SYNTHETIC STUDIES ON SIALOGLYCOCONJUGATES .41. A FACILE TOTAL SYNTHESIS OF GANGLIOSIDE GM2

A stereocontrolled, facile total synthesis of ganglioside GM2 is described. Coupling of 2- (trimethylsilyl)ethyl O-(2,6-di-O-benzyl-beta-D-galactopyranosyl)-(1 --> 4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside (2), prepared from 2-(trimethylsilyl)ethyl beta-lactoside (1) by selective 3',4'-O-isopropylidenation, O-benzylation, and subsequent removal of the isopropylidene group, with methyl (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto-2-nonulopyranosid)onate (4) using N-iodosuccinimide (NIS), gave the trisaccharide (5), which on condensation with methyl 6-O-benzoyl -2-deoxy-3,4-0-isopropylidene-2-phthalimido-1-thio-beta-D-galactopyranoside (11) , gave the protected ganglioside GM2 Oligosaccharide 12. Compound 12 was transformed, via O-deisopropylidenation, O-acetylation, removal of the phthaloyl group, N-acetylation, removal of the benzyl groups followed by O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and subsequent imidate formation, into the final glycosyl donor 19. Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (20) with the alpha-trichloroacetimidate 19 gave the beta-glycoside 21, which on channeling through selective reduction of the azide group, coupling of the amino group with octadecanoic acid, O-deacylation and saponification of the methyl ester group, gave the title ganglioside.