TRICYCLIC ERYTHROMYCIN DERIVATIVES

Abstract: Compounds, or pharmaceutically acceptable salts and esters thereof, of formulae (I); (II); (III) or (IV) wherein A, B, D and E, R<1>, R<2> and Z are specifically defined, having antibacterial activity, pharmaceutical compositions containing said compounds, treatment of antibacterial infections with such compositions, and processes for the preparation of the compounds.

Description: TRICYCLIC ERYTHROMYCLN DERIVATIVES Technical Field The present invention relates to novel semisynthetic macrolides having antibacterial activity and useful in the treatment and prevention of bacterial infections. More particularly, the invention relates to tricyclic erythromycin derivatives, compositions containing such compounds and methods for using the same, as well as processes for making such compounds. 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 antibacterials, 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. ashimura et al. have disclosed 6-O-methylerythromycin derivatives having a tricyclic basic nuclear structure in European Application 559896, published November 1 1, 1991. Also, Asaka et al. have disclosed 5-O-desoaminylerythronolide derivatives containing a tricyclic carbamate structure in PCT Application WO 93/21200, published April 22, 1992. Summary of the Invention The present invention provides a novel class of antibacterial tricyclic erythromycin compounds which possess antibacterial activity. In one aspect of the present invention are disclosed novel tricyclic erythromycin compounds selected from the group having the formulas: as well as the pharmaceutically acceptable salts and esters thereof. In formulas (I) - (IV) above, A, B, D and E are independently selected from the group consisting of: (a) hydrogen; (b) -C6- alkyl, as defined below, optionally substituted with one or more substituents selected from the group consisting of: (i) aryl, as defined below; (ii) substituted-aryl, as defined below; (iii) heteroaryl, as defined below; (iv) substituted-heteroaryl, as defined below; (v) heterocycloalkyl, as defined below; (vi) hydroxy; (vii) Ci-Cό-alkoxy, as defined below; (viii) halogen consisting of Br, Cl, F or I; and (ix) NR 3 R 4 , where R 3 and R 4 are independently selected from hydrogen and Ci-Cό-alkyl, or R 3 and R 4 are taken with the nitrogen atom to which they are connected to form a 3- to 7-membered ring optionally containing a hetero function consisting of -O-, -NH-, -N(Cι-C 6 -alkyl-)-, -N(aryl-Cι-C 6 -alkyl-)-, -N(substituted-aryl-Cι.-C 6 -alkyl- )-, -N(heteroaryl-Cι-C6-alkyl-)-, -N(substituted-heteroaryl-Cι-C6-alkyl-)-, -S- or -S(O) n -, wherein n is 1 or 2; (c) C3-C7-cycloalkyl; (d) aryl; (e) substituted-aryl; (f) heteroaryl; (g) substituted-heteroaryl; (h) heterocycloalkyl; and (i) a group selected from option (b) above further substituted with -M- R 5 , wherein M is selected from the group consisting of 97/17356 (aa) -C(O)-NH-; (bb) -NH-C(O)-; (cc) -NH- (dd) -N(CH 3 )- (ee) -O- (ff) -S(O) n -, wherein n is 0, 1 or 2; and (gg) -C(=NH)-NH-; and R 5 is selected from the group consisting of: (aaa) Ci-Cό-alkyl, optionally substituted with a substituent selected from the group consisting of: (i) aryl; (ii) substituted-aryl; (iii) heteroaryl; and (iv) substituted-heteroaryl; (bbb) aryl; (cce) substituted-aryl; (ddd) heteroaryl; (eee) substituted-heteroaryl; and (ffϊ) heterocycloalkyl; or any one pair of substituents, consisting of AB, AD, AE, BD, BE or DE, is taken together with the atom or atoms to which they are attached to form a 3- to 7-membered ring optionally containing a hetero function consisting of: -O-, -NH-, -N(Cι-C 6 -alkyl-)-, -N(aryl-Cι-C 6 -alkyl-)-, -N(substituted-aryl-Cι-C6-alkyl-)-, -N(heteroaryl-Cι-C6-alkyl-)-, -N(substituted-heteroaryl-C i -Cβ-alkyl-)- , -S- or -S(O) n -, wherein n is 1 or 2; -C(O)-NH-; -C(O)-NR 5 -, wherein R 5 is as described above; -NH-C(O)-; -NR 5 -C(O)-, wherein R 5 is as described above; and -C(=NH)-NH-; R 1 is selected from the group consisting of: (a) hydrogen; (b) hydroxy; (c) -0-Ci-C 3 -alkyl; (d) -0-C3-C5-cycloalkyl; (e) - Cι-C3-alkyl-C3-C5-cycloalkyl; (f) - C(O)-Cι-C3-alkyl; (g) -O-C(O)-O-Cι-C 3 -alkyl; and (h) -O-C(O)-NH-Cι-C 3 -alkyl; R 2 is hydrogen or a hydroxy-protecting group, as defined below; and Z is hydroxy or protected-hydroxy; with the provisos that when the compound is of Formulas (I) or (DT) then A, B, D, and E may not all be hydrogen, D and E may not be Cι-C3-alkyl when A and B are hydrogen, nor may one of D and E be hydrogen and the other be Cι-C3-alkyl when A and B are hydrogen. In another aspect of the present invention are disclosed pharmaceutical compositions comprising a therapeutically effective amount of a compound of the invention in combination with a pharmaceutically acceptable carrier and treatment of antibacterial infections with such compositions. Suitable carriers and methods of formulation are also disclosed. The compounds and compositions of the present invention have antibacterial activity. In a further aspect of the present invention are provided processes for the preparation of tricyclic macrolide derivatives of Formulas (I), (II), (UI) and (IV) above. Detailed Description of the Invention In one embodiment of the present invention are compounds selected from the group having formula (I) above, wherein A, B, D, E, and R l -R 5 are as described above. In a second embodiment of the present invention are compounds selected from the group having formula (II) above, wherein A, B, D, E, R'-R 5 and Z are as described above. In another embodiment of the present invention are compounds selected from the group having formula (UI) above, wherein A, B, D, E, and R l -R 5 are as described above. In yet another embodiment of the present invention are compounds selected from the group having formula (IV) above, wherein A, B, D, E, and R*-R 5 are as described above. In one preferred embodiment of the present invention are compounds of formula (ID) above wherein R 1 is hydrogen, hydroxy or methoxy, R 2 is hydrogen, and A, B, D, E and R!-R 5 are as described above. In another preferred embodiment of the present invention are compounds of formula (ID) above wherein R 1 is hydrogen or methoxy, R 2 is hydrogen, and any three of the A, B, D and E groups are hydrogen and the other group is selected from a singly substituted - C6-alkyl group comprised of -(CH2) m R 6 where m=l, 2, 3 or 4 and R 6 is: (a) aryl; (b) substituted-aryl; (c) heteroaryl; (d) substituted-heteroaryl; (e) heterocycloalkyl; (f) hydroxy; (g) Ci-Qj-alkoxy (h) NR 3 R 4 , where R 3 and R 4 are independently selected from hydrogen and Ci- Cό-alkyl, or R 3 and R 4 are taken with the nitrogen atom to which they are connected to form a 3- to 7-membered ring optionally containing a hetero function consisting of -O-, -NH-, -N(Cι-C6-alkyl-)-, -N(aryl-Cι-C6-alkyl-)-, -N(substituted-aryl-Cι-C6-alkyl-)-, -N(heteroaryl-Cι-C6-alkyl-)-, -N(substituted-heteroaryl-Cι-C6-alkyl-)-, -S- or -S(O) n -, wherein n is 1 or 2; (i) halogen consisting of Br, Cl, F or I; (j) C1-C3 alkyl; or (k) -(CH2) r -(CH 2 ) s -R 7 wherein r=0,l or 2; s=0,l or 2 and M is (aa) -C(O)-NH-; (bb) -NH-C(O)-; (cc) -NH- (dd) -N(CH 3 )- (ee) -O- (ff) -S(O) n -, wherein n is 0, 1 or 2; and (gg) -C(=NH)-NH-; and R is selected from the group consisting of: (aaa) Cι-C3-alkyl, (bbb) aryl; (cce) substituted-aryl; (ddd) heteroaryl; and (eee) substituted-heteroaryl. In yet another preferred embodiment of the present invention are compounds of formula (III) above wherein R 1 is hydrogen or methoxy, R 2 is hydrogen, B=E=H, and A and D taken together is selected from the group consisting of: (a) -CH2-Z-CH2-, wherein Z is (aa) -C(O)-NH-; (bb) -C(O)-NR 5 -, wherein R 5 is selected from the group consisting of: (aaa) Cι-C6-alkyl, optionally substituted with a substituent selected from the group consisting of: (i) aryl; (ii) substituted-aryl; (iii) heteroaryl; and (iv) substituted-heteroaryl; (bbb) aryl; (cce) substituted-aryl; (ddd) heteroaryl; (eee) substituted-heteroaryl; and (fff) heterocycloalkyl; (cc) -NH-C(O)-; (dd) -NR 5 -C(O)-, wherein R 5 is as defined above; (ee) -NH- (ff) -N(CH 3 )- (gg) -O- (hh) -S(O) n -, wherein n is 0, 1 or 2; and (ii) -C(=NH)-NH-; (b) -CH2-N(-(CH ) S -R 7 )-CH2-, wherein s=0, 1 or 2, and R 7 is selected from the group consisting of: (aaa) Cι-C -alkyl, (bbb) aryl; (cce) substituted-aryl; (ddd) heteroaryl; and (eee) substituted-heteroaryl; (c) -CH 2 -N(-(CH2) r M-(CH 2 ) S -R 7 )-CH 2 -, wherein r=0, 1 or 2; s=0, 1 or 2, and M and R 7 are as defined above; and (d) -CH 2 -(CH2)rCH 2 -, wherein r=0, 1 or 2. Representative of the compounds of the invention include: Compound of Formula (IV); R ^methoxy; R^hydrogen; A=B=D=E=hydrogen; Compound of Formula (UI), A=B=E=H, D=benzyl, R^methoxy, R 2 =hydrogen; Compound of Formula (HI), A=B=D=H, E=benzyl, R'=methoxy, R 2 =hydrogen; Compound of Formula (lu); A=benzyl, B=D=E=H, Rl=methoxy; Compound of Formula (III); B=benzyl, A=D=E=H, R ^methoxy, R 2 =hydrogen; Compound of Formula (III); A=E=phenyl, B=D=H, R^methoxy, R 2 =hydrogen; Compound of Formula (HI); A=methyl, B=D=E=H, R^methoxy, R ^hydrogen; Compound of Formula (HI); B=methyl, A=D=E=H, R ^methoxy, R^hydrogen; Compound of Formula (HI); A=D=methyl; B=E=H, R ^methoxy, R 2 =hydrogen; Compound of Formula (UT); A=E=methyl; B=D=H, R ^methoxy, R 2 =hydrogen ; Compound of Formula (ID); B=D=H; A and E taken together is -CH2CH2CH2-, R^methoxy, R 2 =hydrogen; - 1 ■ Compound of Formula (HI); B=E=H; A and D taken together is -CH2CH2CH2CH2-, R ^methoxy, R 2 =hydrogen ; Compound of Formula (I); A=B=D=E=hydrogen; R^hydrogen, R 2 =hydrogen; Compound of Formula (ID): R'=OCH3, R 2 =H; A=B=D=H; E=-CH2NH2; Compound of Formula (ffl): R'=OCH3, R 2 =H; A=B=E=H; D=-CH2NH2; Compound of Formula (TE): R'=OCH3, R 2 =H; B=E=H; A and D taken together is -CH2CH2CH2-; Compound of Formula (ELI): R'=OCH3, R 2 =H; B=E=H; A and D taken together is -CH2OCH2-; Compound of Formula (HI): R l =OCH3, R 2 =H: B=E=H; A and D taken together is -CH2-NH-CH2-; Compound of Formula (HI): R'=OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-N(Cbz)-CH2-; C Coommppoouunndd ooif Formula (HI): R'=OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-N(benzyl)-CH2-; CCoommppoouunndd ooff F Formula (HI): R'=OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-N(benzoyl)-CH2-; Compound of Formula (HI): R'=OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-N(phenyl-CH2-CH2-)-CH2-; Compound of Formula (IH): R'=OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-N(4-Cl-phenyl-CH2-)-CH2-; Compound of Formula (HI): R'=OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-N(4-pyridyl-CH2-)-CH2-; Compound of Formula (HI): R =OCH3, R'=H; B=E=H; A and D taken together is -CH2-N(2-pyridyl-CH2-)-CH2-; Compound of Formula (HI): R'=OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-N(3-pyridyl-CH2-)-CH2-; Compound of Formula (HI): R*=OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-N(4-quinolyl-CH2-)-CH2-; Compound of Formula (IH): R'=OCH3, R 2 =H; B=E=H; A=D=-CH2-O-CH2- phenyl; Compound of Formula (IH): R ! =OCH3, R 2 =H; B=E=H; A=D=-CH2-OH; Compound of Formula (ID): R'=OCH3, R 2 =H; B=E=H; A=D=-CH2-O-phenyl; Compound of Formula (HI): R'=OCH3, R 2 =H; A=B=H; D and E taken together is -CH2-CH2-CH2-CH2-; Compound of Formula (HI): R'=OCH3, R 2 =H; A and B taken together is -CH2-CH2-CH2-CH2-; D=E=H; „...--- * PCT/US96/16585 97/17356 Compound of Formula (HI): R'=OCH3, R 2 =H; A=B=H; D and E taken together is -CH2-O-CH2-; Compound of Formula (IH): R ] =OCH3, R 2 =H; A=D=E=H; B=-CH2-CH2-phenyl ; Compound of Formula (HI): R^OCHS, R 2 =H; A=D=E=H; B=- CH2-CH2-CH2-phenyl ; Compound of Formula (HI): R'=OCH3, R 2 =H: A=D=E=H; B=- CH2-O-CH2-phenyl ; Compound of Formula (HI): R'=OCH3, R 2 =H; A=D=E=H; B=- CH2-CH2-(4-OCH 3 -phenyl ); Compound of Formula (IH): R ] =OCH3, R =H; A=-CH2-CH2-phenyl; B=D=E=H ; Compound of Formula (IH): R'=OCH3, R 2 =H; A=-CH2-CH2-CH2-phenyl; B=D=E=H ; Compound of Formula (III): R'=OCH3, R 2 =H; A=-CH2-O-CH2-phenyl ; B=D=E=H ; Compound of Formula (HI): R'=OCH3, R 2 =H; B=D=E=H; A=- CH2-CH2-(4-OCH 3 -phenyl); Compound of Formula (IH): R*=OCH3, R =H; A=B=D=H; E=-CH2-CH2-Ph; Compound of Formula (IH): R'=OCH3, R 2 =H; A=B=E=H; D=-CH2-CH2-Ph; Compound of Formula (ni): R'=OCH3, R 2 =H; A=B=D=H; E=- CH2-CH2-CH2-Ph; Compound of Formula (HI): R'=OCH3, R 2 =H; A=B=E=H; D=- CH2-CH2-CH2-Ph; Compound of Formula (IH): R'OCHS, R 2 =H; A=- CH2-CH2-OPh; B=D=E=H; Compound of Formula (III): R'=OCH3, R 2 =H; A=- CH2-CH2-NHCbz; B=D=E=H; Compound of Formula (IH) Rl=OCH3, R2=H; A=-CH2-CH2-NH2; B=D=E=H; Compound of Formula (IH): R'=OCH3, R 2 =H; A=- CH2-CO2Benzyl; B=D=E=H; Compound of Formula (HI) Rl=OCH3, R2=H; A=-CH2-COOH; B=D=E=H; Compound of Formula (HI) Rl=OCH3, R2=H; A=-CH2-CH2-OH; B=D=E=H; Compound of Formula (III): R'=OCH3, R 2 =H; A=- CH2-CH2-NH(4-Pyridyl-); B=D=E=H Compound of Formula (IH): R'=OCH3, R 2 =H; A=B=D=H; E=-CH2-OH; Compound of Formula (IH): R'=OCH3, R 2 =H; A=B=E=H; D=-CH2-OH; Compound of Formula (III): R'=OCH3, R 2 =H; A=B=E=H; D=-CH2-NHBenzoyl; Compound of Formula (III): R^OOB, R 2 =H; A=B=E=H; D=-CH2-NHBenzyl; Compound of Formula (III): R'=OCH3, R 2 =H; A=B=D=H; E=-CH2-NHBenzoyl; Compound of Formula (III): R^OCHS, R 2 =H; A=B=D=H; E=-CH2-NHBenzyl; Compound of Formula (IH): R =OCH3, R'=H; B=D=H; A=E=-CH2OCH2(4-Cl- phenyl); Compound of Formula (HI): R'=OCH3, R 2 =H; A=B=E=H; D=-CH2-N(CH 3 )- Benzyl; Compound of Formula (HI): R =OCH3, R =H; A=B=D=H; E=-CH2-N(CH 3 )- Benzyl; Compound of Formula (IH): E=-CH2-NH-phenyl; and Compound of Formula (IH): R =OCH3, R'=H; A=B=E=H; D=-CH2-NH-phenyl. A selected group of representative compounds includes: Compound of Formula (IV); R ^methoxy; R^hydrogen; A=B=D=E=hydrogen; Compound of Formula (HI), A=B=E=H, D=benzyl, R'=methoxy, R 2 =hydrogen; Compound of Formula (HI), A=B=D=H, E=benzyl, R ! =methoxy, R 2 =hydrogen: Compound of Formula (IH); A=benzyl, B=D=E=H, R ^methoxy, R 2 =hydrogen; Compound of Formula (IE); B=benzyl, A=D=E=H, R ^methoxy, R 2 =hydrogen; Compound of Formula (III); A=E=phenyl, B=D=H, R ^methoxy, R 2 =hydrogen; Compound of Formula (HI); A=methyl, B=D=E=H, R ^methoxy, R^hydrogen; Compound of Formula (HI); B=methyl, A=D=E=H, R ^methoxy, R^hydrogen; Compound of Formula (HI); A=D=methyl; B=E=H, R ^methoxy, R 2 =hydrogen; Compound of Formula (HI); A=E=methyl; B=D=H, R ^methoxy, R 2 =hydrogen ; Compound of Formula (IH); B=D=H; A and E taken together is -CH2CH2CH2-, R'=methoxy, R 2 =hydrogen; Compound of Formula (HI); B=E=H; A and D taken together is -CH2CH2CH2CH2-, R ^methoxy, R^hydrogen ; and Compound of Formula (I); A=B=D=E=hydrogen; R^hydrogen, R 2 =hydrogen. One object of the present invention is to provide a process for the preparation of tricyclic macrolide derivatives having the Formulas: wherein A, B, D and E are independently selected from the group consisting of: (a) hydrogen; (b) Ci- j-alkyl, as defined below, optionally substituted with one or more substituents selected from the group consisting of: (i) aryl, as defined below; (ii) substituted-aryl, as defined below; (iii) heteroaryl, as defined below; (iv) substituted-heteroaryl, as defined below; (v) heterocycloalkyl, as defined below; (vi) hydroxy; (vii) Cι-C6-alkoxy, as defined below: (viii) halogen consisting of Br, Cl, F or I; and (ix) NR 3 R 4 , where R 3 and R 4 are independently selected from hydrogen and Cι-C6-alkyl, or R 3 and R 4 are taken with the nitrogen atom to which they are connected to form a 3- to 7-membered ring optionally containing a hetero function consisting of -O-, -NH-, -N(Cι-Cό-alkyl-)-, -N(aryl-Cι-C 6 -alkyl-)-, -N(substituted-aryl-Cι-C 6 -alkyl-)-, -N(heteroaryl-Cι-C6-alkyl-)-, -N(substituted-heteroaryl-Cι-C6-alkyl-)-, -S- or -S(O) n -, wherein n is 1 or 2: (c) C3-C7-cycloalkyl; (d) aryl; (e) substituted-aryl; (f) heteroaryl; (g) substituted-heteroaryl; (h) heterocycloalkyl; and (i) a group selected from option (b) above further substituted with -M- R 5 , wherein M is selected from the group consisting of: (aa) -C(O)-NH-; (bb) -NH-C(O)-; (cc) -NH- (dd) -N(CH 3 )- (ee) - - (rr) -S(O) n -, wherein n is 0, 1 or 2; and (gg) -C(=NH)-NH-; and R 5 is selected from the group consisting of: (aaa) 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; (bbb) aryl; (cce) substituted-aryl; (ddd) heteroaryl; (eee) substituted-heteroaryl; and (fff) heterocycloalkyl; or any one pair of substituents, consisting of AB, AD, AE, BD, BE or DE, is taken together with the atom or atoms to which they are attached to form a 3- to 7-membered ring optionally containing a hetero function consisting of -O-, -NH-, -N(Cι-C 6 -alkyl-)-, -N(aryl-Cι-C 6 -alkyl-)-, -N(substituted-aryl-Cι-C6-alkyl-)-, -N(heteroaryl-Cι -C6-alkyl-)-, -N(substituted-heteroaryl-Cι-C6-alkyl-)-, -S- or -S(O) n -, wherein n is 1 or 2; -C(O)-NH-; -C(O)-NR 5 -, wherein R 5 is as described above; -NH-C(O)-; -NR 5 -C(O)-, wherein R 5 is as described above; and -C(=NH)-NH-; R 1 is selected from the group consisting of: (a) hydrogen; (b) hydroxy; (c) -O-Cι-C 3 -alkyl; (d) -O-C-C 5 -cycloalkyl; (e) -O-Cι-C 3 -alkyl-C 3 -C5-cycloalkyl; (f) -O-C(O)-Cι-C -alkyl; (g) -O-C(O)-O-Cι-C 3 -alkyl; and (h) -O-C(O)-NH-Cι-C3-alk:yl; R 2 is hydrogen or a hydroxy-protecting group, as defined below; and Z is hydroxy or protected-hydroxy; except when the compound is of Formulas (I) or (IH) then A, B, D, and E may not all be hydrogen, D and E may not be Cι-C 3 -alkyl when A and B are hydrogen, nor may one of D and E be hydrogen and the other be Cι-C 3 -alkyl when A and B are hydrogen; the method comprising: (a) treating a compound having the formula , (compound (2) from Scheme 1), , (compound (6) from Scheme 2), , (compound (7) from Scheme 3), or , (compound (9) from Scheme 4), respectively, wherein R 1 is as described above and R 2 is a hydroxy-protecting group, with a base, such as sodium hydride, lithium hydride, potassium carbonate, for example, and followed by reaction with carbonyldiimidazole, in an aprotic solvent, as defined below, which does not adversely affect the reaction, preferably dichloromethane, chloroform, DMF, tetrahydrofuran (THF), N-methyl pyrrolidinone or a mixture thereof, with cooling or heating, depending on the conditions used, at a reaction temperature from -20°C to 70°C, preferably from 0°C to reaction temperature, for a period from 0.5 hours to 10 days, preferably 1-5 days, to prepare first intermediate compounds having the formulas: (compound (3) from Scheme 1), , (compound (6) from Scheme 2), (compound (8) from Scheme 3), or , (compound (10) from Scheme 4), respectively; wherein R 1 and R 2 are as described above; (b) reacting said first intermediate compounds (3), (6), (8), or (10) with a compound having the formula: wherein A, B, D, and E are as described above, preferably in a solvent such as aqueous acetonitrile, DMF or aqueous DMF, to give the bicyclic second intermediate compounds having the formulas: (compound (11), from Scheme 5), (compound (15), from Scheme 7), (compound (19) from Scheme 9), (compound (23), from Scheme 11), respectively; wherein R 1 and R 2 are as described above; (c) deprotecting said second intermediate compounds (11), (15), (19) or (23) by treatment with methanol or ethanol when OR 2 is an ester or with fluoride in THF or acetonitrile when R 2 is a trialkylsilyl group, for from 1 to 24 hours, to give the third intermediate compounds (compound (12), from Scheme 5), (compound (16), from Scheme 7), (compound (20) from Scheme 9), (compound (24) from Scheme 1 1), respectively; and (d) cyclizing said third intermediate compounds (12), (16), (20) or (24) by treatment with dilute acid, such as acetic acid or HCl, for example, in an organic solvent, preferably ethanol or propanol, for a period of from 4 hours to 10 days to give the desired compounds (I), (II), (lu) or (IV) above. Another object of the present invention is to provide an alternate process for the preparation of tricyclic macrolide derivatives having the Formulas: wherein A , B , D and E are independently selected from the group consisting of: (a) hydrogen; (b) Cι-C6-alkyl, as defined below, optionally substituted with one or more substituents selected from the group consisting of: (i) aryl, as defined below: (ii) substituted-aryl, as defined below; (iii) heteroaryl, as defined below; (iv) substituted-heteroaryl, as defined below; (v) heterocycloalkyl, as defined below; (vi) hydroxy; (vii) Cι- ;-alkoxy, as defined below; (viii) halogen consisting of Br, Cl, F or I; and (ix) NR 3 R 4 , where R 3 and R 4 are independently selected from hydrogen and Cj-Cό-alkyl, or R 3 and R 4 are taken with the nitrogen atom to which they are connected to form a 3- to 7-membered ring optionally containing a hetero function consisting of -O-. -NH-, -N(C|-C6-al yl-)-, -N(aryl-Cι-C6-alkyl-)-. -N(substituted-aryl-Cι-C6-alkyl- )-, -N(heteroaryl-C)-C6-alkyl-)-, -N(substituted-heteroaryl-Cι-C6-alkyl-)-, -S- or -S(O) n -, wherein n is 1 or 2; (c) C3-C7-cycloalkyl; (d) aryl; (e) substituted-aryl; (f) heteroaryl; (g) substituted-heteroaryl; (h) heterocycloalkyl; and (i) a group selected from option (b) above further substituted with -M- R 5 . wherein M is selected from the group consisting of: (aa) -C(O)-NH-; (bb) -NH-C(O)-; (cc) -NH- (dd) -N(CH 3 )- (ee) -O- (rr) -S(O)n-, wherein n is 0, 1 or 2; and (gg) -C(=NH)-NH-; and R 5 is selected from the group consisting of: (aaa) Ci-Cό-alkyl, optionally substituted with a substituent selected from the group consisting of: (i) aryl; (ii) substituted-aryl; (iii) heteroaryl; and (iv) substituted-heteroaryl; (bbb) aryl; (cce) substituted-aryl; (ddd) heteroaryl; (eee) substituted-heteroaryl; and (fff) heterocycloalkyl; or any one pair of substituents, consisting of AB, AD, AE, BD, BE or DE, is taken together with the atom or atoms to which they are attached to form a 3- to 7-membered ring optionally containing a hetero function consisting of: -O-, -NH-, -N(Cι-C 6 -alkyl-)-, -N(aryl-Cι-C6-alkyl-)-, -N(substituted-aryl-Cι-C6-alkyl-)-, -N(heteroaryl-Cι-C6-alkyl-)-, -N(substituted-heteroaτyl-Cι-C6-alkyl-)-, -S- or -S(O) n -, wherein n is 1 or 2; -C(O)-NH-; -C(O)-NR 5 -, wherein R 5 is as described above; -NH-C(O)-; -NR 5 -C(O)-, wherein R 5 is as described above; and -C(=NH)-NH-; R 1 is selected from the group consisting of: (a) hydrogen; (b) hydroxy; (c) -O-Cι-C3-alkyl; (d) - C3-C 5 -cycloalkyl; (e) -O-Cι-C3-alkyl-C 3 -C5-cycloalkyl; (f) -O-C(O)-Cι-C 3 -alkyl; (g) -O-C(O)-O-Cι-C -alkyl; and (h) -O-C(O)-NH-Cι-C 3 -alkyl; R 2 is hydrogen or a hydroxy-protecting group, as defined below; and Z is hydroxy or protected-hydroxy; except when the compound is of Formulas (I) or (HI) then A, B, D, and E may not all be hydrogen, D and E may not be Cι-C 3 -alkyl when A and B are hydrogen, nor may one of D and E be hydrogen and the other be Cι-C 3 -alkyl when A and B are hydrogen; the method comprising: (a) treating a compound having the formula: (compound (2) from Scheme 1), , (compound (6) from Scheme 2), (compound (7) from Scheme 3), or , (compound (9) from Scheme 4), respectively, wherein R 1 is as described above and R 2 is a hydroxy-protecting group, with a base, such as sodium hydride, lithium hydride, potassium carbonate, for example, and followed by reaction with carbonyldiimidazole, in an aprotic solvent, as defmed above, which does not adversely affect the reaction, preferably dichloromethane, chloroform, DMF, tetrahydrofuran (THF), N-methyl pyrrolidinone or a mixture thereof, with cooling or heating, depending on the conditions used, at a reaction temperature from -20°C to 70°C, preferably from 0°C to reaction temperature, for a period from 0.5 to 24 hours, preferably 1- 8 hours, to prepare first intermediate compounds having the formulas: , (compound (3) from Scheme 1), , (compound (6) from Scheme 2) (compound (8) from Scheme 3), or , (compound (10) from Scheme 4), respectively; wherein R 1 and R 2 are as described above; (b) reacting said first intermediate compounds (3), (6), (8), or (10) with a compound having the formula: wherein A, B, D, and E are as described above, preferably in a solvent such as aqueous acetonitrile, DMF or aqueous DMF, to give the bicyclic second intermediate compounds: , (compound (14), from Scheme 6, Y=OH), ompound (18), from Scheme 8, Y=OH), , (compound (22) from Scheme 10, Y=OH), or respectively; (c) reacting the hydroxy group of the said bicyclic second intermediate compounds (14), (18), (22) and (26) by treatment triphenylphosphine and diphenyl- phosphoryl azide-DEAD in tetrahydrofuran, under Mitsunobu reaction conditions, to prepare the third intermediate compounds: , (compound (22) from Scheme 10, Y=N 3 ), or respectively; (d) reducing the third intermediate compounds having an azido group, with suitable reducing reagents such as triphenylphosphine-water, hydrogen with a catalyst, sodium borohydride, or dialkylaluminum hydride, to prepare the fourth intermediate compounds having the formulas: , (compound (12), from Scheme 6), , (compound (16), from Scheme 8), , (compound (20) from Scheme 10), or , (compound (24), from Scheme 12), respectively; and (e) cyclizing said fourth intermediate compounds (12), (16), (20) or (24), wherein Y is an amino group, by treatment with dilute acid, such as acetic acid or HCl, for example, in an organic solvent, preferably ethanol or propanol, for a period of from 4 hours to 10 days to give the desired compounds of Formulas (I), (II), (HI) or (IV). In an alternate embodiment of the alternate process above, the third intermediate compounds may be prepared by a two-step sequence (replacing step (c) thereof) which comprises (1) reacting the hydroxy group of the bicyclic second intermediate compounds with an alkyl or aryl sulfonyl chloride, an alkyl or aryl sulfonic anhydride or trifluoromethanesulfonic anhydride in an aprotic solvent at -78°C to reaction temperature to give the corresponding sulfonate, and (2) reacting the said sulfonate with lithium azide or sodium azide in an aprotic solvent at 0°C to 100°C to give the third intermediate compound. Definitions The terms "Cι-C 3 -alkyr' or "Cι-C6-alkyl" as used herein refer to saturated, straight- or branched-chain hydrocarbon radicals containing between one and three or one and six carbon atoms, respectively. Examples of Cι-C 3 alkyl radicals include methyl, ethyl, propyl and isopropyl, and examples of Cι-C6-alkyl radicals include, but are not limited to, methyl, ethyl, propyl, isopropyl, «-butyl, tert-butyl, neopentyl and n-hexyl. The term "Ci-Cβ-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 Cι-C6-alkoxy, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, w-butoxy, t -butoxy, neopentoxy and n-hexoxy. The term "Cι-C 3 -alkyl-amino" as used herein refers to one or two Cι-C 3 -alkyl groups, as previously defined, attached to the parent molecular moiety through a nitrogen atom. Examples of Cι-C3-alkyl-amino include, but are not limited to methylamino, dimethylamino, ethylamino, diethylamino, and propylamino. 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, heterocyclic compounds, such as, for example, tetrahydrofuran and N-methylpyrrolidinone, and ethers such as diethyl ether, bis-methoxymethyl ether. Such compounds are well 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 solubility 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 specialized 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 Wiley & Sons, NY, 1986. The term "aryl" as used herein refers to unsubstituted carbocyclic aromatic groups including, but not limited to, phenyl, 1- or 2-naphthyl and the like. The term "C3-C5-cycloalkyl- and C 3 -C7-cycloalkyl" as used herein refers to carbocyclic groups of 3 to 5 or 3 to 7 carbons, respectively, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl. The term "Cι-C 3 -alkyl-C 3 -C5-cycloalkyl", as used herein refers to a C 3 -C5- cycloalkyl radical, as defined above, attached to a Cι-C 3 -alkyl radical by replacement of a hydrogen atom on the latter. The terms "halo" and "halogen" as used herein refer to an atom selected from fluorine, chlorine, bromine and iodine. 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, pyridinyl, pyrazinyl, pyrimidinyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isooxazolyl, thiadiazolyl, oxadiazolyl, thiophenyl, furanyl, quinolinyl, isoquinolinyl, and the like. The term "heterocycloalkyl" as used herein, refers to a non-aromatic 5-, 6- or 7- membered ring or a bi- or tri-cyclic group comprising fused six-membered rings having between one and three heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein (i) each 5-membered ring has 0 to 1 double bonds and each 6-membered ring has 0 to 2 double bonds, (ii) the nitrogen and sulfur heteroatoms may optionally be oxidized, (iii) the nitrogen heteroatom may optionally be quaternized, and (iv) any of the above heterocyclic rings may be fused to a benzene ring. Representative heterocycles include, but are not limited to, pyrrolidinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, piperidinyl, piperazinyl, oxazolidinyl, isoxazolidinyl, moφholinyl, thiazolidinyl, isothiazolidinyl, and tetrahydrofuryl. "Hydroxy-protecting group", as used herein, refers to an easily removable group to which are 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 limited to, methylthiomethyl, tert-dimethylsilyl, tert-butyldiphenylsilyl, acyl substituted with an aromatic group 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, trimethylsilyl, triethyl silyl, 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 well 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 solubility 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 ai, Vol. ϋ, 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, Cι.-C 3 -alkyl, Cι-C6-alkoxy, methoxymethoxy, amino, or C1-C3- alkyl-amino. 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, Cι-C 3 -alkyl, Q-Cό-alkoxy, methoxymethoxy, amino, or Cι-C3-alkyl-amino. 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, Cι.-C 3 -alkyl, Cι-C6-alkoxy, methoxymethoxy, amino, or Cι-C 3 -alkyl-amino. 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 "pharmaceutically 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 J. 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, camphorsulf onate, citrate, cyclopentanepropionate, 7/, * 1-73■ * 5-6 * PCT/US96/16585 digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate. hexanoate, hydroiodide, 2-hydroxy- ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate salts, and the like. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, loweralkyl sulfonate and aryl sulfonate. As used herein, the term "pharmaceutically acceptable ester" refers to esters which hydrolyze in vivo and include those that break down readily in the human body to leave the parent compound or a salt thereof. Suitable ester groups include, for example, those derived from pharmaceutically acceptable aliphatic carboxylic acids, particularly alkanoic, alkenoic, cycloalkanoic and alkanedioic acids, in which each alkyl or alkenyl moiety advantageously has not more than 6 carbon atoms. Examples of particular esters includes formates, acetates, propionates, butyates, acrylates and ethylsuccinates. The pharmaceutical compositions of the present invention comprise a therapeutically effective amount of a compound of the present invention formulated together with one or more pharmaceutically acceptable carriers. As used herein, the term "pharmaceutically acceptable carrier" means a non-toxic, inert solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type. Some examples of materials which can serve as pharmaceutically acceptable carriers are sugars such as lactose, glucose and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil; safflower oil; sesame oil; olive oil; com oil and soybean oil; glycols; such a propylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol, and phosphate buffer solutions, as well as other non-toxic compatible lubricants such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, releasing agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the composition, according to the judgment of the formulator. The pharmaceutical compositions of this invention can be administered to humans and other animals orally, rectally, parenterally, intracisternally, intravaginally, intraperitoneally, topically (as by powders, ointments, or drops), bucally, or as an oral or nasal spray. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, com, germ, olive, castor, and sesame oils), glycerol, tettahyckofiufuryl 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 sterile injectable solution, suspension or emulsion in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water. Ringer's solution, U.S.P. and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid are used in the preparation of injectables. 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 crystalline or amorphous material with poor water solubility. The rate of absoφtion of the drug then depends upon its rate of dissolution which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absoφtion of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle. Injectable depot forms are made by forrning microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycolide. Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions which are compatible with body tissues. 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 silicic acid, b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia, c) humectants such as glycerol, d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, e) solution retarding agents such as paraffin, f) absoφtion 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 pills, the dosage form may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard- filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions which can be used include polymeric substances and waxes. Solid compositions of a similar type may also be employed as fillers in soft and hard- filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polethylene 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 shells such as enteric coatings, release controlling coatings and other coatings well known in the pharmaceutical formulating art. In such solid dosage forms the active compound may be admixed with at least one inert diluent such as sucrose, lactose or starch. Such dosage forms may also comprise, as is normal practice, additional substances other than inert diluents, e.g., tableting lubricants and other tableting aids such a magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions which can be used include polymeric substances and waxes. Dosage forms for topical or transdermal administration of a compound of this invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or patches. The active component is admixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives or buffers as may be required. Ophthalmic formulation, ear drops, eye ointments, powders and solutions are also contemplated as being within the scope of this invention. The ointments, pastes, creams and gels may contain, in addition to an active compound of this invention, excipients such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth. cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof. Powders and sprays can contain, in addition to the compounds of this invention, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances. Sprays can additionally contain customary propellants such as chlorofluorohydrocarbons. Transdermal patches have the added advantage of providing controlled delivery of a compound to the body. Such dosage forms can be made by dissolving or dispensing the compound in the proper medium. Absoφtion enhancers can also be used to increase the flux of the compound across the skin. The rate can be controlled by either providing a rate controlling membrane or by dispersing the compound in a polymer matrix or gel. 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 therapeutically 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 applicable to any medical treatment. It will be understood, however, that the total daily usage of the compounds and compositions of the present invention will be decided by the attending physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; the activity of the specific compound employed; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific compound employed: the duration of the treatment; drugs used in combination or --,. --- * PCT/US96/16585 97/17356 coincidental with the specific compound employed; and like factors well known in the medical arts. The total daily 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 1000 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 follow are: ALBN for azobisisobutyronitrile; Bu3SnH for tributyltin hydride; CDl for carbonyldiimidazole; DBU for l,8-diazabicyclo[5.4.0]undec-7-ene; DEAD for diethylazodicarboxylate; DMF for dimethyl formamide: DPPA for diphenylphosphoryl azide; EtOAc for ethyl acetate; MeOH for methanol; NaN(TMS)2 for sodium bis(trimethylsilyl)amide; NMMO for N-methylmoφholine N-oxide; TEA for triethylamine; THF for tetrahydrofuran; TPP for triphenylphosphine. Synthetic Methods The compounds and processes of the present invention will be better understood in connection with the following synthetic schemes which illustrate the methods by which the compounds of the invention may be prepared. The groups A, B, D, E, R 1 and R 2 are as defined above unless otherwise noted below. Scheme 1 Preparation of Starting Materials, 12-imidazolylcarbonyloxy macrolide (3). for Compounds of Formula (I) protect R 1 is as described for formula I R 2 is a hydroxy-protecting group (3) R 1 is as described for formula I R 2 is a hydroxy-protecting group Scheme 1 illustrates a general procedure for preparing the starting material, imidazolylcarbonyloxy macrolide (3), for compounds of Formula (I). The 2'- and 4"- hydroxyl groups of compound (1) are protected by reacting (1) with suitable hydroxy group protecting reagents (cf. T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis. 2nd ed., John Wiley & Son, Inc., 1991) such as acetic anhydride, benzoic anhydride, benzyl chloroformate or a trialkylsilyl chloride in an aprotic solvent as defined above, which does not adversely affect the reaction, preferably dichloromethane, chloroform, DMF, tetrahydrofuran (THF), N-methyl pyrrolidinone or a mixture thereof. The protected macrolide (2) is reacted under anhydrous conditions with base such as sodium hydπde, lithium hydπde, potassium carbonate and followed by carbonyldiimidazole to form compound (3) in an aprotic solvent as defined above, which does not adversely affect the reacnon, preferably dichloromethane, chloroform, DMF, tetrahydrofuran (THF), N-methyl pyrrohdinone or a mixture thereof The reacnon may require coolmg or heating, dependmg on the conditions used. The reaction temperature may be from -20°C to 70°C, and preferably from 0°C to reacnon temperature The reacnon may require 0.5 hours to 10 days, and preferably 1-5 days, to complete Scheme 2 Preparaϋon of Starting Mateπals, 12-ιmιdazolylcarbonyloxy macrolide (6). for Compounds of Formula π) p R is as descnbed for formula II (6) (5) R 1 is as described for formula II R 2 is a hydroxy-protecting group R 2 is a hydroxy-protecting group Scheme 2 illustrates a general procedure for preparing the starting mateπals, 12- iimdazolylcarbonyloxy macrolide (6), for the preparations of compounds of formula (II) The cladinose moiety of macrohdes of formula ( 1) is removed either by mild aqueous acid hydrolysis of by enzymauc hydrolysis In accordance with Scheme 2, a suspension of (1) in a solution of protogenic organic solvent (for example methanol, ethanol, isopropanol or butanol) and water is treated with dilute hydrochloric acid, chloroacetic acid, dichloroacetic acid or trifluoroacetic acid for 0.5 to 24 hours. The reaction temperature is preferably -10 to 35 °C to give the des-cladinose compounds (4a). The 2'-hydroxy group of (4a) is protected and converted to (4a) by treatment with a suitable hydroxy protecting reagent (cf. T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis. 