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Development of biologically active natural product-like compound library based on diversity-enhanced extracts

Research Project

Project/Area Number 16H03279
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomolecular chemistry
Research InstitutionTohoku University

Principal Investigator

Kikuchi Haruhisa  東北大学, 薬学研究科, 准教授 (90302166)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywords天然物化学 / 多様性指向型合成 / 化合物ライブラリー / メロテルペノイド / 多様性拡大抽出物
Outline of Final Research Achievements

We proposed a new approach, diversity-enhanced extracts, for increasing the diversity of natural product-like compounds. Diversity-enhanced extracts are prepared from chemical reactions that remodel molecular scaffolds directly on extracts of natural resources. The subsequent isolation of each compound produced from such reactions affords a diverse natural product-like library. Direct, three successive chemical reactions were performed on plant extracts containing a large amount of terpenes to prepare diversity-expanding extracts, which were then separated to give more than 20 kinds of phenolic and pyrone-type merotelpenoids. As a result of carrying out extensive biological activity screening for these compounds, bioactive substances such as osteoclast differentiation inhibitory activity were found.

Academic Significance and Societal Importance of the Research Achievements

本研究課題によって得られた成果は,「多様性拡大抽出物」が構造多様性の高い生物活性を指向した天然化合物類縁体ライブラリーを構築する上で有用な手法であることを実証したものであり,そのような点で学術的に大いに意義があると言える.一方で,本研究課題によって破骨細胞分化抑制作用などの生物活性物質が見出されたことは,創薬等への応用によって社会への成果還元の可能性をもたらすものであり,社会的にも意義があると言える.

Report

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

    (24 results)

All 2019 2018 2017 2016

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (14 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Prenylated quinolinecarboxylic acid derivative prevents neuronal cell death through inhibition of MKK42019

    • Author(s)
      Ogura Masato、Kikuchi Haruhisa、Shakespear Norshalena、Suzuki Toshiyuki、Yamaki Junko、Homma Miwako K.、Oshima Yoshiteru、Homma Yoshimi
    • Journal Title

      Biochemical Pharmacology

      Volume: 162 Pages: 109-122

    • DOI

      10.1016/j.bcp.2018.10.008

    • NAID

      120006821695

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Construction of a Meroterpenoid‐Like Compounds Library Based on Diversity‐Enhanced Extracts2018

    • Author(s)
      Kikuchi Haruhisa、Kawai Kosuke、Nakashiro Yota、Yonezawa Takayuki、Kawaji Kumi、Kodama Eiichi. N.、Oshima Yoshiteru
    • Journal Title

      Chemistry- A European Journal

      Volume: 25 Issue: 4 Pages: 1106-1112

    • DOI

      10.1002/chem.201805417

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Removal of the E-Olefin Barrier of Humulene Leading to Unnatural Terpenoid-like Skeletons2018

    • Author(s)
      Nishimura Takehiro、Kawai Junya、Oshima Yoshiteru、Kikuchi Haruhisa
    • Journal Title

      Organic Letters

      Volume: 20 Issue: 22 Pages: 7317-7320

    • DOI

      10.1021/acs.orglett.8b03259

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Developments toward the Production of Diverse Natural-Product-Like Compounds: Diversity-Oriented Synthesis and Diversity-Enhanced Extracts2018

    • Author(s)
      Oshima Yoshiteru、Kikuchi Haruhisa
    • Journal Title

      HETEROCYCLES

      Volume: 96 Issue: 9 Pages: 1509-1509

    • DOI

      10.3987/rev-18-885

    • NAID

      40021682736

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Production of Novel Bispyrone Metabolites in the Cellular Slime Mold Dictyostelium giganteum Induced by Zinc(II) Ion2017

    • Author(s)
      Van Hai Nguyen, Haruhisa Kikuchi, Hikaru Sasaki, Kyoichi Iizumi, Yuzuru Kubohara, Yoshiteru Oshima
    • Journal Title

      Tetrahedron

      Volume: 73 Issue: 5 Pages: 583-588

    • DOI

      10.1016/j.tet.2016.12.040

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthsis, and Biological Activity of Chlorinated Alkylresorcinols from Dictyostelium Cellular Slime Molds2017

    • Author(s)
      Haruhisa Kikuchi, Ikuko Ito, Katsunori Takahashi, Hirotaka Ishigaki, Kyoichi Iizumi, Yuzuru Kubohara, Yoshiteru Oshima
    • Journal Title

      Journal of Natural Products

      Volume: 80 Issue: 10 Pages: 2716-2722

    • DOI

      10.1021/acs.jnatprod.7b00456

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of Natural Product-Like Compound Library for Drug Discovery Based on Diversity-Enhanced Extracts2017

    • Author(s)
      菊地晴久,大島吉輝
    • Journal Title

      Journal of Synthetic Organic Chemistry, Japan

      Volume: 75 Issue: 4 Pages: 349-359

    • DOI

      10.5059/yukigoseikyokaishi.75.349

    • NAID

      130005627975

    • ISSN
      0037-9980, 1883-6526
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Design and Synthesis of Structure-Simplified Derivatives of Gonytolide for the Promotion of Innate Immune Responses.2016

