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

The N-acetyl GM3 ganglioside (NAcGM3) 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 NAcGM3 in an overall yield of 11.5% at multigram scale.