Synthesis of four glycosides of a disaccharide fragment representing the terminus of the O-polysaccharide of Vibrio cholerae O:1, serotype Inaba, bearing aglycons suitable for linking to proteins

Methyl 4-azido-3-O-benzyl-4,6-dideoxy-α-d-mannopyranoside was converted into the crystalline 2-(trimethylsilyl)ethyl 4-azido-2-O-benzoyl-3-O-benzyl-4,6-dideoxy-α-d-mannopyranoside. Debenzoylation of the latter, followed by glycosylation of the resulting 2-hydroxy derivative with 2-O-acetyl-4-azido-4,6-dideoxy-α-d-mannopyranosyl chloride, gave the 2-(trimethylsilyl)ethyl glycoside of the corresponding disaccharide (8). Deacetylation of 8, followed by reduction of the resulting 4-azido-2-hydroxy derivative with H2S, gave the corresponding amine 10. The latter was treated with 4-O-benzyl-3-deoxy-l-glycero-tetronic acid to give, after debenzylation and acetylation, the fully protected 2-(trimethylsilyl)ethyl α-glycoside of the disaccharide fragment of the O-PS of Vibrio cholerae 0:1, serotype Inaba (13). Compound 13 was transformed into the corresponding 1-trichloroacetimidate which was treated, separately, with methyl 6-hydroxy-hexanoate and 2-(2-methoxycarbonylethylthio)ethanol, to give two analogs of 13 possessing a differing linkage arm, namely the methyl esters 16 and 17. Each of 16 and 17 was treated with aqueous sodium hydroxide, followed by a cation-exchange resin, to give the two corresponding carboxylic acids (19 and 22). Alternately, treatment of 16 and 17 with hydrazine hydrate gave the acid hydrazides 20 and 23.