A synthetic approach to the c-series gangliosides containing sialyl-α(2 → 8) sialyl-α(2 → 8)sialic acid: Synthesis of ganglioside GT4, α(2 → 6)GT4 and GT3

Trimeric sialic acid [Neu5Acα(2→8)Ncu5Acα(2→8)Ncu5Ac. 1] residue-containing gangliosides, GT4, α(2→6)GT4 and GT3, have been synthesized for the first time. Methyl [phenyl 5-acetamido-8-O-[5-acetamido-8-O-(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-d-glycero-α-d-galacto-2- nonulopyranosylono-1″,9′-lactone)-4,7-di-O-acetyl-3,5-dideoxy-d-glycero-α-d-galacto-2-nonulopyranosylono-1′,9-lactone]- 4,7-di-O-acetyl-3,5-dideoxy-2-thio-d-glycero-d-galacto-2-nonulopyranosid]onate (3) was prepared from 1, via lactonization, methyl esterification of the carboxyl group at the reducting end, O-acetylation and conversion of the anomeric acetoxy group into a phenylthio group. Iodonium-promoted glycosylation of 3 with 2-(trimethylsilyl)ethyl 2,6-di-O-benzyl-β-d-galactopyranoside (5), 2-(trimethylsilyl)ethyl 3-O-benzyl-β-d-galactopyranoside (6), 2-(trimethylsilyl)ethyl 2-O-benzoyl-3-O-benzyl-β-d-galactopyranoside (9), and 2-(trimethylsilyl)ethyl 2,3-di-O-benzyl-β-d-galactopyranoside (11) gave the corresponding tetrasaccharides (13–15, 17) having the (Neu5Ac)3-Gal structure. The peracylated oligosaccharides 18 and 24 derived from 13 and 17, and the previously reported lactose derivative 29 were converted into the α-trichloroacetimidates 20, 26 and 31, and coupled with (2S,3R,4E)-2-azido-3-O-benzol-4-octadecene-1,3-diol (21) to afford the corresponding β-glycosides 22, 27 and 32. These protected azidosphingosine derivatives were each transformed into the target gangliosides GT4, α(2 → 6)GT4 and GT3 via selective reduction of the azido group. subsequent coupling with octadecanoic acid, O-deacylation and saponification of the methyl ester and lactone groups.