MXPA00010822A

MXPA00010822A - 2"-deoxy hygromycin derivatives

Info

Publication number: MXPA00010822A
Application number: MXPA/A/2000/010822A
Authority: MX
Inventors: Gerald Linde Ii Robert
Original assignee: Pfizer Products Inc
Priority date: 1998-05-04
Filing date: 2000-11-03
Publication date: 2001-07-31

Abstract

This invention relates to compounds of formula (1) and to pharmaceutically acceptable salts, prodrugs and solvates thereof, wherein R1 and R2 are as defined herein. The compounds of formula (1) are antibacterial and antiprotozoal agents that may be used to treat various bacterial and protozoal infections and disorders related to such infections. The invention also relates to pharmaceutical compositions containing the compounds of formula (1) and to methods of treating bacterial and protozoal infections by administering the compounds of formula (1).

Description

DERIVATIVES OF 2"-DESQXI HIGRQMICINA BACKGROUND OF THE INVENTION This invention relates to novel 2"-deoxy hygromycin A derivatives which are useful as antibacterial and antiprotozoal agents in mammals, including humans, as well as in fish and poultry This invention also relates to pharmaceutical compositions containing the novel compounds and methods for the treatment of bacterial and protozoal infections in mammals, fish and birds, by administering the new compounds to mammals, fish and birds that require such treatment The compounds of the present invention can be obtained from hygromycin A Hygromycin A is a natural product obtained by fermentation, isolated for the first time from Streptomyces hygroscopicus in 1953. As an antibiotic, hygromycin A possesses activity against human pathogens and is reported to possess potent in vitro activity against Serpulina (Treponema) hyodysenteriae, that causes dysentery. Vanas references mention modifications semisynthetic of hygromycin A, including the following: the derivatization of the 5"ketone of hygromycin A to give 2,4-dinitrophenylhydrazone is mentioned in K. Isono et al., J. Antibiotics 1957, 10, 21 and R.L. Mann and D.O. Woolf, J. Amer. Chem. Soc. 1957, 79, 120. K. Isono et al., Ibid, also mention thiosemicarbazone in 5"; reduction of ketone 5"from hygromycin A to alcohol 5" is mentioned in R.L. Mann and D.O. Woolf, Ibid, as well as in S.J. Hecker et al., Bioorg. Med. Chem. Lett. 1992, 2, 533 and S.J. Hecker et al., Bioorg. Med. Chem. Lett. 1993, 3, 295; Furanose analogs are mentioned in B.H. Jaynes et al., Bioorg. Med. Chem. Lett. 1993, 3, 1531 and B.H. Jaynes et al., J. Antibiot. 1992, 45, 1705; the aromatic ring analogues are mentioned in S.J. Hecker et al., Bioorg. Med. Chem. Lett. 1993, 3, 289 and C.B. Cooper et al., Bioorg. Med. Chem. Lett. 1997, 7, 1747; the enamide analogs are mentioned in S.J. Hecker et al., Bioorg. Med. Chem. Lett. 1992, 2, 533; aminociclitol analogues are mentioned in S.J. Hecker et al., Bioorg. Med. Chem. Lett 1992, 2, 1015 and in S.J. Hecker et al., Bioorg. Med. Chem. Lett. 1992, 2, 1043. The hygromycin derivatives of the present invention possess activity against gram-negative and gram-positive bacteria and protozoa. U.S. Provisional Patent Application No. 60/084058, filed May 4, 1998, entitled "Hygromycin A Derivatives" ("Hygromycin A Derivatives") (attorney's file number PC 10057), whose inventors are K.E. Brighty, R.G. Linde II, M. R. Jefson, E.L. cCormick and S.S. Guhan also refers to hygromycin A analogs and is incorporated herein by reference in its entirety.

