Synthetic Studies on Sialoglycoconjugates 31: Synthesis of Ganglioside GM3Analogs Containing the Chemically Modified Sialic Acids

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Abstract
Ganglioside GM3 analogs, containing 4-O- and 9-O-methyl-, and 8-epi-N-acetylneuraminic acids in the place of N-acetylneuraminic acid (Neu5Ac) have been synthesized. The methyl α-2-thioglycosides 10,11, and 12 of 4-O-methyl, 9-O-methyL, and 8-epi-Neu5Ac derivatives were synthesized from methyl (methyl 5-acetamido-3,5-dideoxy-2-thio-D-glycero-α-D-galacto-2-nonulopyranosid)onate as the glycosyl donors. Glycosylation of 2-(trimethylsilyl)ethyl O-(6-O-benzoyl-(β-D-galactopyranosyl)-(l→4)-2,6-di-O-benzoyl-β-D-glucopyranoside (13) with compounds 10, 11, and 12 using dimethyl(methylthio)sulfonium triflate (DMTST) as a glycosyl promoter, gave the corresponding 2-(trimethylsilyl)ethyl sialyl a(2→3′)-β-lactosides 14, 18, and 22, respectively, which were converted, via O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and subsequent imidate formation, into the sialyl α(2→3)-lactose trichloroacetimidates 17, 21, and 25. Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-l,3-diol (26) with compounds 17, 21, and 25 in the presence of boron trifluoride etherate afforded the corresponding β-glycosides 27, 30, and 33 in good yields, which were transformed, via selective reduction of the azide group, coupling with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester group, into the end products 29, 32, and 35, respectively.