Stereoselective synthesis of l-vancosamine methyl β-glycoside by addition of an organocerium reagent to O-benzyloxime ethers

Abstract

The methyl β-glycopyranoside of l-vancosamine ( 1, 3-amino-2,3,6-trideoxy-3-C- methyl- l -lyxo- hexose ), a constituent of vancomycin and related glycopeptide antibiotics, was synthesized stereoselectively from methyl 2,6-dideoxy-β- l -lyxo- hexopyranoside ( 2) in eight steps. Compound 2 was subjected in sequence to regioselective 3- O- p-methoxybenzylation, 4- O- tert-butyldimethylsilylation, oxidative 3- O-deprotection, and pyridinium dichromate oxidation to give methyl 4-O-tert- butyldimethylsilyl-2,6-dideoxy-β- l -threo- hexopyranosid-3-ulose ( 8). O-Benzyloximation of 8 and removal of the tert-butyldimethylsilyl protective group furnished methyl 2,6-dideoxy-β- l -threo- hexopyranosid-3-ulose O- benzyloxime ( 12). Addition of a methylcerium reagent to 12 provided the branched-chain hydroxyamino sugar methyl 3-benzyloxyamino-2,3,6-trideoxy-3-C- methyl-β- l -lyxo- hexopyranoside ( 14) which was easily converted into the title compound by hydrogenolysis. On the other hand, reaction of the 4-benzyl ether 11 with the organocerium reagent gave only traces of the 3- epi-analogue of 14, methyl 4-O- benzyl-3-benzyloxyamino-2,3,6-trideoxy-3-C- methyl-β- l -xylo- hexopyranoside .