BRIEF DESCRIPTION OF THE INVENTION The present invention relates to compounds of the formula and pharmaceutically acceptable salts, prodrugs and solvates thereof, wherein: R1 is H and R2 is -NR3R4, -NR4C (0) R3, -OC (0) NR3R4 or -OR3; or R1 and R2 are taken together to form = 0, = N-OR3, = CR4R3, = CR4C (0) R3, = CR4C (0) OR3 or = CR4 (0) NR3R4; each R3 is independently selected from H, Ci-C10 alkyl, C2-C10 alkenyl, - (CH2) t (C3-C10 cycloalkyl), - (CH2) (aryl Ce-Cio) and - (CH2) t (heterocycle of 4 -10 links), where t is an integer ranging from 0 to 5, said alkyl group optionally containing 1 or 2 heteroradicals selected from O, -S (0) r where j is an integer ranging from 0 to 2, and -N (R7) -, with the proviso that two O atoms, two S atoms or one O atom and one S atom are not directly bonded together; such groups R3 cycloalkyl, aryl and heterocyclic are optionally condensed with a benzene ring, a saturated cyclic group C3-Cß or a heterocyclic group of 4 to 10 links; the radicals - (CH2) t of the above R3 groups optionally include a double or triple carbon-carbon bond where t is an integer between 2 and 5; and the above R3 groups, except H, but including any optional fused ring mentioned above, are optionally substituted with 1 to 5 R5 groups; each R 4 is independently H or C 1 -C 10 alkyl; each R5 is independently selected from C1-C10 alkyl; C3-C10 cycloalkyl, halo, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, -OR6, -C (0) R6, -C (0) OR6, -NR7C (0) OR9, -OC (0) R6, -NR7S02R9, -S02NR6R7, -NR7C (0) R6, -C (0) NR6R7, -S (0), (CH2) m (C10-C10 aryl), -S (0), (C6-C6 alkyl) , where j is an integer that varies between 0 and 2, - (CH2) m (C6-C10 aryl), -0 (CH2) m (C6-C10 aryl), -NR7 (CH2) m (C6-C10 aryl) ) and - (CH2) m (heterocycle of 4 to 10 links), where m is an integer that varies between 0 and 4; said alkyl group optionally contains 1 or 2 heteroradicals selected from O, -S (0) r, where j is an integer ranging from 0 to 2, and -N (R7) -, with the proviso that two O atoms , two atoms of S or one atom of O and another of S are not directly linked together; said R5 cycloalkyl, aryl and heterocyclic groups are optionally fused with a Cß-C -io aryl group, a C 5 -C 3 saturated cyclic group or a 4 to 10-membered heterocyclic group; and said alkyl, cycloalkyl, aryl and heterocyclic R5 groups are optionally substituted with 1 to 5 gjHj substituents independently selected from halo, cyano, nitro, difluoromethoxy, trifluoromethyl, trifluoromethoxy, azido, -NR7S02R9, -S02NR6R7, -C (0) R6, -C (0) OR6, -OC (0) R6, -NR7C (0) OR 9, -NR 7 C (0) R 6, -C (0) NR 6 R 7, -NR 6 R 7, -OR 6, C 1 -C 10 alkyl, - (CH 2) m (C 6 -C 10 aryl) and - (CH 2) m (4 to 10 heterocycle) links), where m is an integer that varies between 0 and 4; each R6 is independently selected from H, C10 alkyl, C3-C10 cycloalkyl, - (CH2) m (C3-C10 aryl) and - (CH2) m (4- to 10-membered heterocycle), where m is an integer which it varies between 0 and 4; said alkyl group optionally includes 1 or 2 heteroradicals selected from O, -S (O), - where j is a number ranging from 0 to 2, and -N (R7) -, with the proviso that two O atoms, two S atoms or one O atom and one S atom are not directly bonded to each other, said R6 cycloalkyl, aryl and heterocyclic groups are optionally fused with a C6-C? ar aryl group, a saturated cyclic group C5-C3 O heterocyclic group of 4 to 10 links; and the above R6 substituents, except H, are optionally substituted with 1 to 5 substituents independently selected from halo, cyano, nitro, difluoromethoxy, trifluoromethyl, trifluoromethoxy, azido, -C (0) R7, -C (0) OR7, - OC (0) R7, -NR7C (0) R8, -C (0) NR7R8, -NR7R8, hydroxy, C? -C6 alkyl and alkoxy each R7 and R3 is independently H or CrC6 alkyl; and R8 is selected from the substituents provided in the definition of R6, except H. Preferred compounds of formula 1 include those in the that R1 and R2 are taken together to form = N-OR3, and R3 is CrC4 alkyl, C2-C4 alkenyl, - (CH2) t (C6-C? o aryl) or - (CH2) t (4 to 4-heterocycle) 10 links), where t is an integer ranging from 0 to 3, the heterocyclic group is optionally condensed with a benzene ring, the aryl group is optionally condensed with a 5- or 6-membered heterocyclic group, and the above R3 groups , including said optionally condensed radicals, are optionally substituted with 1 to 5 substituents independently selected from nitro, halo, C 1 -C 3 alkoxy, C 1 -C 4 alkyl, trifluoromethyl, acetamido, tert-butoxycarbonylamino, tert-butoxycarbonylaminoethyl, tert-butoxycarbonyl, -NR 6 R 7, phenyl , cyclohexyl, carboxy, aminomethyl, difluoromethoxy, trifluoromethoxy, cyano, piperidinyl, morpholino, phenoxy and phenylthio. Other preferred compounds of formula 1 include those in which R 1 and R 2 are taken together to form = N-OR 3 and R 3 is - (CH 2) t (C 6 -C 6 aryl) or - (CH 2) t (4 to 4 heterocycle) 10 links), where t is an integer ranging from 0 to 3, the heterocyclic group is optionally condensed with a benzene ring, the aryl group is optionally condensed with a 5- or 6-membered heterocyclic group, and the above R3 groups , including said optionally condensed radicals, are optionally substituted with 1 to 5 substituents independently selected from nitro, halo, C1-C3 alkoxy, Cr C4 alkyl, difluoromethoxy, trifluoromethyl, acetamido, tert-butoxycarbonyl, tert-butoxycarbonylamino, -NR6R7, phenyl, cyclohexyl, carboxy, tere- butoxycarbonylaminomethyl, to inomethyl, trifluoromethoxy, cyano, piperidinyl, morpholino, phenoxy and phenylthio. Other preferred compounds of formula 1 include those in which R 1 is H, R 2 is -NR 3 R 4, R 4 is H or methyl, and R 3 is - (CH 2) t (C 6 -C 0 aryl) or - (CH 2) t (heterocycle of 4 to 10 links), where t is an integer ranging from 0 to 2, and the group R3 is optionally substituted by 1 to 5 substituents independently selected from halo, C1-C3 alkoxy, C1-C4 alkyl and trifluoromethyl . Other preferred compounds of formula 1 include those in which R1 is H, R2 is -NR4C (0) R3, R4 is H and R3 is C3-C6 cycloalkyl, - (CH2) t (C-C-io aryl) or - (CH2) (heterocycle of 4 to 10 links), where t is an integer that varies between 0 and 2, the aryl group is optionally condensed with a heterocyclic group of 5 or 6 links, the heterocyclic group is optionally condensed with a benzene ring and the above R3 groups, including such optionally condensed radicals, are optionally substituted with 1 to 5 substituents independently selected from halo, C1-C3 alkoxy, C1-C4 alkyl and trifluoromethyl. Other preferred compounds of formula 1 include those in which R1 and R2 are taken together to form = CR4C (0) OR3 or = CRC (0) NR3R4, R4 is H, and R3 is H, d-C6 alkyl, C3 cycloalkyl -C6, - (CH2) t (4- to 10-membered heterocycle), or - (CH2) t (Cß-C-io aryl) where t is an integer ranging from 0 to 2, the aryl group is optionally condensed to a 5- or 6-membered heterocyclic group, the heterocyclic group is optionally condensed to a benzene ring, and the above R3 groups, except H, but including such optionally condensed radicals, are optionally substituted with 1 to 5 independently selected substituents between halo, C1-C3 alkoxy, CrC alkyl, -NR6R7 and trifluoromethyl. Other preferred compounds of formula 1 include those in which R 1 is H, R 2 is -OR 3, and R 3 is C 1 -C 4 alkyl, - (CH 2), (heterocycle of 4 to 10 links), or - (CH 2) t (aryl G3-C10) where t is an integer ranging from 1 to 2, the aryl group is optionally condensed with a 5- or 6-membered heterocyclic group, the heterocyclic group is optionally condensed with a benzene ring, and the groups R3 above, including such optionally condensed radicals, are optionally substituted with 1 to 5 substituents independently selected from halo, C1-C3 alkoxy, C1-C4 alkyl, cyclohexyl, cyano, trifluoromethyl, benzyloxy and trifluoromethyl. Other preferred compounds of formula 1 include those in which R1 is H, R2 is -OC (0) NR3R4, R4 is H and R3 is - (CH2) t (C6-C10 aryl) where t is an integer ranging from 0 and 2 and the group R3 is optionally substituted by 1 to 5 substituents independently selected from halo, C1-C3 alkoxy, C1-C4 alkyl and trifluoromethyl. Preferred specific compounds of formula 1 include those selected from the group consisting of: -Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / fro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl -1-oxo-2 - (? J-propenyl] amino] -1, 2-0-methylene-D-peo-inositol, (Z) -0 - [(3-fluorophenyl) methyl] oxime; 5-Deoxy- 5 - [[3- [4 - [(2,6-d-Deoxy-β-D-eripro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo -2- (? J-propenyl] amino] -1,2-methylene-D-neo-inositol, (?) - 0 - [(3-fluorophenyl) methyl] oxime; 5-Deoxy- 5 - [[3- [4 - [(2,6-dideoxy-ß-D-eripO-hexofurans-5-ulos-1-ylJoxij-S-hydroxyphenylj ^ -methyl-l-oxo ^ -i? J-propenilJaminoj -I .SO-methylene-D-neo-inositol, (? -0 - [(benzofuran-2-yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy) -β-D-er / io-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (○) -propenyl] amino] -1, 2- 0-methylene-D-peo-inositol, (Z) -0 - [(benzofuran-2-yl) methyl] oxime; 5-deoxy-5 - [[3- [4 - [(2,6-dideoxy-β -D-er / rro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1, 2- 0-methylene-D-neo-inositol, (Z) -O-phenylmethyl oxime; 5-deoxy-5 - [[3- [4 - [(2,6-dideoxy-β -D-eprro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1, 2-0-methylene- D-peo-inositol, (E) -O-phenylmethyl oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-isositol, (Z) -0 - [(4-chlorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-ep'fra-hexofurans-5-ulos-1-yl) oxy] -3-hydroxy-phenyl] -2 -methyl-1-oxo-2- (E) -propenyl] amino] -1, 2-0-methylene-D-neo- inositol, (E) -0 - [(4-chlorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-eripro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl- 1-oxo-2- (E) -propenyl] amino] -1,2-O-methylene-D-ioeo-inositol, (Z) -0 - [(3,4-dichlorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-erirro-hexofurans-5-ulos-1-l) oxy] -3-hydroxyphenyl] -2-methyl- 1-oxo-2- ()) -propenyl] amino] -1,2-methylene-D-neo-inositol, (E) -0 - [(3,4-dichlorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-eriyl-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- (E) -propenyl] amino] -1,2-0-methylene-D-neo-inositol, (E) -0 - [(4-pyridinyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-eripro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1 -oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(4,4-morpholinyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, (E) -0- [cyclohexylmethyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-ß-D-er / fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2 -methyl-1-oxo-2- (E) -propenyl] amino] -1,2-O-methylene-D-peo-inositol, (Z) -0 - [(4-fluorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / rro-hexofurans-5-ulos-1-l) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- (E) -propenyl] amino] -1,2-O-methylene-D-peo-inositol, (E) -0 - [(4-fluorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-eripro-hexofurans-5-ulos-1- il) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1,2-O-methylene-D-peo-inositol, (E) -0 - [(2,4-dichlorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / io-hexofurans-5-ulos-1-yl) oxy] -3-hydroxy-phenyl] -2 -methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (E) -0 - [(3,4-difluorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-eriyl-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1 -oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(3,4-dichlorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-d-deoxy-β-D-er) -ra-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2 -methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (E) -0 - [(furan-3-1) ) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-eripro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1 -oxo-2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, (Z) -0 - [(furan-3-yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-d-deoxy-β-D-erfrom-hexofurans-5-ulos-1-l) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, (Z) -0 - [(1,3-benzodioxol-5-yl) ) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / rro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, (E) -0 - [(1,3-benzodioxol-5-yl) methyl) ] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2 -methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (E) -0 - [(3-chlorophenyl) methyl] oxy ma; -Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- ()) -propenyl] amino] -1,2-methylene-D-neo-isositol, ()) -0 - [(4-cyclohexylphenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / io-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- ()) -propenyl] amino] -1,2-methylene-D-neo-inositol, ()) -0 - [(3-aminophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy] -β-D-eriro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl- 1-oxo-2- ()) -propenyl] amino] -1,2-methylene-D-neo-inositol, ()) -0 - [[(4-aminomethyl) phenyl] methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-erira-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1 -oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-isositol, (Z) -0- [3- (4-chlorophenyl) propyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-eriyl-hexofurans-5-ulos-1-yl) oxy] -3-hydroxy-phenyl] -2 -methyl-1-oxo-2- (E) -propenyl] amino] -1,2-O-methylene-D-neo-inositol, (£) -0- [3- (4-chlorophenyl) propyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / io-hexofurans-5-ulos-1-yl) oxy] -3-hydroxy-phenyl] -2 -met.l-1-oxo-2- (£) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(3- (trifluoromethoxy) phenyl) methyl ] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-yl / O-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] - 2-methyl-1-oxo-2- ()) -propenyl] amino] -1,2-methylene-D-neo-inositol, ()) -0 - [(4- (1-piperidinyl) phenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-d-Deoxy-β-D-er / 'I / O-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl ] -2-methyl-1-oxo-2- (£) -propenyl] amino] -1,2-methylene-D-neo- inositol, (E) -0 - [(2-fluorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-β-D-erirro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2 - (E) -propenyl] amino] -1,2-O-methylene-D-peo-inositol, (Z) -0 - [(2-fluorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-ep'fro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl -1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (£) -0 - [(2-phenylthio) etl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-d-Deoxy-β-D-er / γ-r-hexofurans-5-uls-1-yl) oxy] -3-hydroxyphenyl] - 2-methyl-1-oxo-2- ()) -propenyl] amino] -1,2-methylene-D-neo-inositol, ()) -0 - [(benzofuran-5-yl) methyl] ox Ma; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / fra-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-met L-1-oxo-2- ()) -propenyl] amino] -1, 2-0-methylene-D-neo-inositol, (Z) -0 - [(benzofuran-5-yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-errra-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1 -oxo-2- (£) -propenyl] amino] -1,2-methylene-D-neo-inositol, (£) -0 - [(2-phenylimidin-5-yl) methyl ] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-erfrom-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1 -oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-isositol, (£) -0 - [(3-fluoro-4-methoxyphenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-eriyl-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1 -oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (£) -0 - [(3,4-dihydro-2H-1-benzopyran- 4-yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(5,6-dideoxy-5- (methyl (phenylmethyl) amino-a-L- ga / acfo-furans-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (£) -propen? l] am? no] -1, 2-O-methylene-D-neo-mositol, 5-Desox? -5 - [[3- [4 - [(5,6-d? Deox? -5-phen? Lam? No-aL- ga / acne-furans-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (£) -propen? l] am? no] -1, 2-0-metheno-D-neo-mositol, 5-Deox? -5 - [[3- [4 - [(2,6-d? Deox? -5-0 - [(3, 4-d? Chlorophen? L) met? L-ß-Dr /? Bo-furans-1 -? L) ox?] - 3-h? Drox? Phen? L] -2-met? L-1 -oxo -2- (£) -propen? L] am? No] -1, 2-0-methylene-D-neo-inositol, 5-Desox? -5 - [[3- [4 - [(2,6- d? desox? -β-D-epfro-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- ( £) -propen? L] am? No] -1, 2-0-methylene-D-peo-mositol, (£) -0 - [(furan-2-? L) met? L] ox? Ma , 5-Desox? -5 - [[3- [4 - [(ac? Odo-met? L -β-D-er / ioro-hept-5- (E) -enofuranuron-1-? L? Co ) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-O-methylene -D-peo-? Nos? Tol, ethyl ester, 5-Desox? -5- [t3- [4- [N- (furan-2-? L) met? L] - (5-met? L-β -D-eprro-hept-5- (£) -enofuranuron-1-? L-am? Da) ox?] - 3-h? Drox? Phen? L] -2-met? L-1-oxo-2 - (E) -propen? L] am? No] -1, 2-0-met? Leno-D- neo-? nos? tol, 5-Desox? -5 - [[3- [4 - [(2,6-d? desox? -β-D-er; fro-hexofuranos-5-ulos-1-? l ) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (£) -propen? l] am? no] -1, 2-0-methylene -D-peo-inositol, (£) -0- [3- (phen? L) prop? L] ox? Ma, 5-Desox? -5 - [[3- [4 - [(2,6-d ? deox? -β-D-epyro-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E ) -propen? l] am? no] -1, 2-0-methylene-D-neo-mositol, (Z) -0- (2-propen-1-? l) ox? ma, -Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / fro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl -1-oxo-2- (E) -propenyl] amino] -1,2-O-methylene-D-peo-inositol, (£) -0- (2-propen-1-yl) oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / rro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl -1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (£) -0 - [(4-methylphenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / 'f / -o-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-meth1l-1-oxo-2- (£) -propenyl] amino] -1,2-0-methylene-D-peo-inositol, (£) -0 - [(4- methoxyphenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-ß-D-er ('io-hexofurans-5-ulos-1-l) oxy] -3-h! Droxy phenyl] -2-methyl-1-oxo-2- ()) -propenyl] amino] -1,2-0-methylene-D-neo-inositol, ()) -0 - [(3- (trifluoromethyl) phenyl) ) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-5-0 - [(4-chlorophenyl) methyl] -β-D-rii) o-furans-1 -yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- ()) -propenyl] amino] -1,2-methylene-D-peo-inositol; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-erich-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl -1-oxo-2- (E) -propenyl] amino] -1,2-O-methylene-D-neo-inositol, (£) -0- [diphenymyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-5-phenylcarbamate-β-Dr / bo-furans-1-yl) oxy] -3-hydroxyphenyl] -2-methyl- 1-oxo-2- ()) -propenyl] amino] -1,2-O-methylene-D-peo-inositol; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-5 - [(3,4-dichlorophenyl) methyl] carbamate-β-Dr / oo-furans-1-yl) oxy] - 3-hydroxyphenyl] -2-methyl-1- ^ l. ^^ É ^ oxo-2- (E) -propenyl] amino] -1,2-O-methylene-D-r) eo-isosol; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / yl-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] - 2-methy1-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(3-chlorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-eripro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1 -oxo-2- (E) -propenyl] amino] -1, 2-0-methylene-D-peo -nositol, (Z) -0 - [(3-chloro-2-fluorophenyl) methyl ] oxime; 5-deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-eripro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1 -oxo-2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, (E) -0 - [(3-chloro-2-fluorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-d-deoxy-β-D-erpra-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(3-chloro-4-fluorophenyl) methyl ] oxima; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-eriphenyl-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl -1-oxo-2- (E) -propenyl] amino] -1, 2-0-methylene-D-neo-inositol, (E) -0 - [(3-chloro-4-fluorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-erirro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1 -oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(3-chloro-5-fluorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / ia-hexofurans-5-uls-1-yl) oxy] -3-hydroxyphenyl] -2-methyl -1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (E) -0 - [(3-chloro-5-fluorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-eryro-hexofurans-5-ulos-1- il) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(5-chloro-2-fluorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-3-D-eriform-hexofurans-5-yl-1-yl) oxy] 3-hydroxyphenyl] -2-methyl- 1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (E) -0 - [(5-chloro-2-fluorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-SD-er / fro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl- 1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, (ZJ-0 - [(3,5-difluorophenyl) methyl] oxime; 5-Deoxy- 5 - [[3- [4 - [(2,6-dideoxy- / 3-D-ep? Ro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl -1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, (E) -0 - [(3,5-difluorophenyl) methyl] oxime; Deoxy-5 - [[3- [4 - [(2,6-dideoxy-yS-D-eriyl-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1 -oxo-2- (E) -propenyl] amino] -1, 2-0-methylene-D-peo-inositol, (ZJ-O- ^ - chloro-S-fluorophenylJmethyl-oxime; 5-Deoxy-5- [ [3- [4 - [(2,6-d-deoxy- / β-D-erfro-hexofurans-5-ulos-1-l) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo- 2- (E) -propenyl] amino] -1,2-0-methylene-D-neo-isositol, (E) -0 - [(4-chloro-3-fluorophenyl) methyl] oxime; 5-Deoxy- 5 - [[3- [4 - [(2,6-dideoxy- / 3-D-erfro-hexofuranos-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo- 2- (E) -propenyl] amino] -1, 2-0-methylene-D-peo-inositol, (E -0 - [(4-chloro-1,3-benzodioxol-6-yl) ) methyl] oxime; 5-Deoxy-5- [t3- [4 - [(2,6-dideoxy- / 3-D-eriira-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1 -oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, Z) -0 - [(4-chloro-1,3-benzodioxol-6-yl) ) methyl] oxime; -Deoxy-5 - [[3- [4 - [(2,6-dideoxy-^ - D-eryro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl -1-oxo-2- (E) -propenyl] amino] -1,2-methylene-Dr) eo-inositol, (E) -0 - [(5-chloro-1,3-benzodioxole-6- il) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy- / 3-D-er / '-ro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2 -methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(5-chloro-1,3-benzodioxol- 6-yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-d'-deoxy- / 3-D-erirra-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (EJ-0 - [(4-chloro-1,3-benzodioxol-5- L) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy] - / 3-D-erich-hexofurans-5-ulos-1-yl) oxy] - 3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, (ZJ-0 - [(4-chloro -1, 3-benzodioxol-5-yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-JD-eripro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1, 2-0-methylene-D-peo-inositol, (EJ-0 - [( 2,3-dihydrobenzofuran-6-yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy - /? - D-er / yro-hexofurans-5 -ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (ZJ-0 - [(2,3-d.hydrobenzofuran-6-yl) metN] oxima; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy- / 3O-er / fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1, 2-0-methyl leno-D-neo-ino sitol, (? J-0 - [(2,3-dihydrobenzofuran-5-yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy - / ^ D-er / fro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- (E) -propenyl] amino] -1, 2-0-methylene-D-neo- inositol, (ZJ-0 - [(2,3-dihydrobenzofuran-5-yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy- / 9-D-eriyl) -hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1, 2-0-methylene-D- neo-inositol, (? j-0- (1,2,3,4-tetrahydronaphthalene-1-yl) oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy- / 3 -D-er; fro-hexofurans-5-uls-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1, 2-0- methylene-D-peo-isositol, (ZJ-0- [1, 2,3,4-tetrahydronaphthalene-1-yl) oxime; 5-Deoxy-5 - [[3- [4 - [(2,6- dideoxy- / 9-D-er / io-hexofurans-5-ulos-1-yl) oxy] -3-hydroxy-phenyl] -2-methyl-1-oxo-2- (E) -propenl] am No] -1, 2-0-methylene-D-peo-inositol, (E) -0- (7-chloro-1, 2,3,4-tetrahydronaphthalene-1-yl) oxame; 5-Deoxy -5 - [[3- [4 - [(2,6-dideoxy-y3-D-er / fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl -1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Zj-0- (7-chloro-1,2,3,4-tetrahydronaphthalene- 1-il) oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-JD-erií / -o-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl- 1-oxo-2- (E) -propenyl] amino] -1,2-0-methylene-D-neo-inositol, (? J-0- (7-fluoro-1, 2,3,4- tetrahydronaphthalene-1-yl) oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy- / 3-D-erfrom-hexofurans-5-yl-1-yl) oxy] -3 -hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D- / 7eo-inositol, (Zj-0- (7-fluoro-1, 2,3,4-tetrahydronaphthalene-1-yl) oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy- / SD-ep'ro-hexofurans-5-ulos-1- il) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, .E 0- ( 8-Chloro-3,4-dihydro-2 / - / - 1-benzopyran-4-yl) oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-JD- eríf ?? - hexofuranos-5-ulos-1- ^ ?) ox?] - 3-hydrox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1.2-0-met ? leno-D-neo-mositol, (Z) -0- (8-chloro-3,4-d? h? dro-2 / - / - 1-benzop? ran-4-? l) ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Deox? - JD-eprro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? fen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-met? leno-D-neo-mositol, (EJ-0) - (6-chloro-3,4-d? -hydro-2H-1-benzop? Ran-4-? L) ox? Ma, 5-Desox? -5 - [[3- [4 - [(2 , 6-d? Desox? - > 5-D-eprra-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? L-1- oxo-2- (E) -propen? l] am? no] -1, 2-0-methylene-D-neo-inositol, (ZJ-0- (6-chloro-3,4-d? h) ? d-2H-1-benzop? ran-4-? l) ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? - / 3-D- er / fro-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1 -oxo-2- (E) -propen? l] am? no] -1, 2-0-methylene-D-neo-inositol, (E) -0- (8-fluoro-3,4-d? h? dro-2H-1-benzop? ran- 4-? L) ox? Ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Deox? -3-D-epfra-hexofurans-5-ulos-1-? ) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-methylene -D-neo-inositol, ('Z) -0- (8-fluoro-3,4-d? H? Dro-2H-1-benzop? Ran-4-? L ) ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? - /? - D-epfro-hexofuranos-5-ulos-1-? l) ox? ] -3-h? Drox? Phen? L] -2-met? L-1-oxo-2- (E) -propen? L] am? No] -1, 2-0-methylene-D- neo-inositol, (? J-0- (6-fluoro-3,4-d? h? dro-2H-1-benzop? ran-4-? l) ox? ma, 5-Desox? -5- [ [3- [4 - [(2,6-d? Desox? -, r9-D-epfro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen?] - 2-met? L-1-oxo-2- (E) -propen? L] am? No] -1, 2-0-met? Leno-D-neo-inositol, (ZJ-0- (6-fluoro -3,4-d? H? Dro-2H-1-benzop? Ran-4-? L) ox? Ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deoxy? - /? - D-er / io-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? L] am? No] -1,2-0-methylene-D-neo-inositol, (? J-0 - [(qu? Nol? N-2-? L) met? l] ox? ma, -Deoxy-5 - [[3- [4 - [(2,6-dideoxy- / 3-D-erfrom-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (ZJ-O-Kquinolin ^ -iOmethyl-oxime; 5-Deoxy-5 - [[3 - [4 - [(2,6-dideoxy- / 9-D-errro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- ( E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (? J-0 - [(quinolin-3-yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy- / 3-D-er / io-hexofurans-5-uls-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-7eo-inositol, (Z ^ O - [(quinolin-3-yl) methy] oxime; 5-Deoxy-5- [[3- [4 - [(2,6-d-deoxy- / ^ D-er / f / O-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- (E) -propenyl] amino] -1,2-O-methylene-D-peo-inositol, (? J-0- [4- (phenylmethyl) phenylmethyl] oxime; -Dioxy-5 - [[3- [4 - [(2,6-dideoxy-; r9-D-err;? Ro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] - 2-methyl-1-oxo-2- (E) -propenyl] amino] -1,2-O-methylene-D-peo -nositol, (Z) -0- [4- (phenylmethyl) phenylmethyl] oxime; 5-Deoxy 5 - [[3- [4 - [(2,6-dideoxy-jff-D-eriira-hexofurans-5-yl-1-yl) oxy] -3-hydroxy-phenyl] -2-methyl-1- oxo-2- (E) -propenyl] amino] -1,2-O-methylene-D-neo-inositol, (Ex-0- [4- (phenoxy) phenylmethyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy- / 3-D-eripro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2 -methyl-1-oxo-2- (E) -propenyl] amino] -1, 2-0-methylene-D-neo-inositol, () -0- [4- (phenoxy) phenylmethyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-JD-er / fTO-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl- 1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo- inositol, (ZJ-0 - [(4-phenylthiaz-2-yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy- / 3-D-eriyl-hexofurans -5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1, 2-0-methylene-D -neo-inositol, (EJ-0 - [(4-phenylthiaz-2-yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy- / 3-D- er / ith-hexofurans-5-uls-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1, 2-0-methylene -D-peo-inositol, (Z) -0- [1- (2,4-difluorophenyl) propyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-di-deoxy)] / 3-D-ep? Ro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1, 2- 0-methylene-D-neo-inositol, (? -0- [1- (2,4-difluorophenyl) propyl] oxime; 5-deoxy-5 - [[3- [4 - [(2,6-dideoxy- / 3-D-eripro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1, 2-0- methylene-D-neo-inositol, (Zj-0- [1- (3,4-drfluorophenyl) etl] oxy; 5-Deoxy-5 - [[3- [4 - [(2,6- dideoxy- / 3-D-erithio-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1, 2-O-methylene- D-peo-inositol, (E) -0- [1- (3,4-difluorophenyl) ethyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-9-D-eriyl-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1 -oxo-2- (E) -propenyl] amino] -1,2-methylene-D-rneo-inositol, (ZJ-0- [1- (2,4-difluorophenyl) ethyl] oxime; 5-Deoxy -5 - [[3- [4 - [(2,6-dideoxy-SD-eripro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, fE -0- [1- (2,4-difluorophenyl) ethyl] oxime; 5-Deoxy-5 - [[3 - [4 - [(2,6-dideoxy- / SD-erifro-hexofuranos-5-ulos-1- il) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, (Z) -0- [ 1- (3,5-difluorophenol) etl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-JD-eriyl-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo -2- (E) -propenyl] amino] -1, 2-0-methylene-D-peo-inositol, (E-0- [1- (3,5-difluorophenyl) ethyl] oxime; 5-Deoxy -5 - [[3- [4 - [(2,6-dideoxy-> 3-D-er / fro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl- 1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z 0- [1- (3-chloro-2,6-difluorophenyl) ethyl] ox 5-Deoxy-5 - [[3- [4 - [(2,6-d-deoxy- / 3-D-eripro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (? -0- [1- (3-chloro-2 , 6-difluorophenyl) ethyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-y0-D-er / fro-hexofurans-5-ulos-1-yl) ox ] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (EJ-0 - [(3- chloro-2,6-d-fluoro-phenyl) -methyl] oxime; 5-deoxy-5 - [[3- [4 - [(2,6-dideoxy- / 3-D-erirro-hexofurans-5- ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol , (ZJ-0 - [(3-chloro-2,6-difluorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy- / 3-D-errra-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl- 1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (EJ-0 - [(2,4-difluorophenyl) methyl] oxime; Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-eriira-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo -2- (E) -propenyl] amino] -1, 2-0-methylene-D-? 7eo-inositol, fZJ-O- ^^ - difluoropheni methyljoxime; ^ j ^ -Deoxy-5 - [[3- [4 - [(2,6-d-deoxy- / 3-D-arai) / 'non-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl ] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(3,5-dichlorophenyl)] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-deoxy-3-D-arab / 'non-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- (E) -propenyl] amino] -1,2-0-methylene-D-peo-inositol, (? J-0 - [(3,5-dichlorophenyl)] oxime; 5-Deoxy-5 - [[3- [4 - [(6-deoxy-8-D-arab non-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl- 1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, f £J-0 - [(3-chlorophenyl)] oxime; 5-Deoxy-5- [[3- [4 - [(6-deoxy- / 3-D-araD / po-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo- 2- (£) -propenyl] amino] -1,2-methylene-D-neo-inositol, (EJ-0 - [(3-fluorophenyl)] oxime; 5-Deoxy-5- [4 - [( 2,6-dideoxy- / 3-D-erií / "o-hexofuranos-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1, 2-0-methylene-D-neo-inositol, (Z,) - 0 - [(3,5-dichlorophenyl) methyl] oxime; 5-Deoxy-5- [4- [ (2,6-dideoxy- / 3-D-eriyl-hexofurans-5-ulos-1-IJoxiJ-S-hydroxyphenylJ ^ -methyl-l-oxo ^ -CEJ-propeniljaminoj-l ^ -O-methylene-D- neo-inositol, (£) -0 - [(3,5-dichlorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy- / 3-D-er / fro- hexofurans-5-uls-1-yl) oxy] -3-hydroxy-phenyl] -2-methyl-1-oxo-2- ()) -propenyl] amino] -1,2-methylene-D-neo -inositol, (Z) -0- (phenyl) oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy- / ff-D-epyro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1- oxo-2- (E) -propenyl] amino] -1, 2-0-methylene-D-neo- Nositol, (? -O- (phenyl) oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy- / 3-D-eriyl-hexofurans-5-yl-1-yl) oxy] - 3-hydroxyphenyl] -2-methyl-1-oxo-2- ()) -propenyl] amino] -1, 2-0-methylene-D-peo-ositol, (Z) -0- (3- chloro-4-fluorophenyl) oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-? -D-errro-hexofurans-5-yl-1-yl) oxy] -3-hydroxy-phenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (E) -0- (3-chloro-4-fluorophenyl) oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-β-D-eriyl-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo -2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(2,1, 3-benzoxadiazol-5-yl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy- / SD-eriform-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo- 2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (E) -0 - [(2,1, 3-benzoxadiazol-5-yl) methyl] oxime; -Dioxy-5- [4 - [(2,6-dideoxy- / 3-D-eriyl-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo -2- (E) -propenyl] amino] -1, 2-0-methylene-D-peo-inositol, (E) -0 - [(2,3,5,6-te trafluorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-? -D-erifra-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo- 2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, (Z) -0 - [(2,3,5,9-tetrafluorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-y9-D-epyro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2 - (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (E) -0 - [(2,3-difluorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-y5-D-eriyl-hexofurans-5-ulos-1- il) oxy] -3-hydroxyphenyl] -2-methylene-1-oxo-2- (E) -propenyl] amino] -1, 2-0-methylene-D-petrol inositol, (Z) -0 - [(2,3-d if luorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy- / 3-D-erfra-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methylene-1 -oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (E) -0 - [(4-phenyl-furan-3-yl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-d-deoxy- / 3-D-epyro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1- oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(4-phenyl-furan-3-yl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-^ -D-er / io-hexofurans-5-uls-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1- oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (E) -0 - [(4-phenyl-furan-2-yl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-9-D-eriyl-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo- 2- (E) -propenyl] amino] -1, 2-0-methylene-D-peo-inositol, (Z) -0 - [(4-phenyl-furan-2-yl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy- / 3-D-eriyl-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1- oxo-2- (E) -propenyl] amino] -1, 2-0-methylene-D-neo-inositol, (E) -0 - [(2,3-difluoro-6-methoxyphenyl) methyl ] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy- / D-eriphro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1- oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(2,3-difluoro-6-methoxyphenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy- / 3-D-erirro-hexofurans-5-yl-1-yl) oxyl] -3-hydroxyphenyl] -2-methyl-1-oxo- 2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, (E) -0 - [(3-chloro-thiophen-2-yl) methyl] oxime; -Deox? -5- [4 - [(2,6-d? Desox? - / ^ D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? fen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-meth? leno-D-peo-inositol, (Z) - 0 - [(3-chloro-t? Ofen-2-? L) met? L] ox? Ma, 5-Desox? -5- [4 - [(2,6-d? Desox? - ^ D-epfro -hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1 -oxo-2- (E) -propen? l] am? no ] -1, 2-0-methylene-D-neo-inositol, (E) -0 - [(5-chloro-t? Ofen-2? L) met? L] ox? Ma, 5-Deox ? -5- [4 - [(2,6-d? Desox? - / 3-D-eprra-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-methyl-1-oxo-2- (E) -propen? L] am? No] -1, 2-0-methylene-D-neo-mositol, (Z) -0 - [( 5-chloro-t-ofen-2-yl) methyl] ox, and the pharmaceutically acceptable salts, pro-drugs and solvates of said compounds In a more specific embodiment, the present invention includes the following compounds: Deox? -5- [4 - [(2,6-d? Desox? - / 3-D-er / io-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Fen ? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-methylene-D-neo-inositol, (Z) -0 - [(1, 3-benzod? Oxol-5? L) met? L] ox? Ma, 5-Desox? -5- [4 - [(2,6-d? Deox? - ^ D-epfr o-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-methylene-D-peo-inositol, (E) -0 - [(3-chlorophen? l)) met? l] ox? ma, 5-Desox? -5- [ 4 - [(2,6-d? Desox? - / 3-D-eprro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-methylene-D-, f) eo-inositol, (Z) -0 - [(3- chlorofen? l) met? l] ox? ma, 5-Desox? -5- [4 - [(2,6-d? desox? - SD-er / fro-hexofurans-5-ulos-1- il) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (E ) -0 - [(3-fluorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-β-D-er / io-hexofurans-5-uls-1-yl) oxy] -3-hydroxyphenyl] -2-methylene-1 -oxo-2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, (Z) -0 - [(3-fluorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy- / 3-D-eriira-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1- oxo-2- (E) -propenyl] amino] -1,2-O-methylene-D-neo-inositol, (Z) -0 - [(benzofuran-2-yl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy- / 3-D-eripro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl- 1 -oxo-2- (E) -propenyl] amino] -1,2-O-methylene-D-neo-inositol, (Z) -0 - [(3,5-dichlorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-9-D-erirra-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2 - (E) -propenyl] amino] -1,2-O-methylene-D-ioeo-inositol, (Z) -0 - [(3,5-difluorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy- / 3-D-eriyl-hexofurans-5-yl-1-yl) oxy] -3-hydroxy-phenyl] -2-methyl-1 -oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (E) -0 - [(3,5-difluorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-d-deoxy-yβ-D-erfrom-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo -2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, (Z) -0 - [(3-chloro-2-fluorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-jS-D-eripro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2 - (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (E) -0 - [(3-chloro-fluorophenyl) methyl] oxime;5-Deoxy-5- [4 - [(2,6-dideoxy-> 5-D-eripro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo -2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, (Z) -0 - [(3-chloro-4-fluorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-SD-er / f ??-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo -2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (E) -0 - [(3-chloro-4-fluorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy- / 3-D-ef7fro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo- 2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(4-chloro-3-fluorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy- / 3-D-eripro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo -2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, (E) -0 - [(4-chloro-3-fluorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-3-D-er / fro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1 -oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(4-fluorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-5-D-errro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2 - (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (E) -0 - [(4-fluorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy- / SD-errra-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methylene-1-oxo- 2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(4-chlorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy- / JD-er / ia-hexofurans-5-uls-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo- 2- (E) -propenyl] amino] -1,2-methylene-D-neo- inositol, (E) -0 - [(4-chlorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-d-deoxy- / 3-D-er / fro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl- 1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(4-phenyl-furan-2-yl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-? -D-eripro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo -2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(3-chloro-5-fluorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy- / 3-D-epyo-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo- 2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, (E) -0 - [(3,4-difluorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy- / SD-eripro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo- 2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(3,4-difluorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy- / 3-D-eriira-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo- 2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, (E) -0 - [(2,3-difluorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy- / 5-D-erirro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo- 2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(2,3,5,6-tetrafluorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-> SD-ara /) / non-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2 -methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0- (3-chloro-4-fluorophenyl) oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-? -D-araí) non-hexofuranos-5-ulos- 1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, (E) -0- (3-chloro-4-fluorophenyl) oxime; 5-Deoxy-5 - [[3- [4 - [(6-deoxy- / 3-D-araD / po-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl -1-oxo-2- (E) -propenyl] amino] -1,2-O-methylene-D-peo-inositol, (Z) -0 - [(5-chloro-thiophen-2-yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-75-D-er / fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- (E) -propenyl] amino] -1, 2-0-methylene-D-neo-inositol, (E) -0 - [(3-chloro-2,6 -difluorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy- / 3-D-eripro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl- 1 -oxo-2- (E) -propenyl] amino] -1,2-O-methylene-D-neo-inositol, (Z) -0 - [(3-chloro-2,6-difluorophenyl) methyl ] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-> 9-D-erifra-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl -1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, (E) -0 - [(2,4-difluorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-? -D-erythra-hexofurans-5-yl-1-l) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo- 2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, (Z) -0 - [(2,4-difluorophenyl) methyl] oxime; and the pharmaceutically acceptable salts, prodrugs and solvates of said compounds. The invention also relates to a pharmaceutical composition for the treatment of a disorder selected from a bacterial infection, a protozoal infection and disorders related to bacterial infections or protozoal infections, in a mammal, fish or bird, comprising a therapeutically effective amount of a compound of formula 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. The invention also relates to a method for the treatment of a disorder selected from a bacterial infection, a protozoap infection and disorders. related to bacterial infections or protozoa infections, in a mammal, fish or bird, comprising administering to said mammal, fish or bird a therapeutically effective amount of a compound of formula 1 or a pharmaceutically acceptable salt thereof. The term "treating", according to used herein, unless otherwise indicated, means reversing, alleviating, inhibiting the progress or preventing the disorder or condition to which that term applies, or one or more symptoms of such disorder or condition. The term 'treatment' , as used in this document, refers to the fact of treating, as just defined "treat" As used herein, unless otherwise indicated, the terms or phrases "bacterial infection (infections)", "infection (infections) protozoapa (s)" and "disorders related to bacterial infections or protozoa infections. as "include the following pneumonia, otitis media, sinusitis, bronchitis, tonsillitis and mastoiditis related to infection by Streptococcus pneumomae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, Enterococcus faecahs, E faecium, E cassyverus, S epidermidis, S haemolyticus or peptostreptococcus spp, pharyngitis, rheumatic fever and glomerulonephritis related to infection by Streptococcus pyogenes, streptococci of groups C and G, Corynebacterium diphtheriae or Actinobacillus haemolyticum; respiratory tract infections related to infection by Mycoplasma pneumoniae, Legionella pneumophila, Streptococcus pneumonia, Haemophilus influenzae or Chlamydia pneumoniae; blood and tissue infections, including endocarditis and osteomyelitis, caused by S. aureus, S. haemolyticus, E. faecalls, E. faecium, E. durans, including strains resistant to known antibacterials such as, but not limited to, beta-lactams, vancomycin, aminoglycosides, quinolones, chloramphenicol, tetracyclines and macrolides; uncomplicated infections of skin and soft tissues and abscesses, and puerperal fever related to infection by Staphylococcus aureus, coagulase-negative staphylococci (ie, S. epidermidis, S. hemolyticus, etc.), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus agalactiae CF groups (small colony streptococci), viridans streptococci, Corynebacterium minutissimum, Clostridium spp., or Bartonella henselae; acute infections without complications of the urinary tract related to infection by Staphylococcus aureus, coagulase-negative Staphylococcus species, or Enterococcus spp .; urethritis and cervicitis; sexually transmitted diseases related to infection by Chlamydia trachomatis, Haemophilus ducreyi, Treponema pallidum, Ureaplasma urealyticum or Neiserria gonorrheae; toxin diseases related to S. aureus infection (food poisoning and toxic shock syndrome), or Streptococci of groups A, B and C; ulcers related to Helicobacter pylori infection; systemic febrile syndromes related to Borrelia recurrentis infection; Lyme disease related to Borrelia burgdorferi infection; conjunctivitis, keratitis and dacrocystitis related to infection by Chlamydia trachomatis, Neisseria gonorrhoeae, S. aureus, S. pneumoniae, S. pyogenes, H. influenzae or Listeria spp .; disseminated disease of Mycobacterium avium complex (MAC) related to infection by Mycobacterium avium or Mycobacterium intracellulare; infections caused by Mycobacterium tuberculosis, M. leprae, M. paratuberculosis, M. kansasii or M. chelonei; gastroenteritis related to Campylobacter jejuni infection; intestinal protozoa related to infection by Cryptosporidium spp .; odontogenic infection related to viridans streptococcal infection; persistent cough related to Bordetella pertussis infection; Gas gangrene related to infection by Clostridium perfringens or Bacteroides spp .; and atherosclerosis or cardiovascular disease related to infection by Helicobacter pylori or Chlamydia pneumoniae. Bacterial infections and protozoal infections, and disorders related to such infections, which can be treated or prevented in animals, include the following: bovine respiratory disease related to infection by P. haemolytica, P. multocida, Mycoplasma bovis or Bordetella spp.; enteric disease of cattle related to infection by protozoa (ie, coccidia, cryptosporidia, etc.); mastitis Dairy cows related to infection by S. aureus, Strep. uberis, Streptococcus agalactiae, Streptococcus dysgalactiae, Corynebacterium or Enterococcus spp .; respiratory disease of pigs related to infection by A. pleuro, P. multocida or Mycoplasma spp; enteric disease of pigs related to infection by Lawsonla intracellularis, Salmonella or Serpulina hyodysinteriae; Hoof necrosis of cattle related to infection by Fusobacterium spp .; hairy warts of cattle related to infection by Fusobacterium necrophorum or Bacteroides nodosus; Conjunctivitis of bovine cattle related to infection by Moraxella bovis; premature abortion of cattle related to infection by protozoa (ie, neosporium); infections in the skin and soft tissues in dogs and cats, related to infection by S. epidermidis, S. intermedius, coagulase neg staphylococci. or P. multocida; and dental or oral infections in dogs and cats related to infection by Alcaligenes spp., Bacteroides spp., Clostridium spp., Enterobacter spp., Eubacterium, Peptostreptococcus, Porphyromonas or Prevotella. Other bacterial and protozoal infections, and disorders related to such infections, which can be treated or prevented according to the method of the present invention are mentioned in J.P. Sanford et al., "The Sanford Guide To Antimicrobial Therapy", 26th Edition, (Antimicrobial Therapy, Inc., 1996). The term "halo", as used herein, unless otherwise indicated, includes fluorine, chlorine, bromine or iodine. The halo groups - "* - *» "- J¿a- ' Preferred are fluorine, chlorine and bromine. The term "alkyl", as used herein, unless otherwise indicated, includes saturated monovalent hydrocarbon radicals having straight or branched radicals. Said alkyl group may include one or two double or triple bonds. It is understood that for said alkyl group to include a double or triple carbon-carbon bond, at least two carbon atoms in said alkyl group are required. The term "aryl", as used herein, unless otherwise indicated, includes an organic radical derived from an aromatic hydrocarbon by the removal of a hydrogen, such as phenyl or naphthyl.