    • Author(s)
      Haruhisa Kikuchi, Tsuyoshi Hoshikawa, Shoichiro Kurata, Yasuhiro Kato, Yoshiteru Oshima
    • Journal Title

      Journal of Natural Products

      Volume: 79 Issue: 5 Pages: 1259-1266

    • DOI

      10.1021/acs.jnatprod.5b00829

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of Terpenoid Alkaloid-like Compound Library Based on a Humulene Skeleton2016

    • Author(s)
      Haruhisa Kikuchi, Takehiro Nishimura, Eunsang Kwon, Junya Kawai, Yoshiteru Oshima
    • Journal Title

      Chemistry A European Journal

      Volume: 22 Issue: 44 Pages: 15819-15825

    • DOI

      10.1002/chem.201603224

    • NAID

      130007722961

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Monoterpene Indole Alkaloid-like Compounds Based on Diversity-enhanced Extracts of Iridoid-Containing Plants and Their Immune Checkpoint Inhibitory Activity2016

    • Author(s)
      Haruhisa Kikuchi, Keisuke Ichinohe, Shinya Kida, Shinya Murase, Osamu Yamada, Yoshiteru Oshima
    • Journal Title

      Organic Letters

      Volume: 18 Issue: 22 Pages: 5948-5951

    • DOI

      10.1021/acs.orglett.6b03057

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 多様性拡大抽出物を利用したテルペノイドアルカロイド型化合物ライブラリーの創出2019

    • Author(s)
      中野 静香, 河合 航輔, 大島 吉輝, 菊地 晴久
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] パラジウム触媒を利用したカップリング反応に基づく多様性拡大抽出物由来ビアリ-ル・ビアリールアミン型化合物群2019

    • Author(s)
      船山 将太, 大島 吉輝, 菊地 晴久
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Iso-Pictet-Spengler 反応を利用した構造多様なインドールアルカロイド型化合物ライブラリーの創出2019

    • Author(s)
      鈴木 佳英, 一戸 佳祐, 大島 吉輝, 菊地 晴久
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 多様性拡大抽出物から得られたメロテルペノイド化合物群の破骨細胞分化に対する作用2019

    • Author(s)
      米澤 貴之, 渡辺 章夫, 菊地 晴久, 大島 吉輝, 禹 済泰
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Humulene の構造に基づいたアザ中員環形成を指向するテルペノイドアルカロイド型化合物ライブラリーの構築2019

    • Author(s)
      志賀 皓介, 西村 壮央, 菅原 章公, 米澤 貴之, 大島 吉輝, 菊地 晴久
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 多様性拡大抽出物による非天然ビアリール・ビアリールアミン型化合物群の創出2018

    • Author(s)
      船山将太,大島吉輝,菊地晴久
    • Organizer
      日本生薬学会第65回年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 多様性拡大抽出物を用いたビアリール・ビアリールアミン型化合物の創出2018

    • Author(s)
      船山将太,大島吉輝,菊地晴久
    • Organizer
      第57回日本薬学会東北支部大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Humulene を基盤としたアザ中員環含有テルペノイドアルカロイド型化合物群の創出2018

    • Author(s)
      志賀 皓介、西村 壮央、菅原 章公、大島 吉輝、菊地 晴久
    • Organizer
      第57回日本薬学会東北支部大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 多様性拡大抽出物を利用した新規ビアリールアミン型化合物ライブラリーの創出2018

    • Author(s)
      船山将太,菊地晴久,大島吉輝
    • Organizer
      日本薬学会第138年会(金沢)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 多様性拡大抽出物を利用した新規環骨格を有するメロテルペノイド型化合物ライブラリーの創出2017

    • Author(s)
      河合航輔,中城陽太,菊地晴久,大島吉輝
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      東北大学川内北キャンパス(仙台市)
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] Diversity-enhanced Extracts: A New Approach for Enhancing Chemical Diversity of Natural Product-like Compounds2017

    • Author(s)
      Haruhisa Kikuchi, Yoshiteru Oshima
    • Organizer
      26th French-Japanese Symposium on Medicinal & Fine Chemistry
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 多様性拡大抽出物から得られる創薬指向型化合物ライブラリー2017

    • Author(s)
      菊地晴久,河合航輔,一戸佳祐,中城陽太,村瀬新也,喜田進也,山田修,大島吉輝
    • Organizer
      第59回天然有機化合物討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 多様性拡大抽出物を利用したモノテルペンインドールアルカロイド様化合物ライブラリーの創出2016

    • Author(s)
      一戸佳祐,菊地晴久,村瀬新也,喜田進也,山田修,大島吉輝
    • Organizer
      第34回メディシナルケミストリーシンポジウム
    • Place of Presentation
      つくば国際会議場(つくば市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] 多様性拡大抽出物を利用した非天然型メロテルペノイド型化合物ライブラリーの創出2016

    • Author(s)
      河合航輔,中城陽太,菊地晴久,大島吉輝
    • Organizer
      日本生薬学会第63回年会
    • Place of Presentation
      富山国際会議場(富山市)
    • Year and Date
      2016-09-24
    • Related Report
      2016 Annual Research Report

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

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