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Development of aryl coupling reactions using thionium species and application to the synthesis of condensed heterocyclic skeleton

Research Project

Project/Area Number 16K08181
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Chemical pharmacy
Research InstitutionMeiji Pharmaceutical University

Principal Investigator

Higuchi Kazuhiro  明治薬科大学, 薬学部, 准教授 (60360195)

Research Collaborator Tago Takuhiro  
Matsumura Kazunori  
Hui Yi  
Tayu Masanori  
Saito Nozomi  
Sugiyama Shigeo  
Ito Motoki  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords活性チオニウム種 / スルホキシド / ビアリールカップリング / 連続的環化反応 / チオニウム種 / フェノールカップリング / ハークリンA / ラピジレクチンB / チオニウム / ビアリール / カップリング / 有機化学 / 薬学
Outline of Final Research Achievements

We investigated to develop new applications of highly reactive sulfonium species generated from sulfoxides and acid anhydrides. First, an intermolecular reaction was carried out using phenols or phenol ethers as substrates to obtain the desired biaryl compounds. Next, in order to apply this method to intramolecular reactions, we also carried out synthetic studies of two biologically active natural products. As a result of synthesizing a model compound for the key reaction and treating sulfonium species to the compound, it was clarified that the flexibility of the substrate is important.

Academic Significance and Societal Importance of the Research Achievements

スルホキシドを酸無水物により活性化して生成する活性チオニウム種は、従来アルコールを温和な条件下で酸化する化合物として知られていた。しかしながら、活性チオニウム種の反応性に関する研究は、近年活発化してきている。我々は活性チオニウム種の新規反応性を明らかにすることを学術的な目標として研究を行った。また、従来酸化反応は重金属を用いる手法が多いため、本法は環境負荷の少ない化学反応の開発へと発展可能である。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (11 results)

All 2019 2018 2017 2016 Other

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results) Presentation (6 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Remarks (1 results)

  • [Journal Article] A metal-free biaryl coupling reaction activated by a sulfonium salt2018

    • Author(s)
      Higuchi Kazuhiro、Tago Takuhiro、Kokubo Yusuke、Ito Motoki、Tayu Masanori、Sugiyama Shigeo、Kawasaki Tomomi
    • Journal Title

      Organic Chemistry Frontiers

      Volume: 5 Issue: 22 Pages: 3219-3225

    • DOI

      10.1039/c8qo00798e

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 分子間interrupted Pummerer反応を利用したインドール類の官能基化反応2018

    • Author(s)
      田湯 正法, 樋口 和宏, 川﨑 知己
    • Journal Title

      有機合成化学協会誌

      Volume: 76 Pages: 678-689

    • NAID

      130007403450

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Direct C2-Functionalization of Indoles Triggered by the Generation of Iminium Species from Indole and Sulfonium Salt2017

    • Author(s)
      Masanori Tayu, Kazuya Nomura, Koki Kawachi, Kazuhiro Higuchi, Nozomi Saito, Tomomi Kawasaki
    • Journal Title

      Chem. Eur. J.

      Volume: 23 Issue: 45 Pages: 10925-10930

    • DOI

      10.1002/chem.201702338

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Total Synthesis of (+)-Gliocladin C Based on One-Pot Construction of a 3a-(3-Indolyl)pyrroloindoline Skeleton by Sulfonium-Mediated Cross-Coupling of Tryptophan and Indole2017

    • Author(s)
      Tayu, M.; Hui, Y.; Takeda, S.; Higuchi, K.; Saito, N.; Kawasaki, T
    • Journal Title

      Org. Lett.

      Volume: 19 Issue: 24 Pages: 6582-6585

    • DOI

      10.1021/acs.orglett.7b03293

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Activated thionium induced bond formation2019

    • Author(s)
      Kazuhiro HIGUCHI
    • Organizer
      35th International annual meeting in pharmaceutical sciences (IAMPS35) and CU-MPU international collaborative research conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] スルホニウム種を用いたインドールの芳香族求核置換反応2017

    • Author(s)
      田湯 正法, 野村 和也, 河内 晃樹, 樋口 和宏, 齋藤 望, 川﨑 知己
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台、宮城
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] ジアステレオ選択的ピロロインドリン骨格ワンポット構築反応の開発と(+)-gliocladin C 合成研究への応用2017

    • Author(s)
      回芸、田湯正法、武田詩織、樋口和宏、齋藤望、川﨑知己
    • Organizer
      第73回有機合成化学協会関東支部シンポジウム(目白シンポジウム)
    • Related Report
      2017 Research-status Report
  • [Presentation] スルホニウム種によるピロロインドリンワンポット合成法を利用した(+)-gliocladin C の不斉全合成2017

    • Author(s)
      回 芸・田湯正法・武田詩織・樋口和宏・齋藤 望・川﨑知己
    • Organizer
      第47 回 複素環化学討論会
    • Related Report
      2017 Research-status Report
  • [Presentation] Sulfonium Species Mediated Coupling Reaction of Phenol Derivatives2016

    • Author(s)
      Kazuhiro Higuchi, Takuhiro Tago, Yusuke Kokubo, Masanori Tayu, Tomomi Kawasaki and Shigeo Sugiyama
    • Organizer
      French- Japanese Symposium on Medicinal and Fine Chemistry
    • Place of Presentation
      多摩、東京
    • Year and Date
      2016-05-15
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Nucleophilic Aromatic Substitution on Electron-Rich Indoles Mediated by DMSO-Tf2O2016

    • Author(s)
      Masanori Tayu, Koki Kawachi, Kazuya Nomura, Kazuhiro Higuchi, Tomomi Kawasaki, Nozomi Saito
    • Organizer
      French- Japanese Symposium on Medicinal and Fine Chemistry
    • Place of Presentation
      多摩、東京
    • Year and Date
      2016-05-15
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] 明治薬科大学機能分子化学研究室 ホームページ

    • URL

      https://u-lab.my-pharm.ac.jp/~knbskg/index.html

    • Related Report
      2017 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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