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Seed compounds exploratory empowered by catalysis

Research Project

Project/Area Number 18K19156
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 37:Biomolecular chemistry and related fields
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

SOHTOME Yoshihiro  国立研究開発法人理化学研究所, 開拓研究本部, 専任研究員 (50431888)

Project Period (FY) 2018-06-29 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords分子触媒 / 含窒素化合物 / 複素環化合物 / 連続不斉炭素 / 四級炭素 / 生物活性 / 抗感染症剤 / シード化合物 / 有機合成化学 / 不斉触媒 / 酵素 / プロテオミクス / ヘテロ原子 / 触媒
Outline of Final Research Achievements

The primary aim of this project is to identify new classes of biologically active molecules on the bais of the originally developed catalysis. We have developed catalytic strategies to efficiently construct the complex molecules having the sp3-rich scaffold, especially focusing on higher oxidation states, contiguous stereocenters, and quaternary carbons. Among the 700 compounds (including products, starting materials, intermediates, and ligands), we identified the several new compounds, which exhibit unique biological activities with less toxicity. For new seed compounds, we examined the concentration effect to obtain the IC50 value, toxicity test, and structure-activity relationship studies.

Academic Significance and Societal Importance of the Research Achievements

生体分子の機能をより選択的に制御する低分子化合物の創出は、世界有数の少子高齢化社会に突入する我が国において、永続的に取り組むべき課題である。しかしながら、物質化学的興味に触発され、アカデミアで合成された人工分子の多くは、製薬会社が追求するドラックライクネス (リピンスキー則等) の指標から外れている場合が多い。そのため、これらの合成分子は、シード化合物としての可能性は十分に検討されてこなかった。一方、本研究では、独自の化合物ライブラリーの構築、生物活性評価、構造展開研究を有機的に連動させることで、ユニークな生物活性シードを創出できることが示された。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (39 results)

All 2022 2021 2020 2019 2018 Other

All Journal Article (12 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 12 results,  Open Access: 6 results) Presentation (18 results) (of which Int'l Joint Research: 2 results,  Invited: 10 results) Book (1 results) Remarks (8 results)

  • [Journal Article] Dynamics in Catalytic Asymmetric Diastereoconvergent (3 + 2) Cycloadditions with Isomerizable Nitrones and α-Keto Ester Enolates2021

    • Author(s)
      Ezawa Tetsuya、Sohtome Yoshihiro、Hashizume Daisuke、Adachi Masaya、Akakabe Mai、Koshino Hiroyuki、Sodeoka Mikiko
    • Journal Title

      Journal of the American Chemical Society

      Volume: 143 Issue: 24 Pages: 9094-9104

    • DOI

      10.1021/jacs.1c02833

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Propargylic Se-adenosyl-l-selenomethionine: A Chemical Tool for Methylome Analysis2021

    • Author(s)
      Sohtome Yoshihiro、Shimazu Tadahiro、Shinkai Yoichi、Sodeoka Mikiko
    • Journal Title

      Accounts of Chemical Research

      Volume: 54 Issue: 20 Pages: 3818-3827

    • DOI

      10.1021/acs.accounts.1c00395

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes2021

    • Author(s)
      Erna Davydova, Tadahiro Shimazu et al,
    • Journal Title

      Nat. Commun.

      Volume: 12 Issue: 1 Pages: 891-891

    • DOI

      10.1038/s41467-020-20670-7

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cross-Coupling Reactions of Persistent Tertiary Carbon Radicals,2021

    • Author(s)
      Yoshihiro Sohtome, Kyohei Kanomata, Mikiko Sodeoka
    • Journal Title

      Bull. Chem. Soc. Jpn.

      Volume: 94 Issue: 3 Pages: 1066-1079

    • DOI

      10.1246/bcsj.20200376

    • NAID

      130008021808

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 分子空間を操る-超分子化学・触媒化学の融合・進化を目指して2021

    • Author(s)
      五月女宜裕
    • Journal Title

      化学と工業

      Volume: 74 Pages: 83-85

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 金属錯体触媒が形成する分子空間の理解と制御2021

    • Author(s)
      五月女宜裕
    • Journal Title

      化学と工業

      Volume: 74 Pages: 86-86

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regiodivergent Oxidative Cross-Coupling of Catechols with Persistent tert-Carbon Radicals2020

    • Author(s)
      Masumi Sugawara, Rikako Ohnishi, Tetsuya Ezawa, Mai Akakabe, Miki Sawamura, Daiki Hojo, Daisuke Hashizume, Yoshihiro Sohtome, Mikiko Sodeoka
    • Journal Title

      ACS Catalysis

      Volume: 10 Issue: 21 Pages: 895-898

    • DOI

      10.1021/acscatal.0c03986

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Formal Aerobic Oxidative Cross-Coupling of Benzofuranones with Azo Compounds Using Pd-μ-hydroxo Complex2020

    • Author(s)
      Rikako Ohnishi, Masumi Sugawara, Tetsuya Ezawa, Yoshihiro Sohtome, Mikiko Sodeoka
    • Journal Title

      Chem. Pharm. Bull.

