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

Article abstract of DOI:10.1016/S0008-6215(97)00051-7

Trimeric sialic acid [Neu5Acα(2 → 8)Neu5Ac α(2 → 8)Neu5Ac, 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 (2 S,3 R,4E)-2-azido-3-O-benzoyl-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.