2nd ed., John Wiley & Son, Inc., 1991) such as acetic anhydride, benzoyl anhydride, benzyl chloroformate or trialkylsilyl chloride in an aprotic solvent, as defined above, preferably dichloromethane, chloroform, DMF, tetrahydrofuran (THF), N-methyl pyrrolidinone or a mixture thereof. The protected macrolide (4) is reacted under anhydrous conditions with base such as sodium hydride, lithium hydride, potassium carbonate or dimethylaminopyridine and followed by phosgene, diphosgene, triphosgene or benzyl chloroformate in an aprotic solvent as defined above. The reactive intermediate is then trapped with benzyl alcohol to give compound (5). Compound (5) is reacted under anhydrous conditions with NaH and CDl in an aprotic solvent, preferably THF, DMF or a mixture thereof. The reaction may require cooling of heating, depending upon the conditions used. The reaction temperature may be from -20°C to 70°C, and preferably from 0°C to reaction temperature. The reaction may require 0.5 hours to 10 days, and preferably 1-5 days, to complete. Scheme 3 Preparation of Starting Materials, 12-imidazolylcarbonyloxy macrolides. for Compounds of Formula (HI) (7a) (8) R 1 is as described for formula III R 2 is a hydroxy-protecting group Scheme 3 illustrates two general procedures for the synthesis of 12- imidazolylcarbonyloxy macrolide (8), starting materials for the preparation of compounds of formula (HI). In accordance with scheme 3, the 3-hydroxy group of a 2'-protected des- cladinose macrolide (4) is oxidized to the coπesponding 3-oxo compound (7) using a modified Swern oxidation procedure. In scheme 3, suitable oxidizing agents are N- chlorosuccinimide-dimethyl sulfide or carbo&imide-dimethylsulfoxide. In a typical example, (4) is added into a pre-formed N-chlorosuccinimide and dimethyl sulfide complex in a chlorinated solvent such as methylene chloride at -10 to 25 °C. After being stirred for 0.5-4 hours, a tertiary amine such as triethylamine or Hunig's base is added to produce the oxidized compound (7). In the first approach in scheme 3, (7) is reacted with sodium hydride or lithium hydride and CDl under anhydrous conditions in an aprotic solvent as defined above, which does not adversely affect the reaction, preferably dichloromethane, chloroform, DMF, tetrahydrofuran (THF), N-methyl pyrrolidinone or a mixture thereof. The resulting alkoxide is then reacted with excess carbonyldiimidazole for 0.5 hours to 10 days in the same reaction mixture to produce (8). The prefeπed temperature is from -10 °C to reaction temperature. In the second approach in Scheme 3, (7) is converted to (7a) with sodium hydride or lithium hydride and phosgene, diphosgene or triphosgene under anhydrous conditions followed by aqueous work up. Alternatively, (7) is converted to its corresponding 11- mesylate by reacting (7) with methanesulfonic anhydride in pyridine. The 11 -mesylate is then converted to (7a) with an amino base such as DBU or dimethylaminopyridine in acetone or acetonitrile. (7a) is then reacted with sodium hydride or lithium hydride under an ydrous conditions in an aprotic solvent, as defined above, which does not adversely affect the reaction, preferably dichloromethane, chloroform, DMF, tetrahydrofuran (THF), N-methyl pyπolidinone or a mixture thereof. The reactive alkoxide is then reacted with carbonyldiimidazole for 0.5 hours to 10 days in the same reaction mixture to produce (8). The prefeπed temperature is from - 10 °C to reaction temperature. Scheme 4 Preparation of 12-imidazolylcarbonyloxy macrolides (10). for Compounds of Formula (IV) R 1 is as described for formula III R 2 is a hydroxy-protecting group In accordance with Scheme 4, a protected descladinose compound of formula (5) is dissolved in an aprotic solvent such as THF, then reacted with an excess of NaH at from 0°C to -30°C under an inert atmosphere, followed by reaction of the intermediate anion with CS2, then CH3I at -5 to 10°C, to form a 3-O-xanthyl compound. This xanthate intermediate is then reacted with 1.1-1.3 equivalents of Bu3SnH under an inert atmosphere in the presence of a catalytic amount of AIBN in a solvent suitable for a free radical reaction, such as benzene or toluene, for example, at reflux conditions to afford the desired compound (9). Compounds (9) are then reacted with carbonyldiimidazole and NaH under anhydrous conditions in an aprotic solvent, as defined above, which does not adversely affect the reaction, preferably dichloromethane, chloroform, DMF, tetrahydrofuran (THF), N-methyl pyrrolidinone or a mixture thereof, at a temperature from 0°C to reaction temperature for 0.5 hours to 10 days to provide the compounds of formula (10). Scheme 5 Preparation of Compounds of Formula (I) R 1 is as described for formula I R 2 is a hydroxy-protecting group deprotect Compound of Formula (I). In accordance with Scheme 5, a starting material compound of formula (3) is reacted with a diamine compound having substituents A, B, D and E as defined above but with C2 or Cs symmetry or A=B=H, in a suitable solvent such as for example, aqueous acetonitrile, DMF or aqueous DMF, to give the bicyclic compound of formula (11). The and 4" hydroxy protecting group of compound (11) are then removed by standard methods (cf. T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis. 2nd ed., John Wiley & Son, Inc., 1991) to give (12). When OR 2 is an ester, for example, such as acetate or benzoate, the compound may be deprotected by treatment with methanol or ethanol. When R 2 is a trialkylsilyl group, the compound may be deprotected by treatment with fluoride in THF or acetonitrile, for example. Compound (12) is then cyclized by treatment with dilute acid, such as acetic acid or HCl, for example, in a suitable organic solvent, such as methanol, ethanol or propanol, for example, for a period of from 4 hours to 10 days, from reaction temperature to reflux, in order to prepare the compound of formula (13). Scheme 6 Alternate Preparation of Compounds of Formula (I) R' is as descnbed lor formula I R 2 is a hydroxy-protecting group Compound of Formula (I) Scheme 6 illustrates an alternative preparation of compounds of formula (I). Starting mateπal (3) is reacted with a betø-aminoalcohol (Y=OH) having substituents A, B, D and E, as defined above, in a suitable solvent system such as aqueous acetonitrile, DMF or aqueous DMF at 0 - 70 C to give compound (14) where Y=OH. The azido intermediate, compound (14) Y=N3, is prepared by Mitsunobu reaction by reacting compound (14) Y=OH with triphenylphosphine and diphenylphosphoryl azide-DEAD in tetrahydrofuran. Compound (14) is then deprotected by standard methods (cf. T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis. 2nd ed., John Wiley & Son, Inc., 1991). When OR2 is an ester, for example, such as acetate or benzoate, the compound may be deprotected by treatment with methanol or ethanol. When R^ is a trialkylsilyl group, the compound may be deprotected by treatment with fluoride in THF or acetonitrile, for example. The azido intermediate, compound (14) Y=N3, is then reduced to the amino compound (12). Suitable reducing reagents are triphenylphosphine-water, hydrogen with a catalyst, sodium - 41 StBSmUTE SHEET (RULE 26} borohydride, or dialkylaluminum hydride. Compound (12) is then cyclized by treatment with dilute acid, such as acetic acid or HCl, for example, in a suitable organic solvent, such as methanol, ethanol or propanol, for example, for a period of from 4 hours to 10 days, in order to prepare the compound of formula (13). Alternatively in scheme 6, the hydroxy group (Y=OH) in (14) is activated by treatment with sulfonyl chloride, alkyl or aryl sulfonic anhydride or trifluoromethanesufonic anhydride in an aprotic solvent (e.g., diethyl ether, dichloromethane, tetrahydrofuran, chloroform, pyridine or a mixture thereof). The reaction requires cooling or heating, depending on the conditions used. The reaction temperature is preferably -100 to 10 °C. The reaction may require 20 minutes to 24 hours to complete. The activated hydroxy group in (14) (e.g., Y—OSO2CF3) is then converted to the conesponding azide (Y=N3, 14) by reacting with lithium azide or sodium azide in the same solvent described above. The reaction temperature is preferably 0-100 °C. The azido compound is then converted to (13) according to the procedures described above. Scheme 7 Preparation of Compounds of Formula (II) R 1 is as described for formula I R 2 is a hydroxy-protecting group deprotect Compound of Formula (II) In accordance with Scheme 7, a starting material compound (6) is reacted with a diamine compound having substituents A, B, D and E as defined above but with C2 or Cs symmetry or A=B=H, in a suitable solvent such as for example, aqueous acetonitrile, DMF or aqueous DMF, to give the bicyclic compound of formula (15). Compound (15) is then deprotected to prepare the compound of formula (16). The deprotection is accomplished by standard methods described (cf. T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis. 2nd ed., John Wiley & Son, Inc., 1991). When OR 2 is an ester, for example, such as acetate or benzoate, the compound may be deprotected by treatment with methanol or ethanol. When R 2 is a trialkylsilyl group, the compound may be deprotected by treatment with fluoride in THF or acetonitrile, for example. Compound (16) is then cyclized by treatment with dilute acid, such as acetic acid or HCl, for example, in a suitable organic solvent, such as ethanol or propanol, for example, for a period of from 4 hours to 10 days, from reaction temperature to reflux, in order to prepare the compound of formula (17). Scheme 8 Alternate Preparation of Compounds of Formula (TD R 1 is as descnbed for formula I R 2 is a hydroxy-protecting group deprotθct (17) (16) Compound of Formula (II) Scheme 8 illustrates an alternative preparation of compounds of formula (II). Starting material (6) is reacted with a beta-aminoalcohol (Y=OH) having substituents A, B, D and E. as defined above, in a suitable solvent system such as aqueous acetonitrile. DMF or aqueous DMF at 0 - 70 °C to give compound (18) where Y=OH. The azido intermediate, compound (18) Y=N3, is prepared by Mitsunobu reaction by reacting compound ( 18) Y=OH with triphenylphosphine and diphenylphosphoryl azide-DEAD in tetrahydrofuran. Compound (18) is then deprotected to prepare the compound of formula (16) wherein R 2 is H. The deprotection is accomplished by standard methods (cf. T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis. 2nd ed., John Wiley & Son, Inc., 1991). When OR 2 is an ester, for example, such as acetate or benzoate, the compound may be deprotected by treatment with methanol or ethanol. When R 2 is a trialkylsilyl group, the compound may be deprotected by treatment with fluoride in THF or acetonitrile, for example. The azido intermediate, compound (18) Y=N3, is then reduced to the amino compound (16). Suitable reducing reagents are triphenylphosphine-water, hydrogen with a catalyst, sodium borohydride, or dialkylaluminum hydride. Compound (16) is then cyclized by treatment with dilute acid, such as acetic acid or HCl, for example, in a suitable organic solvent, such as methanol, ethanol or propanol, for example, for a period of from 4 hours to 10 days, from reaction temperature to reflux, in order to prepare the compound of formula (17). Alternatively in scheme 8, the hydroxy group (Y=OH) in (18) is activated by treatment with sulfonyl chloride, alkyl or aryl sulfonic anhydride or trifluoromethanesufonic anhydride in an aprotic solvent (e.g., diethyl ether, dichloromethane, tetrahydrofuran, chloroform, pyridine or a mixture thereof. The reaction requires cooling or heating, depending on the conditions used. The reaction temperature is preferably - 100 to 10 °C. The reaction may require 20 minutes to 24 hours to complete. The activated hydroxy group in (18) (e.g., Y=-OSO2CF3) is then converted to the conesponding azide (Y=N3, 18) by reacting with lithium azide or sodium azide in the same solvent described above. The reaction temperature is preferably 0-100 °C. The azido compound is then converted to (13) according to the procedures described above. Scheme 9 Preparation of Compounds of Formula (HI) R 1 is as described for formula I R 2 is a hydroxy-protecting group deprotect deprotect cyclizθ Compound of Formula ( In accordance with Scheme 9, a starting material compound(8) is reacted with a diamine compound having substituents A, B, D and E as defined above but with C2 or Cs symmetry or A=B=H, in a suitable solvent such as for example, aqueous acetonitrile, DMF or aqueous DMF, to give the bicyclic compound of formula (19). Compound (19) is then deprotected prepare the compound of formula (20). The deprotection is accomplished by standard methods (cf. T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis. 2nd ed., John Wiley & Son, Inc., 1991). When OR 2 is an ester, for example, such as acetate or benzoate, the compound may be deprotected by treatment with methanol or ethanol. When R 2 is a trialkylsilyl group, the compound may be deprotected by treatment with fluoride in THF or acetonitrile, for example. Compound (20) is then cyclized by treatment with dilute acid, such as acetic acid or HCl, for example, in a suitable organic solvent, such as ethanol or propanol, for example, for a period of from 4 hours to 10 days, from reaction temperature to reflux, in order to prepare the compound of formula (21). Alternately, as is readily apparent to those skilled in the art it is possible to cyclize compound (19) first, then deprotect, to obtain the compound (21). Scheme 10 Alternate Preparation of Compounds of Formula (UJ) R 1 is as described for formula I R 2 is a hydroxy-protecϊng group Compound of Formula (III) Scheme 10 illustrates an alternative preparation of compounds of formula (lu). Starting material (8) is reacted with a beta-aminoalcohol (Y=OH) having substituents A, B, D and E in a suitable solvent system such as aqueous acetonitrile, DMF or aqueous DMF at 0 - 70 °C to give compound (22) where Y=OH. the azido intermediate, compound (22) Y=N3, is prepared by Mitsunobu reaction by reacting compound (22) Y=OH with triphenyl¬ phosphine and diphenylphosphoryl azide-DEAD in tetrahydrofuran. Compound (22) is then deprotected by standard methods (cf. T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis. 2nd ed., John Wiley & Son, Inc., 1991 ). When OR 2 is an ester, for example, such as acetate or benzoate, the compound may be deprotected by treatment with methanol or ethanol. When R 2 is a trialkylsilyl group, the compound may be deprotected by treatment with fluoride in THF or acetonitrile, for example. The deprotected azido intermediate, compound (22) Y=N3, is then reduced to the amino compound (20). Suitable reducing reagents are triphenylphosphine-water, hydrogen with a catalyst, sodium borohydride, or dialkylaluminum hydride. Compound (20) is then cyclized by treatment with dilute acid, such as acetic acid or HCl, for example, in a suitable organic solvent such as methanol, ethanol or propanol, for example, for a period of from 4 hours to 10 days, from reaction temperature to reflux, in order to prepare the compound of formula (21). Alternatively in scheme 10, the hydroxy group (Y=OH) in (22) is activated by treatment with sulfonyl chloride, alkyl or aryl sulfonic anhydride or trifluoromethanesufonic anhydride in an aprotic solvent (e.g., diethyl ether, dichloromethane, tetrahydrofuran, chloroform, pyridine or a mixture thereof. The reaction requires cooling or heating, depending on the conditions used. The reaction temperature is preferably -100 to 10 °C. The reaction may require 20 minutes to 24 hours to complete. The activated hydroxy group in (22) (e.g., Y=-OSO2CF3) is then converted to the conesponding azide (Y=N3, 14) by reacting with lithium azide or sodium azide in the same solvent described above. The reaction temperature is preferably 0-100 °C. The azido compound is then converted to (13) according to the procedures described above. Scheme 11 Preparation of Compounds of Formula (IV) R 1 is as descnbed for formula I R 2 is a hydroxy-protecting group deprotsct Compound of Formula (IV) In accordance with Scheme 11, a starting material compound (10) is reacted with a diamine compound having substituents A, B, D and E as defined above but with C2 or Cs symmetry or A=B=H, in a suitable solvent such as for example, aqueous acetonitrile, DMF or aqueous DMF, to give the bicyclic compound of formula (23). Compound (23) is then deprotected to prepare the compound of formula (24) by standard methods (cf. T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis. 2nd ed., John Wiley & Son, Inc., 1991). When OR 2 is an ester, for example, such as acetate or benzoate, the compound may be deprotected by treatment with methanol or ethanol. When R 2 is a trialkylsilyl group, the compound may be deprotected by treatment with fluoride in THF or acetonitrile, for example. Compound (24) is then cyclized by treatment with dilute acid, such as acetic acid or HCl, for example, in a suitable organic solvent, such as ethanol or propanol, for example, for a period of from 4 hours to 10 days, from reaction temperature to reflux, in order to prepare the compound of formula (25). Scheme 12 Alternate Preparation of Compounds of Formula (IV) R 1 is as described for formula I R 2 is a hydroxy-protecting group Compound of Formula (IV) Scheme 12 illustrates an alternative preparation of compounds of formula (IV). Starting material (10) is reacted with an beta-aminoalcohol (Y=OH) having substituents A, B, D and E, as defined above, in a suitable solvent system such as aqueous acetonitrile, DMF or aqueous DMF at 0 - 70 °C to give compound (26) where Y=OH. The azido intermediate, compound (26) Y=N3, is prepared by Mitsunobu reaction by reacting compound (26) Y=OH with diphenylphosphoryl azide-DEAD in tetrahydrofuran. Compound (26) is then deprotected by standard methods (cf. T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis. 2nd ed., John Wiley & Son, Inc., 1991). When OR 2 is an ester, for example, such as acetate or benzoate, the compound may be deprotected by treatment with methanol or ethanol. When R 2 is a trialkylsilyl group, the compound may be deprotected by treatment with fluoride in THF or acetonitrile, for example. The deprotected azido intermediate, compound (26) Y=N3, is then reduced to the amino compound (24). Suitable reducing reagents are triphenylphosphine-water, hydrogen with a catalyst, sodium borohydride, or dialkylaluminum hydride. Compound (24) is then cyclized by treatment with dilute acid, such as acetic acid or HCl, for example, in a suitable organic solvent, such as methanol, ethanol or propanol, for example, for a period of from 4 hours to 10 days, in order to prepare the compound of formula (25). Alternatively in Scheme 12, the hydroxy group (Y=OH) in (26) is activated by treatment with sulfonyl chloride, alkyl or aryl sulfonic anhydride or trifluoromethanesufonic anhydride in a solvent does not adversely affect the reaction (e.g., diethyl ether, dichloromethane, tetrahydrofuran, chloroform, pyridine or a mixture thereof. The reaction requires cooling or heating, depending on the conditions used. The reaction temperature is preferably -100 to 10 °C. The reaction may require 20 minutes to 24 hours to complete. The activated hydroxy group in (26) (e.g., Y=-OSO2CF3) is then converted to the conesponding azide (Y=N3, 26) by reacting with lithium azide in the same solvent described above. The reaction temperature is preferably 0-70 °C. The azido compound may be deprotected and converted to (25) according to the procedures described above. The compounds and processes of the present invention will be better understood in connection with the following examples, which are intended as an illustration of and not a limitation upon the scope of the invention. Example 1 la. 5-O-desosarninyl-6-O-meιAylervthronoUde A A sample of clarithromycin (3-O-cladinosyl-5-O-desosaminyl-6-O-methyl- erythronolide A, Abbott Labs, 142.38 g, 190.35 mmol) was suspended in an ethanol-water solution (1700/600 mL), and 341 mL of IN HCl was added. The reaction mixture was stirred for 24 hours, and 2 M NaOH (170 mL) and an additional 250 mL of water were added with vigorous stirring. The precipitate was collected by filtration, washed with water, and dried to afford the title compound (95.00 g, 84%). MS m/z: 590 (M+H) + . lb. 3-O-xanthyl-5-O-desosan^nyl-6-O-meιτιylervτhronolide A To a solution of 5-O-desosaminyl-6-O-methylerythronolide A ( 11.79 g, 20 mmoL, from step la above) in THF (100 mL) at -20°C under an inert atmosphere NaH (1.80 g, 60 mmoL, 60% dispersion) was added slowly over a 5 minute period. Several minutes later CS2 (1.2 mL, 20 mmoL) was added. After 5 minutes of stirring CH3I (1.24 mL, 20 mmol) was added, the reaction mixture was allowed to gradually warm to -5 - 0°C, and the mixture was stirred for 1 hour. The reaction mixture was diluted with EtOAc (400 mL), and the mixture was washed with saturated aqueous NaHCO3 and brine, dried (MgSO4), and concentrated to afford the crude product The residue was purified by chromatography on silica gel, eluting with CHCI3 and CHCl3-MeOH (95:5), to afford the title compound (7.68 g; 56%). MS m z: 680 (M+H)+. Anal. Calcd. for C32H57NO10S2: C, 56.52; H, 8.45; N, 2.06; Found: C, 56.95; H, 8.65; N, 1.92. 