Total synthesis of (±)-aspidospermidine via the regioselective Stille coupling and Diels-Alder reaction of 3,5-dibromo-2-pyrone.Total synthesis of (±)-aspidospermidine via the regioselective Stille coupling and Diels-Alder reaction of 3,5-dibromo-2-pyrone.Total synthesis of (±)-aspidospermidine via the regioselective Stille coupling and Diels-Alder reaction of 3,5-dibromo-2-pyrone.

Abstract

The Aspidosperma family represents one of the largest groups of indole alkaloids, with more than 250 compounds isolated from various natural sources. Because of their intriguing biological activities as well as the unique pentacyclic structural features, intense study has been directed toward their total synthesis over the past 40 years. In order to explore the potential applicability of 2-pyrone Diels-Alder strategy to the target-oriented synthesis, we have investigated the total synthesis of aspidospermidine with the maximum use of the resultant densely functionalized cycloadduct. More importantly, our study would establish a platform for the synthesis of various other structurally related aspidosperma alkaloids including tabersonine, catharanthine, vindoline as well as aspidophytine.