      Volume: 68 Issue: 9 Pages: 895-898

    • DOI

      10.1248/cpb.c20-00359

    • NAID

      130007893863

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multiselective Catalytic Asymmetric Reactions Using alpha-Keto Esters as Pronucleophiles2020

    • Author(s)
      Yoshihiro Sohtome, Mikiko Sodeoka
    • Journal Title

      Synlett

      Volume: 31 Issue: 06 Pages: 523-534

    • DOI

      10.1055/s-0039-1690722

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cross‐Coupling Reaction of Dimer‐Derived Persistent Tertiary‐Carbon‐Centered Radicals with Azo Compounds2019

    • Author(s)
      Ohnishi Rikako、Sugawara Masumi、Akakabe Mai、Ezawa Tetsuya、Koshino Hiroyuki、Sohtome Yoshihiro、Sodeoka Mikiko
    • Journal Title

      Asian Journal of Organic Chemistry

      Volume: 8 Issue: 7 Pages: 1017-1023

    • DOI

      10.1002/ajoc.201900300

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Unveiling epidithiodiketopiperazine as a non-histone arginine methyltransferase inhibitor by chemical protein methylome analyses2018

    • Author(s)
      Yoshihiro Sohtome, Tadahiro Shimazu, Joaquin Barjau, Shinya Fujishiro, Mai Akakabe, Naoki Terayama, Kosuke Dodo, Akihiro Ito, Minoru Yoshida, Yoichi Shinkai, Mikiko Sodeoka
    • Journal Title

      Chem. Commun.

      Volume: 54 Issue: 66 Pages: 9202-9205

    • DOI

      10.1039/c8cc03907k

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Development of Chaetocin and S-Adenosylmethionine Analogues as Tools for Studying Protein Methylation2018

    • Author(s)
      Yoshihiro Sohtome, Mikiko Sodeoka
    • Journal Title

      Chem. Rec.

      Volume: 18 Issue: 12 Pages: 1660-1671

    • DOI

      10.1002/tcr.201800118

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Dynamic catalytic diastereoconvergent (3+2) cycloaddition with alpha-keto ester enolates2022

    • Author(s)
      Yoshihiro Sohtome, Tetsuya Ezawa, Daisuke Hashizume, Masaya Adachi, Mai Akakabe, Hiroyuki Koshino, Mikiko Sodeoka
    • Organizer
      日本化学会第102春季年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 鍵と鍵穴からinduced-fitへ: ジアステレオ収束的(3+2)環化付加2021

    • Author(s)
      五月女宜裕
    • Organizer
      新領域研究グループ「分子空間化学」シンポジウム2020
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 合成化学を起点としたケミカルメチローム解析2021

    • Author(s)
      五月女宜裕
    • Organizer
      日本薬学会第141回年会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 動的反応化学: 分子触媒と酵素の理解と制御を目指して2021

    • Author(s)
      五月女宜裕
    • Organizer
      京都大学化学研究所講演会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 吸熱的結合形成反応: 酸化的分子変換の高度化を目指して2020

    • Author(s)
      五月女宜裕
    • Organizer
      日本化学会新領域研究グループ「分子空間化学」2020オンラインシンポジウム
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Structural diversification of chiral compounds containing adjacent stereocenters based on the catalytic [3+2] cycloaddition of C-cyanonitrones2020

    • Author(s)
      Tetsuya Ezawa, Yoshihiro Sohtome, Mai Akakabe, Daisuke Hashizume, Hiroyuki Koshino, Mikiko Sodeoka
    • Organizer
      日本化学会第100回春季年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Cross-Coupling of Persistent Carbon-Centered Radicals with Azo Compounds2020

    • Author(s)
      Yoshihiro Sohtome, Rikako Ohnishi, Masumi Sugawara, Mai Akakabe, Tetsuya Ezawa, Hiroyuki Koshino, Mikiko Sodeoka
    • Organizer
      日本化学会第100回春季年会
    • Related Report
      2019 Research-status Report
  • [Presentation] タンパク質メチル化反応の検出と制御を目指して2020

    • Author(s)
      五月女宜裕
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Catalytic Asymmetric [3+2] Cycloadditions With alpha-Keto Ester Enolates2019

