalide having the formula halogen-R 1 . To prepare compounds ϋ wherein T is -C(O)-N(R s )-, wherein R s is H or Cι-C6-alkyl, having the formula O-C(O)-N(R s )-R l , compound 8. is treated with a strong base such as NaH, LiH, NaN(TMS)2, or the like, followed by a carbamoylating reagent, or 8 is reacted with the appropriate isocyanate having the formula O=C=N-R l in the presence of a tertiary amine base. Alternately, compound 8 may be reacted with a carbonyl compound such as carbonyl diimidazole or carbonyl bis(benzotriazole) followed by reaction of the intermediate thus formed with an amine having the formula N(R S )H-R l to prepare the desired compound. To prepare compounds H wherein T is -S(O) n -, wherein n is 0, 1 or 2, having the formula O-S(O) n -R l , compound 8. is reacted with the appropriate acid anhydride compound of the formula O-(S(O) n -R l )2 i n an aprotic solvent and in the presence of a tertiary organic amine base, such as triethylamine, dimethylaminopyridine, N-methylmorpholine, N- methylpyrrolidine, or the like, or an inorganic bases such as Na2CO3, K2CO3, NaH, KH, LiH, or the like, at a temperature from about 0 °C to about 150 °C. To prepare compounds JJ. wherein T is -S(O) n -, wherein n is 0, 1 or 2, having the formula O-S(O) n -O-R l , compound 8 is reacted with the appropriate acid chloride of the formula Cl-S(O) n -O-R l under similar conditions. To prepare compounds JJ. wherein T is -P(0)(0R r )n . wherein n is 0, 1 or 2, and R r is Cι-C6-alkyl, having the formula O-P(O)(OR r )n-R . compound H is reacted with the appropriate acid chloride of the formula Cl-P(O)(OR r )n-R t under similar conditions. To prepare compounds JJ. wherein T is -SO2-N(R s )-, wherein R s is as defined previously, having the formula O-SO2-N(R s )-R l , compound 8 is reacted with the appropriate acid chloride of the formula Cl-SO2-N(R s )-R t under similar conditions. To prepare compounds JJ. wherein T is a 2-tetrahydropyranyl heterocycloalkyl group, compound 8. is reacted with 3,4-dihydro-2H-pyτan in an aprotic solvent in the presence of a acid catalyst. The 2' hydroxy protecting group of compounds JO and JJ. may optionaUy be removed by standard methods to give the desired unprotected compounds of formula (I). When RP is an ester such as acetate or benzoate, the compound may be deprotected by treatment with methanol or ethanol. When RP is a trialkylsilyl group, the compound may be deprotected by treatment with fluoride in THF or acetonitrile. The 9-oxime derivatives of compounds JO and ϋ may optionally be prepared by reaction with hydroxylamine hydrochloride in the presence of base, or hydroxylamine in the presence of acid as described in U.S. Patent 5,274,085, to form the compounds of formula (I) wherein X is =N-OH or =N-O-R 1 wherein R 1 is H. Reaction with the substituted hydroxylamine NH2OR 1 , or NH2-O-C(R 5 )(R 6 )-O-R 1 results in the formation of compounds in which R 1 is other than H. Alternately, compounds wherein R 1 is other than H may be prepared by initial formation of the unsubstituted oxime as described above foUowed by reaction with R l X' wherein X' is a suitable leaving group such as halogen. The 9-amino derivatives of compounds JO and JJ . may optionally be prepared by preparing the 9-oxime, reducing the 9-oxime to the 9-amino compound by treatment with a borohydride reducing agent or hydrogen gas in the presence of a noble metal catalyst, then treatment of the amine with the appropriate aldehyde or dialdehyde to prepare an intermediate imine, and reducing the imine by treatment with a borohydride reducing agent or hydrogen gas in the presence of a noble metal catalyst to prepare desired compound wherein the 9-substitutent is an amino group of the formula HNR 7 R 8 wherein R 7 and R 8 are as previously defined. Scheme 1 Scheme 2 Scheme 3 iUustrates the methods used to prepare compounds of formula (II) of the invention. The 6-O- substituted compound 6 may be converted to a hydroxy-protected compound 7 and treated with acid to remove the cladinose to give compound _[ as described in scheme 2. Compound 8 may be treated by oxidation of the hydroxyl group to an oxo group at the 3-position followed by selective reduction at the 3-position to give the compound 8 . wherein the hydroxyl group is in the non-natural (3R form). Alternately, compound 8 may be treated by oxidation of the hydroxyl group to an oxo group at the 3-position foUowed by non-selective reduction to give the compound having 3- and 9-position hydroxyl groups, followed by selective re-oxidation of the 9-OH group to the oxo group, to give the compound 8 wherein the hydroxyl group is in the non-natural (3R form). In these cases, it may be necessary to separate the various isomers by chromatography, as is well know in the art. The isomerization procedures may be interjected into any of the schemes below to give the desired compound having the non-natural (3R) hydroxyl group at the 3-position. Alternately, compound 6 may be converted to a hydroxy-protected compound J4 with a suitable hydroxy protecting group by the procedures referenced previously. Compounds 8 and 14 can then treated with an excess of sodium hexamethyldisilazide or a hydride base in the presence of carbonyldiimidazole in an aprotic solvent for 8 to 24 hours at about -30 °C to room temperature to give compounds 15B and 15A. respectively. The hydride base may be, for example, sodium hydride, potassium hydride, or lithium hydride, and the aprotic solvent may be one as defined previously. The reaction may require coohng or heating from about -20°C to about 70°C, depending on the conditions used, and preferably from about 0°C to about room temperature. The reaction requires about 0.5 hours to about 10 days, and preferably about 1-5 days, to complete. Portions of this reaction sequence follow the procedure described by Baker et al, J. Org. Chem., 1988, 53, 2340, which is incorporated herein by reference. Alternately, treating 8 with a sulfonylating agent, such as methanesulfonyl anhydride, methanesulfonyl chloride, ethanesulfonyl chloride, or p-toluenesulfonyl chloride, in a aprotic solvent with stirring at from about 0°C to ambient temperature for about 1 to about 24 hours to provide a selectively 3-O-sulfonated compound (not shown), followed by treatment of this sulfonated compound with a hydride base in the presence of carbonyldiimidazole in an aprotic solvent gives the desired 2,3 unsaturated compound 15B. Treatment of compound 15A, wherein U is the -Ο-4"-acetylcladinose moiety, with aqueous ammonia results in formation of the cyclic carbamate 16A, wherein U is the -Ο-4"- acetylcladinose moiety R w is absent and R w is H. Treatment of compound 15B, wherein U and U' are taken together to form a double bond, with aqueous ammonia results in formation of the cyclic carbamate 16B, wherein U and U' are taken together to form a double bond. Likewise, reaction of compounds 15A or 15B, wherein U is the -O-4"-acetylcladinose moiety or U and U' are taken together to form a double bond, respectively, with a substituted amine compound of the formula H 2 N-W-R W , wherein W is absent and R w is not H but is otherwise as previously defined, results in formation of the N-substituted cyclic carbamates 16A or 16B, wherein U is the -O-4"-acetylcladinose moiety or U and U' are taken together to form a double bond, respectively, and W is absent. Scheme 3 A. U is 0-4" -acetylcladinose 15A. U is 0-4 "-acetylcladinose: B. U and U' form a double bond 1 B. U and U' form a double bond 18. (ID. U is H 16A 17. (ID. U is OH 19. an. u is 0-τ-R. Also, reaction of compounds 15A or 15B. wherein U is the -O-4"-acetylcladinose moiety or U and U' are taken together to form a double bond, respectively, with a hydroxylamine compound of the formula H2N-W-R W , wherein W is absent or -O- and R w is as previously defined, results in formation of the substituted cyclic carbamate 16A or 16B. wherein U is the -O-4"-acetylcladinose moiety or U and U' are taken together to form a double bond, respectively, W is-O- and R w is as previously defined. Reaction of compound compounds 15A or 15B. wherein U is the -O-4" -acetylcladinose moiety or U and U' are taken together to form a double bond, respectively, with unsubstituted hydrazine results in formation of the cyclic carbamate 16A or 16B, wherein U is the -O-4"- acetylcladinose moiety or U and U' are taken together to form a double bond, respectively, W is -NH- and R w is H. Reaction of compounds 15A or 15B, wherein U is the -O-4"-acetylcladinose moiety or U and U' are taken together to form a double bond, respectively, with a substituted hydrazine compound of the formula H2N-NH-R W wherein R w is not hydrogen but otherwise is as previously defined results in formation of the cyclic carbamate compound 16A or 16B. wherein U is the -O-4"-acetylcladinose moiety or U and U' are taken together to form a double bond, respectively, W is -NH-R W and R w is not hydrogen but otherwise is as previously defined. Alternate or additional procedures may be used to prepare compounds of formula (II). For example, treatment of a compound 15A or 15B, wherein U is the -O-4"-acetylcladinose moiety or U and U' are taken together to form a double bond, respectively, wherein W is absent and R w is H with an alkylating agent having the formula R w -halogen, wherein R w is not hydrogen but otherwise is as previously defined, gives a compound 16A or 16B, wherein U is the -O-4"-acetylcladinose moiety or U and U' are taken together to form a double bond, respectively, W is absent and R w is not hydrogen. Similarly, treatment of a compound 15A or 15B, wherein U is the -O-4"- acetylcladinose moiety or U and U' are taken together to form a double bond, respectively, W is -NH- and R w is H with an alkylating agent having the formula R w -halogen, wherein R w is not hydrogen but otherwise is as previously defined, gives a compound 16A or 16B, wherein U is the -O-4"-acetylcladinose moiety or U and U' are taken together to form a double bond, respectively, W is -NH- and R w is not hydrogen. Treatment of compound 15A or 15B, wherein U is the -O-4"-acetylcladinose moiety or U and U' are taken together to form a double bond, respectively, W is -NH-and R w is H with an acylating agent selected from the group consisting of the acyl halide R w -C(O)-halogen or the acid anhydride (R w -C(O))2-O, wherein R w is not hydrogen but is otherwise as previously defined, gives a compound 16A or 16B. wherein U is the -O-4"-acetylcladinose moiety or U and U' are taken together to form a double bond, respectively, W is -NH-CO- and R w is as previously defined. Treatment of a compound 15A or 15B, wherein U is the -O-4"-acetylcladinose moiety or U and U' are taken together to form a double bond, respectively, W is -NH- and R w is H with an aldehyde R w -CHO, wherein R w is as previously defined, gives a compound 16A or 16B, wherein U is the -O-4" -acetylcladinose moiety or U and U' are taken together to form a double bond, respectively, W is -N=CH- and R w is as previously defined. Removal of the cladinose moiety from a compound 16A by acid hydrolysis as described previously gives a compound 17, which is a compound of formula (II) wherein U is hydroxy and U' is H. Compound JJ. may then be treated by the procedure described previously for the conversion of compound 8 to 10 to give the desired compound JJ . of formula (II) wherein U and U' are H. Compound 17 may also be treated by the procedure described previously for the conversion of compound 8 to JJ, to give the desired compound JJ) of formula (II) wherein U is -O-T-R 1 and U' is H. Optional deprotection of the 2'-hydroxy group from compounds 16B, 17, 18 and \_9_, by the methods described earlier provides the desired unprotected analogous compounds of formula (II). Scheme 4 describes the preparation of compounds of formula (HI). Compound 15A or 15B, wherein U is the -O-4" -acetylcladinose moiety or U and U' are taken together to form a double bond, respectively, is treated with ethylenediamine 20 in a suitable solvent such as aqueous acetonitrile, DMF or aqueous DMF, to give the bicyclic carbamate compound 21A or 21B, wherein U is the -O-4" -acetylcladinose moiety or U and U' are taken together to form a double bond, respectively. Compound 21A or 21B is then cyclized by treatment with dUute acid, such as acetic acid or HCl in a suitable organic solvent such as ethanol or propanol, to give compound 22A or 22B. The cladinose moiety is then removed from compound 22A, wherein U is an -O-4"- acetylcladinose moiety, to give compound 23, which is a compound of formula (III) wherein U is hydroxy and U' is H. Compound 23 is then converted to compounds 24 and 25 by the procedures described in Scheme 3 for conversion of compound J 7 to compounds JJ and 19, respectively. Compounds 22B, 23, 24 and 25 are embodiments of the compounds of formula (HI). Optional deprotection of these compounds may be performed by methods described previously. Scheme 4 25. am. U is O-T-J- Scheme 5 iUustrates the preparation of the cyclic carbonate compounds of formula (IV). In particular, the 2' protected compound 14, prepared as shown in Scheme 3, is converted to the cychc carbonate 26 by controUed reaction at low temperatures (about -30 °C) for a short period (about 30 minutes) with carbonyldiimidazole and sodium hexamethyldisilazide. Alternately, compound 26 is prepared from J4 by careful reaction with sodium hydride or lithium hydride and phosgene, diphosgene or triphosgene under anhydrous conditions with careful control of the amount of base present in order to prevent base catalyzed decarboxylation. Compound 26 is hydrolyzed to give compound 27, which may be isomerized to the(5R) isomer as described above, if so desired. Compound 27 is then converted to compounds 28 or 29 by the procedures described in Scheme 3 for conversion of compound Y∑ to compounds JJ, and JJ), respectively. Compounds 28, and 29 are additional embodiments of the compounds of formula (IV). Optional deprotection of the these compounds is by methods described previously. Scheme 5 27. (IV). U is OH 29. (rv .. U is O-T-R 1 Scheme 6 describes the preparation of compounds of formula (V). Compound 14 may be treated with formaldehyde in the presence of an acid, or with chloroiodomethane in the presence of base (according to the procedure of Hunt et al, J. Antibiotics, (1988), 4 1644) to give the protected 11,12-methylenedioxy compound 30 which is a compound of formula (V) wherein RP is a hydroxy protecting group. This compound may optionaUy then be deprotected at the 2' position by methods described previously to give a 11,12-methylenedioxy compound of formula (V) wherein RP is hydrogen. Compound 30 is hydrolyzed to give compound 31. Compound 3_1 is then converted to compounds 32 or 33 by the procedures described in Scheme 3 for conversion of compound J to compounds JJ and 19, respectively. Compounds 32 and 33 . are additional embodiments of the compounds of formula (V). Optional deprotection of the these compounds is by methods described previously. Scheme 6 31. . U is OH 33. (V . U is 0-T-R 1 Scheme 7 describes representative examples of further elaboration of the 6-position moiety of the compounds of the invention. The desired 6-O-substituted compound may be prepared directly as described above or obtained from chemical modification of an initiaUy prepared 6-O-substituted compound. For example, compound 34 where R is 6-O- CH2CH=CH2 and M' represents the macrolide ring system can be further derivatized. The double bond of the allyl compound can be (a) catalytically reduced to give the 6-O-propyl compound 35; (b) treated with osmium tetroxide to give the 2,3-dihydroxypropyl compound 36 which in turn may be functionalized, such as by esterification with an acylating agent such as an acyl hahde or acyl anhydride, at each oxygen atom to give 37; (c) oxidized with m- chloroperoxybenzoic acid in an aprotic solvent to give the epoxy methyl compound 8 which can be opened with nucleophihc compounds, for example, amines or N-containing heteroaryl compounds, to give compounds with N-containing side chains 39; (d) oxidized under Wacker conditions as described by Henry in "Palladium Catalyzed Oxidation of Hydrocarbons", Reidel Publishing Co., Dordrecht, Holland (1980), to give the 6-O-CH 2 -C(O)-CH 3 compound 40; and (e) ozonized to give the aldehyde 41 which can in turn converted to oximes 42 and 43 by reaction with H2NOR 3 or H2NOH respectively, or reductively aminated, such as with a suitable amine in the presence of a borohydride reducing agent or by formation of the imine and subsequent catalytic reduction, to give the amine 44. Reaction of the oxime 43 with dusopropyl carbodiimide in an aprotic solvent in the presence of CuCl gives the nitrile 45. Reaction of 34 with an aryl hahde under Heck conditions in the presence of (Pd(II) or Pd(O), phosphine, and amine or inorganic base (see Organic Reactions, 1982, 27, 345-390) gives 46. Reduction of the double bond in 46, for example using H2 and palladium on carbon gives 47. Scheme 7 Scheme 8 Ulustrates an alternate procedure for