Studies toward the Synthesis of Azadirachtin, Part 2: Construction of Fully Functionalized ABCD Ring Frameworks and Unusual Intramolecular Reactions Induced by Close-Proximity Effects

Authors

  • K. C. Nicolaou Prof. Dr.,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10 550 North Torrey Pines Road, La Jolla, CA 92 037, USA, Fax: (+1) 858-784-2469
    2. Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92 093, USA
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  • Pradip K. Sasmal Dr.,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10 550 North Torrey Pines Road, La Jolla, CA 92 037, USA, Fax: (+1) 858-784-2469
    2. Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92 093, USA
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  • Theocharis V. Koftis Dr.,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10 550 North Torrey Pines Road, La Jolla, CA 92 037, USA, Fax: (+1) 858-784-2469
    2. Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92 093, USA
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  • Antonella Converso Dr.,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10 550 North Torrey Pines Road, La Jolla, CA 92 037, USA, Fax: (+1) 858-784-2469
    2. Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92 093, USA
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  • Eriketi Loizidou,

    1. Department of Chemistry, San Diego State University, 5500 Campanile Drive, San Diego, CA 92 182, USA
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  • Florian Kaiser Dr.,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10 550 North Torrey Pines Road, La Jolla, CA 92 037, USA, Fax: (+1) 858-784-2469
    2. Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92 093, USA
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  • A. J. Roecker,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10 550 North Torrey Pines Road, La Jolla, CA 92 037, USA, Fax: (+1) 858-784-2469
    2. Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92 093, USA
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  • Constantinos C. Dellios Dr.,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10 550 North Torrey Pines Road, La Jolla, CA 92 037, USA, Fax: (+1) 858-784-2469
    2. Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92 093, USA
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  • Xiao-Wen Sun Dr.,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10 550 North Torrey Pines Road, La Jolla, CA 92 037, USA, Fax: (+1) 858-784-2469
    2. Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92 093, USA
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  • Goran Petrovic Dr.

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10 550 North Torrey Pines Road, La Jolla, CA 92 037, USA, Fax: (+1) 858-784-2469
    2. Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92 093, USA
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  • We thank Dr. D. H. Huang, Dr. G. Siuzdak, and Dr. R. Chadha for NMR spectroscopic, mass spectrometric, and X-ray crystallographic assistance, respectively. Financial support for this work was provided by grants from the National Institutes of Health (USA) and the Skaggs Institute for Chemical Biology, a postdoctoral fellowship from the Alexander von Humboldt Foundation (to F.K.), and a predoctoral fellowship from the Division of Organic Chemistry of the American Chemical Society sponsored by Novartis (to A.J.R.).

Abstract

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The remarkable antifeedant agent and insecticide, azadirachtin (1), has, to date, escaped a total synthesis. The preparation of an advanced precursor has revealed some of the inner intricacies of this uniquely crowded and highly functionalized molecular architecture.

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