Total synthesis and structure revision of didemnaketalB

Haruhiko Fuwa, Takashi Muto, Kumiko Sekine, Makoto Sasaki

    Research output: Contribution to journalArticlepeer-review

    27 Citations (Scopus)

    Abstract

    DidemnaketalB, a structurally complex spiroacetal that exhibits potent HIV-1 protease inhibitory activity, was originally discovered by Faulkner and his colleagues from the ascidian Didemnum sp. collected at Palau. Its absolute configuration was proposed on the basis of degradation/derivatization experiments of the authentic sample. However, our total synthesis of the proposed structure of didemnaketalB questioned the stereochemical assignment made by Faulkner etal. Here we describe in detail our first total synthesis of the proposed structure 2 of didemnaketalB, which features 1)a convergent synthesis of the C7-C21 spiroacetal domain by means of a strategy exploiting Suzuki-Miyaura coupling, 2)an Evans syn-aldol reaction and a vinylogous Mukaiyama aldol reaction for the assembly of the C1-C7 acyclic domain, and 3)a Nozaki-Hiyama-Kishi reaction for the construction of the C21-C28 side chain domain. The NMR spectroscopic discrepancies observed between synthetic 2 and the authentic sample as well as careful inspection of the Faulkner's stereochemical assignment led us to postulate that the absolute configuration of the C10-C20 domain of 2 has been erroneously assigned. Accordingly, the total synthesis of the revised structure 65 was achieved to show that the NMR spectroscopic properties of synthetic 65 were in good agreement with those of the authentic sample. Furthermore, application of the phenylglycine methyl ester (PGME) method to the C7-C21 spiroacetal domain enabled us to establish the absolute configuration of didemnaketalB.

    Original languageEnglish
    Pages (from-to)1848-1860
    Number of pages13
    JournalChemistry - A European Journal
    Volume20
    Issue number7
    DOIs
    Publication statusPublished - 2014 Feb 10

    Keywords

    • natural products
    • spiroacetals
    • stereochemical assignment
    • structure elucidation
    • total synthesis

    ASJC Scopus subject areas

    • Catalysis
    • Organic Chemistry

    Fingerprint Dive into the research topics of 'Total synthesis and structure revision of didemnaketalB'. Together they form a unique fingerprint.

    Cite this