Total Synthesis of Sporolide B

Authors

  • K. C. Nicolaou Prof. Dr.,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA), Fax: (+1) 858-784-2469
    2. Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (USA)
    Search for more papers by this author
  • Yefeng Tang Dr.,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA), Fax: (+1) 858-784-2469
    2. Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (USA)
    Search for more papers by this author
  • Jianhua Wang

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA), Fax: (+1) 858-784-2469
    2. Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (USA)
    Search for more papers by this author

  • We thank Drs. D. H. Huang and G. Siuzdak for NMR spectroscopic and mass spectroscopic assistance, respectively. We thank Dr. R. Hungate and R. Jensen of Amgen, Thousand Oaks, California, for the 13C NMR spectrum of synthetic sporolide B and Prof. W. Fenical for a sample of natural sporolide B. Financial support for this work was provided by the National Institutes of Health (USA), the Skaggs Institute for Research, and an Andrea Elizabeth Vogt Memorial Fellowship (to J.W.).

Abstract

An ocean of discovery: The first total synthesis of the highly oxygenated, marine-derived, natural product sporolide B has been achieved through a convergent strategy. The key steps involve a ruthenium-catalyzed [2+2+2] cycloaddition to assemble the indene structural motif and a thermally induced Diels–Alder-type reaction to forge the macrocycle (see scheme).

original image

Ancillary