The term "4- to 10-membered heterocycle", as used herein, unless otherwise indicated, includes aromatic and non-aromatic heterocyclic groups containing one or more heteroatoms, each being selected from O, S, and N, where each heterocyclic group has 4 to 10 atoms in its ring system. The non-aromatic heterocyclic groups include groups having only 4 atoms in a ring system, but the aromatic heterocyclic groups must have at least 5 atoms in their ring system. Heterocyclic groups include ring systems fused with benzene and ring systems substituted with one or more oxo radicals. An example of a 4-membered heterocyclic group is azetidinyl (azetidine derivative). An example of a 5-membered heterocyclic group is thiazolyl and an example of a 10-membered heterocyclic group is quinolinyl. The examples of the groups non-aromatic heterocyclics are pyrrohdmyl, tetrahydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, tetrahydrothiopyranyl, pipepdmo, morpholmo, thiomorphono, thioxanyl, piperazinyl, azetidinyl, oxetanyl, thietanyl, homopipepdinyl, oxepanyl, tiepanyl, oxazepinyl, diazepinyl, thiazepinyl, 1, 2,3,6- Tetrah? drop? r? d? n? lo, 2-pyrrolone, 3-pyrrolidone, indolmyl, 2H-phenyl, 4H-pyranyl, dioxanil, 1, 3-oxolanyl, pyrazolinyl, dithianyl, dithiolanyl, dihydropyranyl, dihydrothienyl, dihydrofuranyl, pyrazole, imidazo, nyl, imidazolidinyl, 3-azab-c-clo [3-O-hexananyl, 3-azab-c-clo] [4] Ojheptanil, 3H-indolyl and quinolizinyl The examples of aromatic heterocyclic groups are pipdinil, imidazolyl, pi-midinyl, pyrazolyl, triazolyl, pyrazolyl, tetrazolyl, fupol, thienyl, isoxazolyl, thiazole, oxazole, isothiazolyl, pyrrolyl, quinolinyl, isoquinolyl, indole, benzoimidazolyl, benzofuranyl, cinnolinyl, indazolyl, mdolizinyl, phthalazinyl, pipdazinyl, tpazinyl, isomethyl, ptepdinyl, pupnil, oxadiazole, thiadiazolyl, furazanyl, benzofurazanyl, benzothiophenyl, benzothiazolyl, benzoxazole, quinazolinyl, quinoxahnil, naphthipdinyl and furopipdinyl The above groups, as derivatives of the compounds listed above, can be attached to C or joined To N when possible For example, a group derived from pyrrole can be pyrrolid-1α (N-linked) or pyrrol-3α (attached to C) The phrase "pharmaceutically acceptable salts", according to is used herein, unless otherwise indicated, includes salts of acidic or basic groups that may be present in the compounds of the present invention. The compounds of the present invention which are from Basic nature are able to form a wide variety of salts with various inorganic and organic acids. Acids that can be used to prepare pharmaceutically acceptable acid addition salts of such basic compounds are those that form non-toxic acid addition salts, ie, salts that contain pharmacologically acceptable anions, such as the hydrochloride, hydrobromide, hydroiodide salts , nitrate, sulfate, bisulfate, phosphate, acid phosphate, isonicotinate, acetate, lactate, salicylate, citrate, acid citrate, tartrate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate, glucuronate, saccharate, formate, benzoate , glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate and pamoate [i.e., 1,1 '-methylene-bis- (2-hydroxy-3-naphthoate)]. The compounds of the present invention that include a basic radical, such as an amino group, can form pharmaceutically acceptable salts with various amino acids, in addition to the acids mentioned above. The compounds of the present invention which are acidic in nature are capable of forming base salts with various pharmacologically acceptable cations. Examples of such salts include the alkali metal or alkaline earth metal salts, particularly, the calcium, magnesium, sodium and potassium salts, of the compounds of the present invention. The compounds of the present invention have asymmetric centers and, therefore, exist in different enantiomeric forms and diastereomers. This invention relates to the use of all optical isomers and stereoisomers of the compounds of the present invention and mixtures thereof, and to all pharmaceutical compositions and methods of treatment which may employ or contain them. In this aspect, the invention includes the two configurations E and Z of the group -OR3 connected to nitrogen, where R1 and R2 are taken together as an oxime radical of the formula = N-OR3. The compounds of formula 1 can also exist as tautomers. This invention relates to the use of all such tautomers and mixtures thereof. The present invention also includes isotopically-labeled compounds and pharmaceutically acceptable salts thereof, which are identical to those represented in formula 1, except for the fact that one or more atoms have been replaced by an atom having an atomic mass or a mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes that can be incorporated into the compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine and chlorine, such as 2H, 3H, 13C, 14C, 15N, 180, 170, 35S, 18F and 36CI, respectively. The compounds of the present invention, prodrugs thereof, and pharmaceutically acceptable salts of said compounds or of said prodrugs which contain the aforementioned isotopes and / or other isotopes of other atoms, are within the scope of the present invention. Certain isotopically-labeled compounds of the present invention, by example those in which radioactive isotopes such as 3 H and 1 C are incorporated, are useful in drug and / or substrate tissue distribution assays. The tritiated isotopes, i.e., 3H and carbon-14, i.e., 14C, are particularly preferred for their easy preparation and detectability. In addition, replacement with heavier isotopes, such as deuterium, ie, 2H, can produce certain therapeutic advantages resulting from increased metabolic stability, for example, a longer half-life in vivo or the need for a lower dose and, therefore, Therefore, it may be preferred in some circumstances. The isotopically-labeled compounds of formula 1 of this invention and the prodrugs thereof can generally be prepared by performing the procedures described in the schemes and / or in the examples and preparations indicated below., by substitution of an isotopically non-labeled reagent by an isotopically-labeled reagent readily available. This invention also relates to pharmaceutical compositions and methods of treating bacterial infections, by administering prodrugs of the compounds of formula 1. Compounds of formula 1 having free amino, amido, hydroxy or carboxylic groups can be converted to prodrugs . Prodrugs include compounds in which an amino acid residue, or a polypeptide chain of two or more (eg, two, three or four) amino acid residues, is covalently linked via an amide or ester bond to the free amino, hydroxy or carboxylic group of the compounds of formula 1. The Amino acid residues include, but are not limited to, the 20 naturally occurring amino acids commonly designated by three-letter symbols, and also include 4-hydroxyproline, hydroxylysine, demosin, isodemosin, 3-methylhistidine, norvaline, beta-alanine, gamma-acid. aminobutyric acid, citrulline homocysteine, homoserin, omitin and methionine sulfone. Other types of prod are also included. For example, free carboxyl groups can be transformed into alkyl amides or esters. The amide and ester radicals can incorporate groups including, but not limited to, amine and carboxylic acid functionalities. The free hydroxy groups can be transformed, using groups including, but not limited to, hemisuccinates, phosphate esters, dimethylaminoacetates and phosphoryloxymethyloxycarbonyls, as indicated in D. Fleisher, R. Bong, BH Stewart, Advanced DDelivery Reviews (1996) 19, 115. Also included are the carbamate prod of the hydroxy and amino groups, such as the carbonate prod and sulfate esters of hydroxy groups. Also included is the transformation of hydroxy groups such as (acyloxy) methyl and (acyloxy) ethyl ethers in which the acyl group may be an alkyl ester, optionally substituted with groups including, but not limited to, ether, amine and carboxylic acid functionalities, or wherein the acyl group is an amino acid ester as described above. Prod of this type are described in R.P. Robinson et al, J. Medicinal Chemistry (1996) 39, 10 The selective introduction of prodside chains can be carried out on the hydroxy groups of the hygromycin A core molecule. For example, the exhaustive silylation of the six hydroxy groups of hygromycin A can be carried out, for example, with tert-butyl chloride dimethylsilyl. Subjection of the hexasilyl derivative to the action of potassium carbonate in methanol at room temperature selectively removes the phenolic silyl group, allowing further selective modification in that position.

