フグ毒テトロドトキシンの最初の不斉全合成  [in Japanese] The First Asymmetric Total Synthesis of Tetrodotoxin, a Puffer Fish Toxin  [in Japanese]

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Author(s)

    • 磯部 稔 ISOBE Minoru
    • 名古屋大学大学院生命農学研究科 Graduate School of Bioagricultural Science and School of Agricultural Sciences, Nagoya University
    • 西川 俊夫 NISHIKAWA Toshio
    • 名古屋大学大学院生命農学研究科 Graduate School of Bioagricultural Science and School of Agricultural Sciences, Nagoya University

Abstract

Tetrodotoxin, a toxic principle of puffer fish poisoning, is one of the most famous marine natural products because of the complex structure and its potent biological activity. Since the structure elucidation in 1964, the toxin has been recognized as a formidable target molecule for total synthesis. We achieved the first asymmetric total synthesis commencing from 2-acetoxy-tri-<I>O</I>-acetyl-D-glucal as a chiral starting material. Highly hydroxylated cyclohexane was constructed by intramolecular aldol condensation of a precursor having methyl ketone with dihydroxyacetone, which was synthesized through Sonogashira coupling, Claisen rearrangement and regioselective hydroxylations of acetone moiety. Since installation of nitrogen functionality by the attempted Overman rearrangement was unsuccessful, we employed intramolecular conjugate addition of carbamate to unsaturated ester for the purpose. The α-hydroxyl lactone moiety was synthesized by epoxide opening with enolate of aldehyde followed by oxidation-reduction of the resulting cyclic vinylether. The lactone was then protected as ortho ester, and guanidinylation followed by cleavage of the 1, 2-glycol gave a fully protected tetrodotoxin. Protective group elaboration furnished the total synthesis of tetrodotoxin in an enantiomerically pure form.

Journal

  • Journal of Synthetic Organic Chemistry, Japan

    Journal of Synthetic Organic Chemistry, Japan 65(5), 492-501, 2007-05-01

    The Society of Synthetic Organic Chemistry, Japan

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Codes

  • NII Article ID (NAID)
    10020138036
  • NII NACSIS-CAT ID (NCID)
    AN0024521X
  • Text Lang
    JPN
  • Article Type
    ART
  • ISSN
    00379980
  • NDL Article ID
    8817888
  • NDL Source Classification
    ZP11(科学技術--化学・化学工業--有機化学・有機化学工業)
  • NDL Call No.
    Z17-256
  • Data Source
    CJP  NDL  J-STAGE 
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