Catalytic asymmetric synthesis of bioactive N-C axially chiral quinazolinones and their structural property
| Project/Area Number |
17K08220
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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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| Research Field |
Chemical pharmacy
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| Research Institution | Shibaura Institute of Technology |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 軸不斉 / キナゾリノン / エナンチオマー / 自己不均化 / ジアステレオマー / アルキル化 / エノラート / フッ素 / ハロゲン結合 / 不斉触媒反応 / エナンチオマー精製 / ジアステレオ選択性 / 不斉触媒 / エナンチオ選択的 / ジアステレオ選択的 |
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| Outline of Final Research Achievements |
We suceeded in the highly enantioselective synthesis of bioactive N-C axally chiral quinazolin-4-one derivatives through the chiral Pd-catalyzed reductive asymmetric desymmetrization. The achiral MPLC of the optically active quinazolinone products led to the self-disproportionation of enantiomers (SDE) to give the optically pure quinazolinones. Furthermore, the SDE machanism was also revealed. The alpha-alkylation with the chiral enolate prepared from optically pure quinazolinones proceeded with high diastereoselectivity without the any decrease in the optically purity to afford pharmaceutically attractive compounds bearing a chiral center and a chiral axis. In the course of this work, unique N-C axally chiral quinazolin-4-one derivatives having ortho-fluorophenyl group at N3 position were also found.
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| Academic Significance and Societal Importance of the Research Achievements |
今回我々は，生理活性軸不斉キナゾリノン誘導体（GABA受容体アゴニスト）の高エナンチオ選択的触媒的合成と軸不斉キナゾリノン生成物の不斉反応への応用に初めて成功し，不斉反応の新たな手法を開拓すると共に，創薬化学においても極めて魅力的な化合物を創製することができた．また，本研究の途上，アキラルな中圧液体クロマトを用いるエナンチオマーの自己不均化やオルト-フルオロフェニル基を有するユニークな炭素-窒素軸不斉キナゾリノン誘導体も見い出しており，構造化学の観点からも有意義な知見を得た．
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Report
(4 results)
Research Products
(36 results)
