Concise synthesis of ricciocarpin A and discovery of a more potent analogue

Abstract

Cascade reactions enable the rapid build-up of molecular complexity from relatively simple starting materials. Both rapid construction and the ability to prepare related structures are crucial to the study of biological activities. Here, we report an efficient, highly enantioselective and diastereoselective total synthesis of ricciocarpin A. The key feature of the synthesis is a one-pot, three-step, organocatalytic reductive Michael–Tishchenko cascade. The conciseness and flexibility of this approach not only resulted in the synthesis of the natural product, but also of its antipode and four other structural analogues. A preliminary biological evaluation of these compounds identified an analogue with significantly improved molluscicidal activity. An organocatalytic cascade reaction allows the rapid construction of (+)-ricciocarpin A, which exhibits potent molluscicidal activity against the water snails Biomphalaria glabrata. The concise synthesis also allowed the synthesis of five analogues, one of which was shown to have significantly improved biological activity.

Cite this article

Michrowska, A., List, B. Concise synthesis of ricciocarpin A and discovery of a more potent analogue. Nature Chem 1, 225–228 (2009). https://doi.org/10.1038/nchem.215

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