A New and Efficient Approach to Prepare N-Acetyl GM₃ Ganglioside via Trisaccharide [1→4] Lactone

Abstract

The N-acetyl GM 3 ganglioside (NAcGM 3 ) is an important glycosphingolipid currently used to prepare a new therapeutic cancer vaccine. Some quantities of this ganglioside were obtained by using [1→4] lactone as the trisaccharide protective function. Thus, sialylation of hexabenzyllactose acceptor with 5-acetyl neuraminylthiophenyl donor afforded the (2→ 3) trisaccharide as an α/β (3:1) mixture. The α-anomer was isolated through selective [1→4] lactone formation followed by chromatography. The lactone was hydrogenolyzed, per-O-acetylated, and selectively deacetylated, and a trichloroacetimidate donor was synthesized from the obtained compound. Azidosphingosine glycosylation, followed by azide group reduction and acylation of the resulting amino glycoside with stearic acid provided the protected ganglioside, which was finally subjected to the Zemplen's procedure, before saponification, to obtain the NAcGM 3 in an overall yield of 11.5% at multigram scale.

Hydrazoic Acid and Azides

“…Azides can be reduced to the corresponding amines by hydrogen-palladium [98,112], H 2 S [113], triphenylphosphine (Staudinger reduction) [96], lithium aminoborohydrides [114], and other sources.…”