Synthesis of the methyl alpha-glycosides of a di-, tri-, and a tetra-saccharide fragment mimicking the terminus of the O-polysaccharide of Vibrio cholerae O:1, serotype Ogawa.
Methyl 4-(3-deoxy-L-glycero-tetronamido)-4,6-dideoxy-2-O-methyl-alpha-D- mannopyranoside was acetylated, and the fully protected methyl glycoside was treated with dichloromethyl methyl ether-ZnCl2 (DCMME-ZnCl2) reagent to give 3-O-acetyl-4-(2,4-di-O-acetyl-3- deoxy-L-glycero-tetronamido)-4,6-dideoxy-2-O-methyl-alpha-D-mannop yranosyl chloride (3). Condensation of 3 with methyl 3-O-acetyl-4-(2,4-di-O-acetyl-3-deoxy-L-glycero-tetronamido)-4,6- dideoxy-alpha-D-mannopyranoside (4) gave the fully acetylated disaccharide 5, which was deacetylated yielding the methyl alpha-glycoside of title disaccharide. The disaccharide glycosyl donor required for the blockwise synthesis of the title tri- and the tetra-saccharide, 3-O-acetyl-4-(2,4-di-O-acetyl-3-deoxy-L-glycero-tetronamido)-4,6-d ideoxy-2-O- methyl-alpha-D-mannopyranosyl-(1-->2)-3-O-acetyl-4- (2,4-di-O-acetyl-3-deoxy-L-glycero-tetronamido)-4,6-dideoxy-alpha- D- mannopyranosyl chloride (12), was obtained by condensation of 3 with the 1-O-acetyl analog of 4, followed by treatment of the disaccharide formed with DCMME-ZnCl2. The synthesis of the methyl alpha-glycoside of the title trisaccharide involved a condensation of 12 with 4, followed by deacetylation. Similarly, the condensation of 12 with 15, the latter being the analog of 5 having a free HO-2, followed by deacetylation, gave the methyl alpha-glycoside of the title tetrasaccharide. All glycosylation reactions were mediated by silver trifluoromethanesulfonate in the presence of 2,4,6-trimethylpyridine. 4-(3-Deoxy-L-glycero-tetronamido)-4,6-dideoxy-2-O-methyl-alpha,bet a-D- mannopyranose was prepared for the first time. It was characterized by NMR spectroscopy, and via its crystalline per-O-acetyl derivative. It is the saccharide whose alpha-form constitutes the terminal, non-reducing end-group of the O-PS of V. cholerea O:1, serotype Ogawa.
Lei
P
P
NIDDK, National Institutes of Health, Bethesda, MD 20892-0815, USA.
Ogawa
Y
Y
Kovác
P
P
D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D009682:Magnetic Resonance Spectroscopy; D008358:Mannose / Q000031:analogs & derivatives; D008362:Mannosides / Q000138:chemical synthesis* / Q000737:chemistry; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019081:O Antigens / Q000737:chemistry*; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D012703:Serotyping; D014734:Vibrio cholerae / Q000737:chemistry* / Q000145:classification
D008362:Mannosides; D019081:O Antigens; D009844:Oligosaccharides; C057033:4-amino-4,6-dideoxy-D-mannose; D008358:Mannose