DETAILED DESCRIPTION OF THE INVENTION The preparation of the compounds of the present invention is illustrated in the following schemes.

SCHEME 1 SCHEME 1 CONTINUED SCHEME 2 The compounds of the invention preparation are easily prepared. Referring to scheme 1 illustrated above, the starting compound of formula 2 is hygromycin A which can be prepared according to procedures known to those skilled in the art, such as by fermentation of Streptomyces hygroscopicus NRRL 2388. methyl ketone on the furanose sugar of the hygromycin A molecule may exist in the S configuration (hygromycin A) or in the R (ep / '- hygromycin) configuration on the furanose sugar. When published protocols are used as a model for the fermentation and recovery of hygromycin A (U.S. Patent 3,100,176; Antibiotic Chemotherapy (1953) 3: 1268-1278, 1279-1282), the hygromycin product is a mix approximately 3: 1 hygromycin A (the epimer 4"- (S)), with the methyl ketone oriented in beta position in the furanose sugar, as shown, and ep / -higromycin. It is known in the literature (Journal Antibiotics 33 (7), 695-704, 1980) that pure hygromycin A will become epigromycin in alkaline solutions. By careful control of the pH below 6.9 during fermentation, and pH, temperature and exposure of the solvent during the purification process, the final product recovered can be improved at a ratio of 14: 1 hygromycin A: ep / - hygromycin Using this material, substantially individual isomers can be prepared from the 4"- (S) hygromycin for use as templates for further synthetic modification." Hygromycin A enriched in the 4"- (S) epimer is produced by fermentation of Streptomyces hygroscopicus NRRL 2388, or mutants of the same, in a medium with controlled pH less than 6.9, preferably from 6.7 to 6.7, throughout the entire process. The medium contains assimilable sources of carbon, nitrogen and trace elements, as is known to those skilled in the art. The fermentation is carried out at a temperature of about 25-35 ° C, preferably at about 29 ° C. The fermentation is controlled by chromatography, for example, high pressure liquid chromatography. Incubation is continued until the yield of the compound reaches a maximum, generally over a period of about 3 to 10 days, preferably 4 to 6 days. The formation of ep / -higromycin is minimized during the fermentation process by the use of an aqueous buffer (instead of unbuffered water) and by controlling the pH of the active currents up to about 6.0. The formation of ep / -higromycin is also minimized by minimizing the time during which the recovered material is subjected to high temperatures. Thus, when it is necessary to reduce the solvent concentrations, it is preferred to dilute the active streams with the aqueous buffer and avoid the use of rotary evaporation at elevated temperatures. Also, as a means to avoid high temperatures, a resin column can be used to concentrate the active solution before the final purification step, in order to reduce the volume of solution that requires boiling. The final purification step in the process is the concentration of the active pieces to solids using vacuum and a bath at a temperature of about 35-50 ° C. The period in which the solution is subjected to high temperatures can be minimized by boiling in stages. The compounds of formula 1 can be prepared from the compound of formula 4. In this process, the compound of formula 3 (wherein X is a protecting group as described below), is prepared by protecting all hydroxy groups of hygromycin A, with the exception of hydroxy on carbon 2"(C-2"), as their silyl ethers, using an appropriate reagent such as triethylsilyl chloride (TESCI), chloride of trimethylsilyl (TMSCI) or rerc-butyldimethylsilyl chloride (TBDMST). The preferred procedure is 10 eq. of TBDMSCI and imidazole in N, N-dimethylformamide (DMF) at a temperature of 25-40 ° C for 12-36 hours. The compound of formula 4 is then prepared by removing the hydroxy group using the procedure of Barton et al, J. Chem. Soc. Perkln Trans. I 1975, 1574. The preferred procedure in this case is the procedure of Génu-Dellac et al., Carbohydrate Res. 1991, 216, 249. Compounds of formula 1 wherein R 1 and R 2 are taken together to form an oxime of the formula = NOR3, wherein R3 is as defined above, can be prepared by treating the compound of formula 4 with a hydroxylamine of the formula R3ONH2, using the free base or hydroxylamine salt, preferably the free base of hydroxylamine . The reaction is carried out in an inert solvent, such as methanol, with the addition of a base, such as K2C03, if the salt is used, for example the HCl salt of the hydroxylamine, at a temperature ranging between about 0 ° C and 65 ° C, preferably between 0 ° C and 25 ° C. The protecting groups are then removed with acid, such as acetic acid, hydrogen fluoride, hydrogen fluoride-pyridine complex or a fluoride source, such as tetrabutylammonium fluoride (TBAF). The hydroxylamine of formula R3ONH2 can be prepared using one or more procedures described in Bioconjugate Chemistry (1990), 2, 96; Journal of Pharmaceutical Science (1969) 58 138; and Chem. Pharm. Bull (1967) 15, 345. Compounds of formula 1 in which R1 and R2 are taken together to form the ketone of formula = 0, can be prepared by treating the compound of formula 4 with acid, such as acetic acid, hydrogen, hydrogen fluoride-pyridine complex or a fluoride source, such as tetrabutylammonium fluoride (TBAF), preferably hydrogen fluoride-pyridine complex.

The compounds of formula 1 wherein R1 is H and R2 is -NR3R4, where R3 and R4 are as defined above, can be synthesized by reductive amination at the C-5"site of the ketone of the compound of formula 4. combination of R 4 NH 2 and the compound of formula 4 in an inert solvent and treatment with a reducing agent such as NaBH 4, NaBH (OAc) 3 (Ac is acetyl) or NaCNBH provides the product with R3 = H. To convert R3 to a group other than H, a second reductive amination may be carried out with an appropriate aldehyde (or ketone) of the formula R3C (0) H. This can be continued by an Eschweiler-Clark reaction to introduce a methyl group as the R3 substituent. To produce an amide group, such as in which R1 is H and R2 is -NR4C (0) R3, an amine of the formula -NHR4 can be introduced as described above and then an acyl radical of the formula -C can be introduced (0) R3 by treating the intermediate with an activated form of carboxylic acid, such as R3COCI or R3C (0) OC (0) R3, or by using an agent of amide coupling such as 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ), 1 '1 -carbonyl-diimidazole (CDI) or a carbodiimide such as 1,3-dicyclohexylcarbodiimide (DCC). For all the above processes, the protecting groups are removed with acid, such as acetic acid, hydrogen fluoride, hydrogen fluoride-pyridine complex, or a fluoride source, such as TBAF, as the final step. The compounds of formula 1 wherein R1 is H and R2 is -NR4C (0) R3, where R4 is H and R3 is as defined above, can be prepared by using the primary amine obtained by reductive amination of the compound of Formula 4 with an ammonium equivalent, for example, by the use of ammonium acetate and sodium cyanoborohydride or sodium triacetoxyborohydride. Alternatively, this primary amine can be prepared by means of the corresponding azide: (1) the ketone C-5"of the compound of formula 4 is reduced, for example with sodium borohydride, 2) the resulting alcohol is transformed into the mesylate, example, by the action of methanesulfonyl chloride and triethylamine, 3) the mesylate is displaced by azide, for example using sodium azide in DMF, and 4) the azide is reduced to the primary amine using, for example, triphenylphosphine followed by aqueous hydrolysis The reaction of the primary amine with an activated form of R3C (0) OH, for example, R3C (0) CI or R3C (0) OC (0) R3, provides the corresponding amide. Alternatively, amide coupling reagents can be used with R3C (0) OH, such as 1- (3-dimethylaminopropyl) -3- ethyl carbodiimide (EDC), diethyl phosphoryl cyanide (DEPC), DCC, CDI or EEDQ. Finally, all protecting groups are removed using an acid, such as acetic acid, hydrogen fluoride, hydrogen fluoride-pyridine complex or fluoride ion, such as TBAF. To incorporate a R4 group other than H, the amide mentioned above can be alkylated after protecting any of the free hydroxyl groups, for example, as silyl ethers. The alkylation can be carried out with a base and an alkylating agent, such as sodium hydride and an appropriate bromide of the formula R4-Br. The deprotection of the hydroxyl groups is then carried out with an acid, such as acetic acid, hydrogen fluoride, hydrogen fluoride-pyridine or fluoride complex, such as TBAF. | Alternatively, reductive amination may be carried out on the compound of formula 4 with R 4 NH 2, mediated by sodium triacetoxyborohydride or sodium cyanoborohydride. The resulting secondary amine can be acylated as described above, with an activated form of R3C (0) OH, or reacted with R3C (0) OH using an amide coupling reagent. The deprotection of the hydroxyl groups is then carried out as described above. With reference to scheme 2, the compounds of formula 1 wherein R1 is H and R2 is -OR3, where R3 is an alkyl group or a substituted alkyl group, can be prepared by alkylation of the corresponding alcohol of the compound of formula 5 (in that X is a protective group like described above) in which R1 is hydroxyl and R2 is hydrogen. In this process, the C-5"ketone radical of the compound of formula 4 is reduced using an appropriate reducing agent such as sodium borohydride.The resulting C-5" alcohol can then be alkylated with R3-Z, wherein Z is a leaving group such as Cl, Br, I or methanesulfonate, in the presence of a base, such as sodium hydride or potassium ferc-butoxide. The protecting groups are then removed with acid, such as acetic acid, hydrogen fluoride, hydrogen-pi-dine fluoride complex or a source of fluoride, such as TBAF. The compounds of formula 1 wherein R1 is H and R2 is -OR3, where R3 is a heterocyclic or aromatic radical, can be prepared by a Mitsunobu reaction. The alcohol C-5", prepared as described above, is subjected to a reaction of Mitsunobu with R3OH, mediated by triphenylphosphine and diethyl azodicarboxylate.The resulting ether is then deprotected as described above.Alternatively, when R1 is H and R2 is -OR3, where R3 is a heterocyclic or aromatic radical, the C-5 alcohol "derived from the compound of the formula can be transformed into a leaving group, for example bromide or mesylate derivative. The leaving group can then be displaced by R 3 OH using a base, such as sodium hydride, potassium ferc-butoxide or potassium carbonate. The compounds of formula 1 in which R1 is H and R2 is -OC (0) NR3R4 can be prepared by reaction of the C5 alcohol "derivative of the compound of formula 5 as described above, with isocyanate R3NCO in toluene at temperatures of 40 ° C to 100 ° C, preferably 50-80 ° C. The addition of dimethylaminopyridine and triethylamine to the reaction can be advantageous. The product of this reaction, which has R 4 equal to H, can be alkylated to give R 4 equal to C 1 -C 10 alkyl by the use of a base such as sodium hydride and an alkylating agent such as a bromide of the formula R-Br. The deprotection of the hydroxyl groups can then be carried out by the use of a fluoride ion, such as TBAF. The compounds of formula 1 wherein R1 and R2 are taken together to form = CR C (0) R3, = CR4C (0) OR3 or = CR4C (0) NR3R4, where R3 and R4 are as defined above, can prepared by the corresponding Wittig-derived, a / 3-unsaturated ester intermediates or Horitt-Emmons Wittig olefination of ketone C-5"of the compound of formula 4. For example, it can be reacted (carbethoxymethylene) triphenylphosphorane or (carbethoxyethylidene) triphenylphosphorane with the compound of formula 4 to provide the unsaturated ethyl ester The hydrolysis of this ester, for example, with sodium hydroxide, provides the corresponding carboxylic acid (compound of formula 5 in which R1 and R2 are taken together to form = CHC (0) OH At this time, hydroxy groups that have been released in the previous step can be protected, for example, as their TES or TBDMS ethers.To prepare the esters described above, this carboxylic acid can be with R3OH, for example by the action of DCC and 4-dimethylaminopyridine (DMAP), or CDI and a catalytic base such as sodium ethoxide. The deprotection of the hydroxyl groups is then carried out with an acid, such as acetic acid, hydrogen fluoride, hydrogen fluoride-pyridine complex or fluoride ion, such as TBAF. Compounds of formula 1 in which R1 and R2 are taken together to form = CR C (0) NR3R4, can be formed by treatment of the above carboxylic acid intermediate (compound of formula 5 in which R1 and R2 are taken together to form = CHC (0) OH) with an amine of the formula R3NH2 with the use of an amide coupling agent, such as DCC, CDI, EEDQ, DEPC or EDC. On the protected derivative, R4 can be introduced by alkylation, for example, with a base such as sodium hydride or potassium fer- t-butoxide and an alkylating agent such as R4-X, where X is Br, Cl or methanesulfonate. The deprotection of the hydroxyl groups is then carried out as described above. The acetone of formula 1 (R1 and R2 are taken together to form = CR C (0) R3), can be prepared by direct reaction of Wittig or Horner-Emmons of the compound of formula 4 with, for example, the corresponding reagent R3C (0 CHR4-PPh3 (Ph is phenyl) or R3C (0) CHR4-P = 0 (OEt) 2 (Et is ethyl). Alternatively, the compound of formula in which R and R2 are taken together to form = CHC (0) OH can be transformed into the Weinreb amide, for example, by treatment with CDI and N.O-dimethylhydroxylamine. Then, this amide can be reacted with R3-M, where M is a metal ion such as Li or MgBr, for generate the ketone. The aldehyde (ketone structure in which R3 is H) can be prepared by reacting the Weinreb amide with a hydride source, such as diisobutylaluminum hydride (DIBAL) or LiAIH4. Compounds of formula 1 in which R1 and R2 are taken together to form = CR4R3, where R3 and R4 are as defined above, can be prepared by a Wittig or Horner-Emmons reaction of the R-CH ylide (PPh3 ) -R3 or R4-CH (P = 0 (OEt) 2) -R3 with the compound of formula 4. The protecting groups can then be removed as described above. Alternatively, the ketone or aldehyde of formula 5, wherein R1 and R2 are taken together to form = CR4C (0) R3 and = CR4C (0) H, respectively, may be used as the intermediate. These compounds can be obtained by Wittig or Horner-Emmons reaction with an oxygenated triphenyl phosphonium or phosphorane salt., such as Ph3P-C (R3) OMe (Me is methyl). The resulting enol ether can be hydrolysed with mild acid, such as acetic acid or dilute HCl, to produce the aldehyde or ketone. The aldehyde or ketone can then be reacted with an organometallic derivative R4-M, where M is, for example, Li or MgBr, to provide the corresponding alcohol, which can be dehydrated under the action of methanol-sulphonyl chloride to produce the corresponding olefin. Deprotection as described above then provides the compound of formula 1 wherein R1 and R2 are taken together to form = CR4R3. The compound of formula 1 in which R1 and R2 are taken together to form = CR4R3 where R4 is aryl or heteroaryl and R3 is not hydrogen, can be prepared using a palladium catalyzed process. The conversion of the compound of formula 5 in which R3 is -CH (COR3) into an enol ether activated, for example enol triflate, provides an intermediate that can be coupled in a process of Suzuki or Stille-type catalyzed by palladium , with aryl or heteroaryl boronic acids R4B (OH) 2 or aryl tin species, for example, R SnMe3 or R4SnBu3 (Bu is butyl), to provide the unsaturated aryl derivatives. Deprotection as described above then provides the final compound. The compounds of the present invention have asymmetric carbon atoms. Such diastereomeric mixtures can be separated into their individual diastereomers based on their physicochemical differences by methods known to those skilled in the art, for example, by chromatography or fractional crystallization. All such isomers, including mixtures of diastereomers, are considered part of the invention. The compounds of the present invention which are basic in nature are capable of forming a wide variety of different salts with various inorganic and organic acids. Although such salts have to be pharmaceutically acceptable for administration to animals, it is often desirable in practice to initially isolate the compound of the present invention from the reaction mixture in the form of a pharmaceutically unacceptable salt, then simply convert this last in the free base compound by treatment with an alkaline reagent and subsequently converting the last free base to a pharmaceutically acceptable acid addition salt. The acid addition salts of the basic compounds of this invention are readily prepared by treating the basic compound with a substantially equivalent amount of the chosen mineral or organic acid, in an aqueous solvent medium or in a suitable organic solvent, such as methanol or ethanol. After careful evaporation of the solvent, the desired solid salt is easily obtained. The desired acid salt can also be precipitated from a solution of the free base in an organic solvent, by adding an appropriate mineral or organic acid to the solution. The compounds of the present invention which are acidic in nature, are capable of forming base salts with various pharmacologically acceptable cations. Examples of such salts include the alkali metal or alkaline earth metal salts and, particularly, the sodium and potassium salts. All these salts are prepared by conventional techniques. The chemical bases that are used as reagents for preparing the pharmaceutically acceptable base salts of this invention are those which form non-toxic base salts with the acidic compounds of the present invention. Such non-toxic base salts include those derived from pharmacologically acceptable cations such as sodium, potassium, calcium, magnesium, etc. These salts can be easily prepared by treating the corresponding acidic compounds with an aqueous solution containing the Alkali metal alkoxide or desired metal hydroxide and then evaporation of the resulting solution to dryness, preferably under reduced pressure. Alternatively, they can also be prepared by mixing lower alkanolic solutions of the acidic compounds and the alkali metal alkoxide or metal hydroxide together, and then evaporating the resulting solution to dryness in the same manner as indicated above. In any case, stoichiometric amounts of reagents are preferably employed in order to ensure that the reaction is complete and the maximum yield of the desired final product. The antibacterial activity of the compounds of the present invention against bacterial pathogens is demonstrated by the ability of the compounds to inhibit the growth of strains of defined pathogens.

