Synthesis of spacer-equipped phosphorylated di-,tri-and tetrasaccharide fragments of the O-specific polysaccharide of Vibrio cholerae O139

摘要

The synthesis of oligosaccharide fragments of the O-specific polysaccharide of Vibrio cholerae O139 containing a 4,6-cyclic phosphate galactose residue linked to GlcNAc is described.8-Azido-3,6-dioxaoctyl 2,3,4,6-tetra-O-acetyl-beta-D-galactopyr-anosyl-(l->3)-2-acetamido-4,6-O-benzylidene-2-deoxy-beta-D-glucopyranoside,obtained by condensation of 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide and 8-azido-3,6-dioxaoctyl 2-acetamido-4,6-O-benzylidene-2-deoxy-beta-D-glucopyranoside,was converted to 8-azido-3,6-dioxaoctyl 3-O-benzyl-beta-D-galactopyranosyl-(1->3)-2-acetarnido-6-O-benzyl-2-deoxy-beta-D-glucopyranoside(6)by reductive opening of the acetal,followed by deacetylation and selective benzylation.Phosphorylation of 6 furnished two isomeric 4,6-cyclic 2,2,2-trichloroethyl phosphates.Glycosylation of the(S)-phosphate with 2,4-di-O-benzyl-3,6-dideoxy-alpha-L-xylo-hexopyranosyl bromide under halide-assisted conditions gave the desired tetrasaccharide,together with a trisaccharide.Global deprotection and reduction of the azide to an amine was effected by catalytic hydrogenation/hydrogenolysis to give the deprotected tetrasaccharide,which is functionalized for conjugation.