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Synthesis of N-C axially chiral compounds bearing a small group at ortho-position

Research Project

Project/Area Number 20K06945
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
Research InstitutionShibaura Institute of Technology

Principal Investigator

Kitagawa Osamu  芝浦工業大学, 工学部, 教授 (30214787)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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 / アニリン / ジアステレオマー / ハロゲン結合 / チオン / キノリノン
Outline of Research at the Start

軸不斉型アトロプ異性分子は単結合の回転束縛によって生じるキラル化合物である.従来,単結合の回転束縛のためには,単結合周りに一定以上の立体的嵩高さを有する置換基が必要であると考えられてきた.本研究は,炭素-窒素単結合周りにフッ素原子や重水素原子等の極小置換基を有する安定な炭素-窒素軸不斉型アトロプ異性分子(窒素原子上にオルト-フルオロフェニル基やオルト-重水素化フェニル基を有する含窒素芳香族複素環化合物)の創製を目的とする.

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.

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.

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (18 results)

All 2022 2021 2020 Other

All Int'l Joint Research (1 results) Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (8 results) Remarks (2 results)

  • [Int'l Joint Research] エクスマルセイユ大学/レンヌ大学(フランス)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Asymmetric Synthesis of Isotopic Atropisomers based on <i>ortho</i>-CH<sub>3</sub>/CD<sub>3</sub> Discrimination and Their Structural Properties2022

    • Author(s)
      Miwa Shota、Senda Ryunosuke、Saito Kazuya、Sato Azusa、Nakamura Yuko、Kitagawa Osamu
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 87 Issue: 21 Pages: 13501-13507

    • DOI

      10.1021/acs.joc.2c02185

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rotational Behavior of <i>N</i>-(5-Substituted-pyrimidin-2-yl)anilines: Relayed Electronic Effect in Two N?Ar Bond Rotations2022

    • Author(s)
      Homma Daiki、Taketani Shuhei、Shirai Takeshi、Caytan Elsa、Roussel Christian、Elguero Jos?、Alkorta Ibon、Kitagawa Osamu
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 87 Issue: 12 Pages: 8118-8125

    • DOI

      10.1021/acs.joc.2c00845

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Intermolecular Halogen Bond Detected in Racemic and Optically Pure N-C Axially Chiral 3-(2-Halophenyl)quinazoline-4-thione Derivatives2022

    • Author(s)
      Matsui Ryosuke、Niijima Erina、Imai Tomomi、Kobayashi Hiroyuki、Hori Akiko、Sato Azusa、Nakamura Yuko、Kitagawa Osamu
    • Journal Title

      Molecules

      Volume: 27 Issue: 7 Pages: 2369-2369

    • DOI

      10.3390/molecules27072369

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Catalytic Enantioselective Synthesis of N-C Axially Chiral N-(2,6-Disubstituted-phenyl)sulfonamides through Chiral Pd-Catalyzed N-Allylation2022

    • Author(s)
      Fukasawa Sota、Toyoda Tatsuya、Kasahara Ryohei、Nakamura Chisato、Kikuchi Yuuki、Hori Akiko、Richards Gary J.、Kitagawa Osamu
    • Journal Title

      Molecules

      Volume: 27 Issue: 22 Pages: 7819-7819

    • DOI

      10.3390/molecules27227819

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of Isotopic Atropisomerism Based on <i>ortho</i>-H/D Discrimination2021

    • Author(s)
      Saito Kazuya、Miwa Shota、Iida Asumi、Fujimoto Yuuki、Caytan Elsa、Roussel Christian、Kitagawa Osamu
    • Journal Title

      Organic Letters

      Volume: 23 Issue: 19 Pages: 7492-7496

    • DOI

      10.1021/acs.orglett.1c02723

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Studies on Rotational Stability of 2-Aryl-3-(2-fluorophenyl)quinazolin-4-one Derivatives2021

    • Author(s)
      Asumi Iida, Kazuya Saito, Nanami Asada, Yuuki Fujimoto, Osamu Kitagawa
    • Journal Title

      Heterocycles

      Volume: 103 Issue: 1 Pages: 183-183

    • DOI

      10.3987/com-20-s(k)10

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Thionation of Optically Pure N-C Axially Chiral Quinazolin-4-one Derivatives with Lawesson’s Reagent2020

    • Author(s)
      Erina Niijima, Tomomi Imai, Hayate Suzuki, Yuuki Fujimoto, Osamu Kitagawa
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 86 Issue: 1 Pages: 709-715

    • DOI

      10.1021/acs.joc.0c02319

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] CH3/CD3 識別に基づく同位体アトロプ異性キナゾリノンの不斉合成と回転安定性の検証2022

    • Author(s)
      三輪翔太,千田龍之介,齋藤和哉,北川 理
    • Organizer
      第 83 回有機合成化学協会関東支部シンポジウム
    • Related Report
      2022 Annual Research Report
  • [Presentation] オルト-CH3/CD3識別に基づく同位体アトロプ異性分子の合成と検出2022

    • Author(s)
      千田龍之介, 三輪翔太, 齋藤和哉, 北川 理
    • Organizer
      第66回日本薬学会関東支部シンポジウム
    • Related Report
      2022 Annual Research Report
  • [Presentation] N-ピリミジル基を有するオルト置換アニリン誘導体の回転挙動2022

    • Author(s)
      本間大貴, 竹谷修平, 白井毅史, 北川 理
    • Organizer
      第51回複素環化学討論会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 炭素-窒素軸不斉キナゾリンチオンで観察されたキラリティー依存型ハロゲン結合2022

    • Author(s)
      松井綾佑, 新島江里菜, 今井朋美, 北川 理
    • Organizer
      第51回複素環化学討論会
    • Related Report
      2022 Annual Research Report
  • [Presentation] オルト-CH3/CD3識別に基づく炭素-窒素軸不斉型同位体アトロプ異性分子の創製2022

    • Author(s)
      三輪翔太, 千田龍之介, 斎藤和哉, 北川 理
    • Organizer
      第51回複素環化学討論会
    • Related Report
      2022 Annual Research Report
  • [Presentation] N-アミノピリミジル基を有するオルト-置換アニリン誘導体を用いた多機能性プロトンブレーキ分子の創製2021

    • Author(s)
      齋藤和哉,三輪翔太,飯田明日美,藤本裕貴,北川 理
    • Organizer
      第50回 複素環化学討論会
    • Related Report
      2021 Research-status Report
  • [Presentation] N-アミノピリミジル基を有するオルト-置換アニリン誘導体を用いた多機能性プロトンブレーキ分子の創製2021

    • Author(s)
      竹谷修平,白井毅史,本間大貴,北川 理
    • Organizer
      第119回 有機合成シンポジウム
    • Related Report
      2021 Research-status Report
  • [Presentation] オルト-フルオロフェニル基を有する2-アリール-4-キナゾリノン誘導体の炭素-窒素軸の安定性2020

    • Author(s)
      第80回有機合成化学協会関東支部シンポジウム
    • Organizer
      齋藤和哉、飯田明日美、北川理、藤本裕貴
    • Related Report
      2020 Research-status Report
  • [Remarks] Successful Synthesis of Rare Isotopic Atropisomers

    • Related Report
      2022 Annual Research Report
  • [Remarks] Atropisomeric N-Aryl Quinazoline-4-Thiones

    • URL

      https://www.shibaura-it.ac.jp/en/news/nid00001885.html

    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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