Assay The assay described below employs conventional methodology and interpretation criteria and is designed to provide direction of chemical modifications that can produce compounds with antibacterial activity against susceptible and drug resistant organisms including, but not limited to, beta resistance -lactam, macrolides and vancomycin. In this assay, a panel of bacterial strains is assembled to include a variety of target pathogenic species, including representatives of antibiotic-resistant bacteria. The use of this panel allows to determine the chemical structure / activity relationship with regarding the power and spectrum of activity. The assay is performed in microtiter trays and interpreted according to Performace Standards for Antimicrobial Disk Susceptibility Test -Sixth Edition; Approved Standard, published by the guidelines of The National Committee for Clinical Laboratory Standards (NCCLS); To compare the strains, the minimum inhibitory concentration (MIC) is used. The compounds are initially dissolved in dimethylsulfoxide (DMSO) as stock solutions. The activity of the compounds of the present invention can be evaluated according to the Steers replicator technique, which is a conventional in vitro bacterial test procedure written by Steers et al., Antibiotics and Chemotherapy 1959, 9, 307. The activity In vivo of the compounds of the present invention can be determined by conventional animal protection studies well known to those skilled in the art, usually carried out in rodents. According to an in vivo model, the compounds are evaluated for efficacy in models of acute bacterial infection in mice. An example of one such in vivo system is provided as indicated below. Mice (male and female CF1 mice, 18-20 g) are assigned to cages after arrival and allowed to acclimate for 1-2 days before being placed in the study. The watery infection is produced by the intraperitoneal inoculation of bacteria (Staphylococcus aureus, strain 01A1095) suspended in sterile 5% pig stomach mucin. The inoculum is prepared as follows: let the culture grow overnight at 37 ° C on blood agar, collecting the resulting surface growth with sterile brain-cardiac infusion broth and adjusting this suspension to a turbidity that when diluted 1: 10 in 5% pig sterile gastric mucin produces a 100% lethality. Mice (10 per group) are treated subcutaneously, 0.5 hours and 4 hours after exposure. Appropriate untreated (infected but not treated) and positive controls (vancomycin or minocycline, etc.) are included in each study. The percentage of survival is recorded after an observation period of 4 days; the DP5o value (mg / kg / dose calculated to protect 50% of the infected animals) is determined by the probit method. The compounds of the present invention and the pharmaceutically acceptable salts thereof (hereinafter "the active compounds") can be administered orally, parenterally, topically or rectally in the treatment of bacterial and protozoal infections. In general, these compounds are administered in the most desirable manner in doses ranging from about 0.2 mg per kg of body weight and per day (mg / kg / day) and about 200 mg / kg / day in single or divided doses. (ie, from 1 to 4 doses per day), although variations will necessarily occur depending on the species, weight and condition of the subject to be treated and the particular route of administration chosen. However, it is most desirable to employ a dosage level that is in the range of about 3 mg / kg / day to about 60 mg / kg / day. However, variations may occur depending on the species of mammals, fish or bird to be treated and their individual response to said medication, as well as the type of pharmaceutical formulation chosen and the period and time interval in which such administration is to be carried out. In some cases, dosage levels below the lower limit of the aforementioned range may be more than adequate, while in other cases even higher doses may be used without causing any harmful side effects, provided that such higher doses are first divided into several doses. small doses to be administered throughout the day. The active compounds can be administered alone or in combination with pharmaceutically acceptable carriers or diluents by the routes indicated previously, and such administration can be carried out in single or multiple doses. More particularly, the active compounds can be administered in a wide variety of different dosage forms, that is, they can be combined with various inert pharmaceutically acceptable carriers in the form of tablets, capsules, dragees, troches, hard candies, powders, sprays, creams, ointments , aqueous suspensions, injectable solutions, elixirs, syrups and the like. Such carriers include diluents or solid fillers, sterile aqueous media and various non-toxic organic diluents, etc. In addition, oral pharmaceutical compositions can be conveniently sweetened and / or flavored. In general, the active compounds are present in such dosage forms at concentration levels ranging from about 5.0% to about 70% by weight. For oral administration, tablets containing various excipients such as microcrystalline cellulose, sodium citrate, calcium carbonate, dicalcium phosphate and glycine can be used, together with various disintegrants such as starch (preferably corn, potato or tapioca starch), alginic acid and certain complex silicates, together with granulation binders such as polyvinyl pyrrolidone, sucrose, gelatin and gum arabic. In addition, lubricating agents such as magnesium stearate, sodium lauryl sulfate and talc to form tablets are often very useful. Solid compositions of a similar type may also be employed as fillers in gelatin capsules; Preferred materials in this regard also include lactose or milk sugar, as well as high molecular weight polyethylene glycols. When aqueous suspensions and / or elixirs are desired for oral administration, the active compound may be combined with various sweetening or flavoring agents, coloring materials or dyes and, if desired, also with emulsifying and / or suspending agents, together with such diluents such as water, ethanol, propylene glycol, glycerin and various combinations thereof. For parenteral administration, a solution of an active compound in sesame or peanut oil or in aqueous ethanol or propylene glycol can be employed. The use of a cyclodextrin derivative, such as the sodium salt of β-cyclodextrin sulfobutyl ether (cf.

U.S. Patent 5,134,127). Aqueous solutions should be suitably buffered if necessary, and the liquid diluent should first be made isotonic. These aqueous solutions are suitable for intravenous injection purposes. Oily solutions are suitable for intra-articular, intramuscular and subcutaneous injection purposes. The preparation of all these solutions under sterile conditions is easily accomplished by pharmaceutically conventional techniques known to those skilled in the art. In addition, it is also possible to administer the active compounds of the present invention topically, and this can be done by means of creams, jellies, gels, pastes, patches, ointments and the like according to conventional pharmaceutical practice. For administration to animals other than humans, such as cattle or domestic animals, the active compounds can be administered in animal feed or orally in the form of a brew composition. The active compounds can also be administered in the form of liposome delivery systems, such as small unilamellar vesicles, large unilamellar vesicles and multilamellar vesicles. Liposomes can be formed from a variety of phospholipids, such as cholesterol, stearylamine or phosphatidylcholines. The active compounds can also be coupled with soluble polymers as targeting drug vehicles. Such polymers they may include polyvinylpyrrolidone, pyran copolymer, polyhydroxypropylmethacrylamide phenyl, polyhydroxyethylaspartamide-phenol or poly (ethylene oxide) -polylysine substituted with palmitoyl residues. In addition, the active compounds can be coupled to a class of biodegradable polymers useful for achieving controlled release of a drug, for example, polyacid lactic acid, poly (glycolic acid), copolymers of polyacid lactic acid and poly (glycolic acid), poly-epsilon caprolactone, poly (hydroxy butyric acid), polyorthoesters, polyacetals, polyhydropyrans, polycyanoacrylates and crosslinked copolymers or block antiplatics of hydrogels. The present invention is further described and exemplified in the preparations and examples described below. In the preparations and examples "ta" means room temperature, which is a temperature within the range of about 20 to 25 ° C.

PREPARATION 1 Five (5) ml of a frozen lot (stored at -80 ° C in 20% glycerol / 80% inoculum medium) of the culture of Streptomyces hygroscopicus NRRL 2388 was used to inoculate 1 l of hygromycin inoculum medium (13 g / l Corn Products Corp. cereals, 7 g / l Hubinger's starch, 3 g / l Roquette corn mash solids, 7 g / l Amina YTT from Sheffield Brand Products NZ, 0.002 g / l of CoCl2 6H20 from Baker, 0.7 g / l of KH2P04, 1.3 g / l of MgSO4 7H20, 0.7 g / l of ammonium sulfate, 1 drop / flask of Skimmer from Dow Chemical P2000, 2 drops / flask of Colfax soybean oil, pH 7.0 before autoclaving) in a Fernbach flask of 2.8 I. The culture was grown for 3 days at 29 ° C with shaking at 200 rpm on a 2 inch (5.08 cm) vertical displacement stirrer. This developed culture was used to inoculate 8 I of sterile hygromycin fermentation medium (1 g / l of Albaglos calcium carbonate, 5 g / l of YTT amine from Sheffield Brand NZ, 20 g / l of Hubinger starch, 10 g / l of Archer Daniels Midland Nutrisoy flour, 1 ml / l of Dow Chemical P2000 defoamer, 0.002 g / l of Baker's CoCl2 6H20, 2 ml / l of Colfax soybean oil, 10 g / l of cereelly, g / l of NaCl, pH 7.0 before autoclaving) in a 14 liter fermenter vessel (New Brunswick Microferm, New Brunswick, New Jersey) equipped with two 4.75 inch (12.06 cm) Rushton impellers, with a distance of 3.75 inches (9.52 cm) between them. The broth was incubated at 29 ° C with an aeration rate of 8 I / minute and with stirring at 800 rpm. To minimize the formation of ep / '- hygromycin, the pH was maintained between 6.5 and 6.9 for 126 hours, and after 6.2 to 6.6 with H2S0 (15%) for the remainder of the test. The fermentation was collected after a total of 143 hours of incubation. At this time, the ratio between hygromycin A and ep / '- hygromycin was 31: 1. Six liters of broth from the previous fermentation were centrifuged to 8000 rpm for approximately 15 minutes. After centrifugation, the pellet and the supernatant were discarded (at pH 6.4, which according to the HPLC test contained approximately 4.12 grams of hygromycin activity A) was introduced into a column filled with 500 grams of XAD-16 resin (Rohm and Haas (Philadelphia, Pennsylvania) .The resin had previously been equilibrated with two bed volumes of 25 mM disodium phosphate, pH 6.0 (" buffer.) After loading, the column was washed with 2 bed volumes of buffer and 2 bed volumes of 80/20 buffer / methanol and the activity was eluted with 5 bed volumes of a 50/50 buffer mixture. The portions were assayed by HPLC and the portions containing most of the activity (2.730 grams of hygromycin A) were pooled.A part of that XAD-16 eluate (approximately 800 mg of hygromycin A) was diluted in a 10% methanol by the addition of 1.8 liters of buffer and was introduced into a 100 ml CG-161 column (TosoHass (Montgomeryville, Pennsylvania)) which had been equilibrated with 4 bed volumes of a 90/10 buffer mixture. methanol.The product was eluted with 6 volumes of e bed of a 50/50 mixture of buffer / methanol. The portions were assayed by HPLC and the active portions were pooled. The combined portions were evaporated to dryness and according to the test, the solids had a purity of about 65% by weight. A small part of these solids was transferred for the test. About 500 mg of the solids were mixed with 500 ml of water and 500 ml of ethyl acetate and the mixture was stirred for 20 minutes. The two layers were separated and part of the aqueous layer was dried to obtain solids which, according to the test, had a purity of about 52% by weight. These two solids (Nos. 34945-280-1 and 281-1) were tested by NMR and TLC and were found to contain hygromycin A activity. In addition, the NMR showed an hygromycin A / ep / '- hygromycin ratio of approximately 15: 1 PREPARATION 2 Five (5) ml of a frozen lot (stored at -80 ° C in 20% glycerol / 80% inoculum medium) of the culture of Streptomyces hygroscopicus NRRL 2388 was used to inoculate 1 I of hygromycin inoculum medium (13 g / l of cereals from CPC International Inc, 7 g / l of Hubinger starch, 3 g / l of Roquette maize mash solids, 7 g / l of NZ amine YTT, 0.002 g / l of CoCl2 6H20 of Baker, 0.7 g / l of KH2P04, 1.3 g / l of MgSO4 7H20, 0.7 g / l of ammonium sulfate, 1 drop / flask of Dow Chemical P2000 defoamer, 2 drops / flask of Colfax soybean oil, pH 7.0, before autoclaving) in a 2.8 I Fernbach flask. The culture was grown for 2 to 3 days at 29 ° C with shaking at 200 rpm on a 2 inch (5.08 cm) vertical displacement shaker. Two stainless steel fermentors of five hundred gallons (2273 liters) were charged with 380-400 gallons (1727-1818 liters) of the hygromycin fermentation medium (1 g / l calcium carbonate from Mineral Technologies, 5 g / l amine YTT from Sheffield Brand Products NZ, 20 g / l Hubinger starch, 10 g / l Archer Daniels Midland Co. soybean meal, 1 ml / l defoaming agent Dow Chemical P2000, 0.002 g / l of Baker's CoCI2 6H20, 2 g / l of Colfax Inc.'s soybean oil, 10 g / l of cereals from CPC International Inc. and 5 g / l of NaCl from Cargill). The medium was sterilized with 20 psig (138 kPa) of steam for 60 minutes in the fermenters. Then, the medium was cooled using refrigeration coils in the fermenters and the pH was adjusted to 6.5-6.7. The conditions of the fermenters were set so that the air flow rate was 0.566 standard m3 per minute, the temperature was 28 ° C, the ventilation pressure was 5 psig (34.47 kPa) and the pH was maintained between 6.5 and 6.7 with 25% sodium hydroxide and 98% sulfuric acid. Agitation rates in the two fermenters were varied to maintain a dissolved oxygen level greater than 20% saturation level, as measured in the broth immediately prior to inoculation. After fixing the control conditions in the fermentor, five fernbach inoculum flasks were collected in a sterile form in an 8 liter aspirator bottle. This inoculum was then used for the inoculation of an individual, nominal fermenter of five hundred gallons (2273 I) as described above. This procedure was repeated using 4 liters of inoculum, so that one fermenter received four liters of inoculum and the other fermenter received five liters of inoculum. Each fermenter operated for approximately 114 hours, after which the fermenters were interrupted. The pH of the broth was adjusted to 6.3 using 98% sulfuric acid and transferred from the fermenters for recovery. The two fermenters mentioned above (pH = 6.3, with a ratio between hygromycin A and ep / '- hygromycin of about 51: 1) were filtered in a ceramic filtration system. The filtrate (1450 g A, 506 gal) was filled with a 70 gallon (318 liter) XAD-16 resin column. This column had previously been equilibrated with 4 bed volumes of a solution of trisodium phosphate buffer at pH 6.0 ("buffer"). After loading, the column was washed with 2 bed volumes of buffer and 2 bed volumes of 80/20 buffer / methanol. The activity was subsequently eluted from the column with 10 portions (approximately 50 gallons (227 liters) each) of a 50/50 solution of buffer / methanol. The active portions (approximately 1240 g A) were pooled and diluted to a final concentration of 10% methanol by the addition of 1200 gallons (5455 liters) of buffer. The use of dilution (instead of rotary evaporation) to reduce the concentration of methanol, allowed the use of lower temperatures, so as to minimize the amounts of ep / '- hygromycin, which tended to increase at higher temperatures. Half of this solution was introduced into a 40 I CG-161 column (previously equilibrated with 4 bed volumes of a 90/10 buffer / methanol solution). After loading, the column was washed with 4 bed volumes of an 80/20 mixture of buffer / methanol and eluted with 5.5 bed volumes of a 50/50 mixture of buffer / methanol. After regeneration and re-equilibration of the column, the second half of the activity was introduced into the column and eluted as described above. The combined portions of the two tests (120 liters, approximately 1051 grams A) were diluted in % methanol by the addition of buffer. This was reintroduced into the regenerated and rebalanced resin column CG-161. Once the activity in the column was adsorbed, it was eluted with 4 bed volumes of methanol. This step served both to reduce the salts and to increase the concentration of the sample before the final evaporation. The pooled portions of the final GC-161 column were evaporated to dryness to obtain a total of about 1 kg A of hygromycin A activity. The ratio between hygromycin A and ep / '- hygromycin in the final solids was approximately 14.5. :1.