preparing compounds of formula (IT) wherein R is substituted alkenyl. The 6-O-allyl erythromycin compound 16A. wherein R is allyl, is converted to the compound 48 by removing the cladinose and protecting the free 3- hydroxyl group as described in earlier Schemes. Subsequent reaction of the compound 48 with a compound having the formula R**-halogen, wherein R** is aryl, substituted aryl, heteroaryl or substituted heteroaryl, under Heck conditions in the presence of (Pd(II) or Pd(O), phosphine, and amine or inorganic base, gives the desired compound 49 wherein R is substituted alkenyl. Alternately, compound 16A, wherein R is allyl, is converted to the 6-O-(substituted alkenyl) compound of formula 50 by reaction with an aryl hahde, a substituted aryl hahde, an heteroaryl halide or substituted heteroaryl halide under Heck conditions with (Pd(II) or Pd(O), phosphine, and amine or inorganic base, as just described. Compound 50 may then be converted to the desired compound 4J wherein R is substituted alkenyl, by removing the cladinose and optionally deprotecting as described in eartier Schemes. These procedures may be employed whenever any other modification of the 6-O- substitutent is also performed, such as with the modifications described in Schemes 7 or 9. Representative examples of still further elaboration of the 6-position are shown in Scheme 9. The desired 6-O-substituted compound may be prepared by chemical modification of an initially prepared 6-O-propargyl compound. For example, compound 51, which iUustiates a compound of the invention where R is propargyl and M' represents the macrolide ring system, can be further derivatized. The triple bond of compound 51 can be treated with an aryl halide, a substituted aryl halide, a heteroaryl halide or substituted heteroaryl hahde in the presence of Pd(triphenylphosphine)2Cl2 and Cul in the presence of an organic amine, such as triethylamine, to give the compound 52. Compound 52 can be further selectively reduced to the corresponding s-olefin compound 53 by catalytic hydrogenation in ethanol at atmospheric pressure in the presence of 5% Pd BaSO4 and quinoline (Rao et al, J. Org. Chem., (1986), 1: 4158-4159). Compound 51 may also be treated with a boronic acid derivative HB(OR zz ), wherein R zz is H or Cj-Cio-alkyl, in an aprotic solvent at 0 °C to ambient temperature to give compounds 54, which are then treated with Pd(triphenylphosphine)4 and an aryl hahde, a substituted aryl halide, an heteroaryl halide or substituted heteroaryl hahde under Suzuki reaction conditions to give compounds 55. Compound 5 _ may also be treated with N- halosuccinimide in acetic acid to give compounds 56. Also, compound 51 may be treated with a substituted alkenyl halide, such as Ar-CH=CH-halogen, wherein Ar is aryl, substituted aryl, heteroaryl or substituted heteroaryl, in the presence of Pd(triphenylphosphine)2Cl2 and Cul in the presence of an organic amine, such as triethylamine, to give the appropriately substituted compounds 57. Scheme 8 5Q_ 49 Z' is 4"-acetyl-cladinose Scheme 9 The foregoing may be better understood by reference to the foUowing examples which are presented for Ulustration and not to limit the scope of the inventive concept. Examples The procedures described above for preparing the compounds of the present invention wUl be better understood in connection with the following examples, which are intended as an iUustration of and not a Umitation upon the scope of the invention. Various changes and modifications to the disclosed embodiments wiU be apparent to those skilled in the art. Such changes and modifications, including without limitation those relating to the chemical structures, substituents, derivatives, intermediates, syntheses, formulations and/or methods of use of the invention, may be made without departing from the spirit and scope thereof. Example 1 Compound of Formula (I): R is allyl. RP is H. X is O. U is OH Step la: Compound 4 from Scheme 1: V is N-O-(l-isopropoxycyclohexyl). R is aUyl. RP is trimethylsilyl. To a 0 °C solution of 2',4"-to-O-trimethylsUylerythromycin A 9-[Ο-(l- isopropoxycyclohexyl)oxime (1.032 g, 1.00 mmol), prepared according to the method of U.S. Pat. No. 4,990,602 in 5 mL of DMSO and 5 mL of THF was added freshly distilled aUyl bromide (0.73 mL, 2.00 mmol). After approximately 5 minutes, a solution of potassium tert- butoxide (1M 2.0 mL, 2.0 mL) in 5 mL of DMSO and 5 mL of THF was added dropwise over 4 hours. The reaction mixture was taken up in ethyl acetate and washed with water and brine. The organic phase was concentrated in vacuo to give the desired compound (1.062 g) as a white foam. Step lb: Compound 5 from Scheme 1 : V is NOH. R is aUyl. To a solution of the compound from step la (1.7 g) in 17 mL of acetonitrile and 8.5 mL of water was added 9 mL of acetic acid at ambient temperature. After several hours, the reaction mixture was diluted with 200 mL of toluene and concentrated in vacuo. The residue obtained was found to contain unreacted starting material, so additional acetonitrile (15 mL), water (70 mL) and HOAc (2 mL) was added. After 2 hours, an additional 1 mL aUquot of HO Ac was added. After approximately three more hours, the reaction mixture was placed in the freezer overnight. The reaction mixture was allowed to warm to ambient temperature, diluted with 200 mL of toluene and concentrated in vacuo. The residue was chased twice with toluene and dried to constant weight (1.524 g). Step lc: Compound 6 from Scheme 1; R is allyl The compound resulting from step 1 b ( 1.225 g) in 16 mL of 1 : 1 ethanol-water was treated with NaHSO3 (700 mg) and formic acid ( 141 μL) at 86 °C for 2.5 hours. The reaction mixture was allowed to cool to ambient temperature, diluted with 5-6 mL of water, basified with 1 N NaOH to pH 9- 10 and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified by column chromatography, eluting with 1% MeOH in methylene chloride containing 1% ammonium hydroxide, to give 686 mg (57%) of the title compound. !3C NMR (CDC1 3 ) 5 219.3 (C-9), 174.8 (C- 1), 135.5 (C- 17), 1 16.3 (C-18), 101.9 (C- 1'), 95.9 (C-1"), 79.7 (C-5), 78.8 (C-6), 78.5 (C-3), 74.1 (C-12), 72.4 (C-3"), 70.6 (C-1 1), 68.1 (C-5"), 65.5 (C- 16), 65.1 (C2'), 49.0 (C-3" O-CH3), 45.0 (C-2), 44.1 (C-8), 39.7 (NMe ), 37.9 (C-4), 37.1 (C-10), 34.6 (C-2"), 28.4 (C-4'), 21.0, 20.6 (C-3" CH3, C-6' CH3), 20.8 (C-14), 18.3 (C-6"), 18.1 (C-8 CH 3 ), 15.7, 15.6 (C-2 CH 3 , C-6 CH 3 ), 1 1.9 (C- 10 CH3), 10.1 (C- 15), 8.9 (C-4 CH3). MS (FAB) + m/e 774 [M+H]+, 812 (M+K)+. Step Id: Compound of Formula (I): R is allyl. RP is H. X is O, U is OH To a suspension of the compound from step lc (7.73 g, 10.0 mmol) in ethanol (25 mL) and water (75 mL) was added aqueous 1 M HCl (18 mL) over 10 minutes. The reaction mixture was stirred for 9 hours at ambient temperature, then was left standing in the refrigerator overnight. Aqueous 2 M NaOH (9 mL, 18 mmol) was added, which resulted in the formation of a white precipitate. The mixture was dhuted with water and filtered. The solid was washed with water and dried under vacuum to give the des-cladinosyl compound £7 from Scheme 2) (3.11 g). Example 2 Compound of Formula (I): R is allyl. RP is benzoyl. X is O, U is OH To a solution of the product of Example 1 (2.49 g, 4.05 mmol) in dichloromethane (20 mL) was added benzoic anhydride (98%, 1.46 g, 6.48 mmol) and triethylamine (0.90 mL, 6.48 mmol), and the white suspension was stirred for 26 hours at ambient temperature. Aqueous 5% sodium carbonate was added, and the mixture was stirred for 20 minutes then extracted with dichloromethane. The organic phase was washed with aqueous 5% sodium bicarbonate and brine, dried over sodium sulfate and concentrated in vacuo to give a white foam. Chromatography on sihca gel (30% acetone-hexanes) gave the title compound (2.46 g) as a white solid. MS (ESI) m/z 720 [M+H]+. Example 3 Step 3a. Compound 8, Scheme 1; R is -CH2-CH=CH2-(3-quinolinyl), RP is benzoyl. To a sample of the compound from Example 2 (21.57 g, 30 mmol) in acetonitrile (200 mL) were added 3-bromoquinoline (6.1 1 mL, 45 mmol), paUadium acetate (1.03 mg, 4.5 mmol), tri-(o-tolyl)phosphine (2.74 mg, 9.0 mmol) and triethylamine (8.36 mL, 60 mmol). The mixture was degassed by bubbling N2 through it for 30 minutes, sealed in a tube under nitrogen, then heated at 60 °C for 1 hour and at 100 °C for 14 hours. The mixture was cooled to room temperature and diluted with ethyl acetate. The organic phase was separated, washed with saturated NaHCO3 and brine, and dried over MgSO4. The solvent was removed to give crude product which was purified by chromatography on sUica gel, eluting with 40-60% acetone hexane to give the title compound (15.0 g, 60%). MS (ESI) m/z 847 I " M+H1+, HRMS: calcd for C48H67N2O11, 847.4739; found, 847.4434. Step 3b. Compound of Formula (I): R is -CH2-CH=CH2-(3-quinolinyl). RP is H. X is O. U is OH A solution of the compound from step 3b (200 mg, 0.118 mmol) in methanol (5 mL) was stirred at reflux for 6 hours. The reaction mixture was concentrated in vacuo and the residue was purified by chromatography on sUica gel (95:5:0.5 dichloromethane-methanol- ammonia) to give the title compound (170 mg) as a white foam. 1 C NMR (CDCI3): 219.9, 175.0, 150.0, 147.4, 132.8, 129.9, 129.3, 129.1 , 129.0, 128.8, 128.2, 128.0, 126.6, 106.5, 88.3, 79.0, 78.9, 76.6, 74.3, 70.6, 70.2, 69.3, 65.7, 64.0, 45.7, 44.5, 40.3, 38.2, 37.7, 36.0, 28.2, 21.6, 21.3, 19.7, 18.2, 16.4, 15.2, 12.5, 10.6, 8.31. MS m/z 743 [M+H] + . Example 4 Compound of Formula (T): R is -CH2-CH=CH2-f 3-quinolinyl _ RP is H. X is O. U is O-acetyl Step 4a. Compound of Formula (I): R is -CH2-CH=CH2-(3-quinolinyl). RP is benzoyl. X is O. U is O-acetyl A sample of the compound from Example 3, Step 3a (100 mg, 0.118 mmol) was treated with acetic anhydride (29 μL, 0.295 mmol), triethylamine (40 μL, 0.295 mmol) and N,N-dimethylaminopyridine (2 mg, 0.0164 mmol) in dichloromethane (lmL) at room temperature for 3 days. is O-acetyl Methanol (6 mL) was then added to the reaction mixture from Step 4a, and the mixture was heated at reflux for 5 hours to remove the 2 '-benzoyl protecting group. At the completion of the reaction, the solvents were removed by evaporation, and the residue was purified by flash chromatography on sUica gel eluted with dichloromethane/methanol/ammonium hydroxide (10:1:0.05 to 20: 1:0.05) to give the title compound (79.6 mg, 86%) as a white foam. MS (ESI) m/z 785 [M+H] + , HRMS: calcd for C43H65N2O11, 785.4588; found, 785.4593. Example 5 Compound of Formula (I): R is -CH2-CH=CH2-(3-quinolinyl). RP is H, X is O. U is O-(4-methoxy)benzoyl Step 5a. Compound of Formula (I): R is-CH2-CH=CH2-(3-quinolinyl), RP is benzoyl, X is O. U is O-(4-methoxy)benzovI A sample of the compound from Example 3, Step 3a (120 mg, 0.142 mmol) was treated with p-methoxybenzoyl anhydride (80 mg, 0.279 mmol) and N,N- dimethylaminopyridine (20 mg, 0.164 mmol) in anhydrous toluene (lmL) at 100°C for 4 days. Step 5b. Com p ound of Formula (I): R is-C^-CH^CHo-G-quinolinyl). RP is H. X is O. U is O-(4-methoxy)benzoyl Methanol (6 mL) was added to the reaction mixture from Step 5a, and the mixture was heated at reflux for 5 hours to remove the 2'-benzoyl protecting group. At the completion of the reaction, the solvents were removed by evaporation, and the reside was purified by flash chromatography on silica gel eluted with dichloromethane/methanol/ammonium hydroxide (10:1:0.05 to 20:1:0.05) to give the title compound (105 mg, 85%) as a white foam. MS (ESI) m/z 877 [M+H] + , HRMS: calcd for C49H69N2O11, 877.4851; found, 877.4845. Example 6 U is O-methanesulfonyl A sample of the compound from Example 3, Step 3a (4.94 g, 5.84 mmol) was treated methanesulfonyl anhydride (3.75 g, 21.9 mmol) and triethylamine (7.0 mL, 50.2 mmol) in anhydrous dichloromethane (50 mL) at 0°C to room temperature for 20 hours. The mixture was further dUuted with dichloromethane, washed with aqueous NaHCO3, dried, and concentrated. Purification by flashing chromatography on stiica gel with 3:2 hexane/acetone to give 2.14 g of product and 2.00 g of unreacted starting material. A 50 mg sample of the above mixture was heated in methanol (3 mL) at reflux for 3 hours to remove the 2'-benzoyl protecting group. At the completion of the reaction, the solvents were removed by evaporation, and the reside was purified by flash chromatography on sUica gel eluted with dichloromethane/methanol/ammonium hydroxide (10: 1:0.05 to 20: 1:0.05) to give the title compound (105 mg, 85%) as a white foam. MS (ESI) m/z 821 [M+H]+, HRMS: calcd for C 4 2H65N2O12S, 821.4258; found, 821.4258. Example 7 Compound of Formula (I): R is -CH2-CH=CH2-(3-quinolinyl). RP is H. X is_O. U is O-CO- NH-(2-nitrophenyl) Step 7a. Compound of Formula (I): R is -CH2-CH=CH2-(3-quinolinv0. RP is benzoyl. X is O. U is O-CO-NH-(2-nitrophenyl) A sample of the compound from Example 3, Step 3a ( 130 mg, 0.154 mmol) was treated with o-nitrophenyl isocyanate (38.0 mg, 0.0.232 mmol) and N,N- dimethylaminopyridine (24 mg, 0.197mmol) in anhydrous toluene (2 mL) at 100 °C for 4 hours. is O-CO-NH-α-nitrophenvn Methanol (8 mL) was then added to the reaction mixture from Step 7a, and the mixture was heated at reflux for 5 hours to remove the 2 '-benzoyl protecting group. At the completion of the reaction, the solvents were removed by evaporation, and the reside was purified by flash chromatography on sihca gel eluted with dichloromethane/methanol/ammonium hydroxide (10: 1:0.05 to 20:1:0.05) to give the title compound (129 mg, 93%) as a yellow foam. MS (ESI) m/z 907 [M+H] + , HRMS: calcd for C48H67N3O13, 907.4699; found, 907.4690. Example 8 Compound of Formula (ID: R is -CH2-CH=CH2-(3-quinolinvD. RP is H. W is absent. R w is H. U is OH Step 8a. Compound 14 of Scheme 3. R is allyl. RP is acetyl To a solution of the compound from Example 1 (80 g, 103 mmol and DMAP (4.0 g, 32.7 mmol) in dichloromethane (200 mL) was added acetic anhydride (40 mL, 400 mmol). The solution was stirred for 5 hours at ambient temperature, and the mixture was dhuted with dichloromethane (800 mL). The organic phase was washed with 5% Na2CO3, saturated NaHCO3 and brine, and dried over MgSO4. The solvent was removed under vacuum, and the residue was dried. The residue was crystaUized from acetonitrile to give the title compound (60.0 g). MS (APCI) m/z 858 [M+H]+. Step 8b. Compound 15A of Scheme 3, R is allyl, RP is acetyl. U is 4"-acetylcladinose To a solution of the compound from Step 8a (42.85 g, 50 mmol) in THF (250 mL) cooled to -40 °C in a dry ice-acetonitrile bath was added sodium bis(trimethylsUyl)amide (65.0 mL, 1 M in THF, 65.0 mmol) over 30 minutes. After 45 minutes, a solution of 32.43 g (200 mmol) of carbonyldumidazole in 150 mL of THF and 100 mL of DMF was added. The mixture was stirred for 2.5 hours at -40 °C and 1 hours at room temperature. The reaction was quenched by adding a solution of 0.5 M NaH2PO 4 (500 mL). The product was isolated by extraction of the reaction mixture with ethyl acetate. The extract was dried with MgSO4 and concentrated to give the crude product, which was purified by flash chromatography using 40- 60% acetone/hexanes, yielding 46 g (100%) of the title compound. MS (APCI) m/z 934 [M+H]+. Step 8c. Compound 16A of Scheme 3. R is allyl. RP is acetyl, U is 4"-acetylcladinose, W is absent, R w is H To a solution of the compound from Step 8b (40.0 g, 42.9 mmol) in acetonitrile (1000 mL) and THF (100 mL) was added concentrated ammonium hydroxide (28-30%, 120 mL). The mixture was stirred at room temperature for 7 days, then the solvents were removed under vacuum and the residue was taken up in ethyl acetate. The organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was chromato graphed on sihca gel eluting with dichloromethane/MeOH/ammonium hydroxide (10:1:0.05) to give the title compound (23.07 g). MS: [M+H]+ at m/z 883. HRMS: calculated m/z for [M+H]+ C45H74N2O15: 883.5162; Found: 883.5165. 