Synthesis of four structural elements of xylose-containing carbohydrate chains from N-glycoproteins

Abstract

The synthesis of the oligosaccharides β-D-Xylp-(1->2)-β-D-Manp-OMe (12), β-D-Xylp-(1->2)-[α-D-Manp-(1->6)]-β-D-Manp-OMe (17), β-D-Xylp-(1->2)-[α-D-Manp-(1->3)]- β-D-Manp-OMe (21), and β-D-Xylp-(1->2)-[α-D-Manp-(1->3)][α-D-Manp-(1->6)]-β-D-Manp-OMe (25) is described. Methyl 3-O-benzyl-4,6-O-isopropylidene-β-D-mannopyranoside (6) was prepared from the corresponding gluco-epimer (4) by oxidation, followed by stereoselective reduction. Condensation of 6 with 2,3,4-tri-O-acetyl-α-D-xylopyranosyl bromide in the presence of mercuric cyanide gave a 1:9 mixture of methyl 3-O-benzyl-4,6-O-isopropylidene-2-O-(2,3,4-tri-O-acetyl-α- (7a) and -β-D-xylopyranosyl)-β-D-mannopyranoside (7), and then 7 was converted into the acetylated disaccharide-glycoside 11. Regioselective mannosylation, with 2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl bromide, at position 6 of deisopropylidenated 7 (8), using mercuric bromide as a promoter, afforded the trisaccharide-glycoside derivative 13, which was transformed into the acetylated trisaccharide-glycoside 16. The disaccharide derivative 10, obtained from 8, and the trisaccharide derivative 15, obtained from 13, were glycosylated at position 3 with O-(2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl)trichloroacetimidate (19), using trimethylsilyl triflate as a promoter, giving rise to acetylated tri- (20) and tetra-saccharide (24) derivatives, respectively. O-Deacetylation of 11, 16, 20, and 24 gave 12, 17, 21, and 25, respectively.