Synthesis of an S-(α-sialosyl)-(2→9)- O-(α-sialosyl)-(2→3′)-β-lactosylceramide

Abstract

A ganglioside GD 3 analog has been synthesized having an N-acetylneuraminic acid (Neu5Ac) residue α-thioglycosidically linked to C-9 of the Neu5Ac residue in the ganglioside GM 3 structure. Glycosylation of 2-(trimethylsilyl)ethyl O-(6- O-benzoyl-β- d-galactopyranosyl)-(1→4)-2,6-di- O-benzoyl-β- d-glucopyranoside with methyl (methyl 5-acetamido-4,7,8-tri- O-acetyl-9-bromo-3,5,9-trideoxy- d- glycero-α- d- galacto-2-nonulopyranosid)onate, which was prepared from methyl (methyl 5-acetamido-3,5-dideoxy- d- glycero-α- d- galacto-2-nonulopyranosid)onate by 8,9- O-isopropylidenation, O-acetylation, hydrolysis of the isopropylidene group, selective bromination, and O-acetylation, using dimethyl(methylthio)sulfonium triflate (DMTST) as a promoter, gave the α-sialosyl-(2→3′)-lactoside 8. Coupling of the O-acetyl derivative of 8 with the sodium salt of methyl 5-acetamido-4,7,8,9-tetra- O-acetyl-3,5-dideoxy-2-thio- d-(itglycero)-α- d- galacto-2-nonulopyranosonate gave an α-thioglycosidically linked tetrasaccharide. This was converted, via selective removal fo the 2-(trimethylsilyl)ethyl group, trichloroacetimidation, and glycosidation with (2 S,3 R,4 E)-2-azido-3- O-benzoyl-4-octadecene-1,3-diol into a ganglioside precursor. Finally the precursor on selective reduction of the azide group, coupling with octadecanoid acid, O-deacylation, and de-esterification gave the analog, S-( N-acetyl-α-neuraminosyl)-(2→9)- O-( N-acetyl-9-thio-α-neuraminosyl)-(2→3′)-β-lactosylceramide.