4"-acetylcladinose, W is absent, R w is H To a solution of the compound from Step 8c (20.5 g, 23.2 mmol) in acetonitrile (200 mL) were added 3-bromoquinoline (6.47 mL, 31.1 mmol), paUadium acetate (1.07 g, 4.76 mmol), tri-(o-tolyl)phosphine (2.43 g, 7.97 mmol) and triethylamine (9.13 mL, 65.5 mmol). The mixture was degassed by bubbling N2 through it for 30 minutes, sealed in a tube under nitrogen, and heated at 60 °C for 1 hour and 14 hours at 100 °C. The mixture was cooled and dtiuted with ethyl acetate, and the organic layer was separated and washed with saturated NaHCO3 and brine, then dried over MgSO4. The solvents were removed and the crude product was purified by chromatography on sitica gel eluting with 40-60% acetone/hexane to give the title compound (21.0 g). Step 8e. Compound of Formula (O ): R is -CH2-CH=CH2-f 3-quinolinvn. RP is acetyl. U is OH. W is absent. R is H HydrolyticaUy treating the compound of Step 8d with acid according to the procedure of Example 1, Step Id, gave the title compound. MS (APCI) m/z 810 [M+H]+. W is absent. R is H The product of Step 8e ( 100 mg, 0.124 mmol) was heated in refluxing methanol (2 mL) for 3 hours to remove the 2'-acetyl protecting group. At the completion of the reaction, the solvents were removed by evaporation, and the reside was purified by flash chromatography on sUica gel eluted with dichloromethane/methanol ammonium hydroxide (10:1:0.05 to 20: 1:0.05) to give the title compound (90 mg, 94.8%). IH (CDCI3) d 9.06 (IH, d, / = 2.4 Hz), 8.23 (IH, d, J = 2.4 Hz), 8.06 (IH, d, 8.4 Hz), 7.82 (IH, dd, J = 8.7, 1.5 Hz), 7.65 (IH, d, / = 8.1, 1.5 Hz), 7.51 (IH, td, J = 8.1, 1.5 Hz), 6.70 (IH, d, J = 15.9 Hz), 6.39 (IH, dt, J = 15.9, 6.6 Hz), 5.46 (IH, s), 5.18 (IH, dd, J = 10.2, 2.4 Hz), 4.46 (IH, d, J = 7.2 Hz), 3.96 (m, 2H), 3.82 (IH, s), 3.73 (IH, s), 3.63 (IH, d, J = 8.7 Hz), 3.51 (IH, m), 3.24 (IH, dd, J = 9.0, 6.9 Hz), 2.96 (IH, q, J = 6.6 Hz), 2.73 (IH, dq, J = 8.7, 6.6 Hz), 2.61 (IH, m), 2.48 (IH, m), 2.25 (6H, s), 2.03 (IH, dd, J = 14.4, 7.2 Hz), 1.88 (IH, m), 1.66 (IH, m), 1.57 (IH, dd, / = 14.4, 1.0 Hz), 1.51 (IH, m), 1.47 (3H, s), 1.31 (3H, d, J = 6.6 Hz), 1.23 (3H, d, / = 6.0 Hz), 1.19 (3H, d, J = 8.1 Hz), 1.11 (3H, d, J = 6.9 Hz), 1.10 (3H, d, J = 6.6 Hz), 0.85 (3H, t, J = 7.5 Hz). MS (APCI) m/z 768 [M+H]+. Example 9 Compound of Formula (ID: R is -CH2-CH=CH2-(3-quinolinv1 _ RP is H. W is absent. R w is H. U is O-acetyl A mixture of a solution of the compound of Example 8, Step 8e (50 mg, 0.062 mmol) and DMAP (catalytic amount) in pyridine (1.0 mL) and acetic anhydride (0.5 mL) was stirred for 5 hours at ambient temperature. At the completion of the reaction, solvents were removed by evaporation under vacuum. The reside was redissolved in methanol (2 mL) and heated at reflux for 3 hours to selectively remove the 2'-acetyl protecting group. Solvent was evaporated, and the crude product was purified by flash chromatography on sUica gel to give the title compound (35 mg). MS (APCI) m/z 810 {M+H]+, HRMS: calcd for C44H64N3O11, 810.4541; found, 810.4559. Example 10 H, U is O-(4-nitrobenzoyl) A solution of the compound of Example 8, Step 8e, 4-nitrobenzoic anhydride (0.10g, 0.316 mmol), DMAP (0.017 g, 0.135 mmol), and tributylamine (0.05 g, 0/059 mL, 0.247 mmol) in toluene (5 mL) was heated at 100 °C for 4 hours. The solution was diluted with ethyl acetate (40 mL), and the organic layer was washed with sodium carbonate, water and brine, dried (Na2SO4), filtered and concentrated under vacuum. The crude product was purified by flash chromatography (7:3 acetone:hexane) to give 0.075 g (64%) of yeUow foam. The product was dissolved in methanol (5 mL) and heated at reflux for 3 hours. The solvent was removed under vacuum, and the crude product was purified by flash chromatography with (94:5:1 dichloromethane:methanol:ammonium hydroxide) to give 0.075 g (64%) of the title compound. MS (ESI) m/z 917 [M + H]+. Examples 11-25 Following the procedures of Example 10, except substituting the acylating reagent shown in the table below for the 4-nitrobenzoic anhydride of Example 10, the compounds of Examples 11-25 with U as shown in the table below were prepared. H. U is as shown Example 27 Compound of Formula (TD: R is -CH2-CH=CH2-(3-quinolinyl). RP is H. X is O. W is absent. R w is H. U is O-CO-NH-phenyl A solution of the compound of Example 8, Step 8e, (100 mg, 0.124 mmol), phenylisocyanate (19.4 mg, 1.61 mmol), and N,N-dimethylaminopyridine (15.1 mg, 0.124 mmol) in anhydrous toluene (2 mL was heated at 90°C for until the complete consumption of starting material as indicated by TLC analysis. The mixture was cooled to room temperature, and methanol (4 mL) was then added. The mixture was heated at reflux for 4 hours to remove the 2'-acetyl group. Solvents were removed by evaporation, and the residue was purified by flash chromatography on sitica gel eluting first with dichloromethane and then with dichloromethane/methanol/ammonium hydroxide (10:1:0.05) to give the title compound (105 mg, 100%). MS (APCI ) m/z 887 [M+H] + . HRMS: calcd for C49H67N4O11, 887.4806; found, 887.4803 Examples 28-36 Following the procedures of Example 27, except substituting the isocyanate reagent shown in the table below for the phenyl isocyanate of Example 27, the compounds of Examples 28-36 with U as shown in the table below were prepared. H. U is as shown Example 37 Compounds of Formula (TO: R is -CH2-CH=CH2-(3-quinolinyl). RP is H. W is absent. R is To a stirred solution of the compound of Example 7, Step7e, (0.53 g, 0.655 mmol) in pyridine (17 mL), cooled to 0 C was added dropwise 2-chloro-l-ethanesulfonyl chloride (0.32 g, 0.21 mL, 1.97 mmol). The mixture was warmed to ambient temperature and stirred overnight. The mixture was dtiuted with ethyl acetate (40 mL), and the organic layer was washed with saturated sodium bicarbonate, water and brine, dried (Na2SO4), filtered, and concentrated under vacuum. The crude material was purified by column chromatography eluting with 94:5: 1 dichloromethane:methanol:ammonia hydroxide. The product was dissolved in methanol (5 mL) and refluxed for 3 hours. The solvent was removed under vacuum, and the material was purified by column chromatography eluting with 94:5:1 dichloromethane:methanol:ammonia hydroxide, to give the title compound (0.071 g, 13%). MS (ESI) m/z 858 [M+H] + Example 38 Compounds of Formula (TO: R is -CH2-CH=CH2-(3-quinolinyl). RP is H. W is absent. R w is H. U is O-S ( O 2-CH2-CH2-N ( CH 2 To a solution of the compound from Example 37 (0.2g, 0.023 mmol) in acetonitrile (2 mL) was added dimethylamine (0.004 mL, 2M in THF). The solution was stirred for 12 hours, the solvent removed under vacuum, and the material was purified by column chromatography eluting with 70:30:2 acetone:hexane:triethylamine, to give the title compound (0.007g, 34%) of white foam. MS (ESI) m/z 903 [M+H]+. Example 39 Compounds of Formula (TO: R is -CH2-CH=CH2-(3-quinolinyl). RP is H. W is absent. R w is H. U is O-SfOV7-CH2-CH2-S-phenyl FoUowing the procedure of Example 38, except replacing the dimethylamine with thiophenol the title compound was prepared (0.015g, 38%). MS (ESI) m/z 968 [M+H] + . Example 40 H. U is O-allyl To a stirred solution of the compound of Example 8, Step 8e (0.08 g, 0.099 mmol) and aUyl bromide, (0.023g, 0.017 mL, 0.198 mmol) in THF (2 mL) cooled to 0°C was added NaH (0.02 g, 60% in mineral oil, 0.495 mmol). The mixture was stirred overnight, then diluted with ethyl acetate (20 mL), washed with water and brine, dried (Na2SO4), filtered, and concentrated under vacuum. The crude material was purified by column chromatography eluting with 94:5: 1 dicMoromethane:methanol: ammonia hydroxide. The product was dissolved in methanol (5 mL), and refluxed for 3 hours. The solvent was removed under vacuum, and the material was purified by column chromatography eluting with 94:5:1 dichloromethane:methanol:ammonia hydroxide, to give the title compound (0.014 g, 18%) as a white foam. MS (ESI) m/z 808 [M+H]+. Example 41 To a sample of the compound from Example 8, Step 8e (95 mg, 0.117 mmol) in dry THF (2 mL) cooled to -40 °C and flushed with nitrogen was added sodium bis(trimethylsilyl)amide (0.235 mL. 0.235 mmol) dropwise, and the mixture was stirred at -40 °C for 10 minutes. To this mixture was added 4-morpholinecarbonyl chloride (38.5 mg, 0.258 mmol. The mixture was stirred whhe the temperature was raised from -40°C to -10°C over 2 hours. TLC analysis indicated there was some starting material remained. The reaction mixture was cooled to -40°C, the both reagents were added in the same manner described above, and the reaction was let to proceed for an additional 2 hr with temperature slowly rising to room temperature. The reaction was diluted with ethyl acetate, washed with 5% sodium bicarbonate and brine, dried over Na2SO4, and concentrated to give crude product. This material was treated with methanol (6 mL) at refluxing for 4 hours to remove the 2'-acetyl group to give the title compound. MS (ESI) m/z 881 [M+H] + . Calcd for C47H69N4O12, 881.4912; found, 881.4926. Example 42 . s -pyrro ny car ony Following the procedure of Example 41, except replacing the 4-morpholinecarbonyl chloride with pyrohdinylcarbonyl chloride the title compound was prepared in 32 % yield. MS (ESI) m/z 865 [M+H]+. Example 43 Compound of Formula (TO: R is -CH2-CH=CH2-(3-quinolinyl _ RP is H. W is absent. R is H. U is O-(2-tetrahydropyranyl) A sample of the compound from Example 8, Step 8e (50 mg, 0.062 mmol) in dichloromethane (2 mL) was treated with 3,4-dihydro-2H-pyran (0.10 mL, 1.10 mmol) and a catalytic amount of p-toluenesulfonic acid at room temperature for 2 hours. The reaction mixture was washed with aqueous NaHCO3, dried, concentrated. The 2' -acetyl group was removed by the usual treatment with hot methanol to give the title compound after chromatographic purification with 94:5:1 dic_loromethane:methanol:ammonia hydroxide, (38 mg, 73.0%)). MS (ESI) m/z 852 [M+H] + . HRMS: calcd for C47H70N3O11, 852.5010; found, 852.5005. Example 44 Compound of Formula (ID: R is -CH2-CH=CH2-(3-αuinoUnyl). RP is H. W is absent. R w is H. TJ is O-C ( =SVSCH2 To a solution of the compound from Example 8, Step 8e in THF at -20 °C under an inert atmosphere was added excess NaH slowly over a 5 minute period, then after several minutes CS2 was added. Several minutes later methyl iodide was added, and the reaction mixture was aUowed to graduaUy warm to 10°C. After 1 hour the reaction mixture was quenched with ethyl acetate. The organic layer is washed with saturated aqueous NaHCO3 and brine, dried (MgSO4), and concentrated to afford the crude product. Chromatographic purification (sihca, acetone/hexane ranging from 1:1 to 4:1) affords the C-3 xanthate compound. The 2'-acetyl group was removed by treatment overnight with hot methanol to give the title compound. MS (ESI) m/z 858. HRMS: calcd for C44H64N2O10S2, 858.4033; Found, 858.4056. Example 45 Compound of Formula (ID: R is -CH2-CH=CH . RP is H. U and U' taken together are double bond. W is absent. R w is H Step 45a. Compound of Formula (ID: R is -CH2-CH=CH2- RP is benzoyl. U and U' taken together are double bond, W is absent. R w is H To a solution of the compound from Example 2 (10.0 g, 13.9 mmol) and CDI (11.5 g, 69.5 mmol) in THF (160 mL) and DMF (80 mL) cooled at -40 °C in a dry ice-acetonitrile bath was added sodium bis(trimethylsilyl)amide (60.0 mL, 1 M in THF, 60.0 mmol) over 30 minutes. The mixture was stirred for 2.5 hours at -40 °C and for 18 hours at room temperature. The reaction was quenched by adding a solution of 0.5 M NaH2PO4 (200 mL). The product was isolated by extraction of the reaction mixture with ethyl acetate. The extract was dried with MgSO4 and concentrated to give the crude product Without purification this material was dissolved in acetonitrile (160 mL), THF (16 mL) and concentrated ammonium hydroxide (28-30%, 32 mL). The mixture was stirred at room temperature for 3 weeks. Solvents were removed in vacuo, and the residue was taken up in ethyl acetate. The organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was chromatographed on silica gel eluting with dichloromethane/MeOH/ammonium hydroxide (10:1:0.05) to give the title compound. are double bond, W is absent. R w is H A sample of compound from Step 45a was treated with methanol at refluxing for 3 hours to give the title compound. MS (ESI) m/z 623 [M+H]+. Example 46 Compound of Formula (ID: R is -CH2-CH=CH2-(3-quinolinyl). RP is H. U and U' taken together are double bond. W is absent. R w is H To a solution of the compound from Example 45, Step 45b (305 mg, 0.49 mmol) in acetonitrile (4 mL) were added 3-bromoquinoline (0.133 mL, 0.98 mmol), paUadium acetate (22 mg, 0.098 mmol), tri-(o-tolyl)phosphine (45 mg, 0.147 mmol) and triethylamine (0.171 mL, 1.22 mmol). The mixture was degassed by bubbling N2 through for 30 minutes, sealed in a tube under nitrogen, and heated at 60 °C for 1 hour and 14 hours at 80 °C. The mixture was cooled and diluted with ethyl acetate, which was separated and washed with saturated NaHCO3 and brine, then dried over MgSOφ The solvents were removed and the crude product was purified by chromatography on silica gel eluting with 40-60% acetone/hexane to give product (160 mg, 45%). MS m/z 750 {M+H]+. HRMS: calcd for C42H60N3O9, 750.4330; found, 750.4317. Examples 47-49 Following the procedures of Example 46, except substituting the aryl halide reagent shown in the table below for the 3-bromoquinoline reagent of Example 46, the compounds of Examples 47-49 with R as shown in the table below were prepared. Example 50 Compound of Formula (IV): R is -CH2-CH=CH 2 . RP is acetyl. U is OH Step 50a. Compound of Formula (IV). R is -CH2-CH=CH2- RP is acetyl. U is 4"- acetylcladinose To a solution of the compound from Step 8a (10.0 g, 11.6 mmol) in THF (150 mL) cooled to -40 °C in a dry ice-acetonitrUe bath was added sodium bis(trimethylsUyl)amide (12.8 mL, 1 M in THF, 12.8 mmol) over 30 minutes. After 15 minutes, a solution of carbonyldiimidazole (6.8 g, 41.9 mmol) in 90 mL of THF was added. The mixture was stirred for 2.5 hours at -40 °C, and warmed to room temperature for 30 minutes. The reaction was quenched by adding a solution of 0.5 M NaH2PO4 (50 mL). The product was isolated by extraction of the reaction mixture with ethyl acetate. The extract was dried with MgSO 4 and concentrated to give the crude product, which was purified by flash chromatography using 40- 60% acetone/hexanes, yielding 6.41 g (62%) of the title compound. MS (ESI) m/z 884[M+H] + . Step 50b. Com p ound of Formula (IV). R is -CH2-CH=CH . RP is acetyl. U is OH To a solution of the compound from Step 50a (6.35 g, 7.18 mmol) in ethanol (14 mL) and water (14 mL) was added hydrobromic acid (4 mL, 48%, 8.8 M) slowly, which caused the solution to become clear. At the completion of the reaction as judged by TLC, 2 N NaOH (17.8 mL) was added to quench the reaction. Ethanol was removed in vacuo, and the residue was taken up in ethyl acetate (250 mL). The ethyl acetate solution was washed with NaOH (0.5 M), water, brine, dried over Na2SO4, and concentrated. The crude product was purified by sihca gel chromatography with 95:5: 1 CH2Cl2:MeOH:NH4θH to give the title compound as a white foam (3.72 g, 75.8% yield). MS (ESI) m/z 684 [M+H] + . Example 51 Compound of Formula (IV): R is -CH2-CH=CH2-(3-quinolinyl). RP is acetyl. U is OH To a solution of the compound from Example 50 (1.6 g, 2.34 mmol) in acetonitrile (20 mL) were added 3-bromoquinoline (0.51 lg, 2.46 mmol), palladium acetate (53 mg, 0.022 mmol), tri-(o-tolyl)phosphine (71 mg, 0.022 mmol) and triethylamine (0.61 g, 4.68 mmol). The mixture was degassed by bubbling N2 through it for 30 minutes, sealed in a tube under nitrogen, and heated at 60 °C for 1 hour and 14 hours at 100 °C. The mixture was cooled and dUuted with ethyl acetate, and the organic layer was separated and washed with saturated NaHCO3 and brine, then dried over MgSO 4 . The solvents were removed and the crude product was purified by chromatography on silica gel eluting with 40-60% acetone/hexane to give the title compound. MS (ESI) m/z 81 1 [M+H] + . Example 52 Compound of Formula (III): R is -CH2-CH=CH , RP is H. U is OH. U' is H, Step 52a. Compound 21 A of Scheme 3, R is allyl, RP is acetyl To a solution of compound from Example 8, Step 8b (3.65 g, 3.91 mmol) in acetonitrile (40 mL) and THF (4 mL) was added ethylenediamine (2.67 mL, 39.1 mmol). The solution was stirred under nitrogen overnight at room temperature, then heated at 80 °C for 3 hours. Solvents were removed by evaporation, and the residue was taken up in ethyl acetate. The solution was washed with NaHCOβ, brine, dried and concentrated. Step 52b. Compound 22A of Scheme 3, R is allyl. RP is H The compound from Step 52a was redissolved in a mixture of ethanol/acetic acid (40 ιτιL/0.4 mL), and the mixture was heated at reflux for 5 hours. Ethanol was evaporated off, residue was taken up in dichloromethane, which was then washed with aqueous sodium bicarbonate, brine, dried and concentrated. Step 52c. Compound 22A of Scheme 3, R is allyl, RP is acetyl A solution of the crude product from Step 52b in dichloromethane (50 mL) was treated with acetic anhydride (2.40 mL) and triethylamine (3.50 mL) at room temperature for 24 hours. Solvent and unreacted reagents were evaporated off, and the crude product was purified by chromatography with 10: 1:0.05 CH2Cl2:MeOH:NH4OH to give the title compound (2.70 g, 90.2% yield for three steps). MS (ESI) m/z 908 [M+H1+. Step 52d. Compound 22A of Scheme 3. R is allyl. To a suspension of the compound from Step 52c (2.10 g, 2.32 mmol) in ethanol (20 mL) was added aqueous 2 N HCl (20 mL) over 10 minutes. The reaction mixture was stirred at ambient temperature for 16 hours, at which time TLC analysis indicated completion of the reaction. A 50 mL portion of ethyl acetate was added to the reaction mixture foUowed by 20 mL 2 N aqueous NaOH. The mixture was further diluted with ethyl acetate and saturated NaCl. Layers were separated, the organic phase was washed with saturated NaCl solution, dried and concentrated under vacuum to give the des-cladinosyl title compound, (1.29 g, 78.8%). MS (ESI) m/z 708 [M+HJ + ; HRMS: calcd for C37H62 3O10: 708.4435; Found, 708.4420. Step 