title: Synthesis of a Conjugation-Ready, Phosphorylated, Tetrasaccharide Fragment of the O-PS of Vibrio cholerae O139.
abstract: A new pathway to the tetrasaccharide α-Colp-(1→2)-4,6-P-β-d-Galp-(1→3)-[α-Colp-(1→4)]-β-d-GlcpNAc-1-(OCH2CH2)3NH2 has been developed. Glycosylation of 8-azido-3,6-dioxaoctyl 4,6-O-benzylidene-2-deoxy-2-trichloroacetamido-β-d-glucopyranoside with 3,4,6-tri-O-acetyl-2-O-bromoacetyl-α-d-galactopyranosyl bromide afforded the β-linked disaccharide. Debromoacetylation followed by reductive opening of the benzylidene acetal afforded the disaccharide diol acceptor. Halide-assisted glycosylation with 2,4-di-O-benzyl-α-colitosyl bromide gave the 1,2-cis-coupling product. Deacetylation followed by regioselective phosphorylation gave isomeric (R,S)-(P)-4(II),6(II)-cyclic phosphates, which were globally deprotected by one-step catalytic (Pd/C) hydrogenation/hydrogenolysis. The target tetrasaccharide, obtained in high overall yield, is amenable for conjugation to proteins.
authors.affiliation: 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.
authors.forename: Sameh E
authors.initials: SE
authors.lastname: Soliman
authors.affiliation: NIDDK, LBC, Section on Carbohydrates, National Institutes of Health , Bethesda, Maryland 20892-0815, United States.
authors.forename: Pavol
authors.initials: P
authors.lastname: Kováč
mesh_terms: D001686:Biological Phenomena; D002240:Carbohydrate Sequence; D002384:Catalysis; D005960:Glucosides / Q000737:chemistry*; D006031:Glycosylation; D007536:Isomerism; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D010766:Phosphorylation; D041242:Vibrio cholerae O139 / Q000737:chemistry*
chemical_list: C000606076:8-azido-3,6-dioxaoctyl 4,6-O-benzylidene-2-deoxy-2-trichloroacetamido-beta-D-glucopyranoside; D005960:Glucosides; D009844:Oligosaccharides