A facile, regio- and stereo-selective synthesis of ganglioside GM3

Abstract

Gangliosides GM3, containing three different fatty acyl groups at the ceramide moiety, have been synthesized. Coupling of 2-(trimethylsilyl)ethyl O-(6-O-benzoyl-beta-D-galactopyranosyl)-(1----4)- 2,6-di-O-benzoyl-beta-D-glucopyranoside (4), prepared from 2-(trimethylsilyl)ethyl beta-lactoside (1) by selective 3'-O-benzylation, O-benzoylation, and subsequent removal of the benzyl group, with methyl (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-alpha-D- galacto - 2-nonulopyranosid)onate (5) using dimethyl(methylthio)sulfonium triflate as a glycosyl promoter, gave 2-(trimethylsilyl)ethyl O-(methyl 5-acetamido-4,7,8,9-tetra-O- acetyl-3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosylonate++ +)-(2----3)- O-(6-O- benzoyl-beta-D-galactopyranosyl)-(1----4)-2,6-di-O-benzoyl-beta-D- glucopyranoside (6), which was converted, via O-acetylation, selective removal of the 2-(trimethylsilyl)-ethyl group, and subsequent imidate formation, into the alpha-N-acetylneuraminyl-(2----3')-lactose trichloroacetimidate 9. Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (10) with 9 afforded the beta-glycoside 11, which was converted, via selective reduction of the azide group, coupling with fatty acids, O-deacetylation, and de-esterification, into the title compounds.