Relative Reactivity of Benzothiophene-Fused Enediynes in the Bergman Cyclization

Anna G. Lyapunova, Natalia A. Danilkina, Andrey M. Rumyantsev, A. F. Khlebnikov, Mikhail V. Chislov, Galina L. Starova, Elena V. Sambuk, Anastasia I. Govdi, Stefan Brase, Irina A. Balova

Результат исследований: Научные публикации в периодических изданияхстатьянаучнаярецензирование

5 Цитирования (Scopus)

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To find promising analogues of naturally occurring enediyne antibiotics with a sufficient reactivity in the Bergman cyclization and moderately stable under isolation and storage, a scale of relative enediynes reactivity was created on the basis of calculated free activation energies for the Bergman cyclization within 12 known and new benozothio-phene, benzene, and cinnoline annulated 9- and 10-membered enediynes. To verify the predicted reactivity/stability balance, three new carbocyclic enediynes fused to a benzothiophene core bearing 3,4,5-trimethoxybenzene, fluoroisopropyl, and isopropenyl substituents were synthesized using the Nicholas type macrocyclization. It was confirmed that annulation of a 3,4,5-trimethoxybenzene moiety to a 10-membered enediyne macrocycle imparts high reactivity to an enediyne while also conferring instability under ambient temperature. Fluoroisopropyl-substituted 10-membered enediyne from the opposite end of the scale was found to be stable while moderately reactive in the Bergman cyclization. Along with the experimentally confirmed moderate reactivity (DSC kinetic studies), (fluoroisopropyl)enediyne showed a significant DNA damaging activity in plasmid cleavage assays comparable with the known anticancer drug Zeocin.

Язык оригиналаАнглийский
Страницы (с-по)2788-2801
Число страниц14
ЖурналJournal of Organic Chemistry
Том83
Номер выпуска5
DOI
СостояниеОпубликовано - 2 мар 2018

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    @article{4ec3acd2e00b4c1d8883ccc4f804d106,
    title = "Relative Reactivity of Benzothiophene-Fused Enediynes in the Bergman Cyclization",
    abstract = "To find promising analogues of naturally occurring enediyne antibiotics with a sufficient reactivity in the Bergman cyclization and moderately stable under isolation and storage, a scale of relative enediynes reactivity was created on the basis of calculated free activation energies for the Bergman cyclization within 12 known and new benozothio-phene, benzene, and cinnoline annulated 9- and 10-membered enediynes. To verify the predicted reactivity/stability balance, three new carbocyclic enediynes fused to a benzothiophene core bearing 3,4,5-trimethoxybenzene, fluoroisopropyl, and isopropenyl substituents were synthesized using the Nicholas type macrocyclization. It was confirmed that annulation of a 3,4,5-trimethoxybenzene moiety to a 10-membered enediyne macrocycle imparts high reactivity to an enediyne while also conferring instability under ambient temperature. Fluoroisopropyl-substituted 10-membered enediyne from the opposite end of the scale was found to be stable while moderately reactive in the Bergman cyclization. Along with the experimentally confirmed moderate reactivity (DSC kinetic studies), (fluoroisopropyl)enediyne showed a significant DNA damaging activity in plasmid cleavage assays comparable with the known anticancer drug Zeocin.",
    keywords = "TRANSITION-STATE STABILIZATION, NICHOLAS REACTION, ELECTROPHILIC CYCLIZATION, ANTICANCER ANTIBIOTICS, CLICK CHEMISTRY, ENYNE-ALLENES, COMPLEXES, RING, CONSTRUCTION, CYCLOAROMATIZATION",
    author = "Lyapunova, {Anna G.} and Danilkina, {Natalia A.} and Rumyantsev, {Andrey M.} and Khlebnikov, {A. F.} and Chislov, {Mikhail V.} and Starova, {Galina L.} and Sambuk, {Elena V.} and Govdi, {Anastasia I.} and Stefan Brase and Balova, {Irina A.}",
    year = "2018",
    month = "3",
    day = "2",
    doi = "10.1021/acs.joc.7b03258",
    language = "Английский",
    volume = "83",
    pages = "2788--2801",
    journal = "Journal of Organic Chemistry",
    issn = "0022-3263",
    publisher = "American Chemical Society",
    number = "5",

    }

    Relative Reactivity of Benzothiophene-Fused Enediynes in the Bergman Cyclization. / Lyapunova, Anna G.; Danilkina, Natalia A.; Rumyantsev, Andrey M.; Khlebnikov, A. F.; Chislov, Mikhail V.; Starova, Galina L.; Sambuk, Elena V.; Govdi, Anastasia I.; Brase, Stefan; Balova, Irina A.