Experimental procedures for the examples Preparation of the compound of formula 3 A solution of hygromycin A (1 eq.) In dimethylformamide (DMF, 0.1 M) was treated with imidazole (10 eq) and ferd-butyldimethylsilyl chloride (10 eq) at 35 ° C for 14-16 hours. The reaction was poured into water and extracted with ethyl acetate (EtOAc). The combined extracts were dried over MgSO4 and concentrated. The product was obtained after chromatography (5-15% EtOAc / hexanes).

Preparation of the compound of formula 5 A solution of the compound of the formula 3 (1 eq) in dichloromethane was treated with phenyl-ethylchloroformate (3 eq.), Pyridine (5 eq.) And dimethylaminopyridine (0.05 eq.) at room temperature for 2-3 days. After this period, the reaction was diluted with methylene chloride and washed with 0.5 N HCl, with saturated sodium bicarbonate and then with brine. The organics were dried over MgSO4 and concentrated. After chromatography (5-10% EtOAc / hexanes) the desired 2-thiocarbonate was obtained, a solution of the above 2-thiocarbonate (1 eq.) In toluene (0.1 M) was treated with a, a'- azobis (isobutyronitrile) (1 eq.) and tri-n-butyltin hydride (3 eq.) at 90 ° C for 2 hours. The reaction was concentrated and chromatographed (5-10% EtOAc / hexanes) to give the desired compound 2"-deoxy of formula 5.

Preparation of the oxime ethers, examples 1-30 A solution of the compound of formula 4 (1 eq.) In methanol (0.1 M) was treated with the appropriate hydroxylamine at 60 ° C for 30 minutes to 1 hour. The reaction mixture was concentrated and the desired oximes were obtained after chromatography (generally 5-15% EtOAc / (toluene or hexanes)). The removal of the silyl groups was carried out by treating the above oxime with tetrabutylammonium fluoride (10 eq.) In tetrahydrofuran at room temperature, for 12-24 h. The concentrated reaction mixture was passed through a bed of an ion exchange resin (35 g of Dowex 400 resin per g of starting material) and subsequently the desired oxime was obtained in the form of a mixture of the isomers £ and Z after chromatography (generally 5-15% methanol / chloroform). As an alternative, the removal of the silyl groups was carried out by the addition of a solution of tetrahydrofuran, pyridine, hydrogen fluoride-pyridine complex (65 ml, 16.5 ml, 8.25 ml, respectively) to a solution at room temperature of the oxime. above (6 mmol) in tetrahydrofuran (98 ml). The reaction was continued for 24-96 h and was stopped by the addition of sodium bicarbonate. The desired oxime was obtained predominantly in the form of the E-isomer after chromatography (generally 5-15% methanol / chloroform). In the case of example 10, the compound of formula 4 was deprotected by the above process of hydrogen fluoride-pyridine.

Preparation of hydroxylamine reagents for the synthesis of oxime ethers. EXAMPLES 1-30 Most of the hydroxylamine reagents used were commercially available (generally in the form of an acid salt), or were prepared from the corresponding alcohol or halide by the procedures outlined below: 1) Preparation of phthalimide-protected hydroxylamines: From alcohol: A reaction of Mitsunobu with diethyl azodicarboxylate and triphenylphosphine was used to couple N-hydroxyphthalimide and the alcohol of the starting material, according to the procedure of E. Grochowski and J. Jurczak, Synthesis (1976) 682.

From the bromide or chloride: The reaction of N-hydroxyphthalimide (1 equivalent) with the halide starting material (1.2-2 equivalents) in dimethyl sulfoxide solution (DMSO) using potassium carbonate (0.6-2 equivalents) was performed as base. The reactions were carried out at room temperature, generally by stirring overnight. The pouring of the reaction mixture into cold water provided a precipitate, which was filtered to give the phthalimide-protected hydroxylamine. In many cases, this material was directly deprotected; silica gel chromatography could also be used; using mixtures of ethyl acetate-hexane, to purify the phthalimide-protected hydroxylamine. 2) Removal of the phthalimide protecting group to provide the hydroxylamine: The deprotection of the phthalimide-protected hydroxylamine was carried out by reaction with hydrazine hydrate (1-2 equivalents) in ethanol solution, at temperatures that varied between the ambient temperature and the reflux temperature, during periods that varied between 30 minutes and one night. The reaction mixture was filtered and the filtrate was concentrated. This crude product was collected for the next step as such or further purified. Mixing the crude product with chloroform, removing the solids by filtration, and removing the solvent from the filtrate, removes the additional phthalhydrazide. Alternatively, the crude product was dissolved in 1N hydrochloric acid and washed with ether or ethyl acetate. The aqueous layer was basified with saturated potassium carbonate solution and extracted with ether or ethyl acetate. Drying of the final organic layers and removal of the solvent provided the hydroxylamine product. 3) Preparation of 4-phenyl-chloromethylthiazole 4-phenyl-thiazole-2-carbaldehyde was prepared by a procedure analogous to that of K. Inami and T. Shiba, Bull Chem Soc Jpn, 1985, 58, 352. The aldehyde was reduced to corresponding alcohol using sodium borohydride in ethanol. The corresponding chloromethylthiazole was prepared by treatment of the alcohol with thionyl chloride (4 equivalents) in methylene chloride at room temperature for 2-5 hours. 4) Preparation of substituted benzylic alcohols 1- (3-Chloro-2,6-difluoro-phenyl) -ethanol and other phenylethanol derivatives (examples 11, 14, 15, 17, 18) were prepared by treatment of the corresponding phenyl-carboxaldehyde with methylmagnesium bromide (1 equivalent) in THF at room temperature. These were then converted into the corresponding benzyl bromides by treatment with 48% HBr for 1-4 hours. 1- (3-Chloro-2,6-difluoro-phenyl) -carboxaldehyde was prepared from 3-chloro-2,6-difluorobenzene with lithium diisopropylamide and N, N-dimethylformamide in a procedure similar to that of A.S. Cantrell, ef al., J. Medicinal Chemistry 1996, 21, 4261. 2,4-difluoropropiophenone (example 16) was reduced to the corresponding alcohol using sodium borohydride in ethanol.

) Preparation of O-arylhydroxylamines: The substituted phenols were converted to the corresponding O-arylhydroxylamines by the use of mesitylenesulfonylhydroxylamine, as described by Y. Endo, K. Shudo and T. Okamoto, Synthesis 1980, 461. The specific compounds prepared according to the above procedures are illustrated in the following table. In the box "Ex." means example, "Stereo" means stereochemistry of the oxime, "Weight Mol" means molecular weight and "Esp. Mas." It means mass spectrometry.

PICTURE The synthetic procedures described below may also be useful in the preparation of the compounds of the present invention.

Preparation of various alcohol starting materials used in the synthesis of hydroxylamines: The alcohol starting materials can be obtained by reduction of more oxidized commercially available compounds. The 4-cyclohexyl benzoic acid can be reduced with lithium aluminum hydride (2)., 3 equivalents) in tetrahydrofuran to provide the corresponding alcohol. The 3- (4-chlorophenyl) propionic acid can be reduced to the corresponding alcohol using diborane (1.1 equivalents) in tetrahydrofuran, from 0 ° C to room temperature for 5 hours. The 3-trifluoromethoxybenzaldehyde, 3-cyanobenzaldehyde, benzo-2-carboxaldehyde, 1,4-benzodioxan-6-carboxaldehyde and 3-fluoro-4-methoxybenzaldehyde can be reduced to the alcohol derivatives using sodium borohydride in tetrahydrofuran. Magnesium sulphate (4 equivalents) can be treated in methylene chloride, with concentrated sulfuric acid (1 equivalent), followed by 4-chloromethylbenzoic acid (1 equivalent) and tert-butanol (5.1 equivalents). Stirring overnight at room temperature provides the tert-butyl ester. 4-Amino-3,5-dichlorobenzoic acid can be N-acetylated by treatment with acetyl chloride (1.2 equivalents) in dimethylformamide, at 90 ° C, for 4 hours The cooled reaction mixture can be poured into chilled water, frozen and filtered to yield the acetamide derivative. The reduction of the carboxylic acid was carried out with lithium aluminum hydride (2 equivalents) in tetrahydrofuran at 0 ° C for 2 hours, and produced N- (2,6-d? Chloro-4-hydrox? Met? L-phen?) Acetam The amino groups of 3-am? No-benz? alcohol and 4-amino-benzyl alcohol can be protected as the N-tert-BOC derivatives, by treatment with di-tert-butyl dicarbonate (1.1 equivalents) in tetrahydrofuran (THF) at reflux, until it is consumed the starting ammo compound The reaction of ethyl 4-fluorobenzoate with pipepdma (3 equivalents) in acetonitin can be carried out at reflux for 4 days. The dilution of the reaction mixture cooled with a few volumes of water provides a precipitate, which can be filtered to provide 4- (p? pepd? n-1-? l) ethyl benzoate The reduction of the ester with hydride of lithium and aluminum (2 equivalents) in tetrahydrofuran provides the corresponding alcohol The 5-hydroxylmethylbenzofuran can be prepared according to the procedure of K Hiroya, K Hashimura and K Ogasawara, Heterocycles (1994) 38, 2463 El 2 -phen? lp? pm? d? na-5-carboxaldehyde can be prepared according to the procedure of JT Gupton, JE Gall, SW Riesinger et al, J Heterocyc c Chemistry (1991) 28 1281 The aldehyde can be reduced to the corresponding alcohol using sodium borohydride in methanol In the interim United States patent application entitled "Hygromycin A derivatives" (file number of agent PC 10057), mentioned above, other methods that can be followed to prepare the various compounds of the present invention are described. ^^^^^^^

Claims

NOVELTY OF THE INVENTION CLAIMS

1. - A compound of formula or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein: R1 is H and R2 is -NR3R4, -NR4C (0) R3, -OC (0) NR3R4 or OR3; or R1 and R2 are taken together to form = 0, = N-OR3, = CR4R3, = CR4C (0) R3, = CR4C (0) R3 or = CR4C (0) NR3R4 ,; each R 3 is independently selected from H, C 1 -C 0 alkyl, C 2 -C 0 alkenyl 0, - (CH 2) t (C 3 -C 10 cycloalkyl), - (CH 2) (C 6 -C 0 aryl) and - (CH 2) t (heterocycle of 4-10 links), where t is an integer ranging between 0 and 5, said alkyl group optionally contains 1 or 2 heterradicals selected from O, -S (O), - where j is a whole number that varies between 0 and 2, and -N (R7) -, with the proviso that two O atoms, two S atoms or one O atom and one S atom are not linked directly with each other; said R3 cycloalkyl, aryl and heterocyclic groups are optionally fused with a benzene ring, a C5-C8 saturated cyclic group or a 4- to 10-membered heterocyclic group; the radicals - (CH2) t of the above R3 groups optionally include a double or triple carbon-carbon bond where t is an integer between 2 and 5; and the above R3 groups, except H, but including any optional fused ring mentioned above are optionally substituted with 1 to 5 R5 groups; each R 4 is independently H or C 1 -C 10 alkyl; each R5 is independently selected from C1-C10 alkyl, C3-C10 cycloalkyl, halo, cyano, nitro, trifluoromethyl, difluoromethoxy, trirfluoromethoxy, azido, -OR6, C (0) R6, -C (0) OR6, -NR7C (0 ) OR9, OC (0) R6, -NR7S02R9, -S02NR6R7, NR7C (0) R6, -C (0) NR6R7, -NR6R7, -S (0) ¡(CH2) m (aryl Ce-Cι), -S (0) j (d-C6 alkyl), where j is an integer ranging between 0 and 2, - (CH2) m (C6-C aryl 0), -0 (CH2) m (C6-C aryl? 0), NR7 (CH2) m (aryl C6-C? 0) and - (CH2) m (heterocycle of 4 to 10 links), where m is an integer ranging from 0 to 4; said alkyl group optionally contains 1 or 2 heteroradicals selected from O, -S (0) j-, where j is an integer ranging from 0 to 2, and -N (R7) -, with the proviso that two atoms of Or, two atoms of S or one atom of O and another of S are not directly linked together; said R5 cycloalkyl, aryl and heterocyclic groups are optionally fused with a C6-C? ar aryl group, a C5-C6 saturated cyclic group or a 4- to 10-membered heterocyclic group; and said R5 alkyl, cycloalkyl, aryl and heterocyclic groups are optionally substituted with 1 to 5 selected substituents independently from halo, cyano, nitro, difluoromethoxy, trifluoromethyl, trirfluoromethoxy, azido, -NR7S02R9, -S02NR6R7, C (0) R6, -C (0) ORß, OC (0) R6, -NR7C (0) OR9, NR7C ( 0) R6, -C (0) NR6R7, -NR6R7, -OR6, C? -C10 alkyl, - (CH2) m (C6-C? O aryl) and - (CH2) m (4- to 10-membered heterocycle) , where m is an integer that varies between 0 and 4; each R6 is independently selected from H, C1-C10 alkyl, C3-C10 cycloalkyl, - (CH2) m (Ce-Cι aryl) and - (CH 2) m (4- to 10-membered heterocycle), where m is a whole number which varies between 0 and 4; said alkyl group optionally includes 1 or 2 heteroradicals selected from O, -S (O), - where j is an integer ranging from 0 to 2, and -N (R7) -, with the proviso that two O atoms , two atoms of S or one atom of O and another of S are not directly linked together; said R6 cycloalkyl, aryl and heterocyclic groups are optionally fused with a Ce-Cio aryl group, a C5-C8 saturated cyclic group or a 4- to 10-membered heterocyclic group; and the above R6 substituents, except H, are optionally substituted with 1 to 5 substituents independently selected from halo, cyano, nitro, difluoromethoxy, trifluoromethyl, trirfluoromethoxy, azido, C (0) R7, -C (0) OR7, -NR7C (0) R8, -C (0) NR7R8, -NR7R8, hydroxy, C6 alkyl and C6-C6 alkoxy; each R7 and R8 is independently H or Ci-Cß alkyl; and R9 is selected from the substituents provided in the definition of R6, except H.

2. The compound according to claim 1, wherein R1 and R2 are taken together to form = N-OR3, and R3 is C1 alkyl. -C4, C2-C4 alkenyl, - (CH2) t (C6-C? O aryl) or - (CH2) t (4-10 heterocycle) links), where t is an integer ranging from 0 to 3, the heterocyclic group is optionally condensed with a benzene ring, the aryl group is optionally condensed with a 5- or 6-membered heterocyclic group, and the above R3 groups, including said optionally condensed radicals are optionally substituted with 1 to 5 substituents independently selected from nitro, halo, C 1 -C 3 alkoxy, C 1 -C 4 alkyl, trifluoromethyl, acetamido, urea-butoxycarbonylamino, ferc-butoxycarbonylaminomethyl, ferc-butoxycarbonyl, -NR 6 R 7, phenyl, cyclohexyl, carboxy, aminomethyl, difluoromethoxy, trifluoromethoxy, cyano, piperidinyl, morpholino, phenoxy and phenylthio.

3. The compound according to claim 1, wherein R1 and R2 are taken together to form = N-OR3 and R3 is - (CH2) t (aryl Ce-Cio) or - (CH2) t (heterocycle of 4 to 10 links), where t is an integer ranging from 0 to 3, the heterocyclic group is optionally condensed to a benzene ring, the aryl group is optionally condensed to a 5- or 6-membered heterocyclic group, and the groups R3 above, including such optionally condensed radicals, are optionally substituted with 1 to 5 substituents independently selected from nitro, halo, C1-C3 alkoxy, C1-C4 alkyl, trifluoromethyl, acetamido, ferc-butoxycarbonyl, ferc-butoxycarbonylamino, -NR6R7, phenyl , cyclohexyl, carboxy, ferc-butoxycarbonylaminomethyl, aminomethyl, difluoromethoxy, trifluoromethoxy, cyano, piperidinyl, morpholino, phenoxy and phenylthio.

