Synthetic Studies on Sialoglycoconjugates 54: Synthesis of I-Active Ganglioside Analog

Abstract

A stereocontrolled synthesis of I-active ganglioside analog is described. Glycosylation of 2-(trimethylsilyl)ethyl O-(2-O-benzyl-4,6-O-benzylidene-β-d-galactopyranosyl)-(1 → 4)-2,3,6-tri-O-benzyl-β-d-glucopyranoside (5) with methyl 4-O-acetyl-1,6-di-O-benzyl-2-deoxy-2-phthalimido-1-thio-β-d-glucopyranoside (10) by use of N-iodosuccinimide (NIS)-trifluoromethanesulfonic acid (TfOH) gave the desired trisaccharide 11, which was transformed into trisaccharide acceptor 14 via removal of the phthaloyl group followed by N-acetylation, and debenzylidenation. Glycosylation of 14 with methyl 3-O-benzyl-4,6-O-benzylidene-2-deoxy-2-phthalimido-1-thio-β-d-glucopyranoside (8) gave the biantennary compound 15, which was transformed into the acceptor 16. Dimethyl(methylthio)sulfonium triflate (DMTST)-promoted coupling of 16 with methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-d-glycero-α-d-galacto-2-nonulopyranosylonate)-(2→3)-2,4,6-tri-O-benzoyl-1-thio-β-d-galactopyranoside (17) afforded the desired hexasaccharide 19. Coupling of the hexasaccharide acceptor 20, prepared from 19 by reductive ring-opening of benzylidene acetal, with 17 gave octasaccharide derivative 21. Compound 21 was transformed, via removal of the benzyl group followed by O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group and subsequent imidate formation, into the final glycosyl donor 24. Condensation of 24 with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (18) gave the β-glycoside 25, which on channeling through selective reduction of azido group, coupling of the amino group with octadecanoic acid, O-deacylation and saponification of the methyl ester group, gave the title compound 28.