Unified Total Synthesis of Madangamine Alkaloids

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Author(s)

    • Suto Takahiro
    • Department of Applied Chemistry, Faculty of Science and Technology, Keio University
    • Chida Noritaka
    • Department of Applied Chemistry, Faculty of Science and Technology, Keio University
    • Yanagita Yuta
    • Department of Applied Chemistry, Faculty of Science and Technology, Keio University
    • Nagashima Yoshiyuki
    • Department of Applied Chemistry, Faculty of Science and Technology, Keio University
    • Takikawa Shinsaku
    • Department of Applied Chemistry, Faculty of Science and Technology, Keio University
    • Kurosu Yasuhiro
    • Department of Applied Chemistry, Faculty of Science and Technology, Keio University
    • Matsuo Naoya
    • Department of Applied Chemistry, Faculty of Science and Technology, Keio University
    • Miura Kazuki
    • Department of Applied Chemistry, Faculty of Science and Technology, Keio University
    • Simizu Siro
    • Department of Applied Chemistry, Faculty of Science and Technology, Keio University
    • Sato Takaaki
    • Department of Applied Chemistry, Faculty of Science and Technology, Keio University

Abstract

<p>The full details of a unified total synthesis of madangamine alkaloids are disclosed. Our central strategy is based on the construction of a common ABCE-tetracyclic system, followed by the late-stage installation of various D-rings. The common intermediate is assembled through <i>N</i>-acyliminium cyclization of a propargylsilane, and formation of the (<i>Z</i>,<i>Z</i>)-skipped diene. Stereoselective synthesis of the (<i>Z</i>,<i>Z</i>)-skipped diene is especially challenging, and is accomplished by the combination of <i>Z</i>-selective hydroboration of the 1,1-disubstituted allene and subsequent Migita-Kosugi-Stille coupling. Macrocyclic alkylation enables the late-stage variation of the D-rings on the common tetracyclic intermediate, resulting in the collective total syntheses of madangamines A–E. The synthetic madangamine alkaloids exhibited inhibitory activities against a variety of human cancer cell lines.</p>

Journal

  • Bulletin of the Chemical Society of Japan

    Bulletin of the Chemical Society of Japan 92(3), 545-571, 2019

    The Chemical Society of Japan

Codes

  • NII Article ID (NAID)
    130007611672
  • Text Lang
    ENG
  • ISSN
    0009-2673
  • Data Source
    J-STAGE 
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