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

Kuniaki Tatsuta, Seijiro Hosokawa

    研究成果: Article

    6 引用 (Scopus)

    抄録

    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.

    元の言語English
    ページ(範囲)28-40
    ページ数13
    ジャーナルChemical Record
    14
    発行部数1
    DOI
    出版物ステータスPublished - 2014 2

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

    ASJC Scopus subject areas

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

    これを引用

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    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.",
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