Synthesis of disialoganglioside GD1 alpha and its positional isomer.
The first total syntheses of disialoganglioside GD1 alpha and its alpha 2-6 positional isomer are described. Suitably protected pentasaccharide derivatives, derived from known pentasaccharide precursors, were selected as the glycosyl acceptors. Using our facile method of stereoselective alpha-glycosidation of sialic acid, these acceptors were coupled with methyl (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galact o-2- nonulopyranosid)onate in acetonitrile medium in the presence of dimethyl(methylthio)sulfonium triflate (DMTST) to get the desired di-alpha-sialyl hexasaccharide derivatives in moderate yields. The hexasaccharide trichloroacetimidates upon coupling with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol gave the corresponding beta-linked sphingosine glycosides in high yields. These were subjected in sequence to selective reduction of the azido group and coupling of the thus formed amino group with octadecanoic acid, O-deacylation, and saponification of the methyl ester groups to obtain ganglioside GD1 alpha and its positional isomer having the main-chain residue 2-6 linked.
Prabhanjan
H
H
Department of Applied Bioorganic Chemistry, Gifu University, Japan.
Aoyama
K
K
Kiso
M
M
Hasegawa
A
A
D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D005732:Gangliosides / Q000138:chemical synthesis*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D013237:Stereoisomerism
D005732:Gangliosides; C021298:ganglioside, GD1a