1 c . 3-deox v-5-O-desosaminyl-6-O-methylervthronolide A A solution of 3-O-xanthyl-5-O-desosaminyl-6-O-methyl erythronolide A (20.00 g; 29.41 mmoL, from step lb), Bu3SnH (9.49 mL, 35.29 mmol) and AIBN (-50 mg, catalytic) in benzene (200 mL) was heated at reflux (adding 25 mg portions of AIBN periodically) for 8 hours. The organic layer was separated and washed with 10% aqueous KF and brine, dried (MgSO4), and concentrated to afford the crude product as an oil. The residue was purified by chromatography on silica gel, eluting with CHCI3 and CHCI3- MeOH (97.5:2.5). The material was recrystallizated from hexane to afford the title compound (5.48 g; 32%). MS m/z: 574 (M+H) + . Anal. Calcd. for C30H55NO9: C, 62.80; H, 9.66; N, 2.44; Found: C, 63.02; H, 9.74; N, 2.30. Id. 2'-O-acetyl-3-deoxy-5-O-desosarrιinyl-6-O-methylerythronolide A Samples of 3-deoxy-5-O-desosaminyl-6-O-methylerythronolide A (573 mg, 1.0 mmol, from Example lc above), acetic anhydride (0.188 mL) and TEA (0.278 mL) were dissolved in 10 mL of methylene chloride, and the reaction mixture was stirred at reaction temperature for 20 hours. The reaction mixture was diluted with 40 mL of methylene chloride, and the organic solution was washed with saturated aqueous NaHCO3 and brine, dried and concentrated to obtain the title compound (600 mg). MS m/z: 616 (M+H) + . le. Compound (10) from Scheme 4: Rl=methoxy: R2=acetyl A sample of 2 , -O-acetyl-3-deoxy-5-O-desosaminyl-6-O-methylerythronolide A (0.63 g, 1.023 mmol, from Example Id above) was dissolved in 10 mL of THF, and the solution was cooled to -60°C. To this stirred solution was added sodium bis(trimethylsilyl) amide (1.22 mL, 1.0 M in THF). After 4 hours 1,1 -carbonyldiimidazole (0.66 g, 4.09 mmol) was added as a solution in 6 mL of 2:3 DMF:THF, and the reaction mixture was slowly warmed to reaction temperature and stirred for 16 hours. The reaction was quenched by addition of 5% aqueous NaH2PO4, and the resulting mixture was extracted with chloroform. The organic layer was washed with water, dried over MgSO4 and concentrated to give the title compound. MS m/z: 692 (M+H)+. If. Compound ( 23 ) from Scheme 1 1: Ri=methoxy: R2= a cetyl: A=B=D=E=hvdrogen A sample of the compound from step le above (0.25 g, 0.36 mmol) was dissolved in 3 mL of acetonitrile, ethylenediamine (0.24 mL, 3.6 mmol) was added, and the reaction mixture was stirred at reaction temperature for 3 hours. The solvent was removed under vacuum, and the residue was dissolved in ethyl acetate. This solution was washed with saturated aqueous NaHCO3 solution, dried over Na2SO4 and concentrated. The residue was twice purified by flash chromatography on silica gel, eluting with 2-20% ethanol in chloroform containing 0.5-2% NH 4 OH to give the title compound. MS m/z: 684 (M+H) + . 1 g. Compound (24) from Scheme 11: R^=methoxy: A=B=D=E=hvdrogen A sample of the compound from step lf was dissolved in methanol and stirred at reaction temperature for 64 hours. The title compound (170 mg) was obtained after filtration and removal of the solvent. Ih. Compound (IV) : Ri=methoxy: R2=hydrogen: A=B=D=E=hvdrogen A sample of the compound from step 6b (170 mg, 0.265 mmol) was dissolved in 2 mL of ethanol to which was added 0.03 mL of acetic acid, and the reaction mixture was stirred at reaction temperature for 16 hours. The solvent was removed, and the residue was suspended in water. The solution was adjusted to approximately pH 10-11 with 2M NaOH, and the mixture was extracted with ethyl acetate. The organic extract was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by flash chromatography on silica gel, eluting with 10% ethanol in chloroform containing 0.1% NH4OH. The product was re-chromatographed, eluting with 0-15% ethanol in chloroform to give the title compound (55 mg). MS m/z: 624 (M+H) + , 646 (M+NH4) + . Anal. Calcd. for C33H57N3O8: C, 63.53; H, 9.20; N, 6.73; Found: C, 64.68; H, 9.27; N, 7.01. 13 CNMR: C=O (16) 156.3, NCH 2 (17) 42.4, NCH 2 (18) 49.1 Example 2 Compound (8) from Scheme 3: Rl=methoxy: R -=benzoyl 2a. 5-O-desosaπύnyl-6-O-methylervthronolide A A sample of clarithromycin (3-O-cladinosyl-5-O-desosaminyl-6-0- methylerythronolide A, Abbott Labs, 900 g, 1.2 mole) was suspended in water (10.8 L) and ethanol (4.0 L), and the resulting slurry was stirred at reaction temperature until homogeneous (about 20 minutes). HCl (1.00 M, 2.16 L) was added over 15 minutes, and the reaction mixture was stirred for 20 hours. NaOH solution (2.00 M, 1.20 L) was added over 30 minutes until pH 10.5-11.0 was reached, and the reaction mixture was stirred for 2 hours. The precipitate was collected and washed with cold water, which was dried under vacuum at 50°C to afford 601 g of the title compound. MS m/z (M+H) + : 590. 2b. 2'-O-Denzoyl-5-O-desosaminyl-6-O-methylervthronolide A To a solution of 5-O-desosaminyl-6-O-methylerythronolide A, (600 g, 1.01 mol from step 2a above) in methylene chloride (2.0 L) was added 90% technical grade benzoic anhydride (380 g, 1.59 mol). Triethylamine (222 mL, 1.59 mol) was added over 10 minutes, and the thick solution was stirred for 48 hours. Sodium bicarbonate solution (10%, 1.5 L) was added, and the mixture was stirred for 30 minutes. The layers were separated, and the organic fraction was washed with water (3 x 600 mL) and brine (600 mL). The organic layer was dried (Na2SC«4) and filtered, and the volatiles were removed on a rotary evaporator to leave a syrup. Trituration with a warm solution of hexane (2.0 L) and ethyl acetate (100 mL) converted the product to white crystals. The product was filtered, washed with hexane and dried in a vacuum oven ovemight at ambient temperature to give the title compound (691 g). MS m z (M+H) + : 694. 2c. 2'-O-r^nzoyl-5-O-desosarninyl-3-deoxy-3-oxo-6-O-methylervthronolide A A sample of /V-chlorosuccinimide (57.0 g, 0.42 mol) was slurried in anhydrous methylene chloride (600 mL), and dimethyl sulfide (36.0 mL, 0.49 mol) was added dropwise over 30 minutes. A sample of the compound from step 2b (200.0 g, 0.29 mol) was dissolved in methylene chloride (1.20 L), and this solution was added to the reaction mixture over 45 minutes. After stirring for 30 minutes a solution of triethylamine (40.0 mL) in methylene chloride (200 mL) was added dropwise over 30 minutes at 0°C under nitrogen. The resulting solution was washed with sodium bicarbonate (10%, 3 x 600 mL) and brine (600 mL). The organic fraction was dried (Na2SO4) and filtered, and the volatiles were removed on a rotary evaporator to give a thick syrup, which became a solid upon standing. The solid was crushed and dried ovemight at ambient temperature in a vacuum oven to give the title compound (196 g). MS m/z (M+H) + : 692. 2d. 2'-O-benzoyl-5-O-desosaminyl-3-deoxy-3-oxo-6-O- methyl-1 l-O-methanesulfonyl-6-O-methylervthronolide A To a solution of 2'-O-benzoyl-5-O-desosaminyl-3-deoxy-3-oxo-6-O-methyl- erythronolide A from step 2c above (20.00 g, 28.9 mmole) in pyridine (40 mL) cooled to 0° and held under N2 was added methanesulfonic anhydride (14.6 g, 83.81 mmole), and the reaction was allowed to stir at reaction temperature for 17 hours. The pyridine was removed under vacuum, and the residue was dissolved in EtOAc (400 mL). This solution was washed with saturated aqueous NaHCO3, H2O and brine, dried (MgSO4), decolorized with charcoal, and filtered through a diatomaceous earth filter aid. The solvent was removed under vacuum to afford the crude product (24.46 g). This material was taken directly to the next step without further purification. 2e. 10,1 l-anhydro-2'-O-benzoyl-5-O-desosaminyl- 3-deoxy-3-oxo-6-O-methylervthronolide A The mesylate from step 2d above was dissolved in acetone (70 mL), and DBU (5.22 mL, 34.9 mmole) added. After stirring at reaction temperature for 22 hours the acetone was removed under vacuum, EtOAc (250 mL) was added, and the organic layer was washed with 100-mL portions of sat. aq. NaHCO3 (2x), H2O (lx), and brine (lx). The solution was dried (MgSO4), decolorized with charcoal and filtered through a diatomaceous earth filter aid. The solvent was removed under vacuum to afford the crude product (18.54 g). This material was purified by chromatography on silica gel, eluting with 40% ethyl acetate/hexanes containing 0.25 % concentrated NH4OH. The appropriate fractions were combined and concentrated to give the product. MS m/z (M+H) + : 674. 2f. Compound (8) from Scheme 3: Rl=methoxy: R2=benzoyl A 500 mL flask was charged with 60% NaH (1.05 g, 26.3 mmole). The NaH was rinsed with 3 portions of hexanes, and dried under a N 2 stream. Freshly distilled THF (90 mL) was added, and the solution was cooled to 0 °C under N 2 . The 10,11-anhydro compound from step 2d above (8.40 g, 12.5 mmol) was then added over a one minute period. After stirring for 15 minutes, a solution of carbonyl diimidazole (5.98 g, 36.9 mmole) in 60 mL of THF was added to the reaction mixture via cannula over a period of 15 minutes. After stirring for 5 hours, the reaction mixture was quenched with 5% KH 2 PO 4 solution, and the mixture was stirred at 0 °C for 20 minutes. The mixture was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by chromatography on silica gel, eluting with 25% -40% acetone/hexanes. The appropriate fractions were combined and concentrated to give the product MS m/z (M+H) + : 768. l H NMR (CDCI3): 0.90(t, 3H), 0.95(d, 3H), 1.21(d, 3H), 1.27(d, 3H), 1.32(s, 3H), 2.25(s, 6H), 2.78(s, 3H), 2.97(m, IH), 3.58(m, IH), 2.63(q, IH), 4.14(d, IH), 4.50(d, IH), 5.00(dd, IH), 5.65(dd, IH), 6.75(s, IH), 7.05(m, IH), 7.35(m, IH), 7.43(dd, 2H), 7.54(t, IH), 8.02(d, 2H), 8.07(s, IH); 13 C NMR (CDC1 3 ): 204.8, 168.8, 165.0, 145.9, 138.4, 138.1, 137.0, 132.7, 130.8, 130.5, 129.7, 128.2, 117.0, 102.1, 84.5, 81.0, 78.5, 76.9, 72.0, 69.2, 63.7, 50.9, 50.2, 47.2, 40.7, 40.3, 38.8, 31.1, 30.8, 22.5, 20.9, 20.7, 20.0, 18.8, 14.8, 14.2, 13.2, 10.4. Example 3 Compound of Formula (III). A. B & E=hvdrogen. D=benzyl. R-L=methoxy: R =hydrogen 3a. 2-(R)-(BOC-amino)-3-phenyl-l -propanol To a 5.2 g (23.8 mmole) sample of di-t-butyl dicarbonate in 20 mL of methylene chloride held at 0°C was added (R)-2-amino-3-phenyl-l-propanol (3.0 g, 19.8 mmole, Aldrich), and the reaction mixture was stined 1.5 hours at reaction temperature. The solvent was removed, and the residue was dried under high vacuum and taken directly to the next step. 3b. 2-(R)-(BOC-amino)- 1 -O-methanesulfon yloxy-3-phenylpropane The material from step 3a was dissolved in 20 mL of methylene chloride and 5 mL of THF, and the solution was cooled to 0°C. Triethylamine (4.1 mL, 29.4 mmole) was added, then methanesulfonyl chloride ( 1.9 mL, 24.5 mmole) was added slowly. The mixture was stirred 45 minutes at reaction temperature, then the solvent was removed under vacuum. The residue was dissolved in ethyl acetate, and the solution was washed with water and brine, dried (Na2SO4) and filtered. The solvent was removed under vacuum to afford 6.38 g of the title compound. MS m/z (M+H) + : 330, MS m/z (M+NH 4 ) + : 347. 3c. 1 -azido-2-(RV( ' BOC-amino -3-phenvlpropane The compound from step 3b above (6.36 g, 193 mmole) was dissolved in 25 mL of DMF, and 2.5 g (38 mmole) of NaN3 was added. The reaction mixture was stirred for 24 hours at 62 °C. The solution was cooled to reaction temperature, then extracted with ethyl acetate. The organic extract was washed with water and brine, dried (Na2SO4) and filtered. The solvent was removed under vacuum to afford 4.34 g of the title compound. MS m/z (M+H) + : 277, MS m/z (M+NH 4 ) + : 294. 3d. l-azido-2-(R)-amino-3-phenylpropane The compound from step 3c (4.3 g,15.6 mmole) was dissolved in 30 mL of 4 N HCl in ethanol, and the reaction mixture was stirred for 1.5 hours at reaction temperature. The solvent was stripped and chased with ether. The residue was dissolved in water, NaCl was added, and the mixture was extracted with ethyl ether, which was discarded. The aqueous layer was adjusted to pH 12 with K2CO3, saturated with NaCl, then extracted with CHCI3. The organic extract was washed with brine, dried (Na2SO4) and filtered. The solvent was removed under vacuum to afford 2.17 g of the title compound. MS m z (M+H) + : 177, MS m/z (M+NH4) + : 194. 3e. 1. 2-(R)-cUamino-3-phenylpropane A sample of the compound from step 3d (1.2 g, 6.8 mmole) was hydrogenated (4 atm) in ethanol over 1.2 g of 10% Pd/C for 21.5 hours at reaction temperature. The mixture was filtered to remove the catalyst and the solvent was removed to afford the title compound (1.055 g). MS m/z (M+H) + : 151, MS m/z (M+NH4) + : 168. Samples of the compound of formula (8) (Scheme 3; R^methoxy; R^benzoyl; from Example 2, 750 mg, 0.98 mmole) and 1, 2-(R)-diamino-3-phenylpropane (from step 3e above, 1.04 g, 6.92 mmole) were dissolved in 4 mL of acetonitrile and 0.5 mL of water. The reaction mixture was stirred for 24 hours at reaction temperature. The solvent was removed, and the residue was dissolved in ethyl acetate. The solution was washed with water and brine, dried (Na2SO4), filtered, and the solvent was removed. The residue was purified by chromatography on silica gel, eluting with hexane to 30% acetone in hexane to give 236 mg of the title compound. MS m/z (M+H) + : 850. D=benzyl. Rl=methoxy. R2=hvdrogen A sample (217 mg, 0.26 mmole) of the compound from step 3f above in 6 mL of methanol was stirred at reflux for 4 hours. The solvent was removed, and the residue was purified by column chromatography on silica gel, eluting with 1.5% methanol in chloroform containing 1% NH4OH to afford 176 mg of the title compound. MS m/z (M+H) + : 746. A sample of the compound from step 3g (148 mg, 0.20 mmole) was dissolved in 2.6 mL of ethanol, and of acetic acid (0.026 mL, 0.45 mmole) was added. The reaction mixture was stirred for 24 hours at reflux, then the solvent was removed. The residue was dissolved in ethyl acetate, which was washed with aqueous K2CO3, water and brine. The solution was dried (Na2SO 4 ), filtered, and the solvent was removed under vacuum to afford 150 mg of product. This material was purified by column chromatography on silica gel, eluting with 0.5% to 0.6% methanol in chloroform containing 0.5% NH4OH to afford 134 mg of the title compound. MS m/z (M+H)+: 728. *H NMR (CDCI3): 0.82(t, 3H), 1.02(d, 3H), 1.18(d, 3H), 1.32(s, 3H), 1.35(d, 3H), 1.43(s, 3H), 1.50(m, IH), 1.87(m, IH), 2.27(s, 6H), 2.32(s, 3H), 2.56(dd, IH), 2.66(m, 2H), 3.03(m, IH), 3.19(dd, IH), 3.63(s, IH), 3.75(q, IH), 3.94(dd, IH), 4.04(m, IH), 4.13(d, IH), 4.28(d, IH), 4.85(dd, IH). 7.10- 7.35(m, 5H); 13 C NMR (CDC1 3 ): 204.0, 177.8, 169.4, 156.0, 138.3, 130.1 , 127.9, 126.1, 103.9, 81.4, 79.4, 78.5, 76.4, 70.3, 69.5, 65.9, 59.5, 57.9, 51.2, 48.7, 48.3, 46.5, 42.8, 40.2, 38.5, 36.0, 31.6, 28.2, 22.0, 21.2, 19.6, 19.0, 16.7, 14.4, 14.1 , 12.7, 11.0, 10.4; Example 4 Compound of Formula (III). A=B=D=H. E=benzyl. R =methoxy: R =hydrogen 4a. 1 -azido-2-(S)-amino-3-phen yl-propane Following the procedure of Example 3a, except substituting (S)-2-amino-3-phenyl-l- propanol (Aldrich) for the (R)-2-amino-3-phenyl- 1-propanol thereof, and carrying the product forward as in Example 3, steps a-d, the title compound was prepared (1.74 g). MS m/z (M+H) + : 177, MS m/z (M+NH4) + : 194. 4h. 1 ■2-(S)-diamino-3-phenylpropane A sample of the compound from step 4a (790 mg, 4.48 mmole) was dissolved in 30 mL of THF and 6 mL of water, triphenylphosphine (5.0 g, 19.1 mmole) was added, and the reaction mixture was stirred for 24 hours at reflux. The solvent was removed, and the residue was dissolved in 2 N HCl. NaCl was added, and the solution was extracted with ethyl ether. The aqueous layer was adjusted to pH 12 with K2CO3, saturated with NaCl, then extracted with CHCI3 and CHCI3 containing 15% isopropanol. The solvent was removed under vacuum to afford 439 mg of the title compound. MS m z (M+H) + : 151, MS m/z (M+NH4) + : 168. 4c. Compound (19) Scheme 9. A=B=D=H. E=benzyl. Rl=methoxy. R2=benzoyl Samples of the compound of formula (8) (Scheme 3; R^methoxy; R 2 =benzoyl; from Example 2, 450 mg, 0.59 mmole) and l,2-(S)-diamino-3-phenylpropane (from step 4b above, 435 mg, 2.90 mmole) were dissolved in 2 mL of acetonitrile and 0.25 mL of water. The reaction mixture was stirred for 24 hours at reaction temperature. The solvent was removed, and the residue was dissolved in ethyl acetate. The solution was washed with brine, dried (Na2SO4), filtered, and the solvent was removed. The residue was purified by chromatography on silica gel, eluting with hexane to 25% acetone in hexane to give 405 mg of the title compound. MS m/z (M+H) + : 850. 4d. Compound (20). A=B=D=H. E=benzyl. Ri=methoxy. R^hvdrogen A sample (386 mg, 0.45 mmole) of the compound from step 4c above in 7 mL of methanol was stirred at reflux for 4 hours. The solvent was removed, and the residue was purified by column chromatography on silica gel, eluting with 1.5 % methanol in chloroform containing 1% NH 4 OH to afford 315 mg of the title compound. MS m/z (M+H) + : 746. 4e. Compound of Formula (III). A=B=D=H. E=phenyl. Ri=methoxy: R2=hvdrogen Following the procedure of Example 3h, except substituting the (S)-compound (150 mg, 0.20 mmole) from step 4d for the (R)-isomer of 3h, the title compound (136 mg) was prepared. MS m/z (M+H) + : 728. l H NMR (CDCI3): 0.86(t, 3H), 1.08(d, 3H), 1.19(d, 3H), 1.33(s, 3H), 1.39(d, 3H), 1.47(s, 3H), 1.54(m, IH), 1.92(m, IH), 2.28(s, 6H), 2.58(s, 3H), 3.19(dd, IH), 3.52(m, IH), 3.67(s, IH), 3.77(q, IH), 4.12(d, IH), 4.27(d, IH), 4.92(dd, IH), 7.10-7.40(m, 5H); 13 C NMR (CDCI3): 203.7, 176.0, 169.4, 156.5, 139.2, 130.0, 129.7, 128.3, 127.9, 126.3, 126.1, 104.1, 80.9, 80.5, 78.6, 78.1, 70.3, 69.5, 65.9, 62.0, 61.1, 51.2, 49.5, 48.8, 48.6, 45.9, 43.3, 42.9, 41.4, 40.2, 40.0, 35.2, 28.2, 22.2, 21.1, 19.7, 19.4, 17.1, 16.8, 15.3, 14.5, 14.1, 10.4; Example 5 Compound of Formula (IIP: A=benzyl. B=D=E=H. Rl=methoxy. R2=hydrogen Compound (8) (Scheme 3; R I =methoxy; R 2 =benzoyl; from Example 2, 450 mg, 0.59 mmole) and (S)-2-amino-3-phenyl-l -propanol (1.97 g, 13.0 mmole, Aldrich) were dissolved in 4.5 mL of acetonitrile and 0.5 mL of water. The reaction mixture was stirred for 7 days at reaction temperature. The solvent was removed, and the residue was dissolved in ethyl acetate. The solution was washed with 20% aqueous KH2PO4, water and brine, then dried (Na2SO4) and filtered. The solvent was removed, and the residue dried under high vacuum to afford 1.09 g of product. This material was purified by chromatography on silica gel, eluting with hexane to 20% acetone in hexane to give 644 mg of the title compound. MS m/z (M+H) + : 851. 