4. The compound according to claim 1, wherein R1 is H, R2 is -NR3R4, R4 is H or methyl, and R3 is - (CH2), (aryl Ce-Cio) or - (CH2) t (heterocycle of 4 to 10 links), where t is an integer that it varies between 0 and 2, and the group R3 is optionally substituted by 1 to 5 substituents independently selected from halo, C1-C3 alkoxy, C1-C4 alkyl and trifluoromethyl.

5. The compound according to claim 1, wherein R1 is H, R2 is -NR C (0) R3, R4 is H and R3 is C3-C6 cycloalkyl, - (CH2), (C6-C10 aryl) ) or - (CH2) t (4- to 10-membered heterocycle), where t is an integer ranging from 0 to 2, and the aryl group is optionally condensed with a 5- or 6-membered heterocyclic group, the heterocyclic group is optionally condensed with a benzene ring and the above R3 groups, including said optionally condensed radicals, are optionally substituted with 1 to 5 substituents independently selected from halo, C1-C3 alkoxy, C1-C4 alkyl and trifluoromethyl.

6. The compound according to claim 1, wherein R1 and R2 are taken together to form = CR4C (0) OR3 or = CR4C (0) NR3R4, R4 is H, and R3 is H, C? C6, C3-C6 cycloalkyl, - (CH2) t (4- to 10-membered heterocycle), or - (CH2) t (C6-C? 0 aryl), where t is an integer ranging from 0 to 2, and the aryl group is optionally condensed to a 5 or 6 membered heterocyclic group, the heterocyclic group is optionally fused to a benzene ring, and the above R3 groups, except H, but including such optionally condensed radicals are optionally substituted with 1 to 5 selected substituents independently between halo, C1-C3 alkoxy, C1-C4 alkyl, -NR6R7 and trifluoromethyl.

7. The compound according to claim 1, wherein R1 is H, R2 is -OR3, and R3 is C1-C4 alkyl, - (CH2) (4- to 10-membered heterocycle) or - (CH2) t (Aril Ce-Cío) where t is an integer that varies between 1 and 2, the aryl group is optionally condensed with a 5- or 6-membered heterocyclic group, the heterocyclic group is optionally fused with a benzene ring, and the above R 3 groups, including said optionally condensed radicals, are optionally substituted with 1 to 5 substituents independently selected from halo, C1-C3 alkoxy, C1-C4 alkyl, cyclohexyl, cyano, trifluoromethyl, benzyloxy and trifluoromethyl.

8. The compound according to claim 1, wherein R1 is H, R2 is -OC (0) NR3R4, R4 is H and R3 is - (CH2), (C6-C10 aryl) where t is an integer ranging from 0 to 2 and group R3 is optionally substituted by 1 to 5 substituents independently selected from halo, C1-C3 alkoxy, C1-C4 alkyl and trifluoromethyl.

