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-alpha-D-mannopyranoside was converted into the crystalline 2-(trimethylsilyl)ethyl 4-azido-2-O-benzoyl-3-O-benzyl-4,6-dideoxy-alpha-D-mannopyranoside. Debenzoylation of the latter, followed by glycosylation of the resulting 2-hydroxy derivative with 2-O-acetyl-4-azido-4,6-dideoxy-alpha-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 alpha-glycoside of the disaccharide fragment of the O-PS of Vibrio cholerae O: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.
Ogawa
Y
Y
NIDDK, National Institutes of Health, Bethesda, MD 20892-0815, USA.
Lei
P
P
Kovác
D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D022121:Cholera Vaccines; D004187:Disaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008362:Mannosides / Q000138:chemical synthesis; D008969:Molecular Sequence Data; D019081:O Antigens / Q000737:chemistry*; D012210:Rhamnose / Q000031:analogs & derivatives; D012703:Serotyping; D014734:Vibrio cholerae / Q000737:chemistry* / Q000145:classification / Q000276:immunology
D022121:Cholera Vaccines; D004187:Disaccharides; D006027:Glycosides; D008362:Mannosides; D019081:O Antigens; D012210:Rhamnose