52e. Compound of Formula (IIP: R is -CH -CH=CH2- RP is H. U is OH. U' is H A sample of compound from Step 52d was refluxed in methanol for 4 hours to removing the 2'-acetyl group and give the title compound. MS (ESI) m/z 666 [M+H] + . Example 53 Compound of Formula (IIP: R is -CH2-CH=CH2-(3-quinolinyl). RP is H. U is OH. U' is H Step 53a. Compound of Formula (IIP: R is -CH2-CH=CH2-(3-quinolinyl). RP is acetyl. U is OH. U' is H Following the procedure of Example 46, except substituting the compound of Example 52, Step 52d for the starting material in example 46, the title compound was prepared. MS (ESI) m/z 935 [M+H]+. Step 53b. Compound of Formula (IIP: R is -CH9-CH=CH2-(3-αuinolinyl). RP is H. U is OH. U' is H A sample of compound from Step 53a was refluxed in methanol for 4 hours to remove the 2' -acetyl group and give the title compound. MS (ESI) m/z 793 [M + H]+. Example 54 Compound of Formula (IV): R is -CH2-CH=CH2-(3-quinolinyl). RP is H. U is O-C(O)- phenyl Following the C3-O-acylation and C2'-deacetylation procedures described in Example 10, except substituting benzoic anhydride for the acetyl anhydride thereof, the title compound was prepared in two-steps. MS (ESI) m/z 897 [M+H]+. Example 55 Compound of Formula (IV): R is -CH2-CH=CH2-(3-quinolinv_. RP is H. U is O-C(O)-(2- nitrophenyl) Following the C3-O-acylation and C2'-deacetylation procedures described in Example 10, except substituting 2-nitrobenzoic anhydride for the acetyl anhydride thereof, the title compound was prepared in two-steps. MS (ESI) m/z 942 [M+H] + . Example 56 Compound of Formula (ID: R is -CH2-CH=CH . RP is H. W is NH. R w is H. U is OH Step 56a. Compound 16A of Scheme 3. R is aUyl. RP is acetyl. U is 4" -acetylcladinose, W is NH. R is H To a solution of the compound from Step 8b (3.65 g, 3.91 mmol) in acetonitrile (30 mL) and THF (3 mL) was added anhydrous hydrazine (0.37 mL, 11.7 mmol). The solution was stirred under nitrogen at room temperature for 24 hours. Solvents were removed by evaporation, and the residue was purified by silica gel chromatography with acetone/hexanes from 60:40 to 80:20 to give the title compound (0.48 g). MS (ESI) m/z 898 [M+H]+. Step 56b. Compound of Formula (II): R is allyl. RP is acetyl. U is OH. W is NH. R w is H The compound (of formula (Jl): R is -CH2-CH=CH2, RPjs acetyl, W is NH, R w is H, U is 4"-acetylcladinose) from Step 56a was treated with 2 N HCl in ethanol foUowing the procedure of Example 1, Step Id, to give the descladinose compound. Step 56c. Compound of Formula (II): R is -CH -CH=CH2- RP is H. W is NH, R is H. U is OH A sample of the compound from Step 56b was refluxing in methanol for 5 hours removing the 2'-acetyl group to give the title compound. MS (ESI) m/z 656 [M+H] + . Example 57 A sample of the compound from Example 8, Step 8a (compound 14 of Scheme 3) is treated at -30 °C for about 30 minutes with carbonyldiimidazole and sodium hexamethyldisilazide. That intermediate product is treated with ethanolic HCl, to give the intermediate descladinose compound wherein RP is acetyl. This compound is refluxed with methanol overnight. The crude product is purified by chromatography on sUica gel to give the title compound. Example 58 Compound of Formula (V _ R is -CH9-CH=CH2- RP is H. U is O-acetyl A sample of the intermediate descladinose compound wherein RP is acetyl from Example 57 is treated with acetic anhydride to give the intermediate compound wherein RP is acetyl and U is O-acetyl. This compound is refluxed with methanol overnight. The crude product is purified by chromatography on sihca gel to give the title compound. Example 59 Compound of Formula (V): R is -CH2-CH=CH 2 . RP is H. U is H. U' is H A sample of the intermediate descladinose compound wherein RP is acetyl from Example 57 is treated with tri(n-butyl)tin hydride under nitrogen atmosphere and a catalytic amount of AEBN in toluene at reflux to give the 2'acetylated intermediate. The 2'-acetyl group is removed by treatment overnight with hot methanol to give the title compound. Example 60 Compound of Formula (II): R is -CH9-CH=CH9-(3-quinolinyl). RP is H. W is absent, R w is H. U is H. U' is H A sample of the intermediate xanthate compound wherein RP is acetyl from Example 44 is treated with tri(n-butyl)tin hydride under nitrogen atmosphere and a catalytic amount of AIBN in toluene at reflux to give the 2'acetylated intermediate. The 2'-acetyl group is removed by treatment overnight with hot methanol to give the title compound. Example 61 Compound of Formula (IP: W is absent. R is H. R is -O^CHfO). RP is H, U is OH The compound from Example 8, Step 8b, is treated with ozone under N2 followed by treatment with dimethylsulfide and triphenylphosphine. The intermediate is treated with ethanolic HCl, and that product is refluxed with methanol overnight. The crude product is purified by chromatography on sihca gel to give the title compound. Example 62 Compound of Formula (II): W is absent. R w is H. R is -C^C^NHC^-phenyl. RP is H. U is OH The compound from Example 61 is treated with benzylamine in dry dichloromethane in the presence of molecular sieves (4A). The resulting imine is treated with a catalytic amount of 10% Pd on carbon under 1 arm of H2. The intermediate is treated with ethanoUc HCl, and that product is refluxed with methanol overnight. The crude product is purified by chromatography on sihca gel to give the title compound. Example 63 Compound of Formula (ID: W is absent. R w is H, R is -C C NHC CIh-phenvL RP is H. U is OH The compound from Example 61 is treated with phenethylamine in dry dichloromethane in the presence of molecular sieves (4A). The resulting imine is treated with a catalytic amount of 10% Pd on carbon under 1 atm of H2. The intermediate is treated with ethanolic HCl, and that product is refluxed with methanol overnight. The crude product is purified by chromatography on stiica gel to give the title compound. Example 64 RP is H. U is OH The compound from Example 61 is treated with 3-phenyl-l-propylamine in dry dichloromethane in the presence of molecular sieves (4A). The resulting imine is treated with a catalytic amount of 10% Pd on carbon under 1 atm of H2. The intermediate is treated with ethanolic HCl, and that product is refluxed with methanol overnight. The crude product is purified by chromatography on silica gel to give the title compound. Example 65 Compound of Formula (II): W is absent. R w is H. R is -CH2CH2NHCH2CH2CH2CH2- phenyl. RP is H. U is OH The compound from Example 61 is treated with 4-phenyl-l-butylamine in dry dichloromethane in the presence of molecular sieves (4A). The resulting imine is treated with a catalytic amount of 10% Pd on carbon under 1 atm of H2. The intermediate is treated with ethanolic HCl, and that product is refluxed with methanol overnight. The crude product is purified by chromatography on silica gel to give the title compound. Example 66 Compound of Formula (IP: W is absent. R is H, R is -CH2CH2NHCH2CH2CH2- (3-quinolvP. RP is H. U is OH The compound from Example 61 is treated with 3-(3-quinolyl)-l-propylamine in dry dichloromethane in the presence of molecular sieves (4A). The resulting imine is treated with a catalytic amount of 10% Pd on carbon under 1 atm of H2. The intermediate is treated with ethanolic HCl, and that product is refluxed with methanol overnight. The crude product is purified by chromatography on sihca gel to give the title compound. Example 67 Compound of Formula (ID: W is absent. R is H. R is -C^CTbNHC^G-quinolyl). RP is H. U is OH The compound from Example 61 is treated with 3-(aminomethyl)quinoUne in dry dichloromethane in the presence of molecular sieves (4A). The resulting imine is treated with a catalytic amount of 10% Pd on carbon under 1 atm of H2. The intermediate is treated with ethanolic HCl, and that product is refluxed with methanol overnight. The crude product is purified by chromatography on sihca gel to give the title compound. Example 68 Compound of Formula (II): W is absent. R w is H. R is -CH2CH=NO(phenyl), RP is H. U is OH The compound from Example 61 is treated with O-phenylhydroxylamine-HCl in dry dichloromethane in the presence of triethylamine. The intermediate is treated with ethanolic HCl, and that product is refluxed with methanol overnight. The crude product is purified by chromatography on silica gel to give the title compound. Example 69 U is OH The title compound was prepared from the compound of Example 61 (and O- benzylhydroxylamine-HCl in dry dichloromethane in the presence of triethylamine. The intermediate is treated with ethanolic HCl, and that product is refluxed with methanol overnight. The crude product is purified by chromatography on sihca gel to give the title compound. Example 70 is H. U is OH The title compound was prepared from the compound of Example 61 and O-(4- nitrobenzyl)hydroxylamine-HCl in dry dichloromethane in the presence of triethylamine. The intermediate is treated with ethanolic HCl, and that product is refluxed with methanol overnight. The crude product is purified by chromatography on sihca gel to give the title compound. Example 71 H. U is OH The compound from Example 61 and O-(4-quinolyl)methylhydroxylamine in dry dichloromethane in the presence of triethylamine. The intermediate is treated with ethanoUc HCl, and that product is refluxed with methanol overnight. The crude product is purified by chromatography on silica gel to give the title compound. Example 72 Compound of Formula (ID: W is absent, R w is H. R is -CH2CH=NΟCH9(2-quinolyl). RP is H. U is ΟH The title compound was prepared from the compound of Example 62 and O-(2- quinolyl)methylhydroxylamine in dry dichloromethane in the presence of triethylamine. The intermediate is treated with ethanolic HCl, and that product is refluxed with methanol overnight. The crude product is purified by chromatography on sihca gel to give the title compound. Example 73 Compound of Formula (II): W is absent. R w is H. R is -CH2CH=NΟCH2(3-quinolyl). RP is H. U is ΟH The title compound was prepared from the compound of Example 62 and O-(3- quinolyl)methylhydroxylamine in dry dichloromethane in the presence of triethylamine. The intermediate is treated with ethanolic HCl, and that product is refluxed with methanol overnight. The crude product is purified by chromatography on silica gel to give the title compound. Example 74 Compound of Formula (HP: W is absent. R is H. R is -CH2CH Ο). RP is H. U is ΟH The compound from Example 52 is treated with ozone under N2 followed by treatment with dimethylsulfide and triphenylphosphine. The intermediate is treated with ethanoUc HCl, and that product is refluxed with methanol overnight. The crude product is purified by chromatography on silica gel to give the title compound. Example 75 Compound of Formula ( IID: W is absent. R w is H. R is -C CIftNHCIfr-phenyl. RP is H. U is OH The compound from Example 74 is treated with benzylamine in dry dichloromethane in the presence of molecular sieves (4A). The resulting imine is treated with a catalytic amount of 10% Pd on carbon under 1 atm of H2. The intermediate is treated with ethanolic HCl, and that product is refluxed with methanol overnight. The crude product is purified by chromatography on sihca gel to give the title compound. Example 76 Compound of Formula (III): W is absent. R w is H. R is -CH2CH=NO(phenyl). RP is H. U is OH The compound from Example 74 is treated with O-phenylhydroxylamine-HCl in dry dichloromethane in the presence of triethylamine. The intermediate is treated with ethanolic HCl, and that product is refluxed with methanol overnight. The crude product is purified by chromatography on silica gel to give the title compound. Example 77 Compound of Formula (IV): W is absent. R w is H. R is -CH CH(O). RP is H. U is OH The compound from Example 50 is treated with ozone under N2 followed by treatment with dimethylsulfide and triphenylphosphine. The intermediate is treated with ethanolic HCl, and that product is refluxed with methanol overnight. The crude product is purified by chromatography on silica gel to give the title compound. Example 78 Compound of Formula (IV): W is absent. R is H, R is -C^C^NHC^-phenyl. RP is H. U is OH The compound from Example 77 is treated with benzylamine in dry dichloromethane in the presence of molecular sieves (4A). The resulting imine is treated with a catalytic amount of 10% Pd on carbon under 1 atm of H2. The intermediate is treated with ethanoUc HCl, and that product is refluxed with methanol overnight. The crude product is purified by chromatography on silica gel to give the title compound. Example 79 OH The compound from Example 77 is treated with O-phenylhydroxylamine-HCl in dry dichloromethane in the presence of triethylamine. The intermediate is treated with ethanolic HCl, and that product is refluxed with methanol overnight. The crude product is purified by chromatography on sUica gel to give the title compound. Example 80 Compound of Formula (V): W is absent. Rw j s H. R is -CH9CH(O). RP is H. U is OH The compound from Example 57 is treated with ozone under N2 followed by treatment with dimethylsulfide and triphenylphosphine. The intermediate is treated with ethanoUc HCl, and that product is refluxed with methanol overnight. The crude product is purified by chromatography on silica gel to give the title compound. Example 81 is OH The compound from Example 80 is treated with benzylamine in dry dichloromethane in the presence of molecular sieves (4A). The resulting imine is treated with a catalytic amount of 10% Pd on carbon under 1 atm of H2. The intermediate is treated with ethanoUc HCl, and that product is refluxed with methanol overnight. The crude product is purified by chromatography on sihca gel to give the title compound. Example 82 Compound of Formula (V): W is absent, R w is H. R is -CH2CH=NO(phenyl), RP is H. U is OH The compound from Example 80 is treated with O-phenylhydroxylamine-HCl in dry dichloromethane in the presence of triethylamine. The intermediate is treated with ethanoUc HCl, and that product is refluxed with methanol overnight. The crude product is purified by chromatography on sUica gel to give the title compound.

Claims: WHAT IS CLAIMED IS: A compound selected from the group consisting of: (I) or a pharmaceuticaUy acceptable salt, ester or prodrug thereof, wherein Y and Z taken together define a group X, wherein X is selected from the group consisting of (1) =O, (2) =N-OH, (3) =N-O-R 1 where R 1 is selected from the group consisting of (a) unsubstituted C]-C 12- alkyl, (b) Cι-Ci2-alkyl substituted with aryl, (c) Cι-Ci2-alkyl substituted with substituted aryl, (d) Cι-Ci2-alkyl substituted with heteroaryl, (e) C]-Ci2-alkyl substituted with substituted heteroaryl, (f) C3-Ci2-cycloalkyl, and (g) -Si-(R 2 )(R 3 )(R 4 ) wherein R 2 , R3 and R 4 are each independently selected from -C 12- lkyl and aryl; and (4) =N-O-C(R 5 )(R 6 )-O-R 1 where R 1 is as previously defined and R 5 and R 6 are each independently selected from the group consisting of (a) hydrogen, (b) unsubstituted Cι-Ci2-alkyl, (c) Cι-Ci2-alkyl substituted with aryl, (d) Cι-Ci2-alkyl substituted with substituted aryl, (e) Ci-C 12- alkyl substituted with heteroaryl, and (f) Cι-Ci2-alkyl substituted with substituted heteroaryl, or R 5 and R 6 taken together with the atom to which they are attached form a C3-Ci2-cycloalkyl ring; or, one of Y and Z is hydrogen and the other is selected from a group consisting of (1) hydrogen, (2) hydroxy, (3) protected hydroxy, and (4) NR 7 R 8 wherein R 7 and R 8 are independently selected from hydrogen and Ci- C6-alkyl, or R 7 and R 8 are taken with the nitrogen atom to which they are connected to form a 3- to 7-membered ring which, when the ring is a 5- to 7-membered ring, may optionaUy contain a hetero function selected from the group consisting of -O-, -NH-, -N(Cι-C6-alkyl-)-, N(aryl)-, -N(aryl-Cι-C6-alkyl-)-, -N(substituted-aryl-Cι-C6-alkyl-)-, -N(heteroaryl)-, - N(heteroaryl-Cι-C6-alkyl-)-, -N(substituted-heteroaryl-Cι-C6-alkyl-)-, and -S- or -S(O) n -, wherein n is 1 or 2, W is absent or is selected from the group consisting of -O-, -NH-CO-, -N=CH- and -NH-; R w is selected from the group consisting of (1) hydrogen, (2) Ci-Cβ-alkyl optionally substituted with one or more substituents selected from the group consisting of (a) aryl, (b) substituted-aryl, (c) heteroaryl, (d) substituted-heteroaryl, (e) hydroxy, (f) Cι-C 6 -alkoxy, (g) NR 7 R 8 , wherein R 7 and R 8 are as defined previously, and (h) -CH2-M-R 9 , wherein M is selected from the group consisting of: (i) -C(O)-NH-, (ii) -NH-C(O)-, (in) -NH-, (iv) -N=, (v) -N(CH 3 ) -, (vi) -NH-C(O)-O- (vii) -NH-C(O)-NH- (viii) -O-C(O)-NH- (ix) -O-C(O)-O- (x) -O-, (xi) -S(O) n -, wherein n is 0, 1 or 2, (xu) -C(O)-O-, (xiii) -O-C(O)-, and (xiv) -C(O)-, and R 9 is selected from the group consisting of: (i) Ci-Cβ-alkyl, optionally substituted with a substituent selected from the group consisting of (aa) aryl, (bb) substituted-aryl, (cc) heteroaryl, and (dd) substituted-heteroaryl, (ii) aryl, (hi) substituted-aryl, (iv) heteroaryl, (v) substituted-heteroaryl, and (vi) heterocycloalkyl, (3) C3-C 7 -cycloalkyl, (4) aryl, (5) substituted-aryl, (6) heteroaryl, and (7) substituted-heteroaryl; RP is hydrogen or a hydroxy protecting group; R is selected from the group consisting of (1) methyl substituted with a moiety selected from the group consisting of (a) CN, (b) F, (c) -CO2R 10 wherein R 10 is Cι-C3-alkyl or aryl substituted Cι-C3-alkyl, or heteroaryl substituted Cι-C3-alkyl, (d) S(O) n R 10 where n is 0, 1 or 2 and R 10 is as previously defined, (e) NHC(O)R 10 where R 10 is as previously defined, (f) NHC(O)NR π R 12 wherein R 11 and R 12 are independently selected from hydrogen, Cι-C3-alkyl, Cι-C3-alkyl substituted with aryl, substituted aryl, heteroaryl, substituted heteroaryl, (g) aryl, (h) substituted aryl, (i) heteroaryl, and G) substituted heteroaryl, (2) C2-C ιo- alkyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) hydroxy, (c) Cj-C3-alkoxy, (d) C 1 -C3-alkoxy-C \ -C^-alkoxy , (e) oxo, ( ) -N 3 , (g) -CHO, (h) O-SO2- (substituted Ci- -alkyl), (i) -NR 13 R 14 wherein R 13 and R 14 are selected from the group consisting of (i) hydrogen, (ϋ) Cι-Ci2-alkyl, (iii) substituted Cι-Ci2-alkyl, (iv) Cι-C]2-alkenyl, (v) substituted Cι-Ci2-alkenyl, (vi) Cι-Ci2-alkynyl, (vii) substituted Cι-Ci2-aU ynyl, (vhi) aryl, (ix) C3-C8-cycloalkyl, (x) substituted C3-Cs-cycloalkyl, (xi) substituted aryl, (xϋ) heterocycloalkyl, (xiii) substituted heterocycloalkyl, (xiv) Cι-Ci2-alkyl substituted with aryl, (XV) Cι-Ci2-alkyl substituted with substituted aryl, (xvi) Ci-C 12- alkyl substituted with heterocycloalkyl, (xvii) Cι-Ci2-alkyl substituted with substituted heterocycloalkyl, (xviii) Cι-Ci2-alkyl substituted with C3-Cg-cycloalkyl, (xix) Cι-Ci2-alkyl substituted with substituted C3-Cg-cycloalkyl, (xx) heteroaryl, (xxi) substituted heteroaryl, (xxii) Cι-Ci2-alkyl substituted with heteroaryl, and (xxiii) C -Ci2-alkyl substituted with substituted heteroaryl, or R 13 and R 14 are taken together with the atom to which they are attached form a 3- 10 membered heterocycloalkyl ring which may be substituted with one or more substituents independently selected from the group consisting of (i) halogen, (ii) hydroxy, (iii) Cι-C3-alkoxy, (iv) Cι-C3-alkoxy-Cι-C3-alkoxy, (v) oxo, (vi) Cι-C 3 -alkyl, (vii) halo-Cι-C 3 -alkyl, and (vii) Cι-C 3 -alkoxy-Cι-C3-alkyl, (j) -CO2R 10 wherein R 10 is as previously defined, (k) -C(O)NR π R 12 wherein R 1 J and R 12 are as previously defined, (1) =N-O-R 10 wherein R 10 is as previously defined, (m) -C≡N, (n) O-S(O) n R 10 wherein n is 0, 1 or 2 and R 10 is as previously defined, (0) aryl, (p) substituted aryl, (q) heteroaryl, (r) substituted heteroaryl, (s) C3-Cg-cycloalkyl, (t) substituted C3-Cg-cycloalkyl, (u) Cι-Ci2-alkyl substituted with heteroaryl, (v) heterocycloalkyl, (w) substituted heterocycloalkyl, (x) NHC(O)R 10 where R 10 is as previously defined, (y) NHC(O)NR! !R 12 wherein R 11 and R 12 are as previously defined, (z) =N-NR 13 R 14 wherein R 13 and R 14 are as previously defined, (aa) =N-R 9 wherein R 9 is as previously defined, (bb) =N-NHC(O)R 10 wherein R 10 is as previously defined, and (cc) =N-NHC(O)NR 1 *R 12 wherein R 1 ! and R 12 are as previously defined; (3) C3-alkenyl substituted with a moiety selected from the group consisting of (a) halogen, (b) -CHO, (c) -CO2R 10 where R 10 is as previously defined, (d) -C(O)-R 9 where R 9 is as previously defined, (e) -C^NR^R 12 wherein R 11 and R 12 are as previously defined, ( ) -C≡N, (g) aryl, (h) substituted aryl, (i) heteroaryl, (j) substituted heteroaryl, (k) C3-C7-cycloalkyl, and 0) Cι-Ci2-alkyl substituted with heteroaryl, (4) C4-Cιo-alkenyl; (5) C4-C 10- alkenyl substituted with one or more substituents selected from the group 1 consisting of (a) halogen, (b) Cι-C3-alkoxy, (c) oxo, (d) -CHO, (e) -CO2R 10 where R 10 is as previously defined, ( ) -C^NR^R 12 wherein R 11 and R 12 are as previously defined, (g) -NR 13 R 14 wherein R 13 and R 14 are as previously defined, (h) =N-O-R 10 where R 10 is as previously defined, (i) -C≡N, 0 ) O-S(O) n R 10 where n is 0, 1 or 2 and R 10 is as previously defined, 00 aryl, (1) substituted aryl, (m) heteroaryl, (n) substituted heteroaryl, (0) C3-C7-cycloalkyl, (P) Cι-Ci2-alkyl substituted with heteroaryl, (q) NHC(O)R 10 where R 10 is as previously defined, (r) NHC(O)NR π R 12 wherein R 11 and R 12 are as previously defined, (s) =N-NR 13 R 14 wherein R 13 and R 14 are as previously defined, (t) =N-R 9 wherein R 9 is as previously defined, (u) =N-NHC(O)R 10 where R 10 is as previously defined, and (v) =N-NHC(O)NR 11 R 12 wherein R 1 1 and R 12 are as previously defined; (6) C3-Cιo-alkynyl; and (7) C3-Cιo-alkynyl substituted with one or more substituents selected from the group consisting of (a) trialkylsilyl, (b) aryl, (c) substituted aryl, (d) heteroaryl. (e) halogen, and ( ) substituted heteroaryl; U is selected from the group consisting of: (1) hydrogen, (2) hydroxy, (3) protected hydroxy, (4) -O-T-R 1 , wherein T is absent or selected from the group consisting of: (a) -C(O)-, (b) -C(O)-O- (c) -CH 2 -, (d) -C(S)-S-, (e) -C(O)-N(R s )-, wherein R s is H or Cι-C 6 -alkyl, (f) -S(O) n -, wherein n is 0, 1 or 2, (g) -S(O) n -O-, wherein n is 0, 1 or 2, (h) -P(O)(OR r )n-, wherein n is 0, 1 or 2, and R r is Cι-C 6 -alkyl, and (i) -SO2-N(R s )-, wherein R s is as defined previously; and R l is selected from the group consisting of: (a) Cι-C6-alkyl, optionally substituted with a substituent selected from the group consisting of (i) aryl, (ii) substituted-aryl, (hi) heteroaryl, and (iv) substituted-heteroaryl, (v) heterocycloalkyl, (vi) substituted-heterocycloalkyl, (vii) hydroxy, (viii) Cι-C6-alkoxy, (ix) NR 7 R 8 wherein R 7 and R 8 are as defined previously, (b) C3-C6-alkenyl, optionally substituted with a substituent selected from the group consisting of (i) aryl, (ii) substituted-aryl, (hi) heteroaryl, and (iv) substituted-heteroaryl, (v) heterocycloalkyl, (vi) substituted-heterocycloalkyl, (vii) hydroxy, (viii) Cι-C6-alkoxy, (ix) NR 7 R 8 wherein R 7 and R 8 are as defined previously, (c) C3-Ci2-cycloalkyl, optionally substituted with a substituent selected from the group consisting of (i) aryl, (ii) substituted-aryl, (iii) heteroaryl, and (iv) substituted-heteroaryl, (v) heterocycloalkyl, (vi) substituted-heterocycloalkyl, (vii) hydroxy, (viii) Cι-C6-alkoxy, (ix) NR 7 R 8 wherein R 7 and R 8 are as defined previously, (d) aryl, (e) substituted-aryl, (f) heteroaryl, (g) substituted-heteroaryl, and (h) heterocycloalkyl; or in compounds of formula (II) and (III) U is taken together with U' to form a double bond between the carbon atoms to which they are attached; and U' is hydrogen or in compounds of formula (II) and (HI) U' is taken together with U to form a double bond between the carbon atoms to which they are attached. 2. A pharmaceutical composition for treating bacterial infections comprising a therapeuticaUy effective amount of a compound of Claim 1 or a pharmaceuticaUy acceptable salt or ester thereof in combination with a pharmaceuticaUy acceptable carrier. 3. A method for treating bacterial infections comprising administering to a mammal in need of such treatment a pharmaceutical composition containing a therapeutically-effective amount of a compound of Claim 1 or a pharmaceuticaUy acceptable salt or ester thereof. 4. A compound according to Claim 1 having the formula (I) 5. A compound according to Claim 4 wherein Y and Z taken together define a group X which is =O. 6. A compound according to Claim 4 which is selected from the group consisting of: Compound of Formula (I): R is allyl, RP is H, X is O, U is OH; Compound of Formula (I): R is allyl, RP is benzoyl, X is O, U is OH; Compound of Formula (I): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, X is O, U is OH; Compound of Formula (I): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, X is O, U is O- acetyl; Compound of Formula (I): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, X is O, U is O-(4-methoxy)benzoyl; Compound of Formula (I): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, X is O, U is O-methanesulfonyl; and Compound of Formula (I): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, X is O, U is O-CO- NH-(2-nitrophenyl). 7. A process for preparing a compound of formula (I) wherein Y and Z taken together define a group X which is =O, having the formula (IA) (IA) wherein RP is hydrogen or a hydroxy protecting group; R is selected from the group consisting of ( 1 ) methyl substituted with a moiety selected from the group consisting of (a) CN, (b) F, (c) -CO2R 10 wherein R 10 is Cι-C 3 -alkyl or aryl substituted Cι-C3-alkyl, or heteroaryl substituted Cι-C3-alkyl, (d) S(O) n R 10 where n is 0. 1 or 2 and R 10 is as previously defined, (e) NHC(O)R 10 where R 10 is as previously defined, (f) NHC(O)NR π Rl 2 wherein R 1 1 and R 12 are independently selected from hydrogen, Ci-C^-alkyl, Cι-C3~alkyl substituted with aryl, substituted aryl, heteroaryl, substituted heteroaryl, (g) aryl, (h) substituted aryl, (i) heteroaryl, and (j) substituted heteroaryl, (2) C2-Cιo-alkyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) hydroxy, (c) Cι-C3-alkoxy, (d) Cι-C3-alkoxy-Cι-C3-alkoxy, (e) oxo, ( ) -N 3 , (g) -CHO, (h) O-SO2-(substituted Cι-C 6 -alkyl), (i) -NR 13 R 14 wherein R 13 and R 14 are selected from the group consisting of (i) hydrogen, (ii) Ci-Cπ-alkyl, (in) substituted Cι-Ci2-alkyl, (iv) Cι-Ci2-aU enyl, (v) substituted Cι-Ci2-alkenyl, (vi) Cι-Ci2-alkynyl, (vu) substituted Cι-Ci2-alkynyl, (viu) aryl, (ix) C3-C8-cycloalkyl, (x) substituted C3-C8-cycloalkyl, (xi) substituted aryl, (xii) heterocycloalkyl, (xiii) substituted heterocycloalkyl, (xiv) Cι-Ci2-alkyl substituted with aryl, (xv) Cι-Ci2-alkyl substituted with substituted aryl, (xvi) Cι-Ci2-alkyl substituted with heterocycloalkyl, (xvii) Cι-Ci2-alkyl substituted with substituted heterocycloalkyl, (xviii) Cι-Ci2-alkyl substituted with C3-C8-cycloalkyl, (xix) Cι-Ci2-alkyl substituted with substituted C3-C8-cycloalkyl, (xx) heteroaryl, (xxi) substituted heteroaryl, (xxii) Cj-Ci2-alkyl substituted with heteroaryl, and (xxiii) Cι-Ci2-alkyl substituted with substituted heteroaryl, or R 13 and R 14 are taken together with the atom to which they are attached form a 3-10 membered heterocycloalkyl ring which may be substituted with one or more substituents independently selected from the group consisting of (i) halogen, (ii) hydroxy, (iii) Cι-C3-alkoxy, (iv) Cι-C3-alkoxy-Cι-C3-alkoxy, (v) oxo, (vi) Cι-C 3 -alkyl, (vii) halo-Cι-C 3 -alkyl, and (vii) Cι-C3-alkoxy-Cι-C3-alkyl, (j) -CO2R 10 wherein R 10 is as previously defined, (k) -C(O)NR 11 R 12 wherein R 11 and R 12 are as previously defined, (1) =N-O-R 10 wherein R 10 is as previously defined, (m) -C≡N, (n) O-S(O) n R 10 wherein n is 0, 1 or 2 and R 10 is as previously defined, (0) aryl, (p) substituted aryl, (q) heteroaryl, (r) substituted heteroaryl, (s) C3-C8-cycloalkyl, (t) substituted C3-C8-cycloalkyl, (u) Cι-Ci2-alkyl substituted with heteroaryl, (v) heterocycloalkyl, (w) substituted heterocycloalkyl, (x) NHC(O)R 10 where R 10 is as previously defined, (y) NHC(O)NR! !R 1 wherein R 1 1 and R 12 are as previously defined, (z) =N-NR 1 R 14 wherein R 13 and R 14 are as previously defined, (aa) =N-R 9 wherein R 9 is as previously defined, (bb) =N-NHC(O)R 10 wherein R 10 is as previously defined, and (cc) =N-NHC(O)NR 1 !R 12 wherein R 1 l and R 12 are as previously defined; (3) 03-alkenyl substituted with a moiety selected from the group consisting of (a) halogen, (b) -CHO, (c) -CO2R 10 where R 10 is as previously defined, (d) -C(O)-R 9 where R 9 is as previously defined, (e) -C(O)NR l i R 12 wherein R 11 and R 12 are as previously defined, (f) -C≡N, (g) aryl, (h) substituted aryl, (i) heteroaryl, (j) substituted heteroaryl, (k) C 3 -C 7 -cycloalkyl, and (1) Cι-Ci2-alkyl substituted with heteroaryl, (4) C -Cιo-alkenyl; (5) C4-Cιo-alkenyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) Cι-C 3 -alkoxy, (c) oxo, (d) -CHO, (e) -CO2R 10 where R 10 is as previously defined, (f) -C(O)NR 11 R 12 wherein R 11 and R 12 are as previously defined, (g) -NR 13 R 14 wherein R 13 and R 14 are as previously defined, (h) =N-O-R 10 where R 10 is as previously defined, (i) -C≡N, (j) O-S(O) n R 10 where n is 0, 1 or 2 and R 10 is as previously defined, (k) aryl, (1) substituted aryl, (m) heteroaryl, (n) substituted heteroaryl, (o) C3-C7-cycloalkyl, (p) Cι-Ci2-alkyl substituted with heteroaryl, (q) NHC(O)R 10 where R 10 is as previously defined, (r) NHC(O)NR 1 J R 12 wherein R 11 and R 12 are as previously defined, (s) =N-NR 13 R 14 wherein R 13 and R 14 are as previously defined, (t) =N-R 9 wherein R 9 is as previously defined, (u) =N-NHC(O)R 10 where R 10 is as previously defined, and (v) =N-NHC(O)NR! !R 12 wherein R 1 1 and R 12 are as previously defined; (6) C 3 -Cι 0 -alkynyl; and (7) C3-Cιo-alkynyl substituted with one or more substituents selected from the group consisting of (a) trialkylsilyl, (b) aryl, (c) substituted aryl, (d) heteroaryl, (e) halogen, and ( ) substituted heteroaryl; -108- SUBST1TUTE SHEET (RULE 26) and U is selected from the group consisting of: (1) hydrogen, (2) hydroxy, (3) protected hydroxy, (4) -O-T-R 1 , wherein T is absent or selected from the group consisting of: (a) -C(O)-, (b) -C(O)-O- (c) -CH 2 -, (d) -C(S)-S-, (e) -C(O)-N(Rs)-, wherein Rs is H or Cι-C 6 -alkyl, (f) -S(O) n -, wherein n is 0, 1 or 2, (g) -S(O) n -O-, wherein n is 0, 1 or 2, (h) -P(O)(OR r )n-, wherein n is 0, 1 or 2, and R r is Cj- -alkyl, and (i) -SO2-N(R s )-, wherein R s is as defined previously; and R l is selected from the group consisting of: (a) -Cfi-alkyl, optionally substituted with a substituent selected from the group consisting of (i) aryl, (ϋ) substituted-aryl, (ϋi) heteroaryl, and (iv) substituted-heteroaryl, (v) heterocycloalkyl, (vi) substituted-heterocycloalkyl , (vii) hydroxy, (viii) Ci-Cβ-alkoxy, (ix) NR 7 R 8 wherein R 7 and R 8 are as defined previously, (b) C3-C6-alkenyl, optionally substituted with a substituent selected from the group consisting of (i) aryl, (ϋ) substituted-aryl, (hi) heteroaryl, and (iv) substituted-heteroaryl, (v) heterocycloalkyl, (vi) substituted-heterocycloalkyl, (vii) hydroxy, (viii) Cι-C6-alkoxy, (ix) NR 7 R 8 wherein R 7 and R 8 are as defined previously, (c) C3-Ci2-cycloalkyl, optionally substituted with a substituent selected from the group consisting of (i) aryl, (ii) substituted-aryl, (ih) heteroaryl, and (iv) substituted-heteroaryl, (v) heterocycloalkyl, (vi) substituted-heterocycloalkyl, (vii) hydroxy, (viii) Cι-C6-alkoxy, (ix) NR 7 R 8 wherein R 7 and R 8 are as defined previously, (d) aryl, (e) substituted-aryl, (f) heteroaryl, (g) substituted-heteroaryl, and (h) heterocycloalkyl; the method comprising: (a) treating hydroIyticaUy with acid a compound having the formula wherein R is as defined previously, to give a compound having the formula which is a compound of formula (IA) wherein RP is H and U is hydroxy; (b) optionally treating the compound of Step (a) with a hydroxy protecting reagent to give a compound having the formula which is a compound of formula (IA) wherein Rp is a hydroxy-protecting group and U is hydroxy, optionaUy foUowed by converting the compound having the natural (3S) isomeric configuration into the compound having the non-natural (3R) isomeric configuration by oxidation of the 3-hydroxyl group and selective reduction of the 3-oxo group to give the non- natural (3R) isomer; (c) optionaUy treating the compound of formula (IA) wherein Rp is a hydroxy-protecting group and U is hydroxy (the compound from Step (b)) with an excess of NaH in an aprotic solvent followed by reaction of the intermediate anion with CS2 and CH3I to form a xanthate intermediate which is then treated with Bu3SnH under an inert atmosphere in the presence of a catalytic amount of a suitable radical initiator to afford the desired 3-deoxy compound having the formula which is a compound of formula (IA) wherein U is hydrogen; (d) optionaUy treating the compound of formula (IA) wherein Rp is a hydroxy-protecting group and U is hydroxy (the compound from Step (b)) with a hydroxy-protecting reagent to give a compound of formula (IA) wherein Rp is a hydroxy-protecting group and U is a protected hydroxyl group; (e) optionally treating the compound of formula (I A) wherein RP is a hydroxy-protecting group and U is hydroxy (the compound from Step (b)) with base and a reagent L-T-R 1 , wherein T and R l are as previously defined, and L is a suitable reactive leaving group to give compound having the formula (f) optionally deprotecting, and isolating the desired compound of formula (IA). 8. A process according to Claim 7 wherein in step (e) the reagent L-T-R 1 is selected from the group consisting of: (e-i) halogen-C(O)-R t ; (e-ii) O-(C(O)-R t ) 2 ; (e-iii) O-(C(O)-O-Rt) 2 ; (e-iv) halogen-CH2-R t ; (e-v) alkali metal hydride followed by CS2 then followed by halogen-R 1 ; (e-vi) O=C=N-R l ; (e-vii) carbonyl diimidazole followed by N(R S )H-R l ; (e-viiii) Cl-S(O)n-O-R l ; (e-ix) Cl-P(O)(OR r )n-R t ; (e-x) Cl-SO 2 -N(R s )-R t ; 9. A process according to Claim 7 wherein in step (e) the base and the reagent L-T- R l are replaced with 3,4-dihydro-2H-pyran in the presence of a acid catalyst. 