9. The compound according to claim 1, wherein said compound is selected from the group consisting of: 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D- er / 'fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- ()) -propenyl] amino] -1, 2-0- methylene-D-neo-inositol, (Z) -0 - [(3-fluorophenylmethyl); 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] - 2-methyl-1-oxo-2- (E) -propenyl] amino] -1, 2-0- methylene-D-peo-? nos? tol, (E) -0 - [(3-fluorophen?) met? l] ox? ma, 5-Desox? -5 - [[3- [4- [ (2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? L- 1-oxo-2- (E) -propen? L] am? No] -1, 2-0-methylene-D-reo-? -osol, (E) -0 - [(benzofuran-2- (l) methyl] ox, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans-5-ulos- 1 -? L) ox?] - 3-h? Drox? Phen? L] -2-met? L-1 -oxo-2- (E) -propen? L] am? No] -1, 2-0 -met? leno-Dr / eo-inositol, (Z) -0- [benzofuran-2-? l) met? l] ox? ma, 5-Desox? -5 - [[3- [4 - [(2 , 6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? L-1 - oxo-2- (E) -propen? l] am? no] -1, 2-O-methylene-Dr / eo-? nos? tol, (Z) -O-phen? lnet? lox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Deox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3- H? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-met? leno-D-neo-? nos ? tol, (E) -O-phen? lmet? lox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-er / fro- hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-methylene-D-neo-inositol, (Z) -0 - [(4-chlorophen? L) met? L ] ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox ?] - 3-h? Drox? Phen? L] -2-met? L-1-oxo-2- (E) -propen? L] am? No] -1, 2-0-met? Leno-Dr / eo-? nos? tol, (E) -0 - [(4-chlorophen? l) met? l] ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6- d? desox? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2 - (E) -propen? L] am? No] -1, 2-0-methylene-D-neo-mositol, (Z) -0 - [(3,4-d? Chlorophen? L) met? L] ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox? ] -3-h? Drox? Phen? L] -2-met? L-1-oxo-2- (E) -propen? L] am? No] -1, 2-0-methylene-D- / 7eo-? Nos? Tol, (E) -0 - [(3,4-d? Chlorophen? L) met? L] ox? Ma, 5-Desox? -5 - [[3- [4 - [( 2,6-d? Desox? -β-D-erfro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? L-1-oxo -2- (E) -propen? L] am? No] -1, 2-O-met? Leno-D-peo-? Nos? Tol, (E) -0 - [(4-p? Pd? N ? l) met? l] ox? ma, 5-Desox? -5 - [[3- [4- [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? L -1-oxo-2- (£) -propen? L] am? No] -1, 2-0-methylene-D-neo-? Nos? Tol, (Z) -0 - [(4- ( 4-morpholine?) Fen? L) met? L] ox? Ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Deox? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am ? no] -1, 2-O-methylene-D-neo-? nos? tol, (E) -0- [c? Clohex? lmet? l] ox? ma, 5-Desox? -5- [ [3- [4 - [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-methyl-1-oxo-2- (E) -propen? L] am? No] -1, 2-0-methylene-D-peo-? Nos? Tol, (Z) -0 - [(4-flurorophen? L) met? L] ox? Ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Deox? -β-D-er / fro- hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-methylene-D-neo-? Nos? Tol, (£) -0 - [(4-fluorophen? L) met? L] ox? Ma, 5-Desox? -5- [ [3- [4 - [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-methyl-1-oxo-2- (£) -propen? L] am? No] -1, 2-0-methylene-D-neo-? Nos? Tol, (£) -0 - [(2,4-d? Chlorophen? L) met? L] ox? Ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Deox? -β-D- er / f ro-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (£) -propen? l] am? no] -1, 2-0-methylene-D-neo-? nos? tol, (£) -0 - [(3,4-d? fluorophen?) met? l] ox? ma, 5- Desox? -5 - [[3- [4 - [(2,6-d? Deox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? drox? phen? l] -2-met? l-1 -oxo-2- (E) -propen? l] am? no] -1, 2-0-met? leno-D-neo-? nos? tol , (Z) -0 - [(3,4-d? Fluorophen? L) met? L] ox? Ma, 5-Deox? -5 - [[3- [4 - [(2,6-d? Deox ? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (£ ) -propen? l] am? no] -1, 2-0-methylene-Dr / eo-? us? tol, (£) -0 - [(furan-3-? l) met? l] ox ? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox?] -3-h? Drox? Phen? L] -2-met? L-1-oxo-2- (E) -propen? L] am? No] -1, 2-0-met? Leno-D-neo -?? us? tol, (Z) -0 - [(furan-3? l) met? l] ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d) ? deox? -ß-D-er / fro-hexofurans-5-ulos-1- il) oxy] -3-hydroxy-phenyl] -2-methyl-1-oxo-2- ()) -propenyl] amino] -1, 2-0-methylene-D-peo-inositol, ( Z) -0 - [(1,3-benzodioxol-5-yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2 -methyl-1 -oxo-2- (£) -propenyl] amino] -1,2-methylene-D-reo-inositol, (E) -0 - [(1,3-benzodioxol-5-yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-Dr / eo-inositol, (£) -0 - [(3-chlorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxy-phenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1,2-O-methylene-Dr / eo-inositol, (E) -0 - [(4-cyclohexylphenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- ()) -propenyl] amino] -1,2-O-methylene-D-peo-inositol, ()) -0 - [(3-aminophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxy-phenyl] -2 -met.l-1-oxo-2- (£) -propenyl] amino] -1,2-methylene-D- / 7-o-inositol, (E) -0 - [[(4-aminomethyl) phenyl] methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- ()) -propenyl] amino] -1,2-O-methylene-D-neo-inositol, (Z) -0- [3- (4-chlorophenyl) propyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- ()) -propenyl] amino] -1,2-methylene-D-reo-inositol, ()) -0- [3- (4-chlorophenyl) propyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxy-phenyl] - 2-methy1-1-oxo-2- ()) -propenyl] amino] -1,2-methylene-Dr / eo-inositol, (Z) -0 - [(3- (trifluoromethoxy) phenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2- methylene-1-oxo-2- ()) -propen? l] am? no] -1, 2-0-methylene-Dr / eo-? nos? tol, (E) -0 - [( 4- (1-p? Pepd? N? L) phen? L) met? L] ox? Ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Deox? ß-D-er / fro-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (£) - propen? l] am? no] -1, 2-0-methylene-Dr / eo-? nos? tol, (£) -0 - [(2-fluorofen? l) met? l] ox? ma, 5-Desox? -5- [4 - [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? fen? l] -2-met? l-1-oxo-2- (£) -propen? l] am? no] -1, 2-0-met? leno-D-neo-? nos? tol, ( Z) -0 - [(2-fluorophen? L) met? L] ox? Ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Deox? -β-D- er / fro-hexofurans-5-ulos-1 -? l) ox?] - 3-h? drox? phen? l] -2-met? l-1 -oxo-2- (£) -propen? l] am? no] -1, 2-0-methylene-D-peo-inositol, (£) -0 - [(2-phen? lt? o) et? l] ox? ma, 5-Desox? -5- [[3- [4 - [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1 -? L) ox?] - 3-h? Drox? Phen? ] -2-met? L-1-oxo-2- (E) -propen? L] am? No] -1, 2-0-met? Leno-D-peo-? Nos? Tol, (£) - 0 - [(benzofuran-5-? L) met? L] ox? Ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Deox? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -pr open? l] am? no] -1, 2-0-methanole-D- / 7eo-inositol, (Z) -0 - [(benzofuran-5?) met? l] ox? ma, 5 -Dox? -5 - [[3- [4 - [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h ? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-met? leno-D-peo? tol, (£) -0 - [(2-phen? l? r? m? d? n-5-?) met? l] ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1,2-methylene-D-neo-inositol, (£) -0 - [(3-fluoro-4 -metox? phen?) met? l] ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans- 5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? L-1-oxo-2- (E) -propen? L] am? No] -1 , 2-0-met? Leno-D-peo-? Nos? Tol, (E) -0 - [(3,4-d? H? Dro-2H-1-benzop? Ran-4-? L) met ? l] ox? ma, 5-Desox? -5 - [[3- [4 - [(5,6-d? deox? -5- (met? l (phen? lmet? l) am? no-aL -ga / acfo-furans-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1- oxo-2- (E) -propen? l] am? no] -1, 2-0-methylene-D-neo-? nos? tol, 5-Desox? -5 - [[3- [4- [(5,6-d? Deox? -5-phen? Lam? No-aL-ga / acfo-furans-1-? L) ox?] - 3-h? Drox? Phen? L] -2-met L-1-oxo-2- (E) -propen? l] am? no] -1,2-O-methylene-D-neo-? -osol, 5-Deox? -5 - [[ 3- [4 - [(2,6-d? Desox? -5-0 - [(3,4-d? Chlorophen? L) met? L] -β-Dr /? O-furans-1-? ) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-methylene -D-reo-? Nos? Tol, 5-Desox? -5 - [[3- [4 - [(2,6-d? Deox? -β-D-er / fro-hexofurans-5-ulos-1 -? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0- methylene-Dr / eo-? nos? tol, (E) -0 - [(furan-2-? l) met? l] ox? ma, 5-Desox? -5 - [[3- [4- [(Ac ~ do 5-met? l-ß-D-er / fro-hept-5- (E) -enofuranuron-1-? l? co) ox?] - 3-h? drox? phen? l] -2-methyl-1-oxo-2- (E) -propen? L] am? No] -1, 2-0-methylene-Dr / eo-? Us? Tol, ethyl ester, 5- Desox? -5 - [[3- [4- [N- (furan-2-? L) met? L] - (5-met? L -b-D-er / fro-hept-5- (E) -enofuranuron-1-? l-am? da) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no ] -1, 2-0-metheno-D-neo-inositol, 5-Deox? -5 - [[3- [4 - [(2,6-d? Deox? -β-D-er / fro -h exofurans-5-ulos-1-? l) ox? j-3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1.2-0-methylene-Dr / eo-inositol, (E) -0- [3- (phenol) propylene], 5-Desox? -5 - [[3- [4 - [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen?] -2- methanol-1-oxo-2- (E) -propen? l] am? no] -1,2-methyl-D-neo-? -osol tol, (Z) -0- (2 -propen-1-? l) ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans-5-ulos -1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? L-1-oxo-2- (E) -propen? L] am? No] -1, 2- 0-methanole-D-peo-? Nos? Tol, (E) -0- (2-propen-1-yl-oxime, 5-Deox? -5 - [[3- [4 - [(2,6- d? desox? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2 - (E) -propen? L] am? No] -1, 2-0-methylene-D-neo-mositol, (E) -0 - [(4-met? Lfen? L) met? L] ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox? ] -3-h? Drox? Phen? L] -2-met? L-1-oxo-2- (E) - propenyl] amino] -1,2-O-methylene-D-r / eo-inositol, (E) -0 - [(4-methoxyphenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-d-Deoxy-β-D-er / 'fro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] - 2-methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (E) -0 - [(3- (trifluoromethyl) phenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-5-0 - [(4-chlorophenyl) methyl] -β-Dr / 1)? -furans-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1, 2-0-methylene-Dr / eo-inositol; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- (E) -propenyl] amino] -1,2-O-methylene-Dr) eo-inositol, (E) -0- [diphenylmethyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-5-phenylcarbamate-β-Dr / 'f)? -furan-1-yl) oxy] -3-hydroxyphenyl] -2- meth1-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-5 - [(3,4-dichlorophenyl) methyl] carbamate-β-D- / 7Í)? -furans-1-yl ) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (EJ-propenyl] amino] -1, 2-0-methylene-D-peo-inositol; 5-deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1 -oxo -2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(3-chlorophenyl) methyl] oxime; 5-Deoxy-5 - [[ 3- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(3-chloro-2-fluorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-eripro-hexofurans-5-yl-1-yl) oxy] -3-hydroxy-phenyl] -2-methyl-1-oxo- 2- (E) -propenyl] amino] -1,2-methylene-Dr / eo-inositol, (E) -0 - [(3-chloro-2-fluorophenyl) methyl] oxime; 5-Deoxy -5 - [[3- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl- 1-oxo-2- (E) -propenyl] amino] -1,2-methylene-Dr / eo-inositol, (Z) -0 - [(3-chloro-4- fluorofen? l) met? l] ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans-5-ulos -1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? L-1-oxo-2- (E) -propen? L] am? No] -1, 2- 0-methylene-D-peo-inositol, (E) -0 - [(3-chloro-4-fluorophen?) Met? L] ox? Ma, 5-Desox? -5 - [[3- [4- [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? L -1-oxo-2- (E) -propen? L] am? No] -1, 2-O-methylene-Dr / eo-? Nos? Tol, (Z) -0 - [(3-chloro -5-fluorophen?) Met? L] ox? Ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Deox? -β-D-er / fro-hexofurans- 5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? L-1-oxo-2- (E) -propen? L] am? No] -1 , 2-O-methylene-Dr / eo-? Nos? Tol, (E) -0 - [(3-chloro-5-fluorophen? L) met? L] ox? Ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Fen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-met? leno-D-neo-? nos? tol, (Z) -0 - [(5-chloro-2-fluorophen? L) met? L] ox? Ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Deox? -β- D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? L-1-oxo-2- (E) -propen? l] amin] -1, 2-0-methylene-D-reo-? nos? tol, (E) -0 - [(5-c parrot-2-fluorophen?) met? l] ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans -5-ulos-1 -? L) ox?] - 3-h? Drox? Phen? L] -2-met? L-1 -oxo-2- (E) -propen? L] am? No] - 1, 2-0-methylene-Dr / eo-inositol, (Z) -0 - [(3,5-d? Fluorophen?) Met? L] ox? Ma, 5-Desox? -5 - [[3 - [4 - [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2 -met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-methylene-D-reo-? -osol tol, (E) -0- [ (3,5-d? Fluorophen?) Met? L] ox? Ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Deox? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1,2-O-methylene-D-peo-? nos? tol, (Z) -0 - [(4-chloro-3-fluorophen?) met? l] ox? ma, 5- Desox? -5 - [[3- [4 - [(2,6-d? Deox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-met? leno-D-neo-? nos? tol , (E) -0 - [(4-Chloro-3-fluorophenyl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-erythro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxy-phenyl] -2- methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, (E) -0 - [(4-chloro-1,3-benzodioxole -6-yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] - 2-methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(4-chloro-1,3-benzodioxole -6-yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-isositol, (E) -0 - [(5-chloro-1, 3- benzodioxol-6-yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-Dr / eo-inositol, (Z) -0 - [(5-chloro-1,3-benzodioxole -6-yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxy-phenyl] -2 -methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (E) -0 - [(4-chloro-1, 3- benzodioxol-5-yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-d-Deoxy-β-D-er / 'fro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] - 2-methyl-1-oxo-2- (E) -propenyl] amino] -1,2-O-methylene-D-A7eo-inositol, (Z) -0 - [(4-chloro-1, 3 -benzodioxol-5-yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxy-phenyl] -2-methyl-1 -oxo-2- (E) -propenyl] amino] -1, 2-0-methylene-D-neo-isositol, (E) -0 - [(2,3-dihydrobenzofuran -6-yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] - 2-methy1-1-oxo-2- (E) -propenyl] amino] -1,2-O-methylene-D-neo-inositol, (Z) -0 - [(2,3-dihydrobenzofuran-6 -yl) methyl] oxime; 5-Deoxy-5 - [[3- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-ulos-1-yl) oxy] -3- H? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-met? leno-Dr / eo-? nos tol, (E) -0 - [(2,3-d? h? drobenzofuran-5-? l) met? l] ox? ma, 5-Desox? -5 - [[3- [4 - [( 2,6-d? Desox? -β-D-epfro-hexofuranos-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? L-1-oxo -2- (E) -propen? L] am? No] -1, 2-0-methylene-D-neo-? Nos? Tol, (Z) -0 - [(2,3-d? H) Drobenzofuran-5-? l) met? l] ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans -5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? L-1-oxo-2- (E) -propen? L] am? No] - 1, 2-0-met? Leno-D-peo-? Nos? Tol, (E) -0- (1, 2,3,4-tetrah? Dronaphthalene-1-? L) ox? Ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? fen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-O-met? leno-D-peo-? nos? tol, ( Z) -0- (1, 2,3,4-tetrahydro-d-naphthalene-1-? L) ox? Ma, 5-Deox? -5 - [[3- [4 - [(2,6-d? Deox ? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E ) -propen? l] am? no] -1, 2-0-methylene-D-peo-? nos? tol, (E) -0- (7-chloro-1, 2,3,4-tetrah ? dronaphthalene-1-? l) ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans-5-ulos -1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? L-1-oxo-2- (E) -propen? L] am? No] -1, 2- 0-methylene-D-neo-mositol, (Z) -0- (7-chloro-1, 2,3,4-tetrah-dronaphthalene-1-? L) ox? Ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Fen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-met? leno-D-peo-? nos? tol, (E) -0- (7-fluoro-1, 2,3,4-tetrah-dronaphthalene-1-? L) ox? Ma, 5-Deox? -5 - [[3- [4 - [(2,6-d) ? deox? -β-D-enfro-hexofurans-5-ulos-1-? l) ox?] - 3-h? Drox? Phen? L] -2-met? L-1-oxo-2- (E) -propen? L] am? No] -1, 2-0-met? Leno-D-peo- ? tol?, (Z) -0- (7-fluoro-1, 2,3,4-tetrahydro-naphthalene-1-? l) ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Desox? -β-D-eptro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? L- 1-oxo-2- (E) -propen? L] am? No] -1,2-O-methylene-D-peo-? -osol, (E) -0- (8-chloro-3) , 4-d? H? Dro-2 / - / - 1-benzop? Ran-4- ?) ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans-5-ulos-1-? ) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-methylene -Dr / eo-inositol, (Z) -0- (8-chloro-3,4-d? -hydro-2H-1-benzop? Ran-4-? L) ox? Ma, 5-Desox? - 5 - [[3- [4 - [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen ? l] -2-met? l-1-oxo-2- (£) -propen? l] am? no] -1, 2-O-methylene-Dr / eo-? nos? tol, (E ) -0- (6-chloro-3,4-d? -hydro-2H-1-benzop? Ran-4-? L) ox? Ma, 5-Desox? -5 - [[3- [4- [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? L -1-oxo-2- (E) -propen? L] am? No] -1, 2-0-methylene-Dr / eo-? Nos? Tol, (Z) -0- (6-chloro- 3,4-d? H? Dro-2H-1-benzop? Ran-4-? L) ox? Ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Deox ? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E ) -propen? l] am? no] -1, 2-0-methylene-Dr / eo-inositol, (E) -0- (8-fluoro-3,4-d? h? dro-2H- 1-benzop? Ran-4-? L) ox? Ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Deox? -β-D-er / fro-hexofurans- 5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? L-1-oxo-2- (E) -propen? L] am? No] -1 ,2- 0-methylene-Dr / eo-? Nos? Tol, (Z) -0- (8-fluoro-3,4-d? H? Dro-2H-1-benzop? Ran-4-? L) ox ? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox?] -3-h? Drox? Phen? L] -2-met? L-1-oxo-2- (E) -propen? L] am? No] -1, 2-O-met? Leno-D-peo -?? us? tol, (E) -0- (6-fluoro-3,4-d? h? dro-2H-1-benzop? ran-4-? l) ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Fen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-methylene-Dr / eo-inositol, (Z) -0- (6-fluoro-3,4-d? H? Dro-2H-1-benzop? Ran-4-? L) ox? Ma, 5-Desox? -5 - [[3- [4 - [(2, 6-d? Desox? -β-D-er / io-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? L-1-oxo -2- (E) -propen? L] am? No] -1, 2-0-met? Leno-Dr / eo-? Nos? Tol, (E) -0 - [(qu? Nol? N-2 -? l) met? l] ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-epfro-hexofurans-5-ulos-1 -? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0- met? leno-D-neo- inositol, (Z) -0 - [(qu? nol? n-2-? l) met? l] ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d ? desox? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? L] am? No] -1, 2-0-met? Leno-D-rzeo-? Nos? Tol, (E) -0 - [(qu? Nol? N -3? ) met? l] ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans-5-ulos-1- (I) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-met ? leno-Dr / eo-mositol, (Z) -0 - [(qu? nol? n -3? l) met? l] ox? ma, 5-Desox? -5 - [[3- [4- [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? L -1-oxo-2- (E) -propen? L] am? No] -1, 2-0-methylene-D-neo-? Nos? Tol, (E) -0- [4- (phen ? lmet? l) phen? lmet? l] ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans- 5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? L-1-oxo-2- (E) -propen? L] am? No] -1 , 2-0-methylene-D-reo-ε-tol, (Z) -0 - [(4-phen? Lmet? L) phen? Lmet? L] ox? Ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Fen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-met? leno-Dr / eo-? nos? tol, (E) -0- [4- (fen ox?) fen? lmet? l] ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans-5- ulos-1 -? l) ox?] - 3-h? drox? phen? l] -2-met? l-1 -oxo-2- (E) -propen? l] am? noj-1, 2- 0-methylene-D- /? Eo-? Nos? Tol, (Z) -0- [4- (fenox?) Phen? Lmet? L] ox? Ma, 5-Desox? -5 - [[3 - [4 - [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2 -met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-met? leno-D-peo-? nos? tol, (Z) -0- [ (4-phenolite-az-2-?) Met? L] ox? Ma, 5-Deox? -5 - [[3- [4 - [(2,6-d? Deox? -β-D -er / fro-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l ] am? noj-1, 2-O-met? leno-D-peo-? nos? tol, (E) -0 - [(4-phen? lt? az-2-? l) met? l] ox ? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox?] -3-h? Drox? Phen? L] -2-met? L-1-oxo-2- (E) -propen? L] am? No] -1, 2-0-met? Leno-D-neo -? us? tol, (Z) -0- [1- (2,4- d? fluorophen?) prop? l] ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans-5 -ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-O-methylene-D-peo-? Nos? Tol, (E) -0- [1- (2,4-d? Fluorophen? L) prop? L] ox? Ma, 5-Desox? 5 - [[3- [4 - [(2,6-d? Desox? -β-D-epfro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? ] -2-met? L-1-oxo-2- (E) -propen? L] am? No] -1, 2-0-met? Leno-D-neo-? Nos? Tol, (Z) -0- [1- (3,4-d? Fluorophen? L) et? L] ox? Ma, 5-Deox? -5 - [[3- [4 - [(2,6-d ? desox? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? L] am? No] -1, 2-O-methylene-Dr / eo-? Nos? Tol, (E) -0- [1- (3,4-d? Fluorophen? l) et? l] ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans-5-ulos-1 -? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-O- methylene-D-peo-? nos? tol, (Z) -0- [1- (2,4-d? fluorophen? l) et? l] ox? ma, 5-Desox? -5 - [[ 3- [4 - [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen?] - 2-met? L-1-oxo-2- (E) -propen? L] am? No] -1, 2-0-methylene-D-neo-inositol, (E) -0- [1- (2 , 4-d? Fluorophen? L) et? L] ox? Ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Deox? -β-D-er / fro- hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-O-methylene-Dr / eo-? Nos? Tol, (Z) -0- [1 - (3,5-d? Fluorophen? L) et? L] ox? Ma, 5- Desox? -5 - [[3- [4 - [(2,6-d? Deox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-methylene-D-peo-? , (E) -0 - [1- (3,5-d? Fluorophen? L) et? L] ox? Ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Deox? -ß- D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? L-1-oxo-2- (E) -propen? l] amin] -1, 2-0-methylene-Dr / eo-? nos? tol, (Z) -0- [1- (3-chloro-2,6-d? fluorophen? l) et? l] ox? ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans-5-ulos-1? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-methylene- D-neo-inositol, (E) -0- [1- (3-chloro-2,6-d? Fluorophen? L) et? L] ox? Ma, 5-Desox? - 5 - [[3- [4 - [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen ? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-met? leno-D-neo-? nos? tol, (E ) -0 - [(3-chloro-2,6-d? Fluorophen?) Met? L] ox? Ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? deoxy? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- ( E) -propen? L] am? No] -1, 2-0-methylene-D-peo-? -osol, (Z) -0 - [(3-chloro-2,6-d? Fluorophen (l) methyl] ox, 5-Desox? -5 - [[3- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans-5-ulos- 1-) l) ox?] - 3-h? Drox? Phen? L] -2-met? L-1-oxo-2- (E) -propen? L] am? No] -1, 2-0 -met? leno-D-neo-? nos? tol, (E) -0 - [(2,4-d? fluorophen? l) met? l] ox? ma, 5-Desox? -5 - [[3 - [4 - [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2 -met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-methylene-Dr / eo-? nos? tol, (Z) -0- [ (2,4-d? Fluorophen? L) met? L] ox? Ma, 5-Desox? -5 - [[3- [4 - [(2,6-d? Deox? -β-D-ara6 / po-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1 -oxo-2- (E) -propen? l] am? no] -1, 2-O-methylene-D-peo-? nos? tol, (Z) -0 - [(3,5-d? chlorophen? l)] ox? ma, 5-Desox? - 5- [[3- [4 - [(2,6-d? Desox? -β-D-araí) / r / o-hexofurans-5-ulos-1 -? L) ox?] - 3-h? Drox? fen? l] -2-met? l-1 -oxo-2- (E) -propen? l] am? no] -1, 2-0-methylene-D-reo-mositol, (E) -0- [(3,5-d? Chlorophen? L)] ox? Ma, 5-Desox? -5 - [[3- [4 - [(6-d? Deox? -β-D-aray) / r / o -hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no ] -1, 2-0-methylene-D-reo-ε-tol, (E) -0 - [(3-chlorophen? L)] ox? Ma, 5-Desox? -5 - [[3 - [4 - [(6-d? Desox? -β-D-araí) / r / o-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen?] - 2-met? L-1-oxo-2- (E) -propen? L] am? No] -1, 2-0-met? Leno-D-peo-inositol, (E) -0 - [(3 -fluorophen? l)] ox? ma, 5-Deox? -5- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-methylene- D-neo-? Nos? Tol, (Z) -0 - [(3,5-d? Chlorophen? L) met? L] ox? Ma, 5-Desox? -5- [4 - [(2.6 -d? desox? -β-D-er / fro-hexofurans-5- ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1-oxo-2- (E) -? ropenyl] amino] -1,2-methylene-D-peo-inositol, (E) -0 - [(3,5-Dichlorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-d-deoxy-β-D-er / 'fro-hexofurans-5-uls-1-yl) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-Dr / eo-inositol, (Z) -0- (phenyl) oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1- oxo-2- (E) -propenyl] amino] -1,2-O-methylene-D-peo-isositol, (E) -0- (fenii) oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1- oxo-2- (E) -propenyl] amino] -1,2-O-methylene-D-peo-inositol, (Z) -0- (3-chloro-4-fluorophenyl) oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-uls-1-yl) oxy] -3-hydroxyphenyl] -2-methylene- 1-oxo-2- (E) -propenyl] amino] -1,2-methylene-Dr / eo-inositol, (E) -0- (3-chloro-4-fluorophenyl) oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2- methyl-1-oxo-2- (E) -propenyl] amino] -1,2-methylene-Dr / eo-inositol, (Z) -0 - [(2,1, 3-benzoxadiazol-5-yl) ) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-ulos-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1 - oxo-2- (E) -propenyl] amino] -1,2-methylene-D-peo-inositol, (E) -0 - [(2,1, 3-benzoxadiazol-5-yl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-β-D-ep'fro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methylene-1 -oxo-2- (E) -propenyl] amino] -1,2-O-methylene-Dr / eo-inositol, (E) -0 - [(2,3,5,6-tetrafluorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-uls-1-yl) oxy] -3-hydroxyphenyl] -2-methyl- 1-oxo-2- (E) -propenyl] amino] -1,2-methylene-D-neo-inositol, (Z) -0 - [(2,3,5,6-tetrafluorophenyl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-β-D-er-ro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1- oxo-2- (E) - propen? l] am? no] -1, 2-O-methylene-D-reo-? -osol, (E) -0 - [(2,3-d? fluorophen? l) met? l] oxime, 5-Deox? -5- [4 - [(2,6-d? desox? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox?] - 3- h? drox? phen? l] -2-met? l-1-oxo-2- (£) -propen? l] am? no] -1, 2-0-methylene-Dr / eo-inositol, (Z ) -0 - [(2,3-d? Fluorophen? L) met? L] ox? Ma, 5-Desox? -5- [4 - [(2,6-d? Deox? -β-D-er) / fro-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am ? no] -1, 2-0-met? leno-Dr / eo-? nos? tol, (E) -0 - [(4-phen? L-furan-3? L) met? L] ox? Ma, 5-Desox? -5- [4 - [(2,6-d? Deox? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (£) -propen? l] am? no] -1, 2-0-methylene-D-neo-inositol, (Z) -0 - [(4-phenol-furan-3?) met? ] ox? ma, 5-Desox? -5- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox?] - 3 -h? drox? fen? l] -2-met? l-1-oxo-2- (£) -propen? l] am? no] -1, 2-0-methylene-D-neo-? nos? tol, (E) -0 - [(4-phenol-furan-2-? l) met? l] ox? ma, 5-Desox? -5- [4 - [(2,6-d) ? desox? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (£) -propen? L] am? No] -1, 2-0-methylene-D-7eo-inositol, (Z) -0 - [(4-phenol-furan-2-? L) methyl] ox, 5-Desox? -5- [4 - [(2,6-d? deox? -β-D-er / fro-hexofurans-5-ulos-1-? l) ox? ] -3-h? Drox? Phen? L] -2-met? L-1 -oxo-2- (£) -propen? L] am? No] -1, 2-0-methylene-D- /? eo-? nos? tol, (E) -0 - [(2,3-d? fluoro-6-methox? met? l) met? l] ox? ma, 5-Desox? -5- [4 - [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Phen? L] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-methylene-Dr / eo-inositol, (Z) -0 - [(2,3 -d? fluoro-6-methox? phen?) met? l] ox? ma, 5-Desox? -5- [4 - [(2,6-d? deox? -β-D-er / fro- hexofurans-5-ulos-1-? l) ox?] - 3-h? drox? phen? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] -1, 2-0-methylene-Dr / eo-? Nos? Tol, (E) -0 - [(3-chloro-t? Ofen-2-? L) met? L] ox? Ma, 5 -Dox? -5- [4 - [(2,6-d? Desox? -β-D-er / fro-hexofurans-5-ulos-1-? L) ox?] - 3-h? Drox? Fen ? l] -2-met? l-1-oxo-2- (E) -propen? l] am? no] - 1,2-O-methylene-D-peo-inositol, (Z) -0 - [(3-chloro-thiophen-2-yl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1- oxo-2- (E) -propenyl] amino] -1,2-methylene-Dr / eo-inositol, (E) -0 - [(5-chloro-thiophen-2-yl) methyl] oxime; 5-Deoxy-5- [4 - [(2,6-dideoxy-β-D-er / 'fro-hexofurans-5-yl-1-yl) oxy] -3-hydroxyphenyl] -2-methyl-1- oxo-2- (E) -propenyl] amino] -1,2-O-methylene-D-peo-inositol, (Z) -0 - [(5-chloro-thiophen-2-yl) methyl] oxime; and the pharmaceutically acceptable salts, prodrugs and solvates of said compounds.

10. A pharmaceutical composition for the treatment of a bacterial infection, a protozoan infection or a disorder related to a bacterial infection or a protozoal infection, in a mammal, fish or bird, comprising a therapeutically effective amount of a compound of the claim 1 and a pharmaceutically acceptable vehicle.

11. The use of a compound as claimed in claim 1, for the manufacture of a medicament for the treatment of a bacterial infection, a protozoal infection or a disorder related to a bacterial infection or a protozoal infection, in a mammal, fish or bird.

12. A process for preparing a compound of claim 1 wherein R1 and R2 are taken together to form = N-OR3, which comprises treating a compound of the formula wherein X is a protecting group, with a hydroxylamine of the formula H2N-OR3, or a salt of said hydroxylamine, wherein R3 is as defined above, in an inert solvent, with the optional addition of a base if used the hydroxylamine salt, at a temperature ranging from about 0 ° C to 65 ° C, and the subsequent deprotection using a fluoride source.

13. The method of claim 12, wherein said inert solvent is methanol, ethanol or pyridine, or a mixture of the above solvents, said optional bases are Na2C03 or K2C0, said temperature range is from 50 ° C to 60 ° C. ° C and said fluoride source is tetrabutylammonium fluoride or hydrogen fluoride-pyridine complex.