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The Development of Direct Vinylogous Michael Addition of Butenolides to Chromones and Its Application to the Total Synthesis of Natural Products

Research Project

Project/Area Number 20K15966
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
Research InstitutionMicrobial Chemistry Research Foundation

Principal Investigator

Cui Jin  公益財団法人微生物化学研究会, 微生物化学研究所, 研究員 (20839120)

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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordstotal synthesis / asymmetric catalysis / enolate / copper / vinylogous addition / chromone / enolates / natural product / atom-economy / chromanone lactones / catalytic synthesis / butenolides / natural products
Outline of Research at the Start

In this project, a novel catalytic asymmetric synthetic method for the chromone lactone compounds will be established. The intriguing enantioface-differentiation mechanism for the unexpected and unprecedented anti-selectivity will be clarified. (+)-Lachnone C, epi-(+)-microdiplodiasone, (+)-gonytolides C&G and their simplified analogues will be synthesized and subjected to in vitro screening in order to identify the potential antibacterial and/or anticancer lead compounds

Outline of Final Research Achievements

This study achieved the development of a new synthetic method for chromanone lactones. The method is applicable to chromones with different substitution groups and has yielded natural product analogs with excellent diastereo- and enantioselectivity. Additionally, successful syntheses of ent-blennolide B and secalonic acid A were also achieved.

Academic Significance and Societal Importance of the Research Achievements

The method developed in this study could be used for the synthesis of biologically important natural products in an effective manner which may accelerate drug discovery based on natural products.

Report

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

    (10 results)

All 2023 2022 2020 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (5 results) (of which Invited: 1 results) Remarks (1 results)

  • [Journal Article] Asymmetric Syn-Selective Vinylogous Addition of Butenolides to Chromones via Al-Li-BINOL Catalysis2023

    • Author(s)
      Samanta Sadhanendu、Cui Jin、Noda Hidetoshi、Watanabe Takumi、Shibasaki Masakatsu
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 88 Issue: 2 Pages: 1177-1184

    • DOI

      10.1021/acs.joc.2c02731

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bronsted base-catalyzed direct 1,6-conjugate addition of butenolide to p-quinone methides.2023

    • Author(s)
      Jin Cui, Sadhanendu Samanta, Takumi Watanabe, Masakatsu Shibasaki
    • Journal Title

      Asian Journal of Organic Chemistry

      Volume: NA Issue: 7

    • DOI

      10.1002/ajoc.202300176

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Concise and Stereodivergent Approach to Chromanone Lactones through Copper‐Catalyzed Asymmetric Vinylogous Addition of Siloxyfurans to 2‐Ester‐Substituted Chromones2022

    • Author(s)
      Jin Cui, Raphael Oriez, Hidetoshi Noda, Takumi Watanabe, Masakatsu Shibasaki
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 61 Issue: 26 Pages: 1-6

    • DOI

      10.1002/anie.202203128

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Direct catalytic asymmetric and anti-selective vinylogous addition of butenolides to chromones2020

    • Author(s)
      Cui Jin、Kumagai Naoya、Watanabe Takumi、Shibasaki Masakatsu
    • Journal Title

      Chemical Science

      Volume: 11 Issue: 27 Pages: 7170-7176

    • DOI

      10.1039/d0sc01914c

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Concise and Stereodivergent Approach to Chromanone Lactones through Copper-Catalyzed Asymmetric Vinylogous Addition of Siloxyfurans to 2-Ester-Substituted Chromones2023

    • Author(s)
      Jin Cui, Raphael Oriez, Hidetoshi Noda, Takumi Watanabe, Masakatsu Shibasaki
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Development of catalytic asymmetric reactions and its application to the syntheses of bioactive natural products2022

    • Author(s)
      崔 進
    • Organizer
      日本薬学会関東支部オンライン受賞記念講演会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Concise and Stereodivergent Approach to Chromanone Lactones via Copper-Catalyzed Asymmetric Vinylogous Addition of Siloxyfurans to 2-Ester Chromones2022

    • Author(s)
      Jin Cui, Raphael Oriez, Takumi Watanabe, Masakatsu Shibasaki
    • Organizer
      20th Symposium on Organic Chemistry: the Next Generation
    • Related Report
      2021 Research-status Report
  • [Presentation] 環境調和型触媒的不斉ビニロガスマイケル反応を利用したクロマノンラクトン類の合成2020

    • Author(s)
      崔 進, 渡辺 匠, 熊谷 直哉, 柴崎 正勝
    • Organizer
      日本薬学会第140年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Direct Catalytic Asymmetric Vinylogous Addition of Butenolides to Chromones2020

    • Author(s)
      崔 進, 熊谷 直哉, 渡辺 匠, 柴崎 正勝
    • Organizer
      第117回有機合成シンポジウム
    • Related Report
      2020 Research-status Report
  • [Remarks] 微生物化学研究所

    • URL

      https://www.bikaken.or.jp/

    • Related Report
      2020 Research-status Report

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

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