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

Nature Chemistry volume 1, pages 225–228 (2009)Cite this article

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.

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Figure 1: Retrosynthetic strategy to access (+)-1 and analogues.
Figure 2: Two-step synthesis of substrate 3.
Figure 3: Total synthesis of (+)-1 by a reductive Michael–Tishchenko cascade.
Figure 4: Synthesis of (+)-1 analogues.

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Acknowledgements

We thank M. T. Hechavarria Fonseca for early experiments, C. W. Lehmann and J. Rust for X-ray analyses and M. Hannappel for technical assistance. A.M. thanks the Alexander von Humboldt Foundation for a fellowship and Mike Doenhoff for help with the bioassay and for providing the snails (original stock of B. alexandrina supplied by S. Botros). The authors acknowledge generous funding from the Max Planck Society, the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie.

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  1. Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, Mülheim an der Ruhr, 45470, Germany

    Anna Michrowska & Benjamin List

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  1. Anna Michrowska
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Correspondence to Benjamin List.

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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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