Synthesis of sialyl lewis X ganglioside analogues containing modified l-fucose residues

Abstract

Sialyl Le x ganglioside analogues containing 2- epi-, 2,3-di- epi-, 4- epi-, and 2- O-methyl- l-fucose in place of the l-fucose residue 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-tri- O-benzyl-β- d-galactopyranoside with the methyl 1-thioglycoside derivatives of the respective fucose analogues, using dimethyl(methylthio)sulfonium triflate (DMTST) as a promoter, gave the corresponding protected 2-(trimethylsilyl)ethyl deoxy-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. Dimethyl(methylthio)sulfonium triflate-promoted glycosylation of these compounds 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 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. Glycosylation of (2 S,3 R,4 E)-2-azido-3- O-benzoyl-4-octadecene-1,3-diol these 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 gangliosides. The 2-(trimethylsilyl)ethyl glycosides of sialyl Le x oligosaccharides containing modified fucose were also prepared from the intermediates of the ganglioside synthesis.