Scalable, Enantioselective Synthesis of Germacrenes and Related Sesquiterpenes Inspired by Terpene Cyclase Phase Logic

Authors

  • Klement Foo,

    1. Department of Chemistry, The Scripps Research Institute, 10650 North Torrey Pines Road, La Jolla, CA, 92037 (USA)
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    • These authors contributed equally to this work.

  • Ippei Usui,

    1. Department of Chemistry, The Scripps Research Institute, 10650 North Torrey Pines Road, La Jolla, CA, 92037 (USA)
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    • These authors contributed equally to this work.

  • Daniel C. G. Götz,

    1. Department of Chemistry, The Scripps Research Institute, 10650 North Torrey Pines Road, La Jolla, CA, 92037 (USA)
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  • Erik W. Werner,

    1. Department of Chemistry, The Scripps Research Institute, 10650 North Torrey Pines Road, La Jolla, CA, 92037 (USA)
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  • Dane Holte,

    1. Department of Chemistry, The Scripps Research Institute, 10650 North Torrey Pines Road, La Jolla, CA, 92037 (USA)
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  • Phil S. Baran

    Corresponding author
    1. Department of Chemistry, The Scripps Research Institute, 10650 North Torrey Pines Road, La Jolla, CA, 92037 (USA)
    • Department of Chemistry, The Scripps Research Institute, 10650 North Torrey Pines Road, La Jolla, CA, 92037 (USA)
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  • We acknowledge Prof. A. Rheingold and Dr. C. Moore for X-ray crystallographic assistance. Financial support for this work was provided by NIH/NIGMS (GM-097444) and Leo Pharmaceuticals, A*STAR (predoctoral fellowship to K.F.), Uehara Memorial Foundation (postdoctoral fellowship to I.U.), German Academic Exchange Service, DAAD (postdoctoral fellowship to D.C.G.G.), and NSF (predoctoral fellowship to D.H.).

Abstract

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Terpene cyclase phase: Inspired by this logic, a scalable and enantioselective divergent synthesis of germacrane-type sesquiterpenes is developed. Salient features of this work include: 1) the direct ring closure of a farnesol derivative to the 10-membered carbocycle 1, and 2) subsequent synthetic operations on 1 to gain access to different bicyclic frameworks such as guaianes, cadinanes, selinanes, and elemenes.

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