    В: Journal of Organic Chemistry, Том 83, № 5, 02.03.2018, стр. 2788-2801.

    Результат исследований: Научные публикации в периодических изданияхстатьянаучнаярецензирование

    TY - JOUR

    T1 - Relative Reactivity of Benzothiophene-Fused Enediynes in the Bergman Cyclization

    AU - Lyapunova, Anna G.

    AU - Danilkina, Natalia A.

    AU - Rumyantsev, Andrey M.

    AU - Khlebnikov, A. F.

    AU - Chislov, Mikhail V.

    AU - Starova, Galina L.

    AU - Sambuk, Elena V.

    AU - Govdi, Anastasia I.

    AU - Brase, Stefan

    AU - Balova, Irina A.

    PY - 2018/3/2

    Y1 - 2018/3/2

    N2 - To find promising analogues of naturally occurring enediyne antibiotics with a sufficient reactivity in the Bergman cyclization and moderately stable under isolation and storage, a scale of relative enediynes reactivity was created on the basis of calculated free activation energies for the Bergman cyclization within 12 known and new benozothio-phene, benzene, and cinnoline annulated 9- and 10-membered enediynes. To verify the predicted reactivity/stability balance, three new carbocyclic enediynes fused to a benzothiophene core bearing 3,4,5-trimethoxybenzene, fluoroisopropyl, and isopropenyl substituents were synthesized using the Nicholas type macrocyclization. It was confirmed that annulation of a 3,4,5-trimethoxybenzene moiety to a 10-membered enediyne macrocycle imparts high reactivity to an enediyne while also conferring instability under ambient temperature. Fluoroisopropyl-substituted 10-membered enediyne from the opposite end of the scale was found to be stable while moderately reactive in the Bergman cyclization. Along with the experimentally confirmed moderate reactivity (DSC kinetic studies), (fluoroisopropyl)enediyne showed a significant DNA damaging activity in plasmid cleavage assays comparable with the known anticancer drug Zeocin.

    AB - To find promising analogues of naturally occurring enediyne antibiotics with a sufficient reactivity in the Bergman cyclization and moderately stable under isolation and storage, a scale of relative enediynes reactivity was created on the basis of calculated free activation energies for the Bergman cyclization within 12 known and new benozothio-phene, benzene, and cinnoline annulated 9- and 10-membered enediynes. To verify the predicted reactivity/stability balance, three new carbocyclic enediynes fused to a benzothiophene core bearing 3,4,5-trimethoxybenzene, fluoroisopropyl, and isopropenyl substituents were synthesized using the Nicholas type macrocyclization. It was confirmed that annulation of a 3,4,5-trimethoxybenzene moiety to a 10-membered enediyne macrocycle imparts high reactivity to an enediyne while also conferring instability under ambient temperature. Fluoroisopropyl-substituted 10-membered enediyne from the opposite end of the scale was found to be stable while moderately reactive in the Bergman cyclization. Along with the experimentally confirmed moderate reactivity (DSC kinetic studies), (fluoroisopropyl)enediyne showed a significant DNA damaging activity in plasmid cleavage assays comparable with the known anticancer drug Zeocin.

    KW - TRANSITION-STATE STABILIZATION

    KW - NICHOLAS REACTION

    KW - ELECTROPHILIC CYCLIZATION

    KW - ANTICANCER ANTIBIOTICS

    KW - CLICK CHEMISTRY

    KW - ENYNE-ALLENES

    KW - COMPLEXES

    KW - RING

    KW - CONSTRUCTION

    KW - CYCLOAROMATIZATION

    U2 - 10.1021/acs.joc.7b03258

    DO - 10.1021/acs.joc.7b03258

    M3 - статья

    VL - 83

    SP - 2788

    EP - 2801

    JO - Journal of Organic Chemistry

    JF - Journal of Organic Chemistry

    SN - 0022-3263

    IS - 5

    ER -