10. A compound according to Claim 1 having the formula (II) 1 1. A compound according to Claim 8 wherein W is absent and R w is H. 12. A compound according to Claim 8 which is selected from the group consisting of: Compound of Formula (II): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, W is absent, R w is H, U is OH; Compound of Formula (II): R is -CH -CH=CH2-(3-quinolinyl), RP is H, W is absent, R w is H, U is O-acetyl; Compound of Formula (II): R is -CH 2 -CH=CH2-(3-quinolinyl), RP is H, W is absent, R w is H, U is O-(4-nitrobenzoyl),; Compound of Formula (II): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, W is absent, R w is H, U is O-benzoyl; Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R is H, U is O-(3,5-diphenylpyridinecarboxyl); Compound of Formula (II): R is -CH -CH=CH2-(3-quinolinyl), RP is H, W is absent, R w is H, U is O-(2-nitrobenzoyl); Compound of Formula (II): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, W is absent, R is H, U is O-(3,4,5-trimethoxybenzoyl); Compound of Formula (JJ): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R w is H, U is O-(2-thiophenecarboxoyl); Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R is H, U is O-(2-methylbutanoyl); Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R w is H, U is O-(4-bromobenzoyl); Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R w is H, U is O-(4-pyridinecarboxoyl); Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R is H, U is O-(methoxycarbonyl); Compound of Formula (II): R is -CH2-CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R is H, U is O-(l,l-dimethylethoxycarbonyl); Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R is H, U is O-(2-bromobenzoyl); Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R is H, U is O-(4-methoxybenzoyl); Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quino nyl), RP is H, W is absent, R w is H, U is O-(2-furancarboxoyl); Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R w is H, U is O-butanoyl; Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R w is H, U is O-methanesulfonyl; Compound of Formula (II): R is -CH -CH=CH2-(3-quinolinyl), RP is H, W is absent, R is H, U is O-(2-methylpropenoyl); Compound of Formula (II): R is -CH 2 -CH=CH2-(3-quinolinyl), RP is H, X is O, W is absent, R w is H, U is O-CO-NH-phenyl; Compound of Formula (II): R is -CH 2 -CH=CH2-(3-quinolinyl), RP is H, X is O, W is absent, R w is H, U is O-CO-NH-allyl; Compound of Formula (II): R is -CH 2 -CH=CH2-(3-quinolinyl), RP is H, X is O, W is absent, R is H, U is O-CO-NH-CH(C(O)OCH )-CH(CH3) 2 ; Compound of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP is H, X is O, W is absent, R w is H, U is O-CO-NH-CH(CH 3 ) 2 ; Compound of Formula (II): R is -CH2-CH=CH 2 -(3-quinolinyl), RP is H, X is O, W is absent, R is H, U is O-CO-NH-cyclohexyl; Compound of Formula (II): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, X is O, W is absent, R w is H, U is O-CO-NH-(4-fluorophenyl); Compound of Formula (II): R is -CH2-CH=CH 2 -(3-quinolinyl), RP is H, X is O, W is absent, R w is H, U is O-CO-NH-(2-nitrophenyl); Compound of Formula (II): R is -CH2-CH=CH 2 -(3-quinolinyl), RP is H, X is O, W is absent, R w is H, U is O-CO-NH-(4-methyl-2-nitrophenyl); Compound of Formula (II): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, X is O, W is absent, R w is H, U is O-CO-NH-(4-nitrophenyl); Compound of Formula (II): R is -CH2-CH=CH 2 -(3-quinolinyl), RP is H, X is O, W is absent, R is H, U is O-CO-NH-(4-methoxyphenyl); Compounds of Formula (II): R is -CH2-CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R w is H, U is O-S(O) 2 -CH=CH 2 ; Compounds of Formula (II): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, W is absent, R w is H, U is O-S(O)2-CH 2 -CH2-N(CH3) 2 ; Compounds of Formula (II): R is -CH 2 -CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R w is H, U is O-S(O)2-CH 2 -CH -S-phenyl; Compounds of Formula (II): R is -CH2-CH=CH 2 -(3-quinolinyl), RP is H, W is absent, R is H, U is O-allyl; Compound of Formula (II): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, W is absent, R w is H, U is O-(4-morpholinecarbonyl); Compound of Formula (II): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, W is absent, R w is H, U is O-pyrrohdinylcarbonyl; Compound of Formula (II): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, W is absent, R w is H, U is O-(2-tetrahydropyranyl); Compound of Formula (II): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, W is absent, R w is H, U is O-C(=S)-SCH 3 ; Compound of Formula (II): R is -CH2-CH=CH2, RP is H, U and U' taken together are double bond, W is absent, R w is H; Compound of Formula (II): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, U and U' taken together are double bond, W is absent, R w is H; Compound of Formula (II): R is -CH2-CH=CH2-(6-nitro-3-quinolinyl), RP is H, U and U' taken together are double bond, W is absent, R w is H; Compound of Formula (II): R is -CH2-CH=CH2-(6-methoxy-2-naphthyl), RP is H, U and U' taken together are double bond, W is absent, R w is H; Compound of Formula (II): R is -CH2-CH=CH2-(3-(5-(3-isoxazolyl)-2-furanyl)), RP is H, U and U' taken together are double bond, W is absent, R w is H; Compound of Formula (II): R is -CH2-CH=CH 2 , RP is H, W is NH, R w is H, U is OH; Compound of Formula (II): R is -CH2-CH=CH2-(3-quinolinyl), RP is H, W is absent, R w is H, U is H, U' is H; Compound of Formula (II): W is absent, R is H, R is -CH 2 CH(O), RP is acetyl, U is OH; Compound of Formula (II): W is absent, R is H, R is -CH2CH 2 NHCH 2 -ρhenyl, RP is acetyl, U is OH; Compound of Formula (II): W is absent, R is H, R is -CH 2 CH2NHCH 2 CH2-phenyl, RP is acetyl, U is OH; Compound of Formula (II): W is absent, R w is H, R is -CH2CH 2 NHCH2CH 2 CH2-phenyl, RP is acetyl, U is OH; Compound of Formula (II): W is absent, R is H, R is -CH2CH2NHCH2CH2CH2CH2- phenyl, RP is acetyl, U is OH; Compound of Formula (JJ): W is absent, R w is H, R is -CH2CH2NHCH2CH2CH2- (3-quinolyl), RP is acetyl, U is OH; Compound of Formula (II): W is absent, R is H, R is -CH 2 CH2NHCH 2 -(3-quinolyl), RP is acetyl, U is OH; Compound of Formula (II): W is absent, R w is H, R is -CH2CH=NO-(phenyl), RP is acetyl, U is OH; Compound of Formula (II): W is absent, R is H, R is -CH2CH=NOCH2-(phenyl), RP is acetyl, U is OH; Compound of Formula (II): W is absent, R is H, R is -CH 2 CH=NOCH2-(4-NO 2 -phenyl), RP is acetyl, U is OH; Compound of Formula (II): W is absent, R w is H, R is -CH2CH=NOCH2-(4-quinolyl), RP is acetyl, U is OH; Compound of Formula (II): W is absent, R is H, R is -CH2CH=NOCH2-(2-quinolyl), RP is acetyl, U is OH; and Compound of Formula (II): W is absent, R w is H, R is -CH2CH=NOCH2-(3-quinolyl), RP is acetyl, U is OH. 13. A process for preparing a compound having the formula (II) wherein RP is hydrogen or a hydroxy protecting group; R is selected from the group consisting of (1) methyl substituted with a moiety selected from the group consisting of (a) CN, (b) F, (c) -CO2R 10 wherein R 10 is Cι-C3-alkyl or aryl substituted Cι-C3-aIkyl, or heteroaryl substituted Cj-C3-alkyl, (d) S(O) n R 10 where n is 0, 1 or 2 and R 10 is as previously defined, (e) NHC(O)R 10 where R 10 is as previously defined, (f) NHC(O)NR n Rl 2 wherein Rl • and R 12 are independently selected from hydrogen, Ci-C^-alkyl, Cι-C3-alkyl substituted with aryl, substituted aryl, heteroaryl, substituted heteroaryl, (g) aryl, (h) substituted aryl, (i) heteroaryl, and (i ) substituted heteroaryl, (2) C2-Cιo-alkyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) hydroxy, (c) Cι-C3-alkoxy, (d) Cι-C3-alkoxy-Cι-C3-alkoxy, (e) oxo, (f) -N3, (g) -CHO, (h) O-SO2-(substituted Cι-C6-alkyl), (i) -NR 13 R 14 wherein R 13 and R 14 are selected from the group consisting of (i) hydrogen, (ii) Cι-Ci2-alkyl, (hi) substituted Cι-Ci2-alkyl, (iv) Cι-Ci2-alkenyl, (v) substituted Cι-Ci2-alkenyl, (vi) Cι-Ci2-alkynyl, (vh) substituted Cι-Ci2-aU ynyl, (viii) aryl, (ix) C3-C8-cycloalkyl, (x) substituted C3-C8-cycloalkyl, (xi) substituted aryl, (xii) heterocycloalkyl, (xih) substituted heterocycloalkyl, (xiv) Cj-C i 2 - lkyl substituted with aryl, (xv) Cι-Ci2-alkyl substituted with substituted aryl, (xvi) Cj-C i2- alkyl substituted with heterocycloalkyl, (xvii) Cι-Ci2-alkyl substituted with substituted heterocycloalkyl, (xviii) Cι-Ci2-alkyl substituted with C3-Cs-cycloalkyl, (xix) Cι-Ci 2 -alkyl substituted with substituted C3-C8-cycloalkyl, (xx) heteroaryl, (xxi) substituted heteroaryl, (xxii) Cι-Ci2-alkyl substituted with heteroaryl, and (xxiii) Cι-Ci2-alkyl substituted with substituted heteroaryl, or R 13 and R 14 are taken together with the atom to which they are attached form a 3- 10 membered heterocycloalkyl ring which may be substituted with one or more substituents independently selected from the group consisting of (i) halogen, (ϋ) hydroxy, (hi) Cι-C3-alkoxy, (iv) Cι-C3-alkoxy-Cι-C3-alkoxy, (v) oxo, (vi) Cι-C 3 -alkyl, (vh) halo-Cι-C 3 -alkyl, and (vh) Cι-C 3 -alkoxy-Cι-C3-alkyl, (j) -CO2R 10 wherein R 10 is as previously defined, (k) -C(O)NR 11 R 12 wherein R 11 and R 12 are as previously defined, (1) =N-O-R 10 wherein R 10 is as previously defined, (m) -C≡N, (n) O-S(O) n R 10 wherein n is 0, 1 or 2 and R 10 is as previously defined, (o) aryl, (p) substituted aryl, (q) heteroaryl, (r) substituted heteroaryl, (s) C3-C8-cycloalkyl, (t) substituted C3-Cs-cycloalkyl, (u) Cι-Ci2-alkyl substituted with heteroaryl, (v) heterocycloalkyl, (w) substituted heterocycloalkyl, (x) NHC(O)R 10 where R 10 is as previously defined, (y) NHC(O)NR 1 Ϊ R 12 wherein R 11 and R 12 are as previously defined, (z) =N-NR 13 R 14 wherein R 13 and R 14 are as previously defined, (aa) =N-R 9 wherein R 9 is as previously defined, (bb) =N-NHC(O)R 10 wherein R 10 is as previously defined, and (cc) =N-NHC(O)NR n R 12 wherein R * 1 and R 12 are as previously defined; (3) C3-alkenyl substituted with a moiety selected from the group consisting of (a) halogen, (b) -CHO, (c) -CO2R 10 where R 10 is as previously defined, (d) -C(O)-R 9 where R 9 is as previously defined, (e) -C(O)NR 1 'R 12 wherein R 11 and R 12 are as previously defined, (f) -C≡N, (g) aryl, (h) substituted aryl, (i) heteroaryl, (j) substituted heteroaryl, (k) C3-C7-cycloalkyl, and (1) Cι-Ci2-alkyl substituted with heteroaryl, (4) -Cio-alkenyl; (5) C4-C lo- alkenyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) Cι-C 3 -alkoxy, (c) oxo, (d) -CHO, (e) -CO2R 10 where R 10 is as previously defined, (f) -C(O)NR 11 R 12 wherein R 11 and R 12 are as previously defined, (g) -NR 13 R 14 wherein R 13 and R 14 are as previously defined, (h) =N-O-R 10 where R 10 is as previously defined, (i) -C≡N, (j) O-S(O) n R 10 where n is 0, 1 or 2 and R 10 is as previously defined, (k) aryl, (1) substituted aryl, (m) heteroaryl, (n) substituted heteroaryl, (o) C3-C 7 -cycloalkyl, (p) Cι-Ci2-alkyl substituted with heteroaryl, (q) NHC(O)R 10 where R 10 is as previously defined, (r) NHC(O)NR 11 R 12 wherein R 11 and R 12 are as previously defined, (s) =N-NR 13 R 14 wherein R 13 and R 14 are as previously defined, (t) =N-R 9 wherein R 9 is as previously defined, (u) =N-NHC(O)R 10 where R 10 is as previously defined, and (v) =N-NHC(O)NR π R 12 wherein R 1 1 and R 12 are as previously defined; (6) C 3 -Cιo-alkynyl; and (7) C3-Cιo-alkynyl substituted with one or more substituents selected from the group consisting of (a) trialkylsilyl, (b) aryl, (c) substituted aryl, (d) heteroaryl, (e) halogen, and (f) substituted heteroaryl; and U is selected from the group consisting of: (1) hydrogen, (2) hydroxy, (3) protected hydroxy, (4) -O-T-R 1 , wherein T is absent or selected from the group consisting of: (a) -C(O)-, (b) -C(O)-O- (c) -CH 2 -, (d) -C(S)-S-, (e) -C(O)-N(R s )-, wherein R s is H or Cι-C 6 -alkyl, (f) -S(O) n -, wherein n is 0, 1 or 2, (g) -S(O) n -O-, wherein n is 0, 1 or 2, (h) -P(O)(OR r ) n -, wherein n is 0, 1 or 2, and R r is Cι-C6-alkyl, and (i) -SO2-N(R s )-, wherein R s is as defined previously; and R l is selected from the group consisting of: (a) Ci-Cό-alkyl, optionally substituted with a substituent selected from the group consisting of (i) aryl, (ii) substituted-aryl, (hi) heteroaryl, and (iv) substituted-heteroaryl, (v) heterocycloalkyl, (vi) substituted-heterocycloalkyl, (vii) hydroxy, (vi ) Cι-C6-alkoxy, (ix) NR 7 R 8 wherein R 7 and R 8 are as defined previously, (b) C3-C6-alkenyl, optionally substituted with a substituent selected from the group consisting of (i) aryl, (ii) substituted-aryl, (iii) heteroaryl, and (iv) substituted-heteroaryl, (v) heterocycloalkyl, (vi) substituted-heterocycloalkyl, (vh) hydroxy, (vih) Cι-C6-alkoxy, (ix) NR 7 R 8 wherein R 7 and R 8 are as defined previously, (c) C3-Ci2-cycloalkyl, optionally substituted with a substituent selected from the group consisting of (i) aryl, (ii) substituted-aryl, (hi) heteroaryl, and (iv) substituted-heteroaryl, (v) heterocycloalkyl, (vi) substituted-heterocycloalkyl, (vh) hydroxy, (vih) Cι-C6-alkoxy, (ix) NR 7 R 8 wherein R 7 and R 8 are as defined previously, (d) aryl, (e) substituted-aryl, (f) heteroaryl, (g) substituted-heteroaryl, and (h) heterocycloalkyl; or U is taken together with U' to form a double bond between the carbon atoms to which they are attached; U' is hydrogen or is taken together with U to form a double bond between the carbon atoms to which they are attached; W is absent or is selected from the group consisting of -O-, -NH-CO-, -N=CH- and -NH-; and R w is selected from the group consisting of (1) hydrogen, (2) Cι-C6-alkyl optionally substituted with one or more substituents selected from the group consisting of (a) aryl, (b) substituted-aryl, (c) heteroaryl, (d) substituted-heteroaryl, (e) hydroxy, (f) Cι-C 6 -alkoxy, (g) NR 7 R 8 , wherein R 7 and R 8 are as defined previously, and (h) -CH2-M-R 9 , wherein M is selected from the group consisting of: (i) -C(O)-NH-, (ii) -NH-C(O)-, (hi) -NH-, (iv) -N=, (v) -N(CH 3 )-, (vi) -NH-C(O)-O- (vh) -NH-C(O)-NH- (viii) -O-C(O)-NH- (ix) -O-C(O)-O- (x) -o-, (xi) -S(O)rr, wherein n is 0, 1 or 2, (xii) -C(O)-O-, (xiii) -O-C(O)-, and (xiv) -C(O)-, and R 9 is selected from the group consisting of: (i) Cι-C6-alkyl, optionally substituted with a substituent selected from the group consisting of (aa) aryl, (bb) substituted-aryl, (cc) heteroaryl, and (dd) substituted-heteroaryl, (h) aryl, (hi) substituted-aryl, (iv) heteroaryl, (v) substituted-heteroaryl, and (vi) heterocycloalkyl, (3) C -C7-cycloalkyl, (4) aryl, (5) substituted-aryl, (6) heteroaryl, and (7) substituted-heteroaryl; the method comprising: (a) optionaUy treating hydroIyticaUy with acid a compound having the formula 14 wherein R is as defined above and Rp is a hydroxy protecting group to give a compound having the formula 8 wherein U is hydroxy and U' is hydrogen (b) optionaUy treating a compound from Step (a) with an excess of sodium hexamethyldisilazide or a hydride base in the presence of carbonyldumidazole in an aprotic solvent to give a compound having the formula wherein U and U' are taken together to form a double bond; (c) optionally treating a compound from Step (b) with aqueous ammonia to give the deshed compound of formula (II) where U and U' are taken together to form a double bond, W is absent and R w is H; (d) optionally treating a compound from Step (b) with a substituted amine compound of the formula H2N-W-R W , wherein W is absent and R w is not H but is otherwise as previously defined, to give the deshed compound of formula (II) where U and U' are taken together to form a double bond, W is absent and R is not H; (e) optionally treating a compound from Step (b) with a hydroxylamine compound of the formula H2N-W-R W , wherein W is -O- and R w is as previously defined, to give the deshed compound of formula (II) where U and U' are taken together to form a double bond, W is -O- and R w is as previously defined; (f) optionally treating a compound from Step (b) with an unsubstituted hydrazine to give the desired compound of formula (II) where U and U' are taken together to form a double bond, W is -NH- and R is H; (g) optionaUy treating a compound from Step (b) with a substituted hydrazine compound of the formula H2N-NH-R W wherein R is not hydrogen but otherwise is as previously defined to give the deshed compound of formula (II) where U and U' are taken together to form a double bond, W is -NH-R and R is not H; (h) optionaUy treating a compound of formula 14 as defined above with a strong base selected from the group consisting of (i) sodium hexamethyldisUazide and (h) an alkali metal hydride base in the presence of carbonyldumidazole in an aprotic solvent to give a compound having the formula (i) optionally treating a compound from Step (h) with aqueous ammonia to give a compound having the formula (16A) wherein W is absent, R w is H and U is 4"-hydroxy protected cladinose; (j) optionally treating the compound from step (i), wherein W is absent and R w is H and U is 4"-hydroxy protected cladinose, with an alkylating agent selected from the