5b. Compound (22) (Scheme 10), A=benzyl; B=D=E=H. RL=methoxy. R2=benzoyl: Y=azido A sample of the compound from step 5a above (617 mg, 0.72 mmole) was dissolved in 12mL of THF, and triphenylphosphine (610 mg, 2.33 mmole) was added. This solution was cooled to 0°C, DEAD (0.375 mL, 2.38 mmole) was added dropwise over 3 minutes, and the mixture was stirred for 10 minutes. Next was added DPPA (0.515 mL, 2.37 mmole) dropwise over 3 minutes, and the mixture was stirred for 2 hours at 0°C and 48 hours at reaction temperature. The volatiles were removed under vacuum to leave an oily residue. The residue was purified by chromatography on silica gel, eluting with hexane to 30% ethyl acetate in hexane followed by 20% acetone in hexane to afford 321 mg of the title compound. MS m/z (M+H) + : 876. 5c. Compound (22) (Scheme 10), A=benzyl; B=D=E=H. Rl=methoxv. R2=hvdrogen: Y=azido A sample of the compound from step 5b above (317 mg, 0.36 mmole) was dissolved in 5 mL of methanol, and the mixture was stirred at reflux for 4.5 hours. The solvent was removed, the residue was purified by chromatography on silica gel, eluting with 1 : 1 acetone in hexane , and the residue was dried under high vacuum to afford 218 mg of the titie compound. MS m/z (M+H) + : 772. A sample of the compound from step 5c above (208 mg, 0.27 mmole) was dissolved in 3 mL of THF and 0.5 mL of water, triphenylphosphine (425 mg, 1.62 mmole) was added, and the reaction was stirred for 24 hours at reflux. The solvent was removed under vacuum, chased with toluene, and the residue dried under high vacuum. The residue was purified by chromatography on silica gel, eluting with chloroform containing 1.5% methanol and 1% NH4OH to afford 196 mg of the title compound. MS m/z (M+H)+: 746. 5^ Compound of Formula (TH): A=henzv1. B=D=E=H. Rl=methoxv. R2=hvdrogen A sample of the compound from step 5d above (128 mg, 0.17 mmole) was dissolved in 2.3 mL of ethanol and 0.023 mL (0.40 mmole) of acetic acid was added. The reaction mixture was stirred at reflux for 48 hours, and the solvent was removed. The residue was dissolved in ethyl acetate, and the solution was washed with aqueous K2CO3, water and brine. The solution was dried (Na2SO4), filtered, and the solvent was removed under vacuum to afford 100 mg of a tan compound. The residue was purified by chromatography on silica gel, eluting with chloroform containing 0.6% methanol and 0.5% NH 4 OH progressing to chloroform containing 0.7% methanol and 0.5% NH4OH to afford 52 mg of the title compound. MS m/z (M+H) + : 728. *H NMR (CDCI3): 0.86(t, 3H), 1.08(d, 3H), 1.34(d, 3H), 1.37(d, 3H), 1.44(s, 3H), 1.52(s, 3H), 1.93(m, IH), 2.29(s, 6H), 2.48(m, IH), 2.67(dd, IH), 2.86(s, 3H), 3.06(dd, IH), 3.57(m, IH), 3.74(q, IH), 3.86(s, IH), 4.33(d, IH), 4.39(d, IH), 4.95(dd, IH), 7.18-7.40(m, 5H); 13 C NMR (CDC1 3 ): 204.4, 169.6, 155.8, 138.0, 129.5, 129.3, 128.6, 128.5, 126.5, 103.8, 81.4, 78.8, 77.3, 70.3, 69.6, 65.9, 57.3, 53.7, 51.2, 50.8, 49.8, 47.4, 42.7, 40.3, 38.5, 35.6, 31.6, 28.2, 22.6, 22.2, 21.2, 20.6, 20.3. 15.4, 14.9, 14.1, 13.4, 11.1, 10.4; Example 6 Compound of Formula (III): B=benzyl. A=D=E=H. Rl=methoxy. R2=hvdrogen Following the procedures of Example 5, except replacing the (S)-2-amino-3-phenyl- 1-propanol of step 5a with (R)-2-amino-3-phenyl- 1 -propanol (1.97 g, 13.0 mmole, Aldrich), and carrying the product forward according to the procedures of steps 5b-5e, the titie compound (83 mg) was prepared. MS m/z (M+H)+: 728. l H NMR (CDCI3): 0.73(t, 3H), 1.05(d, 3H), 1.24(d, 3H), 1.29(d, 3H), 1.33(s, 3H), 1.37(d, 3H), 1.41(s, 3H), 2.26(s, 6H), 2.44(m, IH), 2.68(m, IH), 2.79(s, 3H), 3.18(dd, IH), 3.46(m, IH), 3.60(s, IH), 3.71(dd, IH), 3.8 l(q, IH), 3.94(dd, IH), 4.30(dd, IH), 4.72(dd, IH), 7.10- 7.38(m, 5H); 13 C NMR (CDCI3): 204.4, 180.7, 169.3, 154.5, 138.4, 128.9, 128.8, 128.6, 128.3, 126.8, 126.2, 125.1, 104.2, 103.7, 81.1, 78.5, 78.3, 78.1, 77.2, 76.2, 70.3, 69.5, 65.8, 65.7, 62.4, 58.1, 53.6, 51.2, 51.0, 49.4, 47.6, 42.9, 40.2, 38.5, 36.7, 36.0, 31.5, 28.2, 25.2, 22.6, 21.6, 21.1, 19.7, 19.3, 16.2, 15.6, 14.6, 14.3, 14.0, 12.6, 11.1, 10.4, 10.2; Example 7 Compound of Formula (III); A=E=phenvI. B=D=H. R =methoxy. R =hvdrogen 7a. Compound (19) from Scheme 9: A=E=phenyl. B=D=H. R-L=methoxy. R2=benzoyl Compound (8) (Scheme 3; R 1 =methoxy; R 2 =benzoyl; from Example 2, 400 mg, 0.52 mmole) and (lS,2S)-l,2-diphenyl-l,2-ethylenediamine (500 mg, 2.36 mmole, Aldrich) were dissolved in 2 mL of acetonitrile and 0.25 mL of water. The reaction mixture was stirred for 10 days at reaction temperature. The mixture was diluted with methylene chloride, the solution was dried over NaCl and Na2SO4, filtered, and the solvent was removed. The residue (958 mg) was taken directly to the next step . MS (m/z) : 666 (M+H) + . 7 b . Compound (19) from S cheme 9; A=E=phenyl. B=D=H. Rl=methoxy. R =hvdrogen The compound from step 7a (958 mg) was dissolved in 15 mL of methanol, and the solution was heated at reflux for 24 hours. The solvent was removed, and the residue was purified by column chromatography on silica gel, eluting with 0 to 5% methanol in methylene chloride to afford 340 mg of the titie product as the ClO-epi- isomer. MS (m/z) : 808 (M+H) + . l H NMR (300 MHz, CDC1 3 ) : δ 6.90-7.20 ( , 10H), 5.48 (dd, IH), 5.04 (d, IH), 4.27 (d, IH), 4.23 (d, 2H), 3.93 (q, IH), 3.76 (d, IH), 3.62 (d, IH, Hl l), 3.52 (m, 2H)3.12-3.22 (m, 4H), 3.07 (s, 3H, OMe), 2.75 (dd, IH), 2.75 (m, IH), 2.2-2.5 (m), 2.24 (s, 6H, NMe 2 ), 1.94 (dq, 2H), 1.59 (s, 3H), 1.46 (d, 3H), 1.29 (d, 3H), 1.22 (d, 3H), 0.90 (t, 3H), 0.84 (d, 3H), 0.73 (d, 3H). 13 C NMR (75 MHz, CDC1 3 ) : δ 214.2, 205.5, 171.0, 156.3, 143.5, 140.5, 128.0, 128.0, 127.9, 127.2, 126.9, 126.8, 104.1, 83.5, 78.8, 78.7, 78.2, 77.4, 77.0, 76.6, 70.2, 69.9, 69.3, 67.6, 65.6, 57.9, 51.7, 50.7, 49.0,48.5, 41.1, 41.0, 40.1, 28.2, 21.2, 21.1, 21.0, 19.3, 18.0, 16.0, 14.4, 10.5, 9.9. 7c. Compound of Formula (HI): A=E=phenyl. B=D=H. Rl=methoxy. R^hvdrogen Following the procedure of Example 5e, except replacing the compound from 5d with the compound from 7b, the title compound was prepared. MS (m/z) : 790 (M+H) + . 13 C NMR (125 MHz, CDC1 3 ): selected signals: δ 203.3, 175.7, 169.5, 156.5, 104.1. Example 8 Compound of Formula (HI): A=methyl. B=D=E=hvdro en. Rl=methoxy. R2=hvdrogen 8a. Compound (22) from Scheme 10; A=methvl. B=D=E=H. Rl=methoxv. R2=benzovl. Y=OH Compound (8) (Scheme 3; R^methoxy; R 2 =benzoyl; from Example 2, 400 mg, 0.52 mmole) and (S)-2-amino-l -propanol (0.200 mL, 2.6 mmole, Aldrich) were dissolved in 0.9 mL of acetonitrile, 0.1 mL of water was added, and the reaction was stirred for 40 hours at reaction temperature. The solvent was removed, and the residue was dissolved in ethyl acetate. The solution was washed with water and brine, dried (Na2SO4), filtered, and the solvent was removed. The residue was purified by chromatography on silica gel, eluting with 20% to 30% acetone in hexane to give 135 mg of the title compound. MS m/z (M+H) + : 775. 8b. Compound (22) from Scheme 10; A=methyl, A sample of the compound from step 8a above (277 mg, 0.362 mmole) was dissolved in 6 mL of THF, and triphenylphosphine (302 mg, 1.15 mmole) was added. This solution was cooled to 0°C, DEAD (0.190 mL, 1.21 mmole) was added dropwise over 3 minutes, and the mixture was stirred for 10 minutes. Next was added DPPA (0.260 mL, 1.21 mmole) dropwise over 3 minutes, and the mixture was stirred for 3 hours at 0°C and 24 hours at reaction temperature. The volatiles were removed under vacuum. The residue was purified by chromatography on silica gel, eluting with 15% to 20% acetone in hexane, then rechromatographed on silica gel, eluting with 40% ethyl acetate in hexane to 25% acetone in hexane, to afford 140 mg of the title compound. MS m/z (M+K) + : 838. 8c. Compound (22) from Scheme 10; A=methyl, B=D=E=H. Rl=methoxy. R2=hvdrogen. Y=azido A sample of the compound from step 8b (133mg, 0.17 mmole) was dissolved in 2 mL of methanol, and the solution was stirred for 4 hours at reflux. The solvent was removed under vacuum, and the residue was dried under high vacuum to give a glassy residue. The residue was purified by chromatography on silica gel, eluting with 1 : 1 acetone in hexane to 100% acetone to afford the title compound (98 mg). MS m/z (M+H) + : 696. 8d. Compound (20) from Scheme 10; A=methvl. B=D=E=H. Ri=methoxv. R2=hvdrogen A sample of the compound from step 8c above (185 mg, 0.27 mmole) was dissolved in 4 mL of THF, and 2 mL of H2O and triphenylphosphine (425 mg, 1.62 mmole) was added. This solution was stirred at reaction temperature for 40 hours and at reflux for 24 hours. The volatiles were removed under vacuum. The residue was purified by chromatography on silica gel, eluting with 3% methanol and 1% NH 4 OH in chloroform to afford the titie compound (128 mg). MS m/z (M+H) + : 670. Sk Compound of Formula (TIT): A=methvl. B=D=E=H. Rl=methoxv. R2-=hvdrogen A sample of the compound from step 8d above (123 mg, 0.18 mmole) was dissolved in 2.6 mL of ethanol and 0.24 mL of acetic acid, the reaction was heated at reflux for 24 hours, then stiπed at reaction temperature for 48 hours. The solvent was removed under vacuum, and the residue was dissolved in ethyl acetate. The solution was washed with 10% aqueous K2CO3, water and brine, then dried (Na2S04) and filtered. The solvent was removed, and residue was dried under high vacuum. The residue was purified by chromatography on silica gel, eluting with 0.5% NH4OH and 2% to 3% methanol in chloroform to afford the titie compound (38 mg). MS m/z (M+H) + : 652. *H NMR (CDCI3): 0.86 (t, 3H), 1.04 (d, 3H), 1.21 (d, 3H), 1.24 (d, 3H), 1.50 (s, 3H), 1.87- 1.98 (m, 2H), 2.26 (s, 6H), 2.41-2.50 (m, I H), 2.78 (s, 3H), 3.1 1-3.23 (m, 3H), 3.51-3.59 (m, IH), 3.76 (dd, IH), 3.76 (s, IH), 3.85 (q, IH), 3.92 (dd, IH), 4.31 (d, IH), 4.37 (d, IH), 4.90 (dd, IH); 13 C NMR (CDC1 3 ): 204.3, 181.5, 169.6, 155.6, 103.7, 81.3, 78.6, 77.9, 76.6, 70.3, 69.5, 65.8, 56.5, 53.4, 51.1, 50.6, 47.4, 47.2, 42.6, 40.2, 38.4, 35.5, 28.1 , 22.0, 21.2, 20.5, 20.1, 15.8, 15.2, 14.8, 13.2, 10.6, 10.3; High resolution mass spectrum: calculated (M+H) + m/z for C3 4 H 5 8N 3 O9=652.4173; observed (M+H) + /z=652.4175. Example 9 Compound of Formula (HI): B=methyl. A=D=E=hvdro en. R-L=methoxy. R2=hvdro en Following the procedures of Example 8, except with a larger amount of the starting compound from Example 2 (1.23 g, 1.6 mmole) and replacing the (S)-2-amino-l -propanol of step 8a with an appropriately larger amount of (R)-2-amino-l -propanol (1.23 mL, 16.2 mmole, Aldrich), carrying the product forward as in steps 8b-8e, the title compound was prepared (71 mg). l H NMR (CDC1 3 ): 0.87 (t, 3H), 1.45 (s, 3H), 1.82-2.01 (dd, 2H), 2.26 (s, 6H), 2.37-2.51 (m, IH), 2.72 (s, 3H), 3.07 (dd, IH), 3.18 (dd, IH), 3.22-3.36 (m, IH), 3.47-3.59 (m, IH), 3.61 (s, IH), 3.77-3.91 (m, 2H), 4.25 (d, IH), 4.29 (d, IH), 5.01 (dd, IH); 13 C NMR (CDC1 3 ): 204.1, 180.7, 169.7, 154.7, 103.8, 80.6, 78.9, 78.5, 76.4, 70.3, 69.6, 65.9, 62.3, 56.6, 53.1, 51.1, 49.3, 47.8, 42.8, 40.2, 38.6, 36.5, 34.6, 31.5, 28.2, 25.3, 22.6, 21.9, 21.2, 20.7, 19.6, 19.3, 17.1, 15.8, 14.4, 14.1, 12.9, 11.0, 10.3; MS (M+H) + mlz=652. High resolution mass spectrum: calculated (M+H) + m/z for C34H 5 8N 3 O9=652.4173; observed (M+H)+ /z=652.4188. Example 10 meso-2.3-bis(methanesulfonvloxv)butane Samples of meso-2,3-butanediol (10 g, 111 mmole, Aldrich) and triethylamine (92.8 mL, 666 mmole) were dissolved in methylene chloride. The solution was cooled to -78°C, and methanesulfonyl chloride (25.8 mL, 333 mmole) was added dropwise. A precipitate formed. The mixture was diluted with additional methylene chloride, and the mixture was stirred for 20 minutes at -78°C and at 0°C for 2 hours. The reaction mixture was warmed to reaction temperature, diluted with additional solvent, and washed with H2O, aqueous NaHCO3 and aqueous NaCl. The organic solution was dried over MgSO4, and the solvent was removed to afford the title compound (25.01 g). 1H NMR (300 MHz, CDC1 3 ) : δ 4.91 (q, 2H), 3.10 (s, 6H), 1.45 (d, 6H). 10b. meso-2.3-diazidobutane A sample of the compound from step 10a (25 g) was dissolved in 250 mL of DMF, and NaN3 (40 g) was added. The mixture was stirred vigorously at 85°C for 24 hours, then cooled to reaction temperature. The mixture was diluted with 800 mL of ether, washed with H2O, aqueous NaHCO3 and aqueous NaCl, then dried over MgSO4. The solution was filtered and concentrated to afford the title compound (13.00 g). Η NMR (300 MHz, CDC1 3 ) : δ 3.50 (m, 2H), 1.30 (d, 6H). 10c. meso-2.3-butanediamine A sample of the compound from step 10b (13.0 g, 125 mmole) was dissolved in ethanol and hydrogenated at 4 atm over 10% Pd/C for 20 hours at reaction temperature. The catalyst was removed by filtration, and the solvent was removed under vacuum to afford the title compound. 1H NMR (300 MHz, CDC1 3 ) : δ 2.70 (m, 2H), 1.45 (br, 4H), 1.05 (d, 6H). MS (m/z) : 89 (M+H) + . A sample of 10,1 l-anhydro-2'-O-benzoyl-5-O-desosaminyl-6-O-methyl-3-oxo- erythronolide A 12-O-imidazolyl carbamate (from Example 2, 500 mg, 0.651 mmole) and meso-2,3-butanediamine (500 mg, from step lOd above) were dissolved in 3 mL of acetonitrile and 0.3 mL of water, and the reaction was stirred for 72 hours at reaction temperature and 17 hours at reflux. The solution was diluted with methylene chloride, dried over NaCl and MgSO4, and filtered. The solvent was removed, and the residue was taken directly to the next step. The compound from step lOd above was dissolved in methanol, and the solution was heated at reflux for 12 hours. The solvent was removed, and the residue was taken directiy to the next step. MS (m/z) : 684 (M+H) + . lOf. Compound of Formula (ITJ): A=D=methyl: B=E=H. R-l=methoxy. R2=hvdrogen To the material from the previous step, dissolved in methanol, acetic acid was added, and the reaction mixture was heated at reflux for 24 hours. A solution of NH3 in methanol was added, and the solution was concentrated. The residue was dissolved in ethyl acetate, and the solution was washed with 1 N NaOH, H2O and brine, then dried over Na2SO 4 . The solvent was removed, and the residue was purified on silica gel, eluting with 10% methanol in methylene chloride to 10% methanol (containing NH3) in methylene chloride to afford the title compound. This material was rechromatographed on pH 8 silica gel, eluting with 4: 1 ethyl acetate:hexane to 100% ethyl acetate to afford 116 mg of the title compound. The NMR analysis confirmed the product to be the A=D=methyl isomer. MS (m/z) : 666 (M+H) + . HRMS Calc. for C^H^O,: 666.4330; Observed: 666.4326. 1H NMR (300 MHz, CDCI 3 ) : δ 4.81 (dd, IH), 4.27 (d, IH), 4.22 (d, 2H), 4.05 (m, IH), 3.96 (m, IH), 3.78 (q, IH), 3.65 (s, IH, Hl l), 3.48 (m, IH), 3.10 (dd, IH), 3.06 (m, IH), 2.75 (q, IH), 2.67 (s, 3H), 2.65 (m, IH), 2.37 (m, 2H), 2.19 (s, 6H), 1.85, 1.49 (m, 2H), 1.59, 1.15 (m, 2H), 1.55 (m, 2H), 1.42 (s, 3H), 1.27 (d, 3H), 1.27 (s, 3H), 1.25 (d, 2H), 1.24 (d, 3H), 1.17 (d, 3H), 1.16 (d, 3H), 1.04 (d, 3H), 0.96 (d, 3H), 0.78 (t, 3H). 13 C NMR (75 MHz, CDC1 3 ) : δ 204.2, 179.0, 169.5, 155.6, 1 18.8, 103.7, 81.3, 78.6, 77.7, 76.8, 70.2, 69.4, 65.8, 56.1, 55.5, 51.9, 51.0, 50.4, 47.0, 42.5, 40.1, 38.4, 35.2, 28.1, 22.3, 22.0, 21.1, 20.7, 20.1, 15.0, 14.8, 13.1, 11.5, 10.6, 12.2. IR (film) : 3460 (w), 2972, 1750, 1718 (w), 1647, 1456, 1423, 1372, 1305, 1246, 1 163, 1 107, 1051, 989, 757 cm '1 . Example 11 Iii 2S. 3S-butanediamine Following the procedures of Example 10 steps a-c, except substituting (R,R)-2,3- butanediol (1 g, 11.1 mmole, Aldrich) for the meso-isomer thereof of step 10a, and carrying the product forward as in steps 10b and 10c, the titie compound (494 mg) was prepared. MS (m/z) : 89 (M+H) + . l H NMR (300 MHz, CDC1 3 ) : δ 2.62 (m, 2H), 1.45 (br s, 4H), 1.08 (d, 6H). A sample of 10,l l-anhydro-2'-O-benzoyl-5-O-desosaminyl-6-O-methyl-3-oxo- erythronolide A 12-O-imidazolyl carbamate (from Example 2, 1.56 g, 2.03 mmole) and 2S, 3S-butanediamine (400 mg, 4.54 mmole, from step l la above) were dissolved in 16 mL of 20% aqueous acetonitrile, and the reaction mixture was stirred at reaction temperature for 7 days. The solution was diluted with methylene chloride, dried over NaCl and MgSO 4 , and filtered. The solvent was removed, and the residue was taken directly to the next step. Ik- Compound (20) from Scheme 9: A=E=methvl: B=D=H. Rl=methoxv The compound from step 1 lb above was dissolved in methanol, and the solution was heated at reflux for 12 hours. The solvent was removed, and the residue was taken directly to the next step. ILL Compound of Formula iTH): A=E=methvl: B=D=H. R-l=methoxy. R2-=hvdro en The material from the previous step was dissolved in 20 mL of ethanol, acetic acid (0.80 mL) was added, and the reaction mixture was heated at reflux for 3 days. NH3/ methanol was added, and the solvent was removed. The residue was dissolved in ethyl acetate, and the solution was washed with 1 N NaOH, H2O and brine, then dried over Na2SO4. The solvent was removed, and the residue was purified on neutral silica gel, eluting with 4: 1 ethyl acetate: hexane to 5% methanol in ethyl acetate to afford 682 mg of the title compound. MS (m/z) : 666 (M+H) + . HRMS Calc. for CssHa^O^ 666.4330; Observed: 666.4333. Η NMR (300 MHz, CDC1 3 ): δ 4.85 (dd, IH), 4.35 (d, IH), 4.30 (d, IH), 4.12 (q, 2H), 3.65 (s to d, IH, J=1.2 Hz), 3.56 (m, IH), 3.46 (br s, IH), 3.21 (dd, IH), 3.13 (t, IH), 2.86 (q, IH), 2.78 (s, 3H), 2.68 (m, 2H), 2.46 (dt, IH), 2.28 (s, 6H), 1.95 (m, IH), 1.68 (m, 3H), 1.52 (s, 3H), 1.38 (d, 3H), 1.36 (d, 3H0, 1.33 (s, 3H), 1.32 (d, 3H), 1.31 (d, 3H), 1.26 (d, 3H), 1.21 (d, 3H), 1.05 (d, 3H), 0.87 (t, 3H). 13 C NMR (75 MHz, CDC1 3 ) : δ 203.9, 177.9, 169.5, 156.4, 103.8, 81.1, 78.5, 78.4, 77.6, 70.3, 69.5, 65.8, 60.4, 56.9, 52.3, 50.9, 50.6, 47.6, 43.9, 40.2, 39.5, 35.0, 28.1, 21.7, 21.1, 20.8, 20.2, 19.9, 18.3, 16.3, 15.6, 14.7, 14.1 , 13.6, 10.1. IR (KBr) : 3441, 2972, 2938, 1755, 1117 (w), 1653, 1457, 1425, 1376, 1306, 1248, 1 167. 1 109, 1053 cm '1 . Example 12 Compound of Formula (HI); B=D=H; A and E taken together is -CH2CH2CH2-. R-L=methoxy. R2=hvdrogen 12a. racemic-trans- 1.2-cvclopentanediamine Following the procedures of Example 10 steps a-c, except substituting (DL)-1,2- cyclopentanediol (5.0 g, 49.0 mmole, Aldrich) for the diol of step 10a, and carrying the product forward as in steps 10b and 10c, the titie compound (2.76 g) was prepared. MS (m/z) : 101 (M+H) + . Η NMR (300 MHz, CDC1 3 ) : δ 2.75 (m, 2H), 2.00 (m, 2H), 1.65 (m, 2H), 1.50 (s, 4H), 1.30 (m, 2H). Samples of 10,1 l-anhydro-2'-O-benzoyl-5-O-desosaminyl-6-O-methyl-3-oxo- erythronolide A 12-O-imidazolyl carbamate (from Example 2, 200 mg, 0.26 mmole) and racemic-trans- 1,2-cyclopentanediamine (104 mg, 1.04 mmole, from step 12a) were dissolved in 20% aqueous acetonitrile, and the reaction mixture was stirred at reaction temperature for 4 days and at reflux for 8 hours. The solution was diluted with 100 mL of ethyl acetate, dried over NaCl and MgSU 4 , and filtered. The solvent was removed, and the residue was purified by chromatography on silica gel, eluting with 5% to 10% methanol in methylene chloride to afford the title compound (88 mg). MS (m/z) : 800 (M+H) + . The compound from step 12b above (88 mg) was dissolved in methanol, and the solution was heated at reflux for 10 hours. The solvent was removed, and the residue was purified by chromatography on silica gel, eluting with 5% methanol in methylene chloride to afford the title compound. MS (m/z) : 696 (M+H) + . 12d. Compound of Formula (HI); B=D=H; A and E taken together is -CH2CH7CH2-. Rl=methoxy. R2=hvdrogen Following the procedure of Example 1 Id the title compound was prepared. MS (m z) : 678 (M+H) + . Example 13 Compound of Formula (HI); B=E=H; A and D taken together is -CH2CH2CH2CH2-. R- =methoxy. R2=hydrogen 13a. Compound ( 19) from Scheme 9; B=E=H; A and D taken together is -CH2 H2CH2CH2-. Rl=methoxv. R2=benzovl Following the procedure of Example 11, step 1 lb, except substituting cis- 1,2- cyclohexanediamine (800 mg, 1.04 mmole, Aldrich) for the diamine thereof, the title compound was prepared. 