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

Abstract

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 H 2S, 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.