Total synthesis of hibarimicinone, a v-Src tyrosine kinase inhibitor possessing the pseudo-dimer structure of tetracycline

Kuniaki Tatsuta, Seijiro Hosokawa

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    The total synthesis of hibarimicinone, a potent v-Src tyrosine kinase inhibitor possessing thirteen stereogenic centers and an axial chirality, has been achieved. The key step to constructing the eight-ring skeleton was the double Michael-Dieckmann-type cyclization (Hauser annulation) using a thiolactone pseudo-dimer. These synthetic studies indicated the efficiency of the thiolactone-employed route to synthesize the multiply functionalized polycyclic compounds. The ABCD-ring moiety including the bridging ether was constructed by a strategy including oxidation of the C-ring hydroquinone and the subsequent transfer of the oxidation stage to the neighboring ring. The atropisomer of hibarimicinone was also synthesized to confirm the structure of the natural product. The total synthesis of hibarimicinone, a potent v-Src tyrosine kinase inhibitor, has been achieved. The key step to constructing the eight-ring skeleton was the double Michael-Dieckmann-type cyclization (Hauser annulation) using a thiolactone pseudo-dimer. The ABCD-ring moiety including the bridging ether was constructed by a strategy including oxidation of the C-ring hydroquinone and the subsequent transfer of the oxidation stage to the neighboring ring. The atropisomer of hibarimicinone was also synthesized to confirm the structure of the natural product.

    Original languageEnglish
    Pages (from-to)28-40
    Number of pages13
    JournalChemical Record
    Volume14
    Issue number1
    DOIs
    Publication statusPublished - 2014 Feb

    Fingerprint

    src-Family Kinases
    Tetracycline
    Dimers
    Oxidation
    Cyclization
    Biological Products
    Skeleton
    Ether
    Ethers
    Polycyclic Compounds
    Chirality
    hibarimicinone
    hydroquinone

    Keywords

    • annulation
    • hibarimicinone
    • stereoselective synthesis
    • tetracycline
    • total synthesis

    ASJC Scopus subject areas

    • Chemistry(all)
    • Chemical Engineering(all)
    • Materials Chemistry
    • Biochemistry
    • Biochemistry, medical
    • Medicine(all)

    Cite this

    Total synthesis of hibarimicinone, a v-Src tyrosine kinase inhibitor possessing the pseudo-dimer structure of tetracycline. / Tatsuta, Kuniaki; Hosokawa, Seijiro.

    In: Chemical Record, Vol. 14, No. 1, 02.2014, p. 28-40.

    Research output: Contribution to journalArticle

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