13b. Compound of Formula (UT); B=E=H; A and D taken together is -CHoC^C^C^-. R^=methoxy. R^=hvdrogen Following the procedures of Example 1 1 steps c and d, substituting the compound of step 13a for the compound of 1 lb thereof, the titie compound was prepared. Η NMR (300 MHz, CDC1 3 ) : δ 4.87 (dd, IH), 4.34 (d, IH), 4.31 (d, IH), 4.10 (br s, IH), 4.07 (br m, IH), 3.84 (q, IH), 3.70 (s, IH, Hl l), 3.56 (m, IH), 3.22 (dd, IH), 3.14 (pent, IH), 2.78 (s, 3H, OMe), 2.49 (m, IH), 2.30 (s, 6H), 1.30-2.00 (m), 1.49 (s, IH), 1.39 (s, 3H), 1.37 (d, 3H), 1.32 (d, 3H), 1.26 (d, 3H), 1.22 (d, 3H), 1.06 (d, 3H), 0.85 (t, 3H). 13 C NMR (75 MHz, CDC1 3 ) : δ 203.8, 178.1, 169.3, 155.6, 103.7, 81.1, 78.6, 78.1, 76.64, 70.2, 69.3, 65.7, 56.3, 55.9, 55.8, 51.0, 50.4, 47.4, 42.6, 40.1, 38.2, 35.4, 34.4, 28.1, 25.2, 25.1, 25.0, 21.9, 21.0, 20.2, 20.1, 19.2, 15.6, 14.7, 12.9, 10.6, 10.2. MS (m/z) : 692 (M+H) + . Example 14 Compound of Formula (HI); A=B=D=E=H. RL=hvdrogen. R2=hvdrogen 14a. 2'-O-acetyl-6-deoxy-ervthromvcin A A sample of 6-deoxyerythromycin A (4.34 g, 6.04 mmole, Abbott Labs) was dissolved in 250 mL of methylene chloride, and acetic anhydride (1.54 g, 15 mmole) and triethylamine (1.22 g, 12 mmole) were added. The reaction mixture was stirred at reaction temperature for 16 hours, then poured into 5% aqueous NaHCO3. The mixture was extracted with methylene chloride, and the organic layer was dried, filtered and concentrated. The residue was chased with toluene, ethylene dichloride, chloroform and methylene chloride. The residue then dried under high vacuum to afford 4.46 g of the title product, which was taken to the next step without further purification. MS m/z (M+H) + : 760. 14b. 2'-O-acetyl-6-deoxy-4"-triethylsilyl-ervthromvcin A A sample of the compound from step 14a (4.44 g, 5.84 mmole) was dissolved in 100 mL of dry methylene chloride, and imidazole (1.59 g, 23.3 mmole) was added. The mixture was cooled to 0°C, and a solution of triethylsilyl chloride (1.76 g, 117 mmole) in 25 mL of methylene chloride dropwise. The reaction mixture was stirred for 1 hour at 0°C and at reaction temperature for 16 hours. The reaction mixture was poured into 5% aqueous NaHCO3, and the mixture was extracted with CHCI3. The organic extract was washed with saturated brine, dried over MgSO4, filtered and concentrated. The residue was dried under high vacuum for 48 hours to afford 5.38 g of the title product, which was taken to the next step without further purification. . MS m/z (M+H) + : 874. 14c . 2'-O- acetyl- 10,11 -arώydro-6-deoxy-4"-triethylsilyl-erythromycin A A sample of the compound from step 14b (5.36 g, 6.13 mmole) was dissolved in 45 mL of dry DMF, and carbonyldiimidazole (4.98 g, 30 mmole) was added. After the reagent had dissolved, the solution was diluted with 15 mL of THF, and the solution was cooled to 0°C. To this solution was added NaH (807 mg, 60% dispersion, 20.2 mmole) in portions. The reaction mixture was stirred for 30 minutes, and 10 mL of H2O was added. The reaction mixture was poured into saturated brine, and the resulting mixture was extracted with ethyl acetate. The ethyl acetate solution was washed with brine, dried over MgSO 4 , filtered and concentrated. The residue was co-distilled with ethylene dichloride, chloroform and methylene chloride. The residue was dried under high vacuum for 16 hours to afford 6.95 g of the title product, which was taken to the next step without further purification. MS m/z (M+H) + : 986. 14d . Compound (11) from Scheme 5; A=B=D=E=H: R-L=hvdrogen. 2'-R2=acetvl: 4"- R^triethvlsilvl A sample of the compound from step 14c (6.93 g, 6.13 mmole) was dissolved in 50 mL of acetonitrile, ethylene diamine was added (4.31 g, 7.19 mmole), and the solution was stirred for 17 hours at reaction temperature. The reaction mixture was poured into saturated brine containing NH4OH. This mixture was extracted with chloroform, and the organic extracts were combined, filtered and concentrated. The residue was co-distilled with ethylene dichloride, chloroform and methylene chloride. The residue was dried under high vacuum for 72 hours to afford 5.77 g of the title product which was taken to the next step without further purification. MS m/z (M+H) + : 924. 14e. Compound (12) from Scheme 5; A=B=D=E=H: R-L=hvdrogen. 2'-R2=4"-R2=hvdrogen A sample of the compound from step 14d (5.75 g) was dissolved in THF (120 mL) and 14.3 mL of tetrabutylammonium fluoride (1 M in THF) was added in one portion. The reaction mixture was stirred at reaction temperature for 4 hours, diluted with 400 mL of methanol, and stirred at reaction temperature for 64 hours. The solution was concentrated and then poured into 5% aqueous NaHCO3 containing 0.5% NH 4 OH. The mixture was extracted with CHCI3, the extract was washed with brine, and dried over MgSO4. The solvent was removed, and the residue was co-distilled with ethylene chloride and methylene chloride. The residue was further dried under vacuum for 16 hours to afford the title compound (5.59 g). 14f . Compound of Formula (I): A=B=D=E=H: R- ivdrogen. R2=hvdrogen A sample of the compound from step 14e (5.56 g, 7.07 mmole) was dissolved in 60 mL of ethanol, and acetic acid (637 mg, 106 mmole) was added. The solution was heated at reflux for 3.5 hours, cooled to reaction temperature, then poured into 5% aqueous NaHCO3. This mixture was extracted with CHCI3, and the organic extracts were combined, dried over MgSO 4 , filtered and concentrated. The residue was co-distilled with ethylene dichloride, chloroform and methylene chloride, then dried under high vacuum for 72 hours to afford 4.12 g of the product This material was purified by chromatography on silica gel, eluting with 1:6 TEA:ethyl acetate, to afford the title compound (1.29 g). MS m/z (M+H) + : 768. l NMR (CDCI3) δ: 0.88 (m), 2.28 (s), 3.28 (s), 4.23 (m), 4.85 (m), 4.92 (m). 1 C NMR (CDCI3) δ: 40.3 (N(CH 3 ) 2 ), 42.8 (NCH2), 49.4 (_____), 49.9 (NCH 2 ), 155.8 (O- CO-N). IR (CDC1 3 ): 1755 cm" 1 . Example 15 Compound of Formula (III): R^OCH^. R 2 =H: A=B=D=H: E=-CH2NH2 15a. 1.2-diazido-3-(BOC-amino)propane A sample of 3-(BOC-amino)propene (Aldrich, 15.72 g, 0.1 mole), manganese triacetate (80.43 g, 0.3 mole) and NaN3 (65.01 g, 1.0 mmole) were suspended in 400 mL of acetic acid, and the mixture was heated at 100°C for 10 minutes. The mixture was cooled in an ice bath and diluted with 400 mL of IN NaOH. The mixture was extracted with ethyl acetate, which was washed with 1 N cold NaOH, H2O, NaHCO3, brine and dried over Na2SO4. The solvent was removed, and the residue was chromatographed on silica gel, eluting with 4: 1 hexane:ether to give 7.18 g of the title compound. MS m/z (M+NH 4 ) + : 259. 15b. 1.2-diamino-3-(BOC-arnino)propane The compound of the previous step was dissolved in ethanol and hydrogenated (4 atm H2) over Pd/C for 22 hours at reaction temperature. The solvent was removed, and the product was taken to the next step. MS m/z (M+H) + : 190. 15c. Compound of Formula (UT): R^OCH?. R 2 =H: A=B=D=H: E=-CH2NH2 Following the procedures of Example 3 steps f-h, samples of the compound of formula (8) (Scheme 3; R 1 =methoxy; R^benzoyl; from Example 2.400 mg, 0.52 mmole) and the compound from step 15b (1.478 g, 7.81 mmol) were reacted and the titie product was obtained. Chromatographic separation of the isomers of the N-BOC compound, followed by deprotection with HCl in ethanol at reaction temperature gives the title compound. MS m z (M+H) + : 889. Example 16 Compound of Formula (HI): R^OCH?. R =H: A=B=E=H: D=-CH2NH2 The compound is obtained by deprotection with HCl in ethanol at reaction temperature of the isomer separated by chromatography from the mixture obtained in Example 15c. Example 17 Compound of Formula (HI): R 1 =OCH3, R^=H: B=E=H: A and D taken together is -CH2CH2CH2- 17a. cyclopentane cis- 1.2 -diamine Following the procedures of Example 10 steps a-c, except substituting cis- 1,2- cyclopentanediol for the diol of step 10a, and carrying the product forward as in steps 10b and 10c, the titie compound is prepared. 17b. Compound of Formula (IH): R 1 =OCH 3 , R 2 =H: B=E=H: A and D taken together is -CH2CH2CH2- Following the procedures of Example 10 steps d-f, except substituting cis-1,2- cyclopentanediamine, from the previous step, for the meso-2,3-butanediamine thereof, the title compound is prepared. Example 18 Compound of Formula (HI): R'=OCH3, R*=H: B=E=H: A and D taken together is -CH2OCH2- 18a. tetrahydrofuran cis-3.4-diamine Following the procedures of Example 10 steps a-c, except substituting 1,4- anhydroerythritol for the diol of step 10a, and carrying the product forward as in steps 10b and 10c, the title compound is prepared. 18b. Compound of Formula (HI): R^OCH?. R^=H: B=E=H: A and D taken together is -CH2OCH2- Following the procedures of Example 10 steps d-f, except substituting tetrahydrofuran cis-3,4-diamine, from the previous step, for the meso-2,3-butanediamine of step lOd, the title compound is prepared. Example 19 Compound of Formula (HI): R'=OCH3, R2=H: B=E=H: A and D taken together is -CH2-NH-CH2- 19a. cis- 3.4-diamino-p yrrolidine Pyrolline (Aldrich) is N-protected by treatment with benzyloxycarbonyloxysuccinimide in ethyl acetate at reaction temperature. The N-Cbz- pyπoline is oxidized with catalytic OSO 4 and excess N-methylmorpholine N-oxide (NNMO) in THF and t-butanol according to the procedure of Tetrahedron Lett., 1976: 1973 to give the N-Cbz-pynoline-3,4-diol. Following the procedures of Example 10 steps a-c, except substituting N-Cbz-pyπoline-3,4-diol for the diol of step 10a, and carrying the product forward as in steps 10b and 10c, the titie compound is prepared. 19b. Compound of Formula (HI) : R^OO- . R^H: B=E=H: A and D taken together is -CH2-NH-CH2- Following the procedures of Example 10 steps d-f, except substituting cis-3,4- diamino-(l-Cbz-pyπolidine), from the previous step, for the meso-2,3-butanediamine of step lOd, the title compound is prepared. Example 20 Compound of Formula (HI): R'=OCH3, R =H: B=E=H: A and D taken together is -CH2-N(Cbz)-CH2- Starting with the Compound of Formula (HI): R^OCH?. R 2 =H; B=E=H; A and D taken together is -CH2-NH-CH2-, from Example 19 above, adding the Cbz group by treatment with benzyloxycarbonyloxysuccinimide in ethyl acetate at reaction temperature, the titie compound is prepared. Example 21 Compound of Formula (HI): R^OCHs, R 2 =H: B=E=H: A and D taken together is -CH2-N(benzyl)-CH2- Starting with the Compound of Formula (HI): R'=OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-NH-CH2-, from Example 19 above, reacting the amine of the -CH2- NH-CH2- group with benzyl chloride in the presence of triethylamine, the titie compound is prepared. Example 22 Starting with the Compound of Formula (HI): R l =OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-NH-CH2-, from Example 19 above, reacting the amine of the -CH2- NH-CH2- group with benzoyl chloride in the presence of triethylamine, the titie compound is prepared. Example 23 Compound of Formula (HI): R'=OCH3, R 2 =H: B=E=H: A and D taken together is -CH2-N(phenyl-CH2-CH2-)-CH2- Starting with the Compound of Formula (HI): R'=OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-NH-CH2-, from Example 19 above, reacting the amine of the -CH2- NH-CH2- group with 2-phenylethyl bromide in the presence of triethylamine, the titie compound is prepared. Example 24 C Coommppoouunndd c of Formula (HI): R'=0CH3, R 2 =H: B=E=H: A and D taken together is -CH2-N(4-Cl- henvl-CH2-)-CH2- Starting with the Compound of Formula (HI): R'=OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-NH-CH2-, from Example 19 above, reacting the amine of the -CH2- NH-CH2- group with 4-chlorobenzyl chloride in the presence of triethylamine, the titie compound is prepared. Example 25 Compound of Formula (HI): R'=OCH3, R 2 =H: B=E=H: A and D taken together is -CH2-N(4-pyridyl-CH2-)-CH2- Starting with the Compound of Formula (HI): R'=OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-NH-CH2-, from Example 19 above, reacting the amine of the -CH2- NH-CH2- group with 4-picolyl chloride in the presence of triethylamine, the title compound is prepared. Example 26 Compound of Formula (HJ): R 1 =OCH3, R 2 =H: B=E=H: A and D taken together is -CH2-N(2-pyridyl-CH2-VCH2- Starting with the Compound of Formula (HI): R'=OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-NH-CH2-, from Example 19 above, reacting the amine of the -CH2- NH-CH2- group with 2-picolyl chloride in the presence of triethylamine, the titie compound is prepared. Example 27 Compound of Formula (HI): R 1 =OCH3, R 2 =H: B=E=H: A and D taken together is -CH2-NH(3-pvridv1-CH 2 -)-CH2- Starting with the Compound of Formula (HI): R'=0CH3, R =H; B=E=H; A and D taken together is -CH2-NH-CH2-, from Example 19 above, reacting the amine of the -CH2- NH-CH2- group with 3-picolyl chloride in the presence of triethylamine, the titie compound is prepared. Example 28 Compound of Formula (HI): R'=OCH3, R 2 =H: B=E=H: A and D taken together is -CH2-N(4-quinolyl-CH2-)-CH2- Starting with the Compound of Formula (HI): R'=OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-NH-CH2-, from Example 19 above, reacting the amine of the -CH2- NH-CH2- group with 4-chloromethylquinoline in the presence of triethylamine, the title compound is prepared. Example 29 Compound of Formula (IID: R-^OCH?. R 2 =H: B=E=H: A=D=-CH2-O-CH2-phenyl 29a. PhCH2OCH2CH(NH2)CH(NH2)CH20CH2Ph Meso-erythritol (Aldrich) is 1 ,4-dibenzylated by reaction with NaH and benzyl bromide in DMF according to the procedure of El Amin et al., J. Org. Chem.44:3442, (1979). Following the procedures of Example 10 steps a-c, except substituting 1,4- dibenzyl-meso-erythritol for the diol of step 10a, and carrying the product forward as in steps 10b and 10c, the title compound is prepared. 29b. Compound of Formula (HI): Following the procedures of Example 10 steps d-f, except substituting PhCH2OCH2CH(NH2)CH(NH2)CH2OCH2Ph, from the previous step, for the meso-2,3- butanediamine of step lOd, the title compound is prepared. Example 30 Compound of Formula (ni): R^OCH^. R 2 =H: B=E=H: A=D=-CH2-OH Starting with the Compound of Formula (UT): R'=OCH3, R 2 =H; B=E=H; A=D=- CH2-O-CH2-phenyl, from Example 29 above, removing the benzyl groups by hydrogenation over Pd/C, the title compound is prepared. Example 31 Compound of Formula (in): R^OCH R 2 =H: B=E=H: A=D=-CH2-O-phenyl Starting with the Compound of Formula (IH): R'=OCH3, R 2 =H; B=E=H; A=D=- CH2-OH, from Example 30 above, reacting the -CH2-OH groups (of substituents A and D) with phenol, triphenylphosphine and DEAD under Mitsunobu conditions the title compound is prepared. Example 32 Compound of Formula (HI): R ! =OCH3, R 2 =H: A=B=H: D and E taken together is -CH2-CH2-CH2-CH2- Following the procedures of Example 3 except substituting 1 -amino- 1 -eye lo- pentanemethanol (Aldrich) for the 2-(R)-amino-3-phenyl- 1 -propanol thereof, the title compound is obtained. Example 33 Compound of Formula (HI): R'=OCH3, R 2 =H: A and B taken together is -CH2-CH2-CH2-CH2-: D=E=H Following the procedures of Example 5, except replacing the (S)-2-amino-3-phenyl- 1 -propanol of step 5a with 1 -amino- 1-cyclopentanemethanol (Aldrich), the title compound is obtained. Example 34 34a. 3-arrιino-3-aminomethyloxetane A sample of tris(hydroxymetiιyl)methylamine (Aldrich) is reacted with di-t- butyldicarbonate and triethylamine to give N-BOC- tris(hydroxymethyl)methylamine. This compound is reacted with 1 equivalent of methanesulfonyl chloride and triethylamine to give 3-(BOC-amino)-3-hydroxymethyloxetane. This compound is converted to the titie compound according to the procedures of Example 3 steps b-e. 34b. Compound of Formula (IH): R'=OCH3, R^=H: A=B=H: D and E taken together is -CH2-O-CH2- Following the procedures of Example 3 steps f-h except substituting the compound from step 34a for the (R)-3-phenyl-l,2-propanediamine thereof, the title compound is obtained. Example 35 Compound of Formula (IH): R^OCH?. R 2 =H: A=D=E=H: B=-CH2-CH2-phenyl Following the procedures of Example 5, except replacing the (S)-2-amino-3-phenyl- 1 -propanol of step 5a with D-homophenylalaninol (prepared by LiAlHLj, reduction of the D- homophenylalanine available from Aldrich), the title compound is obtained. Example 36 Compound of Formula (HI): R^OCH?. R 2 =H: A=D=E=H: B=-CH2-CH2-CH2-phenyl 36a. 2-(R)-amino-5-phenylpentanoic acid (±)-2-Amino-5-phenylpentanoic acid (35 g, from Example 40a) was suspended in water (3 L) and solubilized by adjusting the pH to 12 with 7 N NaOH solution. The pH was readjusted to pH 8 with 1 M phosphoric acid while stirring at 45 °C. The solution was cooled to 40°C, and L-amino acid oxidase (Sigma, 0.7 unit/mg) was added. The reaction was stirred with good aeration for 2 weeks. The reaction mixture was concentrated to 500 mL under vacuum, the pH was adjusted to 5, and the precipitate was collected. The material was recrystallized from ethanol-water to afford 17.32 g of the title compound). 36b. 2-(R)-amino-5-phenylpentanol The compound from step 36a is reduced with LiAHLt under standard conditions to give the title compound. 36c. Compound of Formula (HI): R-^OCTh. R^H: A=D=E=H: B=-CH2-CH2-CH2-phenyl Following the procedures of Example 5, except replacing the (S)-2-amino-3-phenyl- 1 -propanol of step 5a with the 2-(R)-amino-5-phenylpentanol from step 36b, the title compound is obtained. Example 37 Compound of Formula OID: R^OCH . R 2 =H: A=D=E=H: B=-CH2-O-CH2-phenyl 37a. 1 -N- ( CBZ ) -2- ( S ) -diamino-3-O-benzylpropane N-BOC-O-benzyl-D-serine (Bachem) is reduced under the reaction conditions described by Kotokos, Synthesis, 299-301 (1990) to give the N-BOC-O-benzyl-D-serinol. This compound is treated according to the procedures of Example lOa-c to give the coπesponding amine. The amine is converted to the benzyloxycarbonyl (CBZ) derivative, and the BOC group is removed to give the titie compound. 37b. Compound of Formula (HI): Following the procedures of Example 10 steps d-f, except substituting the material from the previous step, for the meso-2,3-butanediamine of step lOd, the title compound is prepared. Example 38 38a. D-homo-O-methvltvrosinol D-Homo-O-methyltyrosine (prepared according to the procedure of Melillo et al., J. Org. Chem., _2:5149-5150 (1987)) is reduced with L1AIH 4 under standard conditions to give the title compound. 38b. Compound of Formula (HI): Following the procedures of Example 5, except replacing the (S)-2-amino-3-phenyl- 1-propanol of step 5a with the compound of step 38a, the titie compound is obtained. Example 39 Compound of Formula (IH): R^OCH.. R 2 =H: A=-CH2-CH2-phenyl: B=D=E=H Following the procedures of Example 5, except substituting L-homophenylalaninol (prepared by LiAlH4 reduction of the L-homophenylalanine (Aldrich) compound) for the (S)-2-amino-3-phenyl-l -propanol of step 5a , the title compound is obtained. Example 40 Compound of Formula (HI); R^OCH?. R 2 =H: A=-CH2-CH2-CH2-phenyl: B=D=E=H 40a. (±)-2-Amino-5-phenvlpentanoic acid Diethyl acetamidomalonate (220 g) in 1 L of absolute ethanol was added to a stirred solution of sodium ethoxide in ethanol, prepared by dissolving sodium (24 g) in absolute ethanol (500 mL), under nitrogen. The reaction mixture was refluxed under nitrogen for 30 minutes, then l-bromo-3-phenylpropane (200g) was added. The reaction mixture was refluxed overnight, cooled to ambient temperature, filtered, and the solvent was removed under vacuum. Concentrated HCl (800 mL) was added to the residue, and the reaction mixture was refluxed for 14 hours. The cooled aqueous solution was washed with ether, and the residual ether in the aqueous phase was removed by bubbling nitrogen through the solution. The pH of the aqueous phase was adjusted to pH 7-8 by the addition of ammonium hydroxide. The title compound was collected by filtration, air dried and recrystallized from ethanol- water (150 g) m.p. 255-257°C. MS m/z: 194 (M+H) + . 40h. (±)- 2-,ιmino-5-phenvlpentanol The compound from step 40a is reduced with LiAlH4 under standard conditions to give the title compound. 