A synthetic approach to the c-series gangliosides containing sialyl-alpha(2-->8)sialyl-alpha(2-->8)sialic acid: synthesis of ganglioside GT4, alpha(2-->6) GT4 and GT3.
Trimeric sialic acid [Neu5Ac alpha(2-->8)Neu5Ac alpha(2-->8)Neu5Ac, 1] residue-containing gangliosides, GT4, alpha(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-alpha-D-galacto-2-nonulopyranosylono-1", 9'-lactone)-4,7-di-O-acetyl-3,5-dideoxy-D- glycero-alpha-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-beta-D-galactopyranoside (5), 2-(trimethylsilyl)ethyl 3-O-benzyl-beta-D-galactopyranoside (6), 2-(trimethylsilyl)ethyl 2-O-benzoyl-3-O-benzyl-beta-D-galactopyranoside (9), and 2-(trimethylsilyl)ethyl 2, 3-di-O-benzyl-beta-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 alpha-trichloroacetimidates 20, 26 and 31, and coupled with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (21) to afford the corresponding beta-glycosides 22, 27 and 32. These protected azidosphingosine derivatives were each transformed into the target gangliosides GT4, alpha(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.
Ando
H
H
Department of Applied Bioorganic Chemistry, Gifu University, Japan.
Ishida
H
H
Kiso
M
M
Hasegawa
A
A
D002240:Carbohydrate Sequence; D005732:Gangliosides / Q000138:chemical synthesis*; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid
D005732:Gangliosides; D019158:N-Acetylneuraminic Acid