2022 Fiscal Year Final Research Report
Development of the methodology for the construction of optically active 3,3-disubstituted piperidine skeletons using organocatalyst and its application for the synthesis of natural products.
| Project/Area Number |
19K06969
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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 47010:Pharmaceutical chemistry and drug development sciences-related
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| Research Institution | International University of Health and Welfare (2021-2022)
Chiba University (2019-2020) |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | アルカロイド / 有機分子触媒 / 不斉全合成 / マイケル付加 / エナミン / ピペリジン |
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| Outline of Final Research Achievements |
We have developed the asymmetric Michael reaction of enamine (3-ethyl-2,3-dehydropiperidine) with acrolein to stereoselectively construct 3,3-disubstituted piperidine skeletons with a quaternary chiral center using organocatalyst. Although acrolein has turned to be commercially unavailable due to its toxicity, we established new reaction condition which proceed using acrolein dimethyl acetal as an alternative. We have achieved efficient total syntheses of several natural alkaloids (vincamine, leucomidines A and C) from the bicyclic key intermediate obtained in this asymmetric reaction. In the nearly future, we plan to achieve efficient total synthesis of further new alkaloids.
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| Free Research Field |
創薬化学
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| Academic Significance and Societal Importance of the Research Achievements |
我々が確立した有機分子触媒を用いたエナミンのアクロレイン誘導体への不斉マイケル反応は、優に50を超えるモノテルペノイドインドールアルカロイドの効率的全合成に利用可能である。モノテルペノイドインドールアルカロイドは非常に複雑な構造と強力な生物活性をもち、医薬品として利用されている化合物も多いことから、本研究が新規創薬シード分子の探索に大きく貢献できると考えている。本反応は触媒量（３％程度）の有機分子触媒で反応が進行することから環境負荷が小さく、高度な手技を必要とせず汎用性・再現性が高いことからも、学術的意義は非常に大きいと言える。
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