group consisting of R w -halogen to give a compound of formula (16A) wherein W is absent, U is 4"-hydroxy protected cladinose, and R w is as defined above; (k) optionally treating a compound from Step (h) with a substituted amine compound of the formula H2N-W-R W , wherein W is absent and R w is as previously defined except not H, to give to give a compound having of formula (16A) wherein W is absent, U is 4"-hydroxy protected cladinose, and R w is as previously defined except not H; (1) optionally treating a compound from Step (h) with a hydroxylamine compound of the formula H2N-W-R W , wherein W is -O- and R w is as previously defined, to give to give a compound of formula (16A) wherein W is -O-, U is 4"-hydroxy protected cladinose, and R is as previously defined; (m) optionally treating a compound from Step (h) with an unsubstituted hydrazine to give to give a compound of formula (16A) wherein W is -NH-, U is 4"-hydroxy protected cladinose, and R is H; (n) optionaUy treating the compound from step (m) wherein W is -NH-, U is 4"-hydroxy protected cladinose, and R w is H with an acylating agent selected from the group consisting of R w -C(O)-halogen or (R w -C(O))2-O to give a compound of formula (16A) wherein W is -NH- CO-, U is 4"-hydroxy protected cladinose, and R w is as defined above; (o) optionaUy treating the compound from step (m) wherein W is -NH-, U is 4"-hydroxy protected cladinose, and R w is H with an aldehyde R w -CHO, wherein R w as defined above to give a compound of formula (16A) wherein W is -N=CH-, U is 4" -hydroxy protected cladinose, and R w is as defined above; (p) optionaUy treating a compound from Step (h) with a substituted hydrazine compound of the formula H2N-NH-R W , wherein R w is as defined above except not hydrogen, to give to give a compound of formula (16A) wherein W is -NH-, U is 4"-hydroxy protected cladinose, and R w is as defined above except not hydrogen; (q) optionaUy treating hydroIyticaUy with acid a compound selected from the group consisting of the compounds of Step (i), Step (j), Step (k), Step (1), Step (m), Step (n), Step (o), and Step (p) to give the deshed compound of formula (II) wherein U is OH, optionally followed by converting the compound having the natural (3S) isomeric configuration into the compound having the non-natural (3R) isomeric configuration by oxidation of the 3-hydroxyl group and selective reduction of the 3-oxo group to give the non-natural (3R) isomer; (r) optionally treating a compound of formula (II) wherein RP is a hydroxy protecting group and U is hydroxy (a compound from Step (q)) with an excess of NaH in an aprotic solvent followed by reaction of the intermediate anion with CS2 and CH3I to form a xanthate intermediate which is then treated with Bu3SnH under an inert atmosphere in the presence of a catalytic amount of a suitable radical initiator to give the deshed compound of formula (II) wherein U is hydrogen; (s) optionally treating a compound of formula (II) wherein RP is a hydroxy protecting group and U is hydroxy (a compound from Step (r) with a reagent L-T-R 1 , wherein T and R l are as previously defined, and L is a suitable reactive leaving group to give the desired compound of formula (II) wherein U is O-T-R 1 ; (t) optionally deprotecting, and isolating the deshed compound of formula (II). 14. A process according to Claim 13 wherein in step (s) the reagent L-T-R 1 is selected from the group consisting of: (e-i) halogen-C(O)-R t ; (e-ii) O-(C(O)-Rt) 2 ; (e-iii) O-(C(O)-O-Rt)2l (e-iv) halogen-CH2-R . (e-v) alkali metal hydride followed by CS2 then followed by halogen-R 1 ; (e-vi) O=C=N-R l ; (e-vii) carbonyl diimidazole foUowed by N(R S )H-R l ; (e-vhh) Cl-S(O) n -O-R t ; (e-ix) Cl-P(O)(OR r )n-R t ; (e-x) Cl-SO 2 -N(R s )-R . 15. A process according to Claim 13 wherein in step (s) the base and the reagent L- T-R l are replaced with 3,4-dihydro-2H-pyran in the presence of a acid catalyst. 16. A compound according to Claim 1 having the formula (EH) 17. A compound according to Claim 12 which is selected from the group consisting of: Compound of Formula (III): R is -CH 2 -CH=CH 2 , RP is H, U is OH, U' is H; Compound of Formula (III): R is -CH2-CH=CH 2 -(3-quinolinyl), RP is H, U is OH, U' is H; Compound of Formula (III): W is absent, R is H, R is -CH2CH(O), RP is H, U is OH; Compound of Formula (III): W is absent, R is H, R is -CH2CH2NHCH2-phenyl, RP is H, U is OH; and Compound of Formula (III): W is absent, R is H, R is -CH2CH=NO(phenyl), RP is H, U is OH. 18. A process for preparing a compound having the formula (HI) wherein RP is hydrogen or a hydroxy protecting group; R is selected from the group consisting of (1) methyl substituted with a moiety selected from the group consisting of (a) CN, (b) F, (c) -CO2R 10 wherein R 10 is Cι-C -alkyl or aryl substituted Cι-C3-alkyl, or heteroaryl substituted Cι-C3-alkyl, (d) S(O) n R 10 where n is 0, 1 or 2 and R 10 is as previously defined, (e) NHC(O)R 10 where R is as previously defined, (f) NHC(O)NR 1 lRl 2 wherein R 11 and R 12 are independently selected from hydrogen, Cι-C3-alkyl, Cι-C3-alkyl substituted with aryl, substituted aryl, heteroaryl, substituted heteroaryl, (g) aryl, (h) substituted aryl, (i) heteroaryl, and (j) substituted heteroaryl, (2) C2-Cιo-alkyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) hydroxy, (c) Cι-C3-alkoxy, (d) Cι-C3-alkoxy-Cι-C3-alkoxy, (e) oxo, (f) -N 3 , (g) -CHO, (h) O-SO2-(substituted Ci-Cβ-alkyl), (i) -NR 13 R 14 wherein R 13 and R 14 are selected from the group consisting of (i) hydrogen, (ii) Cι-Ci2-alkyl, (hi) substituted Cι-Ci2-alkyl, (iv) Ci-C 12- alkenyl, (v) substituted Cι-Ci2-alkenyl, (vi) Cι-Ci2-alkynyl, (vh) substituted Cι-Ci2-alkynyl, (vih) aryl, (ix) C3-C8-cycloalkyl, (x) substituted C3-Cg-cycloalkyl, (xi) substituted aryl, (xii) heterocycloalkyl, (xiii) substituted heterocycloalkyl, (xiv) Cι-Ci2-alkyl substituted with aryl, (xv) Cι-Ci2-alkyl substituted with substituted aryl, (xvi) Cι-Ci2-alkyl substituted with heterocycloalkyl, (xvii) Cι-Ci2-alkyl substituted with substituted heterocycloalkyl, (xviii) Cι-C 2-alkyl substituted with C3-C8-cycloalkyl, (xix) Cι-Ci2-alkyl substituted with substituted C3-C8-cycloalkyl, (xx) heteroaryl, (xxi) substituted heteroaryl, (xxii) Cι-Ci2-alkyl substituted with heteroaryl, and (xxiii) Cι-Ci2-alkyl substituted with substituted heteroaryl, or R 13 and R 14 are taken together with the atom to which they are attached form a 3-10 membered heterocycloalkyl ring which may be substituted with one or more substituents independently selected from the group consisting of (i) halogen, (ii) hydroxy, (hi) Cι-C3-alkoxy, (iv) Cι-C3-alkoxy-Cι-C3-alkoxy, (v) oxo, (vi) Cι-C -alkyl, (vh) halo-Cι-C 3 -alkyl, and (vii) Cι-C3-alkoxy-Cι-C3-alkyl, (j) -CO2R 10 wherein R 10 is as previously defined, (k) -C(O)NR 11 R 12 wherein R 1 * and R 12 are as previously defined, (1) =N-O-R wherein R 10 is as previously defined, (m) -C≡N, (n) O-S(O) n R 10 wherein n is 0, 1 or 2 and R 10 is as previously defined, (o) aryl, (p) substituted aryl, (q) heteroaryl, (r) substituted heteroaryl, (s) C3-C8-cycloalkyl, (t) substituted C3-Cg-cycloalkyl, (u) Cι-Ci2-alkyl substituted with heteroaryl, (v) heterocycloalkyl, (w) substituted heterocycloalkyl, (x) NHC(O)R 10 where R 10 is as previously defined, (y) NHC(O)NR 11 R 12 wherein R 11 and R 12 are as previously defined, (z) =N-NR 13 R 14 wherein R 13 and R 14 are as previously defined, (aa) =N-R 9 wherein R 9 is as previously defined, (bb) =N-NHC(O)R 1 0 wherein R 10 is as previously defined, and (cc) =N-NHC(O)NR 1 !R 12 wherein R 11 and R 12 are as previously defined; (3) C3-alkenyl substituted with a moiety selected from the group consisting of (a) halogen, (b) -CHO, (c) -CO2R 10 where R 10 is as previously defined, (d) -C(O)-R 9 where R 9 is as previously defined, (e) - OJNR^R 12 wherein R 1 1 and R 12 are as previously defined, (f) -C≡N, (g) aryl, (h) substituted aryl, (i) heteroaryl, (j) substituted heteroaryl, (k) C3-C7-cycloalkyl, and (1) Cι-Ci2-alkyl substituted with heteroaryl, (4) -Cio-alkenyl; (5) C4-Cιo-alkenyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) Cι-C3-alkoxy, (c) oxo, (d) -CHO, (e) -CO2R 10 where R 10 is as previously defined, (f) -C(O)NR u R 12 wherein R 1 1 and R 12 are as previously defined, (g) -NR 13 R 14 wherein R 13 and R 14 are as previously defined, (h) =N-O-R 10 where R 10 is as previously defined, (i) -C≡N, (j) O-S(O) n R 10 where n is 0, 1 or 2 and R 10 is as previously defined, (k) aryl, (1) substituted aryl, (m) heteroaryl, (n) substituted heteroaryl, (o) C3-C7-cycloalkyl, (p) Cι-Ci2-alkyl substituted with heteroaryl, (q) NHC(O)R 10 where R 10 is as previously defined, (r) NHC(O)NR 1 ! R 12 wherein R 11 and R 12 are as previously defined, (s) =N-NR 13 R 14 wherein R 13 and R 14 are as previously defined, (t) =N-R 9 wherein R 9 is as previously defined, (u) =N-NHC(O)R 10 where R 10 is as previously defined, and (v) =N-NHC(O)NR 1 ! R 12 wherein R 1 1 and R 12 are as previously defined; (6) C 3 -Cι 0 -alkynyl; and (7) C3-Cιo-alkynyl substituted with one or more substituents selected from the group consisting of (a) trialkylsilyl, (b) aryl, (c) substituted aryl, (d) heteroaryl, (e) halogen, and (f) substituted heteroaryl; U is selected from the group consisting of: (1) hydrogen, (2) hydroxyl, (3) protected hydroxy, (4) -O-T-R 1 , wherein T is absent or selected from the group consisting of: (a) -C(O)-, (b) -C(O)-O- (c) -CH 2 -, (d) -C(S)-S-, (e) -C(O)-N(R s )-, wherein Rs is H or Ci- -alkyl, (f) -S(O) n -, wherein n is 0, 1 or 2, (g) -S(O) n -O-, wherein n is 0, 1 or 2, (h) -P(O)(OR r )n-, wherein n is 0, 1 or 2, and R r is Cι-C 6 -alkyl, and (i) -SO2-N(R s )-, wherein R s is as defined previously; and R l is selected from the group consisting of: (a) Ci-Cg- alkyl, optionally substituted with a substituent selected from the group consisting of (i) aryl, (ϋ) substituted-aryl, (iϋ) heteroaryl, and (iv) substituted-heteroaryl, (v) heterocycloalkyl, (vi) substituted-heterocycloalkyl, (vh) hydroxy, (vih) Ci-Cg-alkoxy, (ix) NR 7 R 8 wherein R 7 and R 8 are as defined previously, (b) C3-C6-alkenyl, optionally substituted with a substituent selected from tne group consisting of (i) aryl, (ii) substituted-aryl, (hi) heteroaryl, and (iv) substituted-heteroaryl, (v) heterocycloalkyl, (vi) substituted-heterocycloalkyl, (vii) hydroxy, (vih) Cι-C6-alkoxy, (ix) NR 7 R 8 wherein R 7 and R 8 are as defined previously, (c) C3-Ci2-cycloalkyl, optionally substituted with a substituent selected from the group consisting of (i) aryl, (ii) substituted-aryl, (hi) heteroaryl, and (iv) substituted-heteroaryl, (v) heterocycloalkyl, (vi) substituted-heterocycloalkyl, (vh) hydroxy, (vih) Cι-C6-alkoxy, (ix) NR 7 R 8 wherein R 7 and R 8 are as defined previously, (d) aryl, (e) substituted-aryl, (f) heteroaryl, (g) substituted-heteroaryl, and (h) heterocycloalkyl; or U is taken together with U' to form a double bond between the carbon atoms to which they are attached; and U' is hydrogen or is taken together with U to form a double bond between the carbon atoms to which they are attached; the method comprising: (a) optionally treating hydroIyticaUy with acid a compound having the formula 14 wherein R is as defined above and RP is a hydroxy protecting group to give a compound having the formula 8 wherein U is hydroxy and U' is hydrogen, optionally followed by converting the compound having the natural (3S) isomeric configuration into the compound having the non-natural (3R) isomeric configuration by oxidation of the 3-hydroxyl group and selective reduction of the 3- oxo group to give the non-natural (3R) isomer; (b) treating a compound selected from the group consisting of compound 14 and compound 8 wherein U is hydroxy and U' is hydrogen with a base selected from the group consisting of sodium hexamethyldistiazide and a metal hydride base in the presence of carbonyldiimidazole in an aprotic solvent to give a compound selected from the group consisting of compounds 15A and 15B. respectively 15A, wherein U is -O-4"-acetyl-cladinose and U' is H, or 15B, wherein U and U' are taken together to form a double bond; (c) treating a compound selected from the group 15A and 15B of step (b) with ethylenediamine to give a bicyclic carbamate compound selected from the group consisting of compounds 21A, wherein U is O-4"-acetylcladinose, and 21B, wherein U and U' form a double bond, respectively, 21A, wherein U is O-4"-acetylcladinose, 21B, wherein U and U' from a double bond, (d) treating the a compound selected from the group 21A and 21B of step (c) with dilute acid to give a compound selected from the group consisting of compounds 22A and 22B. respectively, 22A. U is O-4"-acetylcladinose, and 22B. U and U' form a double bond; (e) hydroIyticaUy removing the cladinose moiety from a compound (22A) from step (d) by treatment with acid, reprotecting the 2' hydroxyl group by treatment with a hydroxy protecting reagent, optionally foUowed by converting the compound having the natural (3S) isomeric configuration into the compound having the non-natural (3R) isomeric configuration by oxidation of the 3-hydroxyl group and selective reduction of the 3-oxo group to give the non- natural (3R) isomer, to give a compound having the formula (23P). which is a compound of formula (EH) wherein RP is H, U is hydroxy and U' is hydrogen; (f) optionaUy treating the 3-hydroxy group of the product compound from step (e) having the formula (III) wherein R is as defined previously and RP is H, U is hydroxy and U' is hydrogen with base and a reagent L-T-R 1 , wherein L is a leaving group and T and R l are as defined previously, to give a compound of formula (III) wherein RP is H, U is -O-T-R 1 and U' is hydrogen; (i) optionaUy treating the 3-hydroxy group of the product compound from step (e) having the formula (III) wherein R is as defined previously and RP is H, U is hydroxy and U' is hydrogen sequentiaUy with an excess of NaH, CS2 and CH3I to form a 3-O-xanthate intermediate which is treated with Bu3SnH in the presence of a radical initiator to give the deshed compound of formula (IH) wherein RP, U and U' are hydrogen; (j) optionaUy deprotecting, and isolating the deshed compound of formula (IH). 19. A process according to Claim 18 wherein in step (f) the reagent L-T-R 1 is selected from the group consisting of: (e-i) halogen-C(O)-R t ; (e-ii) O-(C(O)-R t ) 2 ; (e-iii) O-(C(O)-O-R t ) 2 ; (e-iv) halogen-CH 2 -R t ; (e-v) alkali metal hydride followed by CS2 then followed by halogen-R 1 ; (e-vi) O=C=N-R l ; (e-vii) carbonyl diimidazole followed by N(R S )H-R l ; (e-viiii) Cl-S OVO-R 1 ; (e-ix) Cl-P(O)(OR r ) n -R . (e-x) Cl-SO 2 -N(RS)-R t. 20. A process according to Claim 18 wherein in step (f) the base and the reagent L- T-R l are replaced with 3,4-dihydro-2H-pyran in the presence of a acid catalyst. 