Synthesis of the methyl alpha-glycoside of a trisaccharide mimicking the terminus of the O antigen of Vibrio cholerae O:1, serotype Inaba.
Coupling of methyl 4-amino-4,6-dideoxy-2-O-4-methoxybenzyl-alpha-D-mannopyranoside, obtained from the corresponding 4-azido derivative by treatment with H2S, with 3-deoxy-L-glycero-tetronolactone gave the crystalline methyl 4-(3-deoxy-L-glycero-tetronamido)-4,6-dideoxy-2-O-4-methoxybenzyl- alpha-D- mannopyranoside (7). Subsequent acetylation of 7, followed by O-demethoxybenzylation of the 8 formed gave the crystalline methyl 3-O-acetyl-4,6-dideoxy-4-(2,4-di-O-acetyl-3-deoxy-L-glycero-tetronami do)-alpha- D-mannopyranoside (9), which was used as the key intermediate in the construction of the title trisaccharide. To make a glycosyl donor allowing the extension of the oligosaccharide chain at O-2, compound 9 was converted, via conventional transformations, into 3-O-acetyl-2-O-bromoacetyl-4,6-dideoxy-4-(2,4-di-O-acetyl-3-deoxy-L-glyc ero- tetronamido)-alpha-D-mannopyranosyl chloride (12). Condensation of 12 with 9 afforded the disaccharide 20 having a selectively removable protecting group at O-2(2). The latter was O-debromoacetylated, and the disaccharide nucleophile thus obtained was treated with 2,3-di-O-acetyl-4,6-dideoxy-4-(2,4-di-O-acetyl-3-deoxy-L-glycero-tetr onamido)- alpha-D-mannopyranosyl chloride to give, after O-deacetylation, the target, title trisaccharide. The constituent monosaccharide of the O-specific polysaccharide antigen of Vibrio cholerae serotype Inaba, 4-(3-deoxy-L-glycero-tetronamido)-4,6-dideoxy-D-mannopyranose (18), was obtained from the peracetate of its methyl alpha-glycoside by acetolysis, followed by O-deacetylation. The amorphous compound 18 was characterized by 1H and 13C NMR spectroscopy and through its crystalline alpha-per-O-acetyl derivative.
Lei
P S
PS
NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
Ogawa
Y
Y
Kovác
P
P
D002240:Carbohydrate Sequence; D009682:Magnetic Resonance Spectroscopy; D008759:Methylglycosides / Q000138:chemical synthesis* / Q000737:chemistry; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019081:O Antigens / Q000737:chemistry*; D011135:Polysaccharides, Bacterial / Q000737:chemistry; D012703:Serotyping; D014312:Trisaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D014734:Vibrio cholerae / Q000145:classification / Q000276:immunology*
D008759:Methylglycosides; D019081:O Antigens; D011135:Polysaccharides, Bacterial; D014312:Trisaccharides