Synthesis of deoxy- l-fucose-containing sialyl Lewis X ganglioside analogues

Abstract

Sialyl Le x ganglioside anlogs containing 2-, 3-, and 4-deoxyfucose in the place of l-fucose have been synthesized. Glycosylation of 2-(trimethylsilyl)ethyl O-(2-acetamido-4,6- O-benzylidene-2-deoxy-β- d-glucopyranosyl)(1 → 3)-2,4,6-trio O-benzyl-β- d-galactopyranoside with the methyl 1-thioglycoside derivatives of the respective deoxyfucoses, using dimethyl(methylthio)sulfonium triflate (DMTST) as a promoter, gave the corresponding three protected 2-(trimethylsilyl)ethyl dideoxy-α- l-hexopyranosyl-(1 → 3)- O-2(-acetamido-2-deoxy-β- d-glucopyranosyl) (1 → 3)-β- d-galactopyranosides. These were transformed by reductive ring-opening of their benzylidene acetal groups into the glycosyl acceptors 6, 8, and 10. Dimethyl(methylthio)sulfonium triflate promoted glycosylation of 6, 8, and 10 with methyl O-(methyl 5-acetamido-4,7,8,9-tetra- O-acetyl-3,5-dideoxy- d- galacto-2-nonulopyranosylonate)- (2 → 3)-2,4,6-tri- O-benzoyl-1-thio-β- d-galactopyranoside afforded the desired pentasaccharides, which were converted via reductive removal of their benzyl groups, O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and reaction with trichloroacetonitrile, into the corresponding α-trichloroacetimidates 14, 18, and 22. Glycosylation of (2 S,3 R,4 E)-2-azido-3- O-benzoyl-4-octadecene-1,3-diol with 14, 18, and 22 in the presence of boron trifluoride etherate afforded the expected β-glycosides, which were transformed in good yields, via selective reduction of the azido group, coupling with octadecanoic acid, O-deacylation, and deesterification, into the target compounds.