Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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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
UR - http://www.mendeley.com/research/relative-reactivity-benzothiophenefused-enediynes-bergman-cyclization
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 -
ID: 28186305