Systematic strategy utilizing 1,5-lactamization for the synthesis of the trisialylated galactose unit of c-series gangliosides

Abstract

c-Series gangliosides have important biological roles, but their synthesis is challenging, and natural sources are heterogenous and difficult to purify, so synthetic routes to these compounds are required. Here, a synthetic strategy utilizing 1,5-lactamization to construct the trisialylated galactose framework of c-series gangliosides in complete stereopurity is presented. The transformation enabled not only an increase in the reactivity of the C8 hydroxyl group in sialic acid but also the selective preparation of α-sialosides from a mixture of α- and β-sialylated products. Further, the sialic acid chain could be elongated by repeating the α(2 → 8)-sialylation and 1,5-lactamization steps. Thus, a 1,5-lactamized sialyl acceptor with N-acetyl modification that showed good reactivity for α(2 → 8)-sialylation was prepared. The synthetic strategy presented here is a promising route to the total synthesis of c-series gangliosides, which will aid in the elucidation of their biological significance.