The total synthesis and structure-activity relationships of a highly cytotoxic depsipeptide kulokekahilide-2 and its analogs

Yuuki Takada, Masahiro Umehara, Ryosuke Katsumata, Youichi Nakao, Junji Kimura

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    14 Citations (Scopus)

    Abstract

    We successfully completed the total synthesis of kulokekahilide-2, a cytotoxic depsipeptide from the Cephalaspiedean mollusk Phillinopsis speciosa. We have revised the absolute stereochemistry of kulokekahilide-2 to 21-l-Ala, 24-d-MePhe, 37-l-Ile, 43-d-Ala, 15-d-Hica, and 5S,6S,7S-Dtda. We also investigated the cause of the mis-assignment of the configuration in the originally proposed kulokekahilide-2 and concluded that methanolysis using MeONa caused partial racemization, which led to the mis-assignment. The structure-activity relationships of kulokekahilide-2 and its analogs indicate the importance of an l-amino acid at position 21.

    Original languageEnglish
    Pages (from-to)659-669
    Number of pages11
    JournalTetrahedron
    Volume68
    Issue number2
    DOIs
    Publication statusPublished - 2012 Jan 14

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    Keywords

    • Cyclic depsipeptide
    • Cytotoxicity
    • Kulokekahilide-2
    • Structure-activity relationships
    • Total synthesis

    ASJC Scopus subject areas

    • Biochemistry
    • Organic Chemistry
    • Drug Discovery

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