SYNTHETIC STUDIES ON SIALOGLYCOCONJUGATES 48 - TOTAL SYNTHESIS OF GANGLIOSIDES GM1 AND GD1A

A stereocontrolled, facile total synthesis of gangliosides GM1. and GD 1a, in connection with systematic synthesis of ganglio-series of gangl ioside, is described. Glycosylation of 2-(trimethylsilyl)ethyl -deoxy- beta-D-galactopyranosyl)-(1-->4)-O-(methyl -(1-->4)-2,3,6-tri-O-benzy l-beta-D-glucopyranoside (4), with methyl -benzyl-3-O-benzyl-1-thio-be ta-D-galactopyranoside (8) or methyl O-(methyl 5-acetamido glycero-alp ha-D-galacto-2-nonulopyranozylonate)-(2 ,4,6-tri-O-benzoyl-1-thio-beta -D-galactopyranoside (9) by use of N-iodosuccinimide (NIS)-trifluorome thanesulfonic acid (TfOH) or dimethyl(methylthio) sulfonium triflate ( DMTST) as a promoter, gave the corresponding beta-glycoside 10 and 18 in 66 and 62% yields, which were converted, via reductive removal of t he benzyl groups, O-acetylation, selective removal of the 2-(trimethyl silyl)ethyl group, and subsequent imidate formation, into the alpha-tr ichloroacetimidates 13 and 21. Glycosylation of S,3R,4E)-2-azido-3-O-b enzoyl-4-octadecene-1,3-diol (14) with 13 or 21 by use of trimethylsil yl trifluoromethanesulfonate gave the corresponding beta-glycoside 15 and 22, which on channeling through selective reduction of the azido g roup, coupling of the thus formed amino group with octadecanoic acid, 0-deacylation, and saponification of the methyl ester group, gave the tide gangliosides GM1 and GD1a.