Polycyclic Furanobutenolide-Derived Cembranoid and Norcembranoid Natural Products: Biosynthetic Connections and Synthetic Efforts
The polycyclic furanobutenolide-derived cembranoid and norcembranoid natural products are a family of congested, stereochemically complex, and extensively oxygenated polycyclic diterpenes and norditerpenes. Although the elegant architectures and biological activity profiles of these natural products have captured the attention of chemists since the isolation of the first members of the family in the 1990s, the de novo synthesis of only a single polycyclic furanobutenolide-derived cembranoid and norcembranoid has been accomplished. This article begins with a brief discussion of the proposed biosyntheses and biosynthetic connections among the polycyclic furanobutenolide-derived cembranoids and norcembranoids and then provides a comprehensive review of the synthetic efforts toward each member of the natural product family, including biomimetic, semisynthetic, and de novo synthetic strategies. This body of knowledge has been gathered to provide insight into the reactivity and constraints of these compact and highly oxygenated polycyclic structures, as well as to offer guidance for future synthetic endeavors.
Additional Information© 2017 American Chemical Society. Received: February 7, 2017; Published: May 18, 2017. The authors thank the NIH-NIGMS (R01GM080269), Amgen, the Gordon and Betty Moore Foundation, and Caltech for financial support. R.A.C. gratefully acknowledges the support of this work provided by a fellowship from the National Cancer Institute of the National Institutes of Health (NIH) under Award F31A17435. Dr. Corey Reeves (Caltech), Dr. Aaron Bedell (Stanford), and Mr. James B. C. Mack (Stanford) are also thanked for editorial assistance. Additionally, the authors thank all of the collaborators and co-workers who have contributed to the synthetic efforts toward ineleganolide and the polycyclic furanobutenolide-derived norcembranoids at Caltech for thoughtful insights and acknowledge helpful discussions including Prof. Jennifer L. Roizen, Dr. Russell C. Smith, Prof. Amanda C. Jones, Dr. Scott C. Virgil, Mr. Beau P. Pritchett, Mr. Benzi I. Estipona, Dr. Seo-Jung Han, Prof. Amanda Silberstein, Mr. Chris Reimann, and Dr. David Romney.
Accepted Version - nihms869837.pdf