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

    Research output: Contribution to journalArticle

    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

    Fingerprint

    Depsipeptides
    Structure-Activity Relationship
    Stereochemistry
    Mollusca
    Amino Acids
    kulokekahilide-2

    Keywords

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

    ASJC Scopus subject areas

    • Biochemistry
    • Organic Chemistry
    • Drug Discovery

    Cite this

    The total synthesis and structure-activity relationships of a highly cytotoxic depsipeptide kulokekahilide-2 and its analogs. / Takada, Yuuki; Umehara, Masahiro; Katsumata, Ryosuke; Nakao, Youichi; Kimura, Junji.

    In: Tetrahedron, Vol. 68, No. 2, 14.01.2012, p. 659-669.

    Research output: Contribution to journalArticle

    Takada, Yuuki ; Umehara, Masahiro ; Katsumata, Ryosuke ; Nakao, Youichi ; Kimura, Junji. / The total synthesis and structure-activity relationships of a highly cytotoxic depsipeptide kulokekahilide-2 and its analogs. In: Tetrahedron. 2012 ; Vol. 68, No. 2. pp. 659-669.
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    AU - Kimura, Junji

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