Divergent Synthesis of Nitrogen-Containing Heterocycles by Sequential Reactions and Its Application to Drug Discovery
| Project/Area Number |
18K05103
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 33020:Synthetic organic chemistry-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | イナミド / 複素環 / ルイス酸 / 生物活性物質 / 連続反応 / 酸 / 中員環 / 含窒素複素環合成 / 中員環合成 |
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| Outline of Final Research Achievements |
We have investigated the synthesis of nitrogen-containing heterocycles by Lewis acid-catalyzed cyclization of ynamides. Stereoselective synthesis of spiroindoline skeletons was achieved by sequential cyclization using enamide-ynamide and various external nucleophiles. By slightly adjusting the electronic state of the ynamide-terminus, reactions with different cyclization modes were found to proceed, giving polycyclic quinolines.
Different cyclization reactions proceeded from the almost same substrates, and polysubstituted spiroindoline derivatives and polycyclic quinolines could be synthesized efficiently. Thus, we have achieved the divergent construction of nitrogen-containing heterocycles by multicomponent sequential reactions using enamide-ynamide substrates.
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| Academic Significance and Societal Importance of the Research Achievements |
新しい反応系の開発は、単純に新規反応の開発に貢献するだけでなく、より効率的な医薬品や生理活性物質の合成を可能とする。本研究では、イナミドに対しルイス酸触媒を作用させることによる連続環化反応を用いた多様な官能基を有する含窒素複素環合成法の開発に成功した。得られるスピロインドリンやキノリン誘導体は医薬品など有用化合物に多く見られる基本骨格であり、これらの効率的合成は学術的に意義深い。今後さらなる誘導体合成ならびに生物活性評価などの応用研究も行い、実践的研究につなげていく予定である。
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Report
(4 results)
Research Products
(10 results)
