Regio- and stereo-selective synthesis of ganglioside GM1b and some positional analogs

Abstract

Total synthesis of ganglioside GM1b (IV 3NeuAcGgOse 4Cer) and three of its positional analogs are described. Methyl O-(methyl 5-acetamido-4,7,8,9-tetra- O-acetyl-3,5-dideoxy- d- glycero-α- d- galacto-2-nonulopyranosylonate)- (2 → 3)-2,4,6-tri- O-benzoyl-1-thio-β- d-galactopyranoside ( 7) and methyl O-(methyl 5-acetamido-4,7,8,9-tetra- O-acetyl-3,5-dideoxy- d- glycero-α- d- galacto-2-nonulopyranosylonate)-(2→6)- 2,4-di- O-benzoyl-3- O-benzyl-1-thio-β- d-galactopyranoside ( 8) were the key glycosyl donors, prepared according to our reported methods. Coupling of 3,4,6-tri- O-acetyl-2-deoxy-2-phthalimido-α- d-galactopyranosyl bromide and 2-(trimethylsilyl)ethyl O-(2,3,6-tri- O-benzyl-β- d-galactopyranosyl)-(1→4)-2,3,6-tri- O-benzyl-β- d-glucopyranoside gave a trisaccharide, which after removal of O-acetyl and phthaloyl groups was converted separately, by benzylidenation and dibutyltin oxide-mediated selective benzylation, into two glycosyl acceptors. These were suitable respectively for C-3 and C-6 glycosylation reactions, promoted by dimethyl(methylthio)sulfonium triflate (DMTST), with the donors 7 and 8. The four possible coupling reactions gave the corresponding four pentasaccharide derivatives in high yields, and these were transformed into their respective α-trichloroacetimidates. Glycosylation of (2 S,3 R,4 E)-2-azido-3- O-benzoyl-4-octadecene-1,3-diol with the α-trichloroacetimidates gave the corresponding α-glycosides, which on channeling through selective reduction of the azido group, coupling of the thus formed amino group with octadecanoic acid, O-deacetylation, and saponification of the methyl ester group, gave the title compounds.