    • Author(s)
      Yoshihiro Sohtome, Mikiko Sodeoka
    • Organizer
      27th International Society of Heterocyclic Chemistry Congress (ISHC)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Cross-Coupling of Persistent Tertiary Carbon-Centered Radicals with Azo Compounds2019

    • Author(s)
      Yoshihiro Sohtome, Rikako Ohnishi, Masumi Sugawara, Mai Akakabe, Tetsuya Ezawa, Hiroyuki Koshino, Mikiko Sodeoka
    • Organizer
      4th International Symposium on Precisely Designed Catalysts with Customized Scaffolding
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 分野の垣根を超えた有機反応化学を目指して2019

    • Author(s)
      五月女宜裕
    • Organizer
      北里大学大学院感染制御科学府、公開セミナー
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 持続性ラジカル種を用いるクロスカップリングの新展開2019

    • Author(s)
      五月女宜裕
    • Organizer
      新領域研究グループ「分子空間化学」シンポジウム2019
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 分子触媒と酵素の理解と制御を目指して2019

    • Author(s)
      五月女宜裕
    • Organizer
      柴﨑セミナー
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 安定炭素ラジカル種を用いた連続四置換炭素の構築法の開発2019

    • Author(s)
      大西理華子、菅原真純、赤壁麻衣、五月女宜裕、越野広雪、袖岡幹子
    • Organizer
      日本化学会第99回春季年会
    • Related Report
      2018 Research-status Report
  • [Presentation] alpha-ケトエステルエノレートとC-シアノニトロンとの触媒的不斉[3+2]環化付加型反応2019

    • Author(s)
      江澤哲也、足立雅弥、赤壁麻依、五月女宜裕、袖岡幹子
    • Organizer
      日本化学会第99回春季年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 金属中心キラリティー内包型遷移金属錯体を用いる触媒的不斉反応2019

    • Author(s)
      五月女宜裕
    • Organizer
      錯体化学若手の会・関東支部前期勉強会2018
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 酸素を用いる酸化的炭素-炭素結合形成反応2019

    • Author(s)
      五月女宜裕
    • Organizer
      新領域研究グループ「分子空間化学」シンポジウム
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 安定炭素ラジカル種を用いる連続四置換炭素の構築及びスペクトル解析2018

    • Author(s)
      大西理華子、菅原真純、赤壁麻衣、五月女宜裕、越野広雪、袖岡幹子
    • Organizer
      第8回CSJ化学フェスタ2018
    • Related Report
      2018 Research-status Report
  • [Book] "Design of the chiral environment for catalytic asymmetric acid-base catalysis" in Designed Molecular Space in Material Science and Catalysis2018

    • Author(s)
      Yoshihiro Sohtome, Kazuo Nagasawa, Mikiko Sodeoka
    • Total Pages
      262
    • Publisher
      Springer
    • ISBN
      9789811312564
    • Related Report
      2018 Research-status Report
  • [Remarks] ジアステレオ収束的な(3+2)環化付加型反応の開発-鍵と鍵穴から誘導適合へ-

    • URL

      https://www.riken.jp/press/2021/20210610_3/index.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] 動的ジアステレオ収束型触媒反応

    • URL

      https://www.chemistry.or.jp/division-topics/2021/10/post-202.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] 位置多様性・脱水素型クロスカップリング

    • URL

      https://www.chem-station.com/blog/2020/11/coupling.html

    • Related Report
      2020 Research-status Report
  • [Remarks] 位置多様性・脱水素型クロスカップリングの開発

    • URL

      https://www.riken.jp/pr/news/2020/20201218_2/index.html?fbclid=IwAR20Ccl_UckP5cODEkA6cLTak6jTkz7lo

    • Related Report
      2020 Research-status Report
  • [Remarks] 位置多様性・脱水素型クロスカップリング -ラジカル・酸/塩基反応の協奏により反応位置を操る-

    • URL

      https://www.riken.jp/press/2020/20201022_1/index.html

    • Related Report
      2020 Research-status Report
  • [Remarks] 理研プレスリリース

    • URL

      http://www.riken.jp/pr/press/2018/20180806_2/

    • Related Report
      2018 Research-status Report
  • [Remarks] Chem-Station スポットライトリサーチ

    • URL

      https://www.chem-station.com/blog/2018/09/methylation.html

    • Related Report
      2018 Research-status Report
  • [Remarks] Cover Picture in Chem. Rec.

    • URL

      https://onlinelibrary.wiley.com/doi/10.1002/tcr.201881201

    • Related Report
      2018 Research-status Report

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Published: 2018-07-25   Modified: 2023-01-30  

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