Total synthesis of antitumor macrolide, rhizoxin and chemistry of acylsilane

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    Abstract

    The first total synthesis of the antitumor macrolide rhizoxin in a highly stereocontrolled manner was described. The construction of the key building fragments required for the total synthesis of the antitumor macrolide rhizoxin, that arose from our retrosynthetic analysis of rhizoxin in an optically pure form by concise and efficient sequence analyses, was described. Synthesis of the right-wing was started from the chiral half-ester generated by asymmetric hydrolysis of the corresponding meso-diester using pig liver esterase. The remaining chiral centers of the fragment was constracted by cyclic hydroboration. Synthesis of the left-wing was also accomplished starting from (S)-methyl 3- hydroxy-2-methylpropionate which had been prepared by enzyme mediated transformation. Coupling of the right-wing and the left-wing was accomplished by Julia coupling, and the macrocyclic lactone was constructed by the intramolecular Horner-Emmons reaction. The control of the stereoselective epoxidations was well achieved after the formation of an unsaturated 16-membered macrocyclic lactone. Chromophore-side-chain moiety was constructed at the final stage by the reaction of the phosphineoxide in 80% yield with high selectivity (E/Z=>20/1). The present methodology will be useful for the synthesis of the homologues and man-made rhizoxin.

    Original languageEnglish
    Pages (from-to)486-508
    Number of pages23
    JournalYakugaku Zasshi
    Volume117
    Issue number8
    Publication statusPublished - 1997 Aug

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    Keywords

    • Antitumor macrolide
    • Asymmetric hydrolysis
    • First total synthesis
    • Meso-diester
    • Pig liver esterase
    • Stereoselective epoxidation

    ASJC Scopus subject areas

    • Molecular Medicine

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