Total Synthesis of Strempeliopidine and Non-Natural Stereoisomers through a Convergent Petasis Borono–Mannich Reaction

Abstract

Strempeliopidine is a member of the monoterpenoid bisindole alkaloid family, a class of natural products that have been shown to elicit an array of biological responses including modulating protein−protein interactions in human cancer cells. Our synthesis of strempeliopidine leverages palladium-catalyzed decarboxylative asymmetric allylic alkylations to install the requisite allcarbon quaternary centers found in each of the two monomeric natural products, aspidospermidine and eburnamine. Initial studies employing Suzuki−Miyaura cross-coupling followed by diastereoselective hydrogenation provided evidence for a structural reassignment of the natural product. Our final synthetic sequence employs a diastereoselective Petasis borono−Mannich reaction to couple eburnamine to a trifluoroborate aspidospermidine derivative. These convergent approaches enabled the synthesis of eight diastereomers of this heterodimer and offer support for the reassignment of the absolute configuration of strempeliopidine.

Enantioselective Total Synthesis of (−)-Hunterine A Enabled by a Desymmetrization/Rearrangement Strategy

“…Because of its structural complexity from a synthetic perspective, unique scaffold within the historic class of MIA natural products, as well as its intriguing biological activity, we were motivated to pursue a total synthesis of hunterine A. Although our group has completed total syntheses of several MIAs and bisindole dimers, the unique structure of hunterine A necessitated the development of a distinct synthetic approach.…”