21. A compound according to Claim 1 having the formula (IV) 22. A compound according to Claim 15 which is selected from the group consisting of: Compound of Formula (EV): R is -CH 2 -CH=CH 2 , RP is acetyl, U is OH; Compound of Formula (IV): R is -CH2-CH=CH2-(3-quinolinyl), RP is acetyl, U is OH. Compound of Formula (IV): R is -CH2-CH=CH 2 -(3-quinolinyl), RP is H, U is O-C(O)- phenyl; Compound of Formula (IV): R is -CH2-CH=CH 2 -(3-quinolinyl), RP is H, U is O-C(O)-(2- nitrophenyl); Compound of Formula (IV): W is absent, R w is H, R is -CH2CH(O), RP is H, U is OH; Compound of Formula (IV): W is absent, R w is H, R is -CH2CH2NHCH 2 -phenyl, RP is H, U is OH; and Compound of Formula (EV): W is absent, R is H, R is -CH2CH=NO(phenyl), RP is H, U is OH. 23. A process for preparing a compound having the formula (EV) wherein RP is hydrogen or a hydroxy protecting group; R is selected from the group consisting of (1) methyl substituted with a moiety selected from the group consisting of (a) CN, (b) F, (c) -CO2R 10 wherein R 10 is Cι-C 3 -alkyl or aryl substituted Cι-C3-alkyl, or heteroaryl substituted Cι-C3-alkyl, (d) S(O) n R 10 where n is 0, 1 or 2 and R 10 is as previously defined, (e) NHC(O)R 10 where R 10 is as previously defined, (f) NHC(O)NR 1 lRl 2 wherein R 11 and R 12 are independently selected from hydrogen, Cι-C3-alkyl, Cι-C3-alkyl substituted with aryl, substituted aryl, heteroaryl, substituted heteroaryl, (g) aryl, (h) substituted aryl, (i) heteroaryl, and (!) substituted heteroaryl, (2) C2-Cιo-alkyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) hydroxy, (c) Cι-C3-alkoxy, (d) Cι-C3-alkoxy-Cι-C3-alkoxy, (e) oxo, ( ) -N 3 , (g) -CHO, (h) O-SO2- (substituted Cι-C6-alkyl), 0) -NR 13 R 14 wherein R 13 and R 14 are selected from the group consisting of (i) hydrogen, (ii) Cι-Ci2-alkyl, (hi) substituted Cι-Ci2-alkyl, (iv) Cι-Ci2-alkenyl, (v) substituted Cι-Ci2-alkenyl, (vi) Cι-Ci2-alkynyl, (vh) substituted Ci-Cj2-alkynyl, (viii) aryl, (ix) C3-C8-cycloalkyl, (x) substituted C3-C8-cycloalkyl, (xi) substituted aryl, (xh) heterocycloalkyl, (xiii) substituted heterocycloalkyl, (xiv) Cι-Ci2-alkyl substituted with aryl, (xv) Cι-Ci2-alkyl substituted with substituted aryl, (xvi) Cι-Ci2-alkyl substituted with heterocycloalkyl, (xvii) Cι-Ci2-alkyl substituted with substituted heterocycloalkyl, (xviii) Cι-Ci2-alkyl substituted with C3-Cg-cycloalkyl, (xix) Cι-Ci2-alkyl substituted with substituted C3-C8-cycloalkyl, (xx) heteroaryl, (xxi) substituted heteroaryl, (xxii) Cι-Ci2-aU yl substituted with heteroaryl, and (xxiii) Cι-Ci2-alkyl substituted with substituted heteroaryl, or R 13 and R 14 are taken together with the atom to which they are attached form a 3-10 membered heterocycloalkyl ring which may be substituted with one or more substituents independently selected from the group consisting of (i) halogen, (h) hydroxy, (hi) Cι-C3-alkoxy, (iv) Cι-C3-alkoxy-Cι-C3-alkoxy, (v) oxo, (vi) Cι-C 3 -alkyl, (vh) halo-Cι-C -alkyl, and (vh) Cι-C 3 -alkoxy-Cι-C3-alkyl, (j) -CO2R 10 wherein R 10 is as previously defined, (k) -C^NRHR 12 wherein R 1 * and R 12 are as previously defined, (1) =N-O-R 10 wherein R 10 is as previously defined, (m) -C≡N, (n) O-S(O) n R 10 wherein n is 0, 1 or 2 and R 10 is as previously defined, (o) aryl, (p) substituted aryl, (q) heteroaryl, (r) substituted heteroaryl, (s) C3-C8-cycloalkyl, (t) substituted C3-C8-cycloalkyl, (u) Cι-Ci2-alkyl substituted with heteroaryl, (v) heterocycloalkyl, (w) substituted heterocycloalkyl, (x) NHC(O)R 10 where R 10 is as previously defined, (y) NHC(O)NR π R 12 wherein R 11 and R 12 are as previously defined, (z) =N-NR 13 R 14 wherein R 13 and R 14 are as previously defined, (aa) =N-R 9 wherein R 9 is as previously defined, (bb) =N-NHC(O)R 10 wherein R 10 is as previously defined, and (cc) =N-NHC(O)NR 1 !R 12 wherein R 1 1 and R 12 are as previously defined; (3) C3-alkenyl substituted with a moiety selected from the group consisting of (a) halogen, (b) -CHO, (c) -CO2R 10 where R l0 is as previously defined, (d) -C(O)-R 9 where R 9 is as previously defined, (e) -C(O)NR 11 R 12 wherein R 1 * and R 12 are as previously defined, (f) -C≡N, (g) aryl, (h) substituted aryl, (i) heteroaryl, (j) substituted heteroaryl, (k) C3-C 7 -cycloalkyl, and (1) Cι-Ci2-alkyl substituted with heteroaryl, (4) C4-Cιo-alkenyl; (5) C4-C 10- alkenyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) Cι-C -alkoxy, (c) oxo, (d) -CHO, (e) -CO2R 10 where R 10 is as previously defined, (f) -C^NR^R 12 wherein R 1 ] and R 12 are as previously defined, (g) -NR 13 R 14 wherein R 13 and R 14 are as previously defined, (h) =N-O-R 10 where R 10 is as previously defined, (i) -C≡N, (j) O-S(O) n R 10 where n is 0, 1 or 2 and R 10 is as previously defined, (k) aryl, (1) substituted aryl, (m) heteroaryl, (n) substituted heteroaryl, (o) C3-C7-cycloalkyl, (p) C -Ci2-alkyl substituted with heteroaryl, (q) NHC(O)R 10 where R 10 is as previously defined, (r) NHC(O)NR! !R 12 wherein R 1 1 and R 12 are as previously defined, (s) =N-NR 1 R 14 wherein R 13 and R 14 are as previously defined, (t) =N-R 9 wherein R 9 is as previously defined, (u) =N-NHC(O)R 10 where R 10 is as previously defined, and (v) =N-NHC(O)NR R 12 wherein R 11 and R 12 are as previously defined; (6) C 3 -Cιo-alkynyl; and (7) C3-Cιo-alkynyl substituted with one or more substituents selected from the group consisting of (a) trialkylsilyl, (b) aryl, (c) substituted aryl, (d) heteroaryl, (e) halogen, and (f) substituted heteroaryl; U is selected from the group consisting of: (1) hydrogen, (2) hydroxyl, (3) protected hydroxy, (4) -O-T-R 1 , wherein T is absent or selected from the group consisting of: (a) -C(O)-, (b) -C(O)-O- (c) -CH 2 -, (d) -C(S)-S-, (e) -C(O)-N(Rs)-, wherein R s is H or Cι-C 6 -alkyl, (f) -S(O) n -, wherein n is 0, 1 or 2, (g) -S(O) n -O-, wherein n is 0, 1 or 2, (h) -P(O)(OR r )n . wherein n is 0, 1 or 2, and R r is Cι-C 6 -alkyl, and (i) -SO2-N(R s )-, wherein R s is as defined previously; and R l is selected from the group consisting of: (a) Ci-Cζ-alkyl, optionally substituted with a substituent selected from the group consisting of (i) aryl, (ϋ) substituted-aryl, (ϋi) heteroaryl, and (iv) substituted-heteroaryl, (v) heterocycloalkyl, (vi) substituted-heterocycloalkyl , (vh) hydroxy, (vih) Cι-C6-alkoxy, (ix) NR 7 R 8 wherein R 7 and R 8 are as defined previously, (b) C3-C6-alkenyl, optionally substituted with a substituent selected from the group consisting of (i) aryl, (ϋ) substituted-aryl, (hi) heteroaryl, and (iv) substituted-heteroaryl, (v) heterocycloalkyl, (vi) substituted-heterocycloalkyl, (v ) hydroxy, (viii) Cι-C6-alkoxy, (ix) NR 7 R 8 wherein R 7 and R 8 are as defined previously, (c) C3-Ci2-cycloalkyl, optionally substituted with a substituent selected from the group consisting of (i) aryl, (ϋ) substituted-aryl, (iϋ) heteroaryl, and (iv) substituted-heteroaryl, (v) heterocycloalkyl, (vi) substituted-heterocycloalkyl , (vh) hydroxy, (v i) Cι-C6-alkoxy, (ix) NR 7 R 8 wherein R 7 and R 8 are as defined previously, (d) aryl, (e) substituted-aryl, ( ) heteroaryl, (g) substituted-heteroaryl, and (h) heterocycloalkyl; the method comprising: (a) optionally treating a compound having the formula 14 wherein R is as defined above and Rp is a hydroxy protecting group, with carbonyldiimidazole and sodium hexamethyldisilazide for a short time at about -30 °C to give a compound having the formula 29 (b) optionally treating a compound having the formula 14 as shown in Step (a) with an alkali metal hydride and a carbonylating agent selected from the group consisting of phosgene, diphosgene and triphosgene under anhydrous conditions with careful control of the amount of base present in order to prevent base catalyzed decarboxylation to give a compound having the formula 29 as shown in Step (a); (c) treating hydroIyticaUy with acid a compound having the formula 29 to give a compound of formula (IV) wherein U is hydroxy and Rp is a hydroxy protecting group, optionally followed by converting the compound having the natural (3S) isomeric configuration into the compound having the non-natural (3R) isomeric configuration by oxidation of the 3-hydroxyl group and selective reduction of the 3-oxo group to give the non-natural (3R) isomer; (d) optionaUy treating a compound of formula (EV) wherein U is hydroxy and RP is a hydroxy protecting group (a compound from Step (c)) with an excess of NaH in an aprotic solvent followed by reaction of the intermediate anion with CS2 and CH3I to form a xanthate intermediate which is then treated with Bu3SnH under an inert atmosphere in the presence of a catalytic amount of a suitable radical initiator to give the deshed compound of formula (EV) wherein U is hydrogen and RP is a hydroxy protecting group; (e) optionally treating a compound of formula ( V) wherein U is hydroxy and RP is a hydroxy protecting group (a compound from Step (c)) with base and a reagent L-T-R 1 , wherein T and R l are as previously defined, and L is a suitable reactive leaving group to give the deshed compound of formula (EV) wherein U is O-T-Ri and RP is a hydroxy protecting group; (f) optionally deprotecting, and isolating the deshed compound of formula (EV). 24. A process according to Claim 24 wherein in step (e) the reagent L-T-R 1 is selected from the group consisting of: (e-i) halogen-C(O)-R t ; (e-ii) O-(C(O)-R t ) 2 ; (e-iii) O-(C(O)-O-R t ) 2 ; (e-iv) halogen-CH2-R l ; (e-v) alkali metal hydride followed by CS2 then followed by halogen-R 1 ; (e-vi) O=C=N-R l ; (e-vii) carbonyl diimidazole foUowed by N(R S )H-R l ; (e-viiii) Cl-S(O) n -O-R t ; (e-ix) Cl-P(O)(OR r )n-R . (e-x) Cl-SO 2 -N(Rs)-Rt. 25. A process according to Claim 24 wherein in step (e) the base and the reagent L- T-R l are replaced with 3,4-dihydro-2H-pyran in the presence of a acid catalyst. 26. A compound according to Claim 1 having the formula (V) (V), 27. A compound according to Claim 18 which is selected from the group consisting of: Compound of Formula (V): R is -CH2-CH=CH 2 , RP is H, U is OH; Compound of Formula (V): R is -CH2-CH=CH , RP is H, U is O-acetyl; Compound of Formula (V): R is -CH2-CH=CH , RP is H, U is H, U' is H; Compound of Formula (V): W is absent, R w is H, R is -CH 2 CH(O), RP is H, U is OH; Compound of Formula (V): W is absent, R is H, R is -CH 2 CH 2 NHCH2-phenyl, RP is H, U is OH; and Compound of Formula (V): W is absent, R is H, R is -CH 2 CH=NO(phenyl), RP is H, U is OH. 28. A process for preparing a compound having the formula (V) wherein RP is hydrogen or a hydroxy protecting group; R is selected from the group consisting of (1) methyl substituted with a moiety selected from the group consisting of (a) CN, (b) F, (c) -CO2R 10 wherein R 10 is Cι-C3-alkyl or aryl substituted Cι-C3-alkyl, or heteroaryl substituted Cι-C3-alkyl, (d) S(O) n R 10 where n is 0, 1 or 2 and R 10 is as previously defined, (e) NHC(O)R 10 where R 10 is as previously defined, (f) NHC(O)NR! !Rl 2 wherein R 1 1 and R 12 are independently selected from hydrogen, Cι-C3-alkyl, Cι-C3-alkyl substituted with aryl, substituted aryl, heteroaryl, substituted heteroaryl, (g) aryl, (h) substituted aryl, (i) heteroaryl, and (j) substituted heteroaryl, (2) C2-Cιo-alkyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) hydroxy, (c) Cι-C3-alkoxy, (d) Cι-C3-alkoxy-Cι-C3-alkoxy, (e) oxo, (f) -N3, (g) -CHO. (h) O-SO -(substituted Ci- -alkyl), (i) -NR 13 R 14 wherein R 13 and R 14 are selected from the group consisting of (i) hydrogen, (ii) Cι-Ci2-alkyl, (hi) substituted Cι-Ci2-alkyl, (iv) Cι-Ci2-alkenyl, (v) substituted Cι-Ci2-alkenyl, (vi) Cι-Ci2-alkynyl, (vh) substituted Cι-Ci2-alkynyl, (viii) aryl, (ix) C3-C8-cycloalkyl, (x) substituted C3-Cg-cycloalkyl, (xi) substituted aryl, (xii) heterocycloalkyl, (xhi) substituted heterocycloalkyl, (xiv) Ci-C 12- alkyl substituted with aryl, (xv) Cι-Ci2-alkyl substituted with substituted aryl, (xvi) Cι-Ci2-alkyl substituted with heterocycloalkyl, (xvii) Cι-Ci2-alkyl substituted with substituted heterocycloalkyl, (xviii) Cι-Ci2-alkyl substituted with C3-Cg-cycloalkyl, (xix) Cι-Ci2-alkyl substituted with substituted C3-Cg-cycloalkyl, (xx) heteroaryl, (xxi) substituted heteroaryl, (xxii) Cι-Ci2-alkyl substituted with heteroaryl, and (xxiii) Cι-Ci2-alkyl substituted with substituted heteroaryl, or R 13 and R 14 are taken together with the atom to which they are attached form a 3-10 membered heterocycloalkyl ring which may be substituted with one or more substituents independently selected from the group consisting of (i) halogen, (ii) hydroxy, (hi) Cι-C3-alkoxy, (iv) Cι-C3-alkoxy-Cι-C3-alkoxy, (v) oxo, (vi) Cι-C 3 -alkyl, (vii) halo-Cι-C3-alkyl, and (vh) Cι-C3-alkoxy-Cι-C3-alkyl, (j) -CO2R 10 wherein R 10 is as previously defined, (k) -C(O)NR 11 R 12 wherein R 1 ] and R 12 are as previously defined, (1) =N-O-R 10 wherein R 10 is as previously defined, (m) -C≡N, (n) O-S(O) n R 10 wherein n is 0, 1 or 2 and R 10 is as previously defined, (o) aryl, (p) substituted aryl, (q) heteroaryl, (r) substituted heteroaryl, (s) C3-C8-cycloalkyl, (t) substituted C3-Cg-cycloalkyl, (u) Cι-Ci2-alkyl substituted with heteroaryl, (v) heterocycloaUcyl, (w) substituted heterocycloalkyl, (x) NHC(O)R 10 where R 10 is as previously defined, (y) NHC(O)NR n R 12 wherein R 11 and R 12 are as previously defined, (z) =N-NR 13 R 14 wherein R 13 and R 14 are as previously defined, (aa) =N-R 9 wherein R 9 is as previously defined, (bb) =N-NHC(O)R 10 wherein R 10 is as previously defined, and (cc) =N-NHC(O)NR 1 l R 12 wherein R 11 and R 12 are as previously defined; (3) C3-alkenyl substituted with a moiety selected from the group consisting of (a) halogen, (b) -CHO, (c) -CO2R 10 where R 10 is as previously defined, (d) -C(O)-R 9 where R 9 is as previously defined, (e) -C(O)NR π R 12 wherein R 11 and R 12 are as previously defined, (f) -C≡N, (g) aryl, (h) substituted aryl, (i) heteroaryl, (j) substituted heteroaryl, (k) C3-C7-cycloaIkyl, and (1) Cι-Ci2-alkyl substituted with heteroaryl, (4) C 4 -Cιo-alkenyl; (5) C4-Cιo-alkenyl substituted with one or more substituents selected from the group consisting of (a) halogen, (b) Cι-C 3 -alkoxy, (c) oxo, (d) -CHO, (e) -CO2R 10 where R 10 is as previously defined, (f) -C(O)NR π R 12 wherein R 1 * and R 12 are as previously defined, (g) -NR 13 R 14 wherein R 13 and R 14 are as previously defined, (h) =N-O-R 10 where R 10 is as previously defined, (i) -C≡N, (j) O-S(O) n R 10 where n is 0, 1 or 2 and R 10 is as previously defined, (k) aryl, (1) substituted aryl, (m) heteroaryl, (n) substituted heteroaryl, (o) C3-C7-cycloalkyl, (p) Cι-Ci2-alkyl substituted with heteroaryl, (q) NHC(O)R 10 where R 10 is as previously defined, (r) NHC(O)NR 1 !R 12 wherein R 1 * and R 12 are as previously defined, (s) =N-NR 13 R 14 wherein R 13 and R 14 are as previously defined, (t) =N-R 9 wherein R 9 is as previously defined, (u) =N-NHC(O)R 10 where R 10 is as previously defined, and (v) =N-NHC(O)NR 1 i R 12 wherein R 1 ! and R 12 are as previously defined; (6) C 3 -Cιo-alkynyl; and (7) C3-Cιo-alkynyl substituted with one or more substituents selected from the group consisting of (a) trialkylsilyl, (b) aryl, (c) substituted aryl, (d) heteroaryl, (e) halogen, and (f) substituted heteroaryl; U is selected from the group consisting of: (1) hydrogen, (2) hydroxy, (3) protected hydroxy, (4) -O-T-R 1 , wherein T is absent or selected from the group consisting of: (a) -C(O)-, (b) -C(O)-O- (c) -CH 2 -, (d) -C(S)-S-, (e) -C(O)-N(Rs)-, wherein Rs is H or Cι-C6-alkyl, (f) -S(O) n -, wherein n is 0, 1 or 2, (g) -S(O) n -O-, wherein n is 0, 1 or 2, (h) -P(O)(OR r )n-, wherein n is 0, 1 or 2, and R r is Cι-C6-alkyl, and (i) -SO2-N(R s )-, wherein R s is as defined previously; and R l is selected from the group consisting of: (a) Ci-Cg-alkyl, optionally substituted with a substituent selected from the group consisting of (i) aryl, (h) substituted-aryl, (hi) heteroaryl, and (iv) substituted-heteroaryl, (v) heterocycloalkyl, (vi) substituted-heterocycloalkyl, (vh) hydroxy, (vih) Cι-C6-alkoxy, (ix) NR 7 R 8 wherein R 7 and R 8 are as defined previously, (b) C3-C6-alkenyl, optionally substituted with a substituent selected from the group consisting of (i) aryl, (ii) substituted-aryl, (iii) heteroaryl, and (iv) substituted-heteroaryl, (v) heterocycloalkyl, (vi) substituted-heterocycloalkyl, (vh) hydroxy, (vih) Cι-C6-alkoxy, (ix) NR 7 R 8 wherein R 7 and R 8 are as defined previously, (c) C3-Ci2-cycloalkyl, optionally substituted with a substituent selected from the group consisting of (i) aryl, (ii) substituted-aryl, (hi) heteroaryl, and (iv) substituted-heteroaryl, (v) heterocycloalkyl, (vi) substituted-heterocycloalkyl, (vh) hydroxy, (vih) Cι-C6-alkoxy, (ix) NR 7 R 8 wherein R 7 and R 8 are as defined previously, (d) aryl, (e) substituted-aryl, (f) heteroaryl, (g) substituted-heteroaryl, and (h) heterocycloalkyl; the method comprising: (a) treating a compound having the formula 14 wherein R is as defined above and Rp is a hydroxy protecting group, with a reagent selected from the group consisting of (i) formaldehyde in the presence of an acid and (h) chloroiodomethane in the presence of base, to give a compound having the formula 23. (b) treating hydroIyticaUy with acid a compound from Step (a) having the formula 33 to give a compound of formula (V) wherein U is hydroxy and Rp is a hydroxy protecting group, optionally foUowed by converting the compound having the natural (3S) isomeric configuration into the compound having the non-natural (3R) isomeric configuration by oxidation of the 3- hydroxyl group and selective reduction of the 3-oxo group to give the non-natural (3R) isomer; (c) optionaUy treating a compound of formula (V) wherein U is hydroxy and RP is a hydroxy protecting group (a compound from Step (b)) with an excess of NaH in an aprotic solvent followed by reaction of the intermediate anion with CS2 and CH3I to form a xanthate intermediate which is then treated with Bu3SnH under an inert atmosphere in the presence of a catalytic amount of a suitable radical initiator to give the deshed compound ot formula (V) wherein U is hydrogen and RP is a hydroxy protecting group; (d) optionaUy treating a compound of formula (EV) wherein U is hydroxy and RP is a hydroxy protecting group (a compound from Step (b)) with base and a reagent L-T-R 1 , wherein T and R l are as previously defined, and L is a suitable reactive leaving group to give the deshed compound of formula (V) wherein U is O-T-R 1 and RP is a hydroxy protecting group; (e) optionally deprotecting, and isolating the deshed compound of formula (V). 29. A process according to Claim 29 wherein in step (e) the reagent L-T-R 1 is selected from the group consisting of: (e-i) halogen-C(O)-R l ; (e-ii) O-(C(O)-R t ) 2 ; (e-ih) O-(C(O)-O-R t ) 2 ; (e-iv) halogen-CH2-R . (e-v) alkali metal hydride followed by CS2 then followed by halogen-R 1 ; (e-vi) O=C=N-R t ; (e-vii) carbonyl diimidazole foUowed by N(R S )H-R t ; (e-vhh) Cl-S(O) n -O-R t ; (e-ix) Cl-P(O)(OR r )n-R . (e-x) Cl-SO 2 -N(Rs)-Rt. 30. A process according to Claim 29 wherein in step (e) the base and the reagent L- T-R l are replaced with 3,4-dihydro-2H-pyran in the presence of a acid catalyst.

Inventors: CHU DANIEL T, LI LEPING, OR YAT SUN, RUPP MICHAEL J, CHU, DANIEL, T., LI, LEPING, OR, YAT, SUN, RUPP, MICHAEL, J.
Applicants: ABBOTT LAB, ABBOTT LABORATORIES
Application year: 1998
Main classification: C07H17
IPC codes: A61K31, A61P31, C07H17