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Studies towards total synthesis of anti-HIV conocurvone and construction of trimeric structure using benzyne intermediates

Research Project

Project/Area Number 19K06975
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 InstitutionHiroshima University

Principal Investigator

Kumamoto Takuya  広島大学, 医系科学研究科(薬), 教授 (50292678)

Project Period (FY) 2019-04-01 – 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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsベンザイン / クロメン / Diels-Alder 反応 / 抗 HIV / 3量体 / コノクルボン / 環化付加反応 / 抗HIV / 抗HIV-1
Outline of Research at the Start

植物由来成分であるコノクルボンは,HIV-1の阻害と,クロメノキノン骨格が3つ連なった構造をもつことの2つの特徴を有します.私はこの研究で,このような3量体の効率的合成法と,コノクルボンの抗HIV-1活性の本質を探究します.クロメノキノンの構築にはフランとベンザインの環化付加反応を用い,3量体の形成には3連結フランを用います.まず3連結フランを合成し,環化付加反応を試みることでコノクルボンの合成を目指します.併せて,機能は同じでも少し構造の異なる3連結フランの代替化合物からも3量体を合成し,種々の3量体の生物活性を系統的に比較することで,コノクルボンのもつ抗HIV-1活性の本質に迫ります.

Outline of Final Research Achievements

The total synthesis of anti-HIV active conocurvones with trimeric chromenoquinone structure was investigated based on the Diels-Alder (DA) reaction of trifuran and optically active chromene-derived benzynes. The intramolecular SNAr of fluorinated cinnamic alcohols allowed the efficient synthesis of the desired optically active chromenes. In the synthesis of linked furanones, two types of furanones with side chains were synthesized. We also investigated the synthesis of a simple trimeric structure that is expected their anti-HIV activity, using mucobromic acid as a starting material, which has two leaving groups and a furanone structure. Synthesis of the trimer structure was achieved by the introduction of azide groups and subsequent DA reaction of the azides and benzyne.

Academic Significance and Societal Importance of the Research Achievements

オーストラリア原産植物が産出するコノクルボンが抗 HIV 活性をもつことに着目し,本化合物とその類縁体の合成を検討した.コノクルボンはクロメノキノン構造が3つ連続した構造をもち,3つの連結したフラン環に3分子のクロメン環を反応させることでその構造を構築することとした.このうち,クロメン環の光学活性体の効率的合成法を確立し,さらに3つの連結したフラン環の原料となる側鎖をもつフラノンの合成を達成した.

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (17 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (2 results) Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (6 results) (of which Int'l Joint Research: 4 results,  Invited: 4 results) Book (1 results) Remarks (4 results)

  • [Int'l Joint Research] Institut Ruder Boskovic(クロアチア)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Ruder Boskovic Institute(クロアチア)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Asymmetric Total Synthesis of Brasiliquinones B and C via Oxidative Cyclization of a Hydroquinone-Silyl Enol Ether Hybrid2022

    • Author(s)
      Miyake Hiroki、Nakajima Ryo、Kumamoto Takuya
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 87 Issue: 18 Pages: 12491-12497

    • DOI

      10.1021/acs.joc.2c01653

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Actinorhodin Biosynthesis Terminates with an Unprecedented Biaryl Coupling Reaction2022

    • Author(s)
      Hashimoto Makoto、Watari Susumu、Taguchi Takaaki、Ishikawa Kazuki、Kumamoto Takuya、Okamoto Susumu、Ichinose Koji
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 62 Issue: 5

    • DOI

      10.1002/anie.202214400

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Total Synthesis of 6-Deoxydihydrokalafungin, a Key Biosynthetic Precursor of Actinorhodin, and Its Epimer2021

    • Author(s)
      Kumamoto Takuya、Kainuma Mika、Takahashi Azusa、Matsuo Yoshika、Katakawa Kazuaki、Taguchi Takaaki、Ichinose Koji
    • Journal Title

      Molecules

      Volume: 26 Issue: 21 Pages: 6397-6397

    • DOI

      10.3390/molecules26216397

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemistry of Anti-HIV Active Trimeric Pyranonaphthoquinone Conocurvone: Synthetic Studies towards Monomeric Teretifolione B and Related Compounds2020

    • Author(s)
      Kumamoto Takuya, Katakawa Kazuaki
    • Journal Title

      HETEROCYCLES

      Volume: 100 Issue: 2 Pages: 177-193

    • DOI

      10.3987/rev-19-915

    • NAID

      120006843586

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] Synthetic Studies toward Natural Xanthone Blennolides via Spirochromanones2022

    • Author(s)
      Takuya Kumamoto
    • Organizer
      ICPAC Kota Kinabalu 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Synthetic study towards anticancer aromatic polyketides antibiotics,2021

    • Author(s)
      Takuya Kumamoto
    • Organizer
      Hiroshima University and Council of Scientific & Industrial Research JOINT INTERNATIONAL WORKSHOP
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Teretifolione B 全合成に向けた SNAr をもちいた光学活性ベンゾクロメン類の不斉構築2021

    • Author(s)
      若宮 優貴、熊本 卓哉
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Synthetic study toward chromene / xanthone natural products2021

    • Author(s)
      熊本 卓哉
    • Organizer
      Joint Symposium between CSIR-CDRI and HiU-P-DDS
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] クロメン・クロマノン系天然由来生物活性化合物の合成研究2020

    • Author(s)
      熊本 卓哉
    • Organizer
      立命館大学 精密合成化学セミナー (第4回)
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Synthetic study toward polyketide antibiotics2020

    • Author(s)
      熊本 卓哉
    • Organizer
      HU and BITS Pilani 2nd Joint Workshop
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] Cycloaddition Reactions: Advances in Research and Applications2019

    • Author(s)
      Davor Margetic (Editor), Takuya Kumamoto, Kazuaki Katakawa
    • Total Pages
      304
    • Publisher
      Nova Science Publisher
    • ISBN
      9781536154207
    • Related Report
      2019 Research-status Report
  • [Remarks] 広島大学大学院 医系科学研究科 創薬合成化学研究室 ホームページ

    • URL

      https://synorgchem.hiroshima-u.ac.jp/

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
  • [Remarks] 広島大学大学院 医系科学研究科 創薬合成化学研究室 ホームページ

    • URL

      https://synorgchem.hiroshima-u.ac.jp/index.html

    • Related Report
      2020 Research-status Report
  • [Remarks] 広島大学「光」ドラッグデリバリー研究拠点 紹介 Youtube サイト

    • URL

      https://youtu.be/ABBjWRzu-QY

    • Related Report
      2020 Research-status Report
  • [Remarks]

    • URL

      http://synorgchem.hiroshima-u.ac.jp/research.html

    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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