A Total Synthesis of Taxol

Authors

  • John J. Masters,

    Corresponding author
    1. Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10021 (USA). Telefax: Int. code + (212)772-8691
    • Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10021 (USA). Telefax: Int. code + (212)772-8691
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  • J. T. Link,

    1. Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10021 (USA). Telefax: Int. code + (212)772-8691
    Current affiliation:
    1. Department of Chemistry, Havemeyer Hall, Columbia University, New York, NY 10027 (USA). Telefax: Int. code + (212)854-7142
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  • Lawrence B. Snyder,

    1. Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10021 (USA). Telefax: Int. code + (212)772-8691
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  • Wendy B. Young,

    1. Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10021 (USA). Telefax: Int. code + (212)772-8691
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  • Prof. Samuel J. Danishefsky

    1. Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10021 (USA). Telefax: Int. code + (212)772-8691
    Current affiliation:
    1. Department of Chemistry, Havemeyer Hall, Columbia University, New York, NY 10027 (USA). Telefax: Int. code + (212)854-7142
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  • This research was supported by National Institutes of Health (NIH, grant no. AI 16949). A Damon Runyon-Walter Winchell Cancer Fund Postdoctoral Fellowship to J. J. M. and an American Cancer Society Postdoctoral Fellowship to W. B. Y. are gratefully acknowledged. We thank Susan de Gala, Yale University, for crystallographic analysis and Dr. G. Sukenick, Memorial Sloan-Kettering Cancer Center, for mass spectrometric analyses.

Abstract

original image

The intramolecular Heck reaction of 1 to 2 is the cornerstone of this total synthesis of taxol (see conversion below). The route starts with the (S)-Wieland Miescher ketone, and the oxetane ring is installed early in the synthesis. Elaboration to a CD ring fragment, addition of an A ring nucleophile, and further manipulations yield the appropriate starting material (1) for the Heck reaction. After this key step yielding 2, the synthesis of baccatin III (and thence taxol) concludes with the cleavage of the exo double bond at C-10 and oxygenation at C-9 and C-13.

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