Synthesis and selectin-binding activity of N-deacetylsialyl Lewis X ganglioside☆

Abstract A novel analogue of sialyl Lewis X ganglioside, N -deacetylsialyl Lewis X ganglioside, was synthesized. Methyl 4,7,8,9-tetra- O -acetyl-3,5-dideoxy-5-trifluoroacetamido- d - glycero -α- d - galacto -2-nonulopyranosylonate-(2→3)-2,4,6-tri- O -benzoyl- d -galactopyranosyl trichloroacetimidate was coupled with 2-(trimethylsilyl)ethyl [2-acetamido-6- O -benzyl-2-deoxy-3- O -(4-methoxybenzyl)-β- d -glucopyranosyl]-(1→3)-[2,4,6-tri- O -benzyl-β- d -galactopyranosyl]-(1→4)-2,3,6-tri- O -benzyl-β- d -galactopyranoside to give the desired pentasaccharide in high yield. The glycosylation of the pentasaccharide acceptor, which was derived from its precursor by removal of the 3-methoxybenzyl group, with the phenyl 1-thioglycoside derivative of l -fucose using N -iodosuccinimide–trifluoromethanesulfonic acid as promoter, produced the hexasaccharide. Proper manipulation of the protecting groups of the hexasaccharide afforded the corresponding glycosyl imidate, which was coupled with (2 S ,3 R ,4 E )-2-azido-3- O -benzoyl-4-octadecene-1,3-diol. Selective reduction of the azido group, N -acylation with octadecanoic acid, and the complete removal of the protecting groups gave the desired N -deacetylsialyl Lewis X ganglioside. L-Selectin bound more strongly to N -deacetylsialyl Lewis X ganglioside than to the sialyl Lewis X ganglioside, whereas E- and P-selectins bound equally well to the two gangliosides.