40c. Compound of Formula (HI): R-^OCT . R^H: A=-CH2-CH2-CH2-phenyl: B=D=E=H Following the procedures of Example 5, except replacing the (S)-2-amino-3-phenyl- 1 -propanol of step 5a with the (±)- 2-amino-5-phenylpentanol from step 40b, and separating the isomers by chromatography the titie compound is obtained. Example 41 Compound of Formula (IH): R^OCH?. R 2 =H: A=-CH2-O-CH2-phenyl : B=D=E=H Following the procedures of Example 37, except substituting the N-BOC-O-benzyl- L-serine (Sigma) for the N-BOC-O-benzyl-D-serine thereof the title compound is prepared. Example 42 Compound of Formula (TTT): R^OCHs, R 2 =H: B=D=E=H: A=-CH2-CH2-(4-OCH 2 -phenyl) __ L-homo-O-methvltvrosinol L-Homo-O-methyltyrosine (prepared according to the procedure of Melillo et ai, J. Org. Chem., 5 >:5149-5150 (1987)) is reduced with LiAlH4 under standard conditions to give the title compound. 42b. Compound of Formula (HI): R^OCH?. R 2 =H: B=D=E=H: A=-CH2-CH2-(4-OCH2-phenyl) Following the procedures of Example 5, except replacing the (S)-2-amino-3-phenyl- 1 -propanol of step 5a with the compound of step 42a, the title compound is obtained. Example 43 Compound of Formula (TTT): R^OCH^. R 2 =H: A=B=D=H: E=-CH2CH2Ph Following the procedures of Example 3 except replacing the 2-(R)-amino-3-phenyl- 1 -propanol of step 3a thereof with L-homo-phenylalaninol (prepared by LJAIH4 reduction under standard conditions of the L-homo-phenylalanine compound available from Aldrich) the titie compound is prepared. Example 44 Compound of Formula (III): R^OCH^. R^H: A=B=E=H: D=-CH2CH2Ph Following the procedures of Example 3 except replacing the 2-(R)-amino-3-phenyl- 1 -propanol of step 3a thereof with D-homo-phenylalaninol (prepared by L1AIH4 reduction under standard conditions of the D-homo-phenylalanine compound available from Aldrich) the titie compound is prepared. Example 45 Compound of Formula (III): R^OOh. R 2 =H: A=B=D=H: E=-CH2CH2CH2Ph Following the procedures of Example 3 except replacing the 2-(R)-amino-3-phenyl- 1 -propanol of step 3a thereof with (±)- 2-amino-5-phenylpentanol (prepared in Example 40b) and separating the desired isomer by chromatography the titie compound is prepared. Example 46 Compound of Formula CUT): R^OO R 2 =H: A=B=E=H: D=-CH2CH2CH2Ph Following the procedures of Example 3 except replacing the 2-(R)-amino-3-phenyl- 1 -propanol of step 3a thereof with 2-(R)-amino-5-phenylpentanol (prepared in Example 36b) the title compound is prepared. Example 47 Compound of Formula (IH) Rl=OCH 2 . R2=H: A=-CH2CH2OPh: B=D=E=H 47a. N-α-Boc-L-homo-serine benzvl ester The title compound is prepared from N-α-Boc-L-aspartic acid α-benzyl ester, ethyl chloroformate, N-methylmorpholine and sodium borohydride in tetrahydrofuran and methanol according to the procedures described by Kokotos, Synthesis, (1990): 299-301. 47b. 4-Phenoxy-2-(S)-Boc-aminobutyric acid benzyl ester A solution of N-α-Boc-L-homo-serine benzyl ester, phenol and triphenylphosphine in THF is treated with diethylazodicarboxylate (DEAD) at 0 °C. After being stirred at reaction temperature for 2 hours, the reaction is worked up and product purified by silica gel chromatography. (cf. Organic Reactions, Vol. 42, John Wiley & Son, Inc, 1992). 47c. 4-phenoxy-2-(S)-Boc-aminobutane- l-ol Lithium aluminum hydride is added into a stirred solution of 4-phenoxy-2-(S)-Boc- aminobutyric acid benzyl ester, from step 47b, in THF at 0 °C. The reaction mixture is heated to reflux for 0.5 hour and cooled to ice-cold temperature. Water, equal weight to the lithium aluminum hydride used, is added and stirred at reaction temperature overnight. The reaction is diluted with ethyl acetate and dried over sodium sulfate. After filtration and removal of solvent in vacuo, the product is purified by silica gel chromatography. 47 d. 4-phenoxy-2-(S)- aminobutane- 1 -ol The amino protecting group of 4-phenoxy-2-(S)-Boc-aminobutane-l-ol from step 47c is removed by treatment of the protected compound with hydrogen chloride in dioxane. (cf. T. W. Greene and P. G. M. Wuts: Protective Groups in Organic Synthesis. 2nd ed., John Wiley and Son, 1991, pp 309-315.) 47e. Compound (22) Scheme 10: R^=OCH : R 2 =Bz: A=-CH2CH2-OPh: B=D=E=H: Y=OH The title compound is prepared from 4-phenoxy-2-(S)-aminobutane-l-ol and compound (8) in aqueous acetonitrile according to the procedures described in Example 5. 47f. Compound (20) Scheme 10: R^OCH 2 : A=-CH2CH2-OPh: B=D=E=H The title compound is prepared from the compound of step 47d according to the procedures described in Example 5. 47g. Compound of Formula (HI) Rl=OCH 2 . R2=H: A=-CH2CH2OPh: B=D=E=H The titie compound of Example 47 is prepared from the compound of 47f according to the procedures described in Example 5. Example 48 Compound of Formula (HI) Rl=OCH 2 . R2=H: A=-CH2CH2NHCbz: B=D=E=H 48a. N-α-(S)-Boc -N-γ-Cbz-2.4-diaminobutyric acid benzyl ester Diphenylphosphoryl azide is added into a solution of N-α-(S)-Boc-L-glutamic acid α -benzyl ester in THF and the resulting solution is refluxed for 2 hours. Benzyl alcohol is added and the reaction mixture is refluxed for an additional hour. The product is purified by silica gel chromatography. 48b. N-α-(S)-Boc -N-γ-Cbz-2.4-diamino-butane-l-ol Lithium aluminum hydride is added into a stirred solution of N-α-(S)-Boc -N-γ-Cbz- diaminobutyric acid benzyl ester, from step 48a, in THF at 0 °C. The reaction mixture is heated to reflux for 0.5 hour and cooled to ice-cold temperature. Water, equal weight to the lithium aluminum hydride used, is added and stirred at reaction temperature ovemight. The reaction is diluted with ethyl acetate and dried over sodium sulfate. After filtration and removal of solvent in vacuo, the product is purified by silica gel chromatography. 48c. 2-(S)-4-N-Cbz-diamino-l -butanol The amino protecting group of N-α-(S)-Boc -N-γ-Cbz-2,4-diamino-butane-l-ol from step 48b is removed by treatment of the protected compound with hydrogen chloride in dioxane according to literature method. (cf. T. W. Greene and P. G. M. Wuts: Protective Groups in Organic Synthesis. 2nd ed., John Wiley and Son, 1991, pp 309-315.) 48d. Compound (22) Scheme 10: R^OCH R 2 =Bz: A=-CH2CH2-NHChz: B=D=E=H: Y=OH The title compound is prepared from 2-(S)-arnino-4-N-γ-Cbz-diamino-butane-l-ol, from step 48c, and compound (8) from Scheme 3 in aqueous acetonitrile according to the procedures described in Example 5. 48e. Compound (20) Scheme 10: R^OCH A=-CH2CH2-NHCbz: B=D=E=H The titie compound is prepared from the compound of step 48d according to the procedures described in Example 5. 48f . Compound of Formula (IIT R 1 =OCH . R2=H: A=-CH2CH2NHCbz: B=D=E=H The titie compound is prepared from the compound of step 48e according to the procedures described in Example 5. Example 48-A Compound of Formula (HD Rl=OCH . R2=H: A=-CH2CH2NH2: B=D=E=H The titie compound is prepared from the compound of Example 48 and hydrogen in the presence of Pd-C in ethanol. Example 49 Compound of Formula (HTi Rl=OCH 2 . R2=H: A=-CH2CO2Bzl: B=D=E=H 49a. 4-hvdroxy-3-N-(S)-Boc-aminobutyric acid benzyl ester The title compound is prepared from N-α-Boc-L-aspartic acid γ-benzyl ester, ethyl chloroformate, N-methylmorpholine and sodium borohydride in tetrahydrofuran and methanol according to the procedures described by Kokotos, Synthesis, (1990): 299-301. 49b. 4-hvdroxv-3-(S)-aminobutvric acid benzyl ester The amino protecting group of 4-hydroxy-3-N-(S)-Boc-aminobutyric acid benzyl ester, from step 49a, is removed by treatment of the protected compound with hydrogen chloride in dioxane according to literature method. (cf. T. W. Greene and P. G. M. Wuts: Protective Groups in Organic Synthesis. 2nd ed., John Wiley and Son, 1991, pp 309-315.) 49c. Compound (22) Scheme 10: R^OCH 2 : R 2 =Bz: A=-CH2CO2Bzl: B=D=E=H: Y=OH The title compound is prepared from 4-hydroxy-3-(S)-aminobutyric acid benzyl ester, from step 49b and compound (8) of Scheme 3 in aqueous acetonitrile according to the procedures described in Example 5. 49d. Compound (20) Scheme 10: R^OCH^ A=-CH2CO2Bzl: B=D=E=H The titie compound is prepared from the compound of step 49c according to the procedures described in Example 5. 49e. Compound of Formula (IH) R 1 =OCH . R2=H: A=-CH2CO2Bzl: B=D=E=H The title compound is prepared from compound from the compound of step 49d according to the procedures described in Example 5. Example 49-A Compound of Formula (HD Rl=OCH 2 . R2=H: A=-CH2COOH: B=D=E=H The titie compound is prepared from the compound of Example 49 and hydrogen in the presence of Pd-C in ethanol. Example 49-B Formula (HI) Rl=OCH . R2=H: A=-CH2CH2OH: B=D=E=H The titie compound is prepared from the title compound of Example 49-A, ethyl chloroformate, N-methylmorpholine and sodium borohydride in tetrahydrofuran and methanol according to the procedures described by Kokotos, Synthesis, (1990): 299-301. Example 50 Compound of Formula (HI) Rl=OCH 2 . R2=H: A=-CH2CH2NH(4 , -Pyridyl): B=D=E=H The title compound is prepared from the compound of Example 48-A, 4- chloropyridine, and CuO or CuBr-K2CO3 heated at 70-90 °C overnight. The reaction mixture is partitioned between ethyl acetate and water. The organic phase is washed once with dilute hydrochloric acid followed by saturated sodium bicarbonate. The product is purified by silica gel chromatography. Example 51 Compound of Formula (IH): R^QOh. R 2 =H: A=B=D=H: E=-CH2OH 51a. 1.2-diamino-3-propanol Allyl acetate (Aldrich) is reacted with manganese triacetate, sodium azide and acetic acid. The resulting compound is treated with NaHCO3 and methanol followed by hydrogenation to give the title compound. 1 b. Compound of Formula (HP: R-^OCH?. R 2 =H: A=B=D=H: E=-CH2OH Following the procedures of Example 3 steps f-h, except substituting l,2-diamino-3- propanol from the previous step, for the 1, 2-(R)-diamino-3-phenylpropane thereof, the title compound is prepared, and the diastereomers are separated by chromatography. Example 52 Compound of Formula (IH): R^OCT R 2 =H: A=B=E=H: D=-CH2θH The compound is separated from the diastereomeric mixture of Example 5 lb by chromatography. Example 53 The compound is prepared from the compound of Example 16 by treatment with benzoyl chloride and TEA. Example 54 Compound of Formula (III): R^OO R^H: A=B=E=H: D=-CH2NHBenzyl The compound is prepared from the compound of Example 16 by treatment with benzaldehyde, NaCNBH3 and acetic acid in methanol at reaction temperature. Example 55 Compound of Formula (HI): R-^OCH^ R 2 =H: A=B=D=H: E=-CH2NHBenzoyl The compound is prepared from the compound of Example 15 by treatment with benzoyl chloride and TEA. Example 56 The compound is prepared from the compound of Example 15 by treatment with benzaldehyde, NaCNBH3 and acetic acid in methanol at reaction temperature. Example 57 Compound of Formula (HI): R 1 =OCH . R^H: B=D=H: A=E=-CH2OCH2(4-CI-phenyl-) (R.R)-(+)- 1.4- bis-O- ( 4-chlorobenzyl)-2.3-butanediamine Following the procedure of Example 10 steps a-c, replacing the meso-2,3-butanediol thereof with (R,R)-(+)-l,4- bis-O-(4-chlorobenzyl)-D-threitol (Aldrich) the titie compound is obtained. 57b. Compound of Formula (EH): R^OCH^ R^H: B=D=H: A=E=-CH2OCH2(4-Cl-phenyl-) Following the procedures of Example 10 steps d-f, replacing the meso-2,3- butanediamine of step d thereof with the diamine from step 57 a, the title compound is prepared. Example 58 The titie compound is prepared by treating the compound of Example 54 with HCHO, NaCNBH3 and acetic acid in methanol at reaction temperature. Example 59 The titie compound is prepared by treating the compound of Example 56 with HCHO, NaCNBH3 and acetic acid in methanol at reaction temperature. Example 60 Compound of Formula CUT): R x R 2 =H: A=B=D=H: E=-CH2-NH-phenyl The titie compound is prepared by treating the compound of Example 51 with triphenyl phosphine, DEAD and aniline under Mitsunobu conditions. Example 61 The titie compound is prepared by treating the compound of Example 52 with triphenyl phosphine, DEAD and aniline under Mitsunobu conditions. Example 62 In Vitro Assay of Antibacterial Activity Representative compounds of the present invention were assayed in vitro for antibacterial activity as follows: Twelve petri dishes containing successive aqueous dilutions of the test compound mixed with 10 mL of sterilized Brain Heart Infusion (BHT) 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 pattems 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 2 Antibacterial Activity (MICs) of Selected Compounds Ery A Cmpd of Cmpd of MICROORGANISM (Ref. std) Ex 1 Ex 3 STAPHYLOCOCCUS AUREUS ATCC 6538P 0.2 6.2 0.39 STAPHYLOCOCCUS AUREUS A5177 6.2 6.2 0.39 STAPHYLOCOCCUS AUREUS A-5278 >100 >100 >100 STAPHYLOCOCCUS AUREUS CMX 642A 0.39 6.2 0.39 STAPHYLOCOCCUS AUREUS NCTC10649M 0.2 6.2 0.39 STAPHYLOCOCCUS AUREUS CMX 553 0.2 6.2 0.39 STAPHYLOCOCCUS AUREUS 1775 >100 >100 >100 STAPHYLOCOCCUS EPIDERMIDIS 3519 0.39 12.5 0.39 ENTEROCOCCUS FAECIUM ATCC 8043 0.05 0.78 0.05 STREPTOCOCCUS BOVIS A-5169 0.05 0.39 0.02 STREPTOCOCCUS AGALACTIAE CMX 508 0.05 0.39 0.01 STREPTOCOCCUS PYOGENES EES61 0.05 0.39 0.01 STREPTOCOCCUS PYOGENES 930 >100 >100 100 STREPTOCOCCUS PYOGENES PIU 2548 6.2 0.78 na M1CROCOCCUS LUTEUS ATCC 9341 0.02 0.39 0.1 MICROCOCCUS LUTEUS ATCC 4698 0.2 0.39 0.39 ESCHERICHIA COLI JUHL 100 na >100 ESCHERICHIA COLI SS 0.2 na na ESCHERICHIA COLI DC-2 >100 0.78 >100 ESCHERICHIA COLI H560 25 50 >100 ESCHERICHIA COLI KNK 437 50 25 >100 ENTEROBACTER AEROGENES ATCC 13048 100 >100 >100 KLEBSIELLA PNEUMONIAE ATCC 8045 100 >100 >100 PROVIDENCIA STUARTII CMX 640 >100 100 >100 PSEUDOMONAS AERUGINOSA BMH10 >100 >100 >100 PSEUDOMONAS AERUGINOSA 5007 >100 >100 >100 PSEUDOMONAS AERUGINOSA K799 WT 50 >100 >100 PSEUDOMONAS AERUGINOSA K799/61 0.78 >100 3.1 PSEUDOMONAS CEPACIA 2961 >100 12.5 >100 ACINETOBACrER CALCOACEΗCUS CMX 669 6.2 >100 >100 PSEUDOMONAS AERUGINOSA DPHD-5263 >100 50 >100 PSEUDOMONAS AERUGINOSA DPHD-2862 >100 >100 >100 CANDIDA ALBICANS CCH 442 >100 >100 >100 MYCOBACTERIUM SMEGMATIS ATCC 114 0.02 3.1 >100 Table 2 Antibacterial Activity (MICs) of Selected Compounds Cmpd of Cmpd of Cmpd of MICROORGANISM Ex 4 Ex 6 Ex 8 STAPHYLOCOCCUS AUREUS ATCC 6538P 0.2 0.1 0.78 STAPHYLOCOCCUS AUREUS A5177 0.2 0.05 0.78 STAPHYLOCOCCUS AUREUS A-5278 >100 >100 >100 STAPHYLOCOCCUS AUREUS CMX 642A 0.78 0.1 0.78 STAPHYLOCOCCUS AUREUS NCTC10649M 0.78 0.1 0.78 STAPHYLOCOCCUS AUREUS CMX 553 0.78 0.2 0.78 STAPHYLOCOCCUS AUREUS 1775 >100 >100 >100 STAPHYLOCOCCUS EPIDERMIDIS 3519 0.78 0.1 0.78 ENTEROCOCCUS FAECIUM ATCC 8043 0.1 0.1 0.78 STREPTOCOCCUS BOVIS A-5169 0.02 0.01 0.1 STREPTOCOCCUS AGALACTIAE CMX 508 0.005 0.02 0.1 STREPTOCOCCUS PYOGENES EES61 0.05 0.02 0.1 STREPTOCOCCUS PYOGENES 930 >100 >100 >100 STREPTOCOCCUS PYOGENES PIU 2548 na 0.39 0.78 MICROCOCCUS LUTEUS ATCC 9341 0.1 0.02 1.56 MICROCOCCUS LUTEUS ATCC 4698 0.39 0.1 1.56 ESCHERICHIA COLI JUHL >100 12.5 100 ESCHERICHIA COLI SS na 0.02 0.78 ESCHERICHIA COLI DC-2 100 12.5 50 ESCHERICHIA COLI H560 25 3.1 25 ESCHERICHIA COLI KNK 437 >100 6.2 100 ENTEROBACTER AEROGENES ATCC 13048 100 12.5 100 KLEBSIELLA PNEUMONIAE ATCC 8045 >100 12.5 100 PROVIDENCIA STUARTΗ CMX 640 >100 100 >100 PSEUDOMONAS AERUGINOSA BMH10 >100 50 100 PSEUDOMONAS AERUGINOSA 5007 >100 100 >100 PSEUDOMONAS AERUGINOSA K799/WT >100 25 100 PSEUDOMONAS AERUGINOSA K799/61 1.56 0.39 na PSEUDOMONAS CEPACIA 2961 >100 50 >100 ACINETOBACTER CALCOACEΗCUS CMX 669 25 12.5 25 PSEUDOMONAS AERUGINOSA DPHD-5263 >100 12.5 >100 PSEUDOMONAS AERUGINOSA DPHD-2862 >100 100 >100 CANDIDA ALBICANS CCH 442 100 >100 >100 MYCOBACTERIUM SMEGMATIS ATCC 114 na na 6.2 Table 2 Antibacterial Activity (MICs) of Selected Compounds Cmpd of Cmpd of Cmpd of MICROORGANISM Ex 9 Ex 10 Ex 11 STAPHYLOCOCCUS AUREUS ATCC 6538P 0.39 0.39 0.39 STAPHYLOCOCCUS AUREUS A5177 0.39 na 0.39 STAPHYLOCOCCUS AUREUS A-5278 >100 >100 >100 STAPHYLOCOCCUS AUREUS CMX 642A 0.39 0.39 0.39 STAPHYLOCOCCUS AUREUS NCTC10649M 0.2 0.39 0.39 STAPHYLOCOCCUS AUREUS CMX 553 0.39 0.39 0.39 STAPHYLOCOCCUS AUREUS 1775 >100 >100 >100 STAPHYLOCOCCUS EPIDERMIDIS 3519 0.39 0.39 0.39 ENTEROCOCCUS FAECIUM ATCC 8043 0.05 na 0.1 STREPTOCOCCUS BOVIS A-5169 na 0.05 0.01 STREPTOCOCCUS AGALACTIAE CMX 508 0.01 na 0.05 STREPTOCOCCUS PYOGENES EES61 0.01 na 0.005 STREPTOCOCCUS PYOGENES 930 >100 >100 >100 STREPTOCOCCUS PYOGENES PIU 2548 0.39 0.39 0.39 MICROCOCCUS LUTEUS ATCC 9341 0.1 0.1 0.2 MICROCOCCUS LUTEUS ATCC 4698 0.39 0.2 0.39 ESCHERICHIA COLI JUHL na 25 25 ESCHERICHIA COLI SS na 0.2 0.39 ESCHERICHIA COLI DC-2 25 25 25 ESCHERICHIA COLI H560 25 25 6.2 ESCHERICHIA COLI KNK 437 100 na 25 ENTEROBACTER AEROGENES ATCC 13048 25 50 25 KLEBSIELLA PNEUMONIAE ATCC 8045 25 na 12.5 PROVIDENCIA STUARTII CMX 640 >100 >100 >100 PSEUDOMONAS AERUGINOSA BMH10 100 >100 >100 PSEUDOMONAS AERUGINOSA 5007 >100 >100 >100 PSEUDOMONAS AERUGINOSA K799/WT 100 na >100 PSEUDOMONAS AERUGINOSA K799/61 6.2 na na PSEUDOMONAS CEPACIA 2961 >100 100 >100 ACINETOBACTER CALCOACETICUS CMX 669 12.5 25 6.2 PSEUDOMONAS AERUGINOSA DPHD-5263 >100 >100 >100 PSEUDOMONAS AERUGINOSA DPHD-2862 >100 >100 >100 CANDIDA ALBICANS CCH 442 >100 >100 >100 MYCOBACTERIUM SMEGMATIS ATCC 114 3.1 6.2 6.2

Claims: WHAT IS CLAIMED IS: A compound selected from the group having the formulas: as well as the pharmaceutically acceptable salts and esters thereof wherein: A, B, D and E are independently selected from the group consisting of: (a) hydrogen; (b) Ci- -alkyl, optionally substituted with one or more substituents selected from the group consisting of: (i) aryl; (ii) substituted-aryl; (iii) heteroaryl; (iv) substituted-heteroaryl; (v) heterocycloalkyl; (vi) hydroxy; (vii) Ci-Cό-alkoxy; (viii) halogen consisting of Br, Cl, F or I; and (ix) NR 3 R 4 , where R 3 and R 4 are independently selected from hydrogen and Cj- -alkyl, or R 3 and R 4 are taken with the nitrogen atom to which they are connected to form a 3- to 7-membered ring optionally containing a hetero function consistmg of -O-, -NH-, -N(Cι-C6-alkyl-)-, -N(aryl-Cι-C 6 -alkyl-)-, -N(substituted-aryl-Cι-C 6 -alkyl-)- , -N(heteroaryl-Cι-C6-alkyl-)-, -N(substituted-heteroaryl-C]-C6-alkyl-)-, -S- or -S(O) n -, wherein n is 1 or 2; (c) C3-C7-cycloalkyl; (d) aryl; (e) substituted-aryl; (f) heteroaryl; (g) substituted-heteroaryl; (h) heterocycloalkyl; and (i) a group selected from option (b) above further substituted with -M- R 5 , wherein M is selected from the group consisting of: (aa) -C(O)-NH-; (bb) -NH-C(O)-; (cc) -NH- (dd) -N(CH 3 )- (ee) -O- (ff) -S(O)n-, wherein n is 0, 1 or 2; and (gg) -C(=NH)-NH-; and R 5 is selected from the group consisting of: (aaa) Ci-C^-alkyl, optionally substituted with a substituent selected from the group consisting of: (i) aryl; (ii) substituted-aryl; (iii) heteroaryl; and (iv) substituted-heteroaryl; (bbb) aryl; (cce) substituted-aryl; (ddd) heteroaryl; (eee) substituted-heteroaryl; and (fff) heterocycloalkyl; or any one pair of substituents, consisting of AB, AD, AE, BD, BE or DE, is taken together with the atom or atoms to which they are attached to form a 3- to 7-membered ring optionally containing a hetero function consisting of -O-, -NH-, -N(Cι-C 6 -alkyl-)-, -N(aryl-Ci-C 6 -alkyl-)-, -N(substituted-aryl-Cι- -alkyl-)-, -N(heteroaryl-Cι-C6-alkyl-)-, -N(substituted-heteroaryl-Cι-C6-alkyl-)-, -S- or -S(O) n -, wherein n is 1 or 2; -C(O)-NH-; -C(O)-NR 5 -, wherein R 5 is as described above; -NH-C(O)-; -NR 5 -C(O)-, wherein R 5 is as described above; and -C(=NH)-NH-; R 1 is selected from the group consisting of: (a) hydrogen; (b) hydroxy; (c) -O-Cι-C 3 -alkyl; (d) -O-C3-C5-cycloalkyl; (e) -O-Cι-C3-alkyl-C3-C5-cycloalkyl; (f) -O-C(O)-Cι-C 3 -alkyl; (g) - C(O)-O-Cι-C 3 -alkyl: and (h) -O-C(O)-NH-Cι-C 3 -alkyl; R 2 is hydrogen or a hydroxy-protecting group; and Z is hydroxy or protected-hydroxy; with the provisos that when the compound is of Formulas (I) or (HI) then A, B, D, and E may not all be hydrogen, D and E may not be Cι-C3-alkyl when A and B are hydrogen, nor may one of D and E be hydrogen and the other be Cι-C3-alkyl when A and B are hydrogen. 2. A compound according to Claim 1 having the formula: , wherein A, B, D, E, and R R 5 are as described therein. 