Enediyne Quinone Imines: Truncated, Biologically Active Dynemicin Congeners

Authors

  • Matthew D. Shair,

    1. Sloan-Kettering Institute for Cancer Research Laboratory for Bioorganic Chemistry 1275 York Avenue, Box 106, New York, NY 10021 (USA) Telefax: Int. code + (212)772–8691
    2. Department of Chemistry, Havemeyer Hall Columbia University, New York, NY 10027 (USA)
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  • Prof. Samuel J. Danishefsky,

    Corresponding author
    1. Sloan-Kettering Institute for Cancer Research Laboratory for Bioorganic Chemistry 1275 York Avenue, Box 106, New York, NY 10021 (USA) Telefax: Int. code + (212)772–8691
    2. Department of Chemistry, Havemeyer Hall Columbia University, New York, NY 10027 (USA)
    • Sloan-Kettering Institute for Cancer Research Laboratory for Bioorganic Chemistry 1275 York Avenue, Box 106, New York, NY 10021 (USA) Telefax: Int. code + (212)772-8691
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  • Taeyoung Yoon,

    1. Sloan-Kettering Institute for Cancer Research Laboratory for Bioorganic Chemistry 1275 York Avenue, Box 106, New York, NY 10021 (USA) Telefax: Int. code + (212)772–8691
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  • Ting-Chao Chou

    1. Sloan-Kettering Institute for Cancer Research Laboratory for Bioorganic Chemistry 1275 York Avenue, Box 106, New York, NY 10021 (USA) Telefax: Int. code + (212)772–8691
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  • This work was supported by the National Institutes of Health (Grant CA 28824). A predoctoral fellowship from Memorial Sloan-Kettering Cancer Center to M.D.S. is gratefully acknowledged. We thank Professor A. G. Myers for an advanced copy of his manuscript in which related developments are described.

Abstract

original image

An intermediate in the total synthesis of dynemicin A, quinone imine 1 can be used as a dienophile. But 1 is also a potent cytotoxic agent against human cancer cell lines since it is able to cleave DNA. In vitro and in vivo studies showed that 1 is more effective than two frequently applied antitumor drugs. Quinone imine 1 was synthesized by the rapid oxidation of a fleeting hydroisoquinone intermediate.

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