A TOTAL SYNTHESIS OF SIALYL DIMERIC LE(X) GANGLIOSIDE

The first total synthesis of tumor-associated glycolipid antigen; sialyl dimeric Le(X), is described. Regioselective glycosylation of the suitably protected Lewis X (LE(X)) pentasaccharide derivative 6 with phenyl 4-O-acetyl-6-O-benzy1-2-deoxy-3-O-(4-methoxybenzyl)-2-phthalimido-1-thio-beta-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-alpha-D-galacto-2-nonulopyranosylonate)-(2-->3)-2,4,6-tri-O-benzoyl-1-thio-beta-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) asa promoter to give the desired nonasaccharide 15. After replacing the benzyl groups of 15 by the acetyl groups, the 2-(trimethylsilyl)ethyl group at the reducing end was selectively transformed into the alpha-trichloroacetimidate 18. Coupling of 18 with (2S, 3R, 4E)-2-azido-3-0-tert-butyldiphenylsilyl-4-octadecene-1,3-diol (19) gave-the corresponding beta-glycoside 20, which was transformed, via selective reduction of the azide group, coupling with octadecanoic acid, O-desilylation, O-deacylation, and hydrolysis of the methyl ester group, into the title ganglioside 1 in good yield.