Synthesis of a position isomer of ganglioside GD 3having an α-Neu5Ac-(2→9)-α-Neu5Ac linkage

Abstract

A position isomer of ganglioside GD 3 has been synthesized in which N-acetylneuraminic acid (Neu5Ac) is linked α-glycosidically at C-9 of the Neu5Ac residue of the ganglioside GM 3 structure. The coupling of 2-(trimethylsilyl)ethyl O-(6- O-benzoyl-β- d-galactopyranosyl)-(1→4)-2,6-di- O-benzoyl-β- d-glucopyranoside with methyl O-(methyl 5-acetamido-4,7,8,9-tetra- O-acetyl-3,5-dideoxy- d- glycero-α- d- galacto-2-nonulopyranosylonate)-(2→ 9)-(methyl 5-acetamido-4,7,8-tri- O-acetyl-3,5-dideoxy-2-thio- d- glycero- d- galacto-2-nonulopyranosid)onate, prepared from the corresponding 2-(trimethylsilyl)ethyl glycoside by selective removal of the 2-(trimethylsilyl)ethyl group, 1- O-acetylation, and introduction of the methylthio group with trimethyl(methylthio)silane, using N-iodosuccinimide-trifluoromethanesulfonic acid as a glycosylation catalyst, gave a tetrasaccharide ( 5). Compound 5 was converted, via O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and subsequent imidate formation, into a protected α-Neu5Ac-(2→9)-α-Neu5Ac-(2→3′)-α-lactosyl trichloroacetimidate ( 8). Glycosylation of (2 S,3 R,4 E)-2-azido-3- O-benzoyl-4-octadecene-1,3-diol with 8 afforded a ceramide precursor which was transformed, via selective reduction of the azido group, coupling with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester groups, into to the title ganglioside.