Synthesis of a series of ganglioside GM 3 analogs containing a deoxy- N-acetylneuraminic acid residue

Abstract

Ganglioside GM 3 analogs containing 4-, 7-, 8-, and 9-deoxy- N-acetylneuraminic acids in the place of N-acetylneuraminic acid (Neu5Ac) have been synthesized. Glycosylation of 2-(trimethylsilyl)ethyl O-(6- O-benzoyl-β- d- galactopyranosyl)-(1 → 4)-2,6-di- O-benzoyl-β- d-glucopyranoside with the methyl 2-thioglycoside derivatives of the respective deoxy- N-acetylneuraminic acids, using dimethyl(methylthio)sulfonium triflate as a promoter, gave the four required 2-(trimethylsilyl)ethyl α-sialosyl-(2 → 3b)-β-lactosides. These were converted via O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and subsequent imidate formation, into the corresponding α-sialosyl-(2 → 3b)-α-lactose trichloroacetimidates 15, 17, 19, and 21. Glycosylation of (2 S,3 R,4 E)-2-azido-3- O-benzoyl-4-octadecene-1,3-diol with 15, 17, 19, and 21 in the presence of boron trifluoride etherate afforded the expected β glycosides, which were transformed in good yields, via selective reduction of the azido group, coupling with octadecanoic acid, O-deacylation, and de-esterification, into the target compounds.