Original Article

Progress towards the total synthesis of hamigerans C and D: a direct approach to an elaborated 6-7-5 carbocyclic core

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Abstract

The hamigeran family of natural products has been the target of numerous synthetic efforts because of its biological activity and interesting structural properties. Herein, we disclose our efforts toward the synthesis of hamigerans C and D, unique among the initially isolated members because of their 6-7-5 carbocyclic core. Our approach directly targets this tricyclic motif by sequential Negishi and Heck coupling reactions, yielding an advanced intermediate with all necessary carbons and sufficient functionality poised for completion of the synthesis of these two natural products.

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Acknowledgements

Dedicated to Prof K. C. Nicolaou for his tremendous scientific contributions to the total synthesis of highly complex and biologically important natural products. We thank NIH-NIGMS (R01GM080269) for supporting this research. DCD would like to thank the NSF (predoctoral research fellowship, No. DGE-1144469) and Caltech for financial support. Dr David VanderVelde (Caltech) is thanked for aid in NMR structural determination. Dr Allen Hong and Dr Scott Virgil are thanked for helpful discussions.

Author information

Author notes

    • Thomas Jensen

    Current address: Discovery Chemistry and DMPK, H. Lundbeck A/S, 2500 Valby, Denmark.

Affiliations

  1. The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA

    • Douglas Charles Duquette
    • , Thomas Jensen
    •  & Brian Mark Stoltz

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Competing interests

Dedicated to Professor KC Nicolaou for his tremendous scientific contributions to the total synthesis of highly complex and biologically important natural products.

Corresponding author

Correspondence to Brian Mark Stoltz.

Supplementary information

Supplementary Information accompanies the paper on The Journal of Antibiotics website (http://www.nature.com/ja)