Synthetic Studies on Sialoglycoconjugates 85: Synthesis of Sialyl Lewis X Ganglioside Analogs Containing a Variety of Anionic Substituents in Place of Sialic Acid

Abstract

Three sialyl-Le^x ganglioside analogs containing carboxymethyl, sulfate, and phosphate groups in place of the sialic acid moiety, have been synthesized. Glycosylation of 2-(trimethylsilyl)ethyl O-(2,3,4-tri-O-benzyl-α-L-fucopyranosyl)-(1→3)-O-(2-acetamido-6-O-benzyl-2-deoxy-β-d-glucopyranosyl) - (1→3) - 2, 4, 6-tri-O-benzyl-β-d-galactopyranoside (10) with methyl 2,4,6-tri-O-benzoyl-3-O-(methoxycarbonyl)methyl-1-thio-β-d-galactopyranoside (6) or methyl 2-O-benzoyl-4,6-O-benzylidene-3-O-levulinoyl-1-thio-β-d-galactopyranoside (9) using dimethyl-(methylthio)sulfonium triflate (DMTST) as a promoter, afforded the corresponding tetrasaccharide derivatives 11 and 19. Compounds 11 and 19 were converted into the α-trichloroacetimidates 14 and 23, via reductive removal of the benzyl and benzylidene groups, O-acetylation, removal of the 2-(trimethylsilyl)ethyl group, and treatment with trichloroacetonitrile, which, on coupling with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (15) or 2-(tetradecyl)hexadecan-1-ol (24), gave the lipophilic derivatives 16 and 25. Compound 16 was transformed, via selective reduction of the azido group, condensation with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester group, into the title compound 18 in good yield. Compound 25 was treated with hydrazine acetate to give compound 26, which in turn was transformed, via sulfation or phosphorylation, and O-deacylation, into the target compounds 28 and 31.