A Total Synthesis of Sialyl Dimeric LexGanglioside1

Abstract

Abstract The first total synthesis of tumor-associated glycolipid antigen, sialyl dimeric Lex, is described. Regioselective glycosylation of the suitably protected Lewis X (Lex) pentasaccharide derivative 6 with phenyl 4-O-acetyl-6-O-benzyl-2-deoxy-3-O-(4-methoxy-benzyl)-2-phthalimido-1-thio-β-d-glucopyranoside (5) gave the hexasaccharide 7, which was converted, via removal of the phthaloyl groups and selective N-acetylation, into the hexasaccharide acceptor 9. Dimethyl(methylthio)sulfonium triflate (DMTST) promoted glycosylation of 9 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 (10) afforded regioselectively the expected octasaccharide 11, which was converted into 13 via O-acetylation and removal of the methoxybenzyl group. Fucosylation of 13 with the methyl thioglycoside 14 was performed by use of N-iodosuccinimide (NIS)-trifluoromethanesulfonic acid(TfOH) as a promoter to give th...