Stereoselective Syntheses of the Conjugation-Ready, Downstream Disaccharide and Phosphorylated Upstream, Branched Trisaccharide Fragments of the O-PS of Vibrio cholerae O139.
N-Bromosuccinimide-mediated 4,6-O-benzylidene ring opening in 8-azido-3,6-dioxaoctyl 4,6-O-benzylidene-2-deoxy-2-trichloroacetamido-β-D-glucopyranoside afforded the corresponding 4-O-benzoyl-6-bromo-6-deoxy analogue, which was coupled with 3,4,6-tri-O-acetyl-2-O-benzyl-α-D-galactopyranosyl chloride to give the 1,2-cis α-linked disaccharide as the major product. Conventional hydroxyl group manipulation in the latter and products of further conversions gave the desired, functionalized disaccharide α-D-GalpA-(1→3)-β-D-QuipNAc. The rare, foregoing sequence forms the downstream end in the O-specific polysaccharide of both Vibrio cholerae O22 and O139. Halide-assisted glycosylation at 4(I)-OH in 8-azido-3,6-dioxaoctyl 6-O-benzyl-2-deoxy-3-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-2-trichloroacetamido-β-D-glucopyranoside, obtained by regioselective reductive opening of the acetal ring in the parent 4(I),6(I)-O-benzylidene derivative, with 2,4-di-O-benzyl-α-colitosyl bromide, gave exclusively the α-linked trisaccharide. The latter was sequentially deacetylated and selectively benzylated to give 8-azido-3,6-dioxaoctyl 2,4-di-O-benzyl-3,6-dideoxy-α-L-xylo-hexopyranosyl-(1→4)-[3-O-benzyl-β-D-galactopyranosyl-(1→3)]-6-O-benzyl-2-deoxy-2-trichloroacetamido-β-D-glucopyranoside. Subsequent selective phosphorylation of the triol, thus obtained, with 2,2,2-trichloroethyl phosphorodichloridate afforded isomeric (R,S)-(P)-4(II),6(II)-cyclic phosphates, which were both obtained in crystalline form and fully characterized. Each of the latter was globally deprotected by catalytic (Pd/C) hydrogenation/hydrogenolysis to give the desired, amino-functionalized, spacer-equipped, phosphorylated upstream trisaccharide fragment of the O-PS of V. cholerae O139.
†NIDDK, LBC, Section on Carbohydrates, National Institutes of Health, Bethesda, Maryland 20892-0815, United States.|‡Department of Chemistry, Faculty of Science, Alexandria University, Alexandria 21321, Egypt.
Sameh E
SE
Soliman
†NIDDK, LBC, Section on Carbohydrates, National Institutes of Health, Bethesda, Maryland 20892-0815, United States.
Pavol
P
Kováč
D000081:Acetamides / Q000737:chemistry*; D001597:Benzylidene Compounds / Q000737:chemistry*; D001974:Bromosuccinimide / Q000737:chemistry*; D004187:Disaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D006031:Glycosylation; D009844:Oligosaccharides / Q000737:chemistry; D010766:Phosphorylation; D014312:Trisaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D041242:Vibrio cholerae O139
D000081:Acetamides; D001597:Benzylidene Compounds; D004187:Disaccharides; D009844:Oligosaccharides; D014312:Trisaccharides; D001974:Bromosuccinimide