3. A compound according to Claim 1 having the formula: , wherein A, B, D, E, R*-R 5 and Z are as described therein. A compound according to Claim 1 having the formula: O , wherein A, B, D, E, and R R5 are as described therein. 5. A compound according to Claim 1 having the formula: , wherein A, B, D, E, and R*-R 5 are as described therein. 6. A compound according to Claim 4 wherein R 1 is hydrogen, hydroxy or methoxy, R 2 is hydrogen, and A, B, D, E and R ! -R 5 are as described therein. 7. A compound according to Claim 6 wherein R 1 is hydrogen or methoxy, R 2 is hydrogen, and any three of the A, B, D and E groups are hydrogen and the other group is selected from a singly substituted Cι-C6-alkyl group comprised of -(CH2) m R 6 where m=l, 2, 3 or 4 and R 6 is: (a) aryl; (b) substituted-aryl; (c) heteroaryl; (d) substituted-heteroaryl; (e) heterocycloalkyl; (f) hydroxy; (g) Ci-Cβ-alkoxy (h) NR 3 R 4 , where R 3 and R 4 are independently selected from hydrogen and Ci-C^-alkyl, or R 3 and R 4 are taken with the nitrogen atom to which they are connected to form a 3- to 7-membered ring optionally containing a hetero function consisting of -O-, -NH-, -N(Cι-C 6 -alkyl-)-, -Ntaryl-Ci- -alkyl-)-, -N(substituted-aryl-Cι-C6-alkyl-)-, -N(heteroaryl-Cι-C6-alkyl-)-, -N(substituted-heteroaryl-Cι-C6-alkyl-)-, -S- or -S(O) n -, wherein n is 1 or 2; (i) halogen consisting of Br, Cl, F or I; (j) C1-C3 alkyl; or (k) -(CH 2 ) r M-(CH2) s -R 7 wherein r=0,l or 2; s=0,l or 2 and M is (aa) -C(O)-NH-; (bb) -NH-C(O)-; (cc) -NH- (dd) -N(CH )- (ee) -O- (π) -S(O) n -, wherein n is 0, 1 or 2; and (gg) -C(=NH)-NH-; and R 7 is selected from the group consisting of: (aaa) Cι-C 3 -alkyl, (bbb) aryl; (cce) substituted-aryl; (ddd) heteroaryl; and (eee) substituted-heteroaryl. 8. A compound according to Claim 7 wherein R 1 is hydrogen or methoxy, R 2 is hydrogen, B=E=H, and A and D taken together is selected from the group consisting of: (a) -CH2-Z-CH2-, wherein Z is (aa) -C(O)-NH-; (bb) -C(O)-NR 5 -, wherein R 5 is selected from the group consisting of: (aaa) Cι-C6-alkyl, optionally substituted with a substituent selected from the group consisting of: (i) aryl; (ii) substituted-aryl; (iii) heteroaryl; and (iv) substituted-heteroaryl; (bbb) aryl; (cce) substituted-aryl; (ddd) heteroaryl; (eee) substituted-heteroaryl; and (fff) heterocycloalkyl; (cc) -NH-C(O)-; (dd) -NR 5 -C(O)-, wherein R 5 is as defined above; (ee) -NH- (ff) -N(CH 3 )- (gg) -O- (hh) -S(O) n -, wherein n is 0, 1 or 2; and (ii) -C(=NH)-NH-; (b) -CH2-N(-(CH2) S -R 7 )-CH2-, wherein s=0,l or 2, and R 7 is selected from the group consisting of: (aaa) Cι.-C3-alkyl, (bbb) aryl; (cce) substituted-aryl; (ddd) heteroaryl; and (eee) substituted-heteroaryl; (c) -CH2-N(-(CH 2 ) r M-(CH2)s-R 7 )-CH2-, wherein r=0,l or 2; s=0, 1 or 2, and M and R 7 are as defined above; and (d) -CH2-(CH2) Γ CH2-, wherein r=0,l or 2. 9. A compound according to Claim 1 which is: Compound of Formula (IY); R ^methoxy; R^hydrogen; A=B=D=E=hydrogen; Compound of Formula (HI), A=B=E=H, D=benzyl, R ^methoxy, R 2 =hydrogen; Compound of Formula (UI), A=B=D=H, E=benzyl, R ^methoxy, R 2 =hydrogen; Compound of Formula (TU); A=benzyl, B=D=E=H, R ^methoxy, R 2 =hydrogen; Compound of Formula (HI); B=benzyl, A=D=E=H, R^methoxy, R 2 =hydrogen; Compound of Formula (III); A=E=phenyl, B=D=H, R 1 =methoxy, R 2 =hydrogen; Compound of Formula (HI); A=methyl, B=D=E=H, R 1 =methoxy, R^hydrogen; Compound of Formula (OI); B=methyl, A=D=E=H, R^methoxy, R^hydrogen; Compound of Formula (HI); A=D=methyl; B=E=H, R ^methoxy, R 2 =hydrogen; Compound of Formula (HI); A=E=methyl; B=D=H, R^methoxy, R 2 =hydrogen ; Compound of Formula (HI); B=D=H; A and E taken together is -CH2CH2CH2-, R J =methoxy, R 2 =hydrogen; Compound of Formula (HI); B=E=H; A and D taken together is -CH2CH2CH2CH2-, R ^methoxy, R^hydrogen ; Compound of Formula (I); A=B=D=E=hydrogen; R^hydrogen, R 2 =hydrogen; Compound of Formula (IH): R ! =OCH3, R 2 =H; A=B=D=H; E=-CH2NH2; Compound of Formula (IH): R =OCH3, R'=H; A=B=E=H; D-CH2NH2: Compound of Formula (HI): R =OCH3, R"=H; B=E=H; A and D taken together is -CH2CH2CH2-; Compound of Formula (HI): =OCH3, R 2 =H; B=E=H; A and D taken together is -CH2OCH2-; Compound of Formula (HI): =OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-NH-CH2-; Compound of Formula (HI): R l =OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-N(Cbz)-CH2-; Compound of Formula (HI): =OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-N(benzyl)-CH2-; Compound of Formula (HI): R'=OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-N(benzoyl)-CH2-; Compound of Formula (HI): R'=OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-N(phenyl-CH2-CH2-)-CH2-; Compound of Formula (HI): R'=OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-N(4-Cl-phenyl-CH2-)-CH2-; Compound of Formula (HI): =OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-N(4-pyridyl-CH2-)-CH2-; Compound of Formula (HI): R'=OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-N(2-pyridyl-CH2-)-CH2-; Compound of Formula (HI): R^OCTO, R 2 =H; B=E=H; A and D taken together is -CH2-N(3-pyridyl-CH2-)-CH2-; Compound of Formula (HI): =OCH3, R 2 =H; B=E=H; A and D taken together is -CH2-N(4-quinolyl-CH2-)-CH2-; Compound of Formula (IH): =OCH3, R'=H; B=E=H; A=D=-CH2-O-CH2- phenyl; Compound of Formula (IH) R =OCH3, R'=H; B=E=H; A=D=-CH2-OH; Compound of Formula (IH) R'=OCH3, R 2 =H; B=E=H; A=D=-CH2-O-phenyl; Compound of Formula (HI) R'=OCH3, R 2 =H; A=B=H; D and E taken together is -CH2-CH2-CH2-CH2-; Compound of Formula (HI): R =OCH3, R =H; A and B taken together is -CH2-CH2-CH2-CH2-; D=E=H; Compound of Formula (HI): R =OCH3, R =H; A=B=H; D and E taken together is -CH2-O-CH2-; Compound of Formula (HI) =OCH3, R 2 =H; A=D=E=H; B=-CH2-CH2-phenyl Compound of Formula (HI) R'=OCH3, R 2 =H; A=D=E=H; B=- CH2-CH2-CH2-phenyl ; Compound of Formula (HI): R^OCHS, R 2 =H; A*=D=E=H; B=- CH2-0-CH2-phenyl ; Compound of Formula (HI): R ] =OCH3, R 2 =H; A=D=E=H; B=- CH2-CH2-(4-OCH -phenyl ); Compound of Formula (HI): R^OCHS, R 2 =H; A=-CH2-CH2-phenyl; B=D=E=H ; Compound of Formula (IH): R ! =OCH3, R 2 =H; A=-CH2-CH2-CH2-phenyl; B=D=E=H ; Compound of Formula (III): R'=OCH3, R 2 =H; A=-CH2-O-CH2-phenyl ; B=D=E=H ; Compound of Formula (HI): R 1 =OCH3, R 2 =H; B=D=E=H; A=- CH2-CH2-(4-OCH 3 -phenyl); Compound of Formula (IH): R'=OCH3, R 2 =H; A=B=D=H; E=-CH2-CH2-Ph; Compound of Formula (IH): R ] =OCH3, R 2 =H; A=B=E=H; D=-CH2-CH2-Ph; Compound of Formula (HI): R'=OCH3, R 2 =H; A=B=D=H; E=- CH2-CH2-CH2-Ph; C Coommppoouunndd o < f Formula (HI): R'=OCH3, R 2 =H; A=B=E=H; D=- CH2-CH2-CH2-Ph; Compound of Formula (IH): R'=OCH3, R 2 =H; A=- CH2-CH2-OPh; B=D=E=H; Compound of Formula (HI): R'=OCH3, R 2 =H; A=- CH2-CH2-NHCbz; B=D=E=H; Compound of Formula (IH) Rl=OCH3, R2=H; A=-CH2-CH2-NH2; B=D=E=H; Compound of Formula (IH): R'=OCH3, R 2 =H; A=- CH2-CO2Benzyl; B=D=E=H; Compound of Formula (HI) Rl=OCH3, R2=H; A=-CH2-COOH; B=D=E=H; Compound of Formula (HI) Rl=OCH3, R2=H; A=-CH2-CH2-OH; B=D=E=H; Compound of Formula (III): R'=OCH3, R 2 =H; A=- CH2-CH2-NH(4-Pyridyl-); B=D=E=H Compound of Formula (IH): R'=OCH3, R 2 =H; A=B=D=H; E=-CH2-OH; Compound of Formula (IH): R^OOO, R 2 =H; A=B=E=H; D=-CH2-OH; Compound of Formula (III): A=B=E=H; D=-CH2-NHBenzoyl; Compound of Formula CUT): A=B=E=H; D=-CH2-NHBenzyl; Compound of Formula (ni): R'=OCH3, R =H; A=B=D=H; E=-CH2-NHBenzoyl; Compound of Formula (III): R'=OCH3, R 2 =H; A=B=D=H; E=-CH2-NHBenzyl; Compound of Formula (ID): R ! =OCH3, R 2 =H; B=D=H; A=E=-CH2OCH2(4-Cl- phenyl); Compound of Formula (HI): R ! =OCH3, R 2 =H; A=B=E=H; D=-CH2-N(CH 3 )- Benzyl; Compound of Formula (HI): R'=OCH3, R 2 =H; A=B=D=H; E=-CH2-N(CH 3 )- Benzyl; Compound of Formula (III): R , ι =OCH3. R ^ =H; A=B=D=H; E=-CH2-NH-phenyl; 95 or Compound of Formula (IH): R'=OCH3, R 2 =H; A=B=E=H; D=-CH2-NH-phenyl. 10. A compound according to Claim 1 which is: Compound of Formula (IV); R ^methoxy; R^hydrogen; A=B=D=E=hydrogen; Compound of Formula (HI), A=B=E=H, D=benzyl, R ^methoxy, R 2 =hydrogen; Compound of Formula (HI), A=B=D=H, E=benzyl, R^methoxy, R 2 =hydrogen; 5 Compound of Formula (HI); A=benzyl, B=D=E=H, Rl=methoxy, R2=hydrogen; Compound of Formula (HI); B=benzyl, A=D=E=H, R 1 =methoxy, R 2 =hydrogen; Compound of Formula (III); A=E=phenyl, B=D=H, R^methoxy, R 2 =hydrogen; Compound of Formula (HI); A=methyl, B=D=E=H, R ^methoxy, R2=hydrogen; Compound of Formula (HI); B=methyl, A=D=E=H, R 1 =methoxy, R^hydrogen; 10 Compound of Formula (HI); A=D=methyl; B=E=H, R ^methoxy, R 2 =hydrogen; Compound of Formula (HI); A=E=methyl; B=D=H, R 1 =methoxy, R 2 =hydrogen ; Compound of Formula (IH); B=D=H; A and E taken together is -CH2CH2CH2-, R ^methoxy, R 2 =hydrogen; Compound of Formula (HI); B=E=H; A and D taken together is -CH2CH2CH2CH 2 -, 15 R ^methoxy, R 2 =hydrogen ; or Compound of Formula (I); A=B=D=E=hydrogen; R^hydrogen, R 2 =hydrogen. 11. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to any of Claims 1 through 8 in combination with a pharmaceutically acceptable carrier. 12. A method for controlling a bacterial infection in a mammal comprising administering to an animal a therapeutically-effective pharmaceutical composition containing a compound according to any of Claims 1 through 8. 13. A process for the preparation of tricyclic macrolide compounds having the Formulas: wherein A, B, D and E are independently selected from the group consisting of: (a) hydrogen; (b) Cι-C6-alkyl, as defmed below, optionally substituted with one or more substituents selected from the group consisting of: (i) aryl, as defined below; (ii) substituted-aryl, as defined below; (iii) heteroaryl, as defined below; (iv) substituted-heteroaryl, as defined below; (v) heterocycloalkyl, as defined below; (vi) hydroxy; (vii) Ci-Cό-alkoxy, as defined below; (viii) halogen consisting of Br, Cl, F or I; and (ix) NR 3 R 4 , where R 3 and R 4 are independently selected from hydrogen and Ci- -alkyl, or R 3 and R 4 are taken with the nitrogen atom to which they are connected to form a 3- to 7-membered ring optionally containing a hetero function consisting of -O-, -NH-, -N(Cι-C 6 -alkyl-)-, -N(aryl-Cι-C 6 -alkyl-)-, -N(substituted-aryl-Cι-C6-alkyl- )-, -N(heteroaryl-Cι-C6-alkyl-)-, -N(substituted-heteroaryl-Cι-C6-alkyl-)-, -S- or -S(O) n -, wherein n is 1 or 2; (c) C3-C7-cycloalkyl; (d) aryl; (e) substituted-aryl; (f) heteroaryl; (g) substituted-heteroaryl; (h) heterocycloalkyl; and (i) a group selected from option (b) above further substituted with -M- R 5 , wherein M is selected from the group consisting of (aa) -C(O)-NH-; D 97/17356 (bb) -NH-C(O)-; (cc) -NH- (dd) -N(CH 3 )- (ee) -O- (rr) -S(O) n -, wherein n is 0, 1 or 2; and (gg) -C(=NH)-NH-; and R 5 is selected from the group consisting of: (aaa) -Co-alkyl, optionally substituted with a substituent selected from the group consisting of: (i) aryl; (ii) substituted-aryl; (iii) heteroaryl; and (iv) substituted-heteroaryl; (bbb) aryl; (cce) substituted-aryl; (ddd) heteroaryl; (eee) substituted-heteroaryl; and (fff) heterocycloalkyl; or any one pair of substituents, consisting of AB, AD, AE, BD, BE or DE, is taken together with the atom or atoms to which they are attached to form a 3- to 7-membered ring optionally containing a hetero function consisting of -O-, -NH-, -N(Cι-C 6 -alkyl-)-, -N(aryl-Cι-C6-alkyl-)-, -N(substituted-aryl-Cι-C6-alkyl-)-, -N(heteroaryl-Cι- -alkyl-)-, -N(substituted-heteroaryl-Ci-C6-alkyl-)-, -S- or -S(O) n -, wherein n is 1 or 2; -C(O)-NH-; -C(O)-NR 5 -, wherein R 5 is as described above; -NH-C(O)-; -NR 5 -C(O)-, wherein R 5 is as described above; and -C(=NH)-NH-; R 1 is selected from the group consisting of: (a) hydrogen; (b) hydroxy; (c) -O-Cι-C -alkyl; (d) -O-C3-C 5 -cycloalkyl; (e) -O-Cι-C3-alkyl-C3-C 5 -cycloalkyl; (f) - C(O)-Cι-C3-alkyl; (g) -O-C(O)-O-Cι-C 3 -alkyl; and (h) -O-C(O)-NH-Ci-C 3 -alkyl; R 2 is hydrogen or a hydroxy-protecting group, as defined below; and Z is hydroxy or protected-hydroxy; except when the compound is of Formulas (I) or (HI) then A, B, D, and E may not all be hydrogen, D and E may not be Cι-C3-alkyl when A and B are hydrogen, nor may one of D and E be hydrogen and the other be Cι-C3-alkyl when A and B are hydrogen; the method comprising: (a) treating a compound having the formula: , respectively, wherein R 1 is as described above and R 2 is a hydroxy-protecting group, with a base, and followed by reaction with carbonylo irnidazole, in an aprotic solvent, at a reaction temperature from -20°C to 70°C, for a period from 0.5 hours to 10 days, to prepare first intermediate compounds having the formulas: , respectively; wherein R 1 and R 2 are as described above; (b) reacting said first intermediate compounds with a compound having the formula: wherein A, B, D, and E are as described above, to give the bicyclic second intermediate compounds having the formulas: , respectively; wherein R 1 and R 2 are as described above; (c) deprotecting said second intermediate compounds by treatment with methanol or ethanol when OR 2 is an ester or with fluoride in THF or acetonitrile when R 2 is a trialkylsilyl group, for from 1 to 24 hours, to give the third intermediate compounds: respectively; and (d) cyclizing said third intermediate compounds by treatment with dilute acid, in an organic solvent, for a period of from 4 hours to 10 days to give the desired compounds (I), (II), (IH) or (IV) above. 14. A process according to Claim 13 wherein: in step (a) the aprotic solvent is selected from the group consisting of dichloro¬ methane, chloroform, DMF, tetrahydrofuran (THF), N-methyl pyπolidinone or a mixture thereof, the reaction temperature is from 0°C to reaction temperature, and the period of reaction is 1-8 hours; in step (b) the reaction is run in aqueous acetonitrile, DMF or aqueous DMF; in step (c) deprotecting said second intermediate compounds by treatment with methanol or ethanol when OR 2 is an ester or with fluoride in THF or acetonitrile when R 2 is a trialkylsilyl group, for from 1 to 24 hours; and in step (d) cyclizing said third intermediate compounds by treatment with dilute acetic acid or HCl in ethanol or propanol for a period of from 4 hours to 10 days to give the desired compounds. 15. A process for the preparation of tricyclic macrolide derivatives having the Formulas: wherein A, B, D and E are independently selected from the group consisting of: (a) hydrogen; (b) Cι-C6-alkyl, as defined below, optionally substituted with one or more substituents selected from the group consisting of: (i) aryl, as defined below; (ii) substituted-aryl, as defined below; (ϋi heteroaryl, as defined below; (iv substituted-heteroaryl, as defined below; (v) heterocycloalkyl, as defined below; (vi) hydroxy; (vii) Ci-Ce-alkoxy, as defined below; (viii) halogen consisting of Br, Cl, F or I; and (ix) NR 3 R 4 , where R 3 and R 4 are taken with the nitrogen atom to which they are connected to form a 3- to 7-membered ring optionally containing a hetero function consisting of -O-, -NH-, -N(Cι-C6-alkyl-)-, -N(aryl-Cι-C6-alkyl-)-, -N(substituted-aryl-Cι-C6-alkyl-)-, -N(heteroaryl-Cι-C6-alkyl-)-, -N(substituted-heteroaryl- Ci-Cό-alkyl-)-, -S- or -S(O) n -, wherein n is 1 or 2; (c) C3-C7-cycloalkyl; ( ) aryl; (e) substituted-aryl; (f) heteroaryl; ( (gg)) substituted-heteroaryl; (h) heterocycloalkyl; and (i) a group selected from option (b) above further substituted with -M- R 5 , wherein M is selected from the group consisting of (aa) -C(O)-NH-; (bb) -NH-C(O)-; (cc) -NH- (dd) -N(CH3)- (ee) -O- (rr) -S(O) n -, wherein n is 0, 1 or 2; and (gg) -C(=NH)-NH-; and R 5 is selected from the group consisting of: (aaa) Cι-C6-alkyl, optionally substituted with a substituent selected from the group consisting of: (i) aryl; (ii) substituted-aryl; (iii) heteroaryl; and (iv) substituted-heteroaryl; (bbb) aryl; (cce) substituted-aryl; (ddd) heteroaryl; (eee) substituted-heteroaryl; and (fff) heterocycloalkyl; or any one pair of substituents, consisting of AB, AD, AE, BD, BE or DE, is taken together with the atom or atoms to which they are attached to form a 3- to 7-membered ring optionally containing a hetero function consisting of: -O-, -NH-, -N(Cι-C 6 -alkyl-)-, -N(aryl-Cι-C6-alkyl-)-, -N(substituted-aryl-Cι-C6-alkyl-)-, -N(heteroaryl-Cι - -alkyl-)-, -N(substituted-heteroaryl-Cι- -alkyl-)-, -S- or -S(O) n -, wherein n is 1 or 2; -C(O)-NH-; -C(O)-NR 5 -, wherein R 5 is as described above; -NH-C(O)-; -NR 5 -C(O)-, wherein R 5 is as described above; and -C(=NH)-NH-; R 1 is selected from the group consisting of: (a) hydrogen; (b) hydroxy; (c) -O-Cι-C 3 -alkyl; (d) -O-C3-C5-cycloalkyl; (e) -O-Cι-C3-alkyl-C 3 -C 5 -cycloalkyl; (f) -O-C(O)-Cι-C3-alkyl; (g) - C(O)-O-Cι-C 3 -alkyl; and (h) -O-C(O)-NH-Cι-C 3 -alkyl; R 2 is hydrogen or a hydroxy-protecting group, as defined below; and Z is hydroxy or protected-hydroxy; except when the compound is of Formulas (I) or (HI) then A, B, D, and E may not all be hydrogen, D and E may not be C1-C3 -alkyl when A and B are hydrogen, nor may one of D and E be hydrogen and the other be Cι-C3-alkyl when A and B are hydrogen; the method comprising: (a) treating a compound having the formula: , respectively, wherein R 1 is as described above and R 2 is a hydroxy-protecting group, with a base, and followed by reaction with carbonyldiimidazole, in an aprotic solvent, at a reaction temperature from -20°C to 70°C, for a period from 0.5 to 24 hours, to prepare first intermediate compounds having the formulas: , respectively; wherein R 1 and R 2 are as described above; (b) reacting said first intermediate compounds with a compound having the having the formula: 90 wherein A, B, D, and E are as described above to give the bicyclic second intermediate compounds: , respectively; (c) reacting the hydroxy group of the said bicyclic second intermediate compounds by treatment with triphenylphosphine and diphenylphosphoryl azide in tetrahydrofuran, under Mitsunobu reaction conditions, to prepare the third mtermediate compounds: i l l , respectively; (d) reducing the third intermediate compounds having an azido group, with reducing reagents to prepare the fourth intermediate compounds having the formulas: respectively; and (e) cyclizing said fourth intermediate compounds by treatment with a dilute acid, 100 in an organic solvent, for a period of from 4 hours to 10 days to give the desired compounds of Formulas (I), (II), (HI) or (IV). 16. The process as in Claim 15 wherein: in step (a) the base is sodium hydride, lithium hydride, or potassium carbonate, the aprotic solvent is dichloromethane, chloroform, DMF, tetrahydrofuran (THF), N-methyl pyπolidinone or a mixture thereof, the reaction temperature is from 0°C to reaction 5 temperature, and the reaction period is from 1-8 hours; in step (b) the solvent is aqueous acetonitrile, DMF or aqueous DMF; in step (c) the reagents are triphenylphosphine and diphenylphosphoryl azide-DEAD in tetrahydrofuran, under Mitsunobu reaction conditions; in step (d) the reducing reagent is triphenylphosphine-water, hydrogen with a 10 catalyst, sodium borohydride, or diajJeylalurninum hydride; in step (e) cyclizing said third intermediate compounds by treatment with dilute acetic acid or HCl in ethanol or propanol for a period of from 4 hours to 10 days to give the desired compounds. 17. The process as in Claim 15 wherein: step (c) is replaced with a two-step sequence which comprises (1) reacting the hydroxy group of the bicyclic second intermediate compounds thereof with an alkyl or aryl sulfonyl chloride, an alkyl or aryl sulfonic anhydride or trifluoromethanesulfonic anhydride in an aprotic solvent at -78°C to reaction temperature to give the coπesponding sulfonate, and (2) reacting the said sulfonate with lithium azide or sodium azide in an aprotic solvent at 0°C to 100°C to give the third intermediate compound.

Inventors: CHU DANIEL T, ELLIOTT RICHARD L, HALLAS ROBERT, OR YAT SUN, PHAN LY TAM, SPINA KENNETH P, CHU, DANIEL, T., ELLIOTT, RICHARD, L., HALLAS, ROBERT, OR, YAT, SUN, PHAN, LY, TAM, SPINA, KENNETH, P.
Applicants: ABBOTT LAB, ABBOTT LABORATORIES
Application year: 1996
Main classification: C07H17
IPC codes: A61K31, A61P31, C07H17