Total Synthesis of Halipeptins A and D and Analogues

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
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  • David W. Kim,

    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
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  • Daniel Schlawe 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
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  • Dimitrios E. Lizos 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
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  • Rita G. de Noronha,

    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
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  • Deborah A. Longbottom 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
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  • We thank Dr. D. H. Huang and Dr. G. Siuzdak for NMR spectroscopic and mass spectrometric assistance, respectively. Financial support for this work was provided by the National Institutes of Health (USA), the CaPCURE Foundation, the Skaggs Institute for Chemical Biology, a predoctoral fellowship from the Foundation for Science and Technology, Portugal (grant SFRH/BD/5371/2001 to R.G.N.), and postdoctoral fellowships from the Ernst Schering Research Foundation (to D.S.) and the Royal Society Fulbright Commission (to D.A.L.).

Abstract

original image

Trügerische Ringe: Die Halipeptine A (1 a) und D (1 b) und einige ihrer Analoga wurden aus den Fragmenten 2 und 3 a bzw. 3 b synthetisiert. Zu den Schlüsselschritten zählten die Bildung von Peptidbindungen, ein DAST-vermittelter Thiazolin-Aufbau und eine Makrolactamisierung. Im Unterschied zu (möglicherweise verunreinigtem) Material aus natürlichen Quellen war synthetisches 1 b nur schwach wirksam gegen Tumorzellen. DAST=(Diethylamino)schwefeltrifluorid.

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