2022 Fiscal Year Final Research Report
Synthesis of N-C axially chiral compounds bearing a small group at ortho-position
| Project/Area Number |
20K06945
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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 | Shibaura Institute of Technology |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | アトロプ異性 / 軸不斉 / キナゾリノン / キナゾリンチオン / フッ素 / 重水素 / 不斉触媒 / エナンチオマー |
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| Outline of Final Research Achievements |
Atropisomeric axially chiral molecules are chiral compounds owing to the rotational restriction around a single bond and they have been widely used as chiral catalysts, chiral ligands and chiral resolution reagents. In general, sterically bulky substituents are required for the stable atropisomeric structure. We suceeded in the synthesis of stable atropisomeric compounds (N-C axially chiral quinazolin-4-ones) bearing a small group such as fluorine and deuterio atoms around the chiral axis. Furthremore, the isotopic atropisomers based on H/D and CH3/CD3 descrimination were prepared, and the relation between rotational stability about the N-Ar bond and electronic effect of a substituent were also revealed.
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| Free Research Field |
薬系化学および創薬関連科学
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| Academic Significance and Societal Importance of the Research Achievements |
不斉軸周りにフッ素原子や重水素原子を有する（オルト-H/FおよびH/D識別に基づく）安定なアトロプ異性化合物はこれまで一般的ではなく，構造化学の観点から大変興味深い（学術的新規性）．同時に本研究は，同位体アトロプ異性という新たな研究分野も開拓したことになる．
また，本研究の標的分子である３位窒素原子上に芳香族置換基を有するキナゾリノン誘導体は多様な生理活性を有することが知られており，フッ素原子や重水素原子を選択的に導入したキナゾリノン生成物は，創薬科学（薬物代謝研究や重薬への応用）の観点からも有用と考えられる．
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