Total Synthesis of Eleutherobin

Authors

  • Prof. Dr. K. C. Nicolaou,

    Corresponding author
    1. Department of Chemistry and The Skaggs Institute for Chemical Biology The Scripps Research Institute, 10550 North Torrey Pines Road la Jolla, California 92037 (USA), Fax: Int. code +(619)784-2469, e-mail: kcn@scripps.edu and Department of Chemistry and Biochemistry University of California, San Diego 9500 Gilman Drive, La Jolla, California 92093 (USA)
    • Department of Chemistry and The Skaggs Institute for Chemical Biology The Scripps Research Institute, 10550 North Torrey Pines Road La Jolla, California 92037 (USA), Fax: Int. code +(619)784-2469, e-mail: kcn@scripps.edu and Department of Chemistry and Biochemistry University of California, San Diego 9500 Gilman Drive, La Jolla, California 92093 (USA)
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  • Dr. Floris van Delft,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology The Scripps Research Institute, 10550 North Torrey Pines Road la Jolla, California 92037 (USA), Fax: Int. code +(619)784-2469, e-mail: kcn@scripps.edu and Department of Chemistry and Biochemistry University of California, San Diego 9500 Gilman Drive, La Jolla, California 92093 (USA)
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  • Dr. Takashi Ohshima,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology The Scripps Research Institute, 10550 North Torrey Pines Road la Jolla, California 92037 (USA), Fax: Int. code +(619)784-2469, e-mail: kcn@scripps.edu and Department of Chemistry and Biochemistry University of California, San Diego 9500 Gilman Drive, La Jolla, California 92093 (USA)
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  • Dr. Dionisios Vourloumis,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology The Scripps Research Institute, 10550 North Torrey Pines Road la Jolla, California 92037 (USA), Fax: Int. code +(619)784-2469, e-mail: kcn@scripps.edu and Department of Chemistry and Biochemistry University of California, San Diego 9500 Gilman Drive, La Jolla, California 92093 (USA)
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  • Dr. Jinyou Xu,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology The Scripps Research Institute, 10550 North Torrey Pines Road la Jolla, California 92037 (USA), Fax: Int. code +(619)784-2469, e-mail: kcn@scripps.edu and Department of Chemistry and Biochemistry University of California, San Diego 9500 Gilman Drive, La Jolla, California 92093 (USA)
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  • Dr. Seijiro Hosokawa,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology The Scripps Research Institute, 10550 North Torrey Pines Road la Jolla, California 92037 (USA), Fax: Int. code +(619)784-2469, e-mail: kcn@scripps.edu and Department of Chemistry and Biochemistry University of California, San Diego 9500 Gilman Drive, La Jolla, California 92093 (USA)
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  • Jeffrey Pfefferkorn,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology The Scripps Research Institute, 10550 North Torrey Pines Road la Jolla, California 92037 (USA), Fax: Int. code +(619)784-2469, e-mail: kcn@scripps.edu and Department of Chemistry and Biochemistry University of California, San Diego 9500 Gilman Drive, La Jolla, California 92093 (USA)
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  • Dr. Sanghee Kim,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology The Scripps Research Institute, 10550 North Torrey Pines Road la Jolla, California 92037 (USA), Fax: Int. code +(619)784-2469, e-mail: kcn@scripps.edu and Department of Chemistry and Biochemistry University of California, San Diego 9500 Gilman Drive, La Jolla, California 92093 (USA)
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  • Dr. Tianhu Li

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology The Scripps Research Institute, 10550 North Torrey Pines Road la Jolla, California 92037 (USA), Fax: Int. code +(619)784-2469, e-mail: kcn@scripps.edu and Department of Chemistry and Biochemistry University of California, San Diego 9500 Gilman Drive, La Jolla, California 92093 (USA)
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  • We thank Dr. W. Fenical for preprints of refs. [2, 25] as well as selected spectra of eleutherobin, and Dr. D. H. Huang and Dr. G. Siuzdak for NMR spectroscopic and mass spectrometric assistance, respectively. This work was supported by The Skaggs Institute for Chemical Biology, the National Institutes of Health USA, CaP CURE, Novartis, and by fellowships from the Netherlands Organization for Scientific Research (NWO) (to F. v. D.), Novartis (to D. V.), the Japanese Society for the Promotion of Science for Young Scientists (to S. H.), and the Department of Defense, USA (to J. P.). F. v. D., T. O., D. V., J. X., and S. H. contributed equally to this project.

Abstract

original image

Taxol-like activity is exhibited by eleutherobin (1), one of the most promising antitumor agents isolated from nature in recent years. The first total synthesis of this compound also provided a route to two biologically active analogues, thus enabling the first structure–activity relationships within the eleutherobin family to be established.

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