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Synthesis and bio-functional analysis of marine polyketide natural product with potent cell proliferation-promoting activity.

Research Project

Project/Area Number 16K13082
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Biomolecular chemistry
Research InstitutionTohoku University

Principal Investigator

Sasaki Makoto  東北大学, 生命科学研究科, 教授 (80235267)

Research Collaborator Tsuda Masashi  
Konoki Keiichi  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsアンフィリオニン-5 / 細胞増殖促進活性 / 全合成 / 立体配置決定 / 機能解析 / 機能解明 / アンフィリオニン-5
Outline of Final Research Achievements

Amphirionin-5, a marine polyketide natural product, exhibits potent cell proliferation-promoting activity on murine bone marrow stromal cells and murine osteoblastic cells at nanomolar concentrations. Our efforts towards the total synthesis and complete configurational assignment of amphirionin-5 to clarify its biological activity were conducted. The relative configuration of the C1-C12 portion of amphirionin-5 was established by the stereodivergent synthesis of six diastereomeric model compounds and comparison of their NMR spectroscopic data with those reported for the natural product. This study led to the elucidation of the relative configuration between C4/C5 and C9/C12 and to the reassignment of the proposed configuration of the C9 position of amphirionin-5. Assignment of the unexplored relative configuration of C23/C26 was also attempted through a similar complementary use of organic synthesis and NMR analysis.

Academic Significance and Societal Importance of the Research Achievements

アンフィリオニン-5 は、マウス骨髄由来間葉系幹細胞及び骨芽細胞の増殖を促進する生物機能を持つこれまでに前例のない海洋ポリケチド天然物である。アンフィリオニン-5 の構造を基盤とした新規細胞増殖促進分子の創製・機能解明のためには立体化学に関する情報は不可欠である。本研究では、適切に設計した部分構造の合成と天然物とのNMR データの比較によるC9/C12 及びC23/C26 位の相対配置を決定し、「不斉中心の立体配置の違いが、2 つのメチレン鎖を介した炭素のNMR 化学シフト値にもわずかではあるが明瞭に影響を及ぼす」ことを実証した。

Report

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

    (34 results)

All 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (12 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 12 results,  Acknowledgement Compliant: 3 results) Presentation (15 results) Book (4 results) Remarks (2 results)

  • [Int'l Joint Research] University of Santiago de Compostela(Spain)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Studies towards the total synthesis of Caribbean ciguatoxin C-CTX-1: Synthesis of the LMN-ring fragment through reductive olefin cross-coupling2018

    • Author(s)
      Makoto Sasaki, Kotaro Iwasaki, Keisuke Arai
    • Journal Title

      org. Lett.

      Volume: 20 Issue: 22 Pages: 7163-7166

    • DOI

      10.1021/acs.orglett.8b03102

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Total Synthesis of (-)‐Enigmazole A2018

    • Author(s)
      K. Sakurai, M. Sasaki, H. Fuwa
    • Journal Title

      Angewandte Chemie, International Edition

      Volume: 57 Issue: 18 Pages: 5143-5146

    • DOI

      10.1002/anie.201801561

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Total Synthesis of Polycavernosides A and B, Two Lethal Toxins from Red Alga.2017

    • Author(s)
      Kotaro Iwasaki, Satori Sasaki, Yusuke Kasai, Yuki Kawashima, Shohei Sasaki, Takanori Ito, Mari Yotsu-Yamashita, Makoto Sasaki.
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 82 Issue: 24 Pages: 13201-13219

    • DOI

      10.1021/acs.joc.7b02293

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tetracyclic Truncated Analogue of the Marine Toxin Gambierol Modifies NMDA, Tau, and Amyloid β Expression in Mice Brains: Implications in AD Pathology2017

    • Author(s)
      Eva Alonso, Andres C. Vieira, Ines Rodoriguez, Rebeca Alvarino, Sandra Gegunde, Haruhiko Fuwa, Yuto Suga, Makoto Sasaki, Amparo Alfonso, Jose Mannuel Cifuentes, Luis M. Botana
    • Journal Title

      ACS Chemical Neuroscience

      Volume: 8 Issue: 6 Pages: 1358-1367

    • DOI

      10.1021/acschemneuro.7b00012

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cytotoxicity of goniodomin A and B in non contractile cells2016

    • Author(s)
      B. Espina, E. Cagide, M. C. Louzao, N. Vilarino, M. R. Vieytes, Y. Takeda, M. Sasaki, and L. M. Botana
    • Journal Title

      Toxicol. Lett.

      Volume: 250-251 Pages: 10-20

    • DOI

      10.1016/j.toxlet.2016.04.001

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Total Synthesis and Complete Stereostructure of a Marine Macrolide Glycoside, (-)-Lyngbyaloside B2016

    • Author(s)
      H. Fuwa, N. Yamagata, Y. Okuaki, Y. Ogata, A. Saito, M. Sasaki
    • Journal Title

      Chemistry - A European Journal

      Volume: 22 Issue: 20 Pages: 6815-6829

    • DOI

      10.1002/chem.201600341

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Toward the total synthesis of amphidinolide N: Synthesis of the C8-C29 fragment2016

    • Author(s)
      Y. Kawashima, A. Toyoshima, H. Fuwa, and M. Sasaki
    • Journal Title

      Org. Lett.

      Volume: 18 Issue: 9 Pages: 2232-2235

    • DOI

      10.1021/acs.orglett.6b00871

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Effect of Carbon Chain Length in Acyl Coenzyme A on the Efficiency of Enzymatic Transformation of Okadaic Acid to 7-O-Acyl Okadaic Acid2016

    • Author(s)
      Sachie Furumochi, Tatsuya Onoda, Yuko Cho, Haruhiko Fuwa, Makoto Sasaki, Mari Yotsu-Yamashita, Keiichi Konoki
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 26 Issue: 13 Pages: 2992-2996

    • DOI

      10.1016/j.bmcl.2016.05.027

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Toward the Total Synthesis of Amphidinolide N: Convergent Synthesis of the C1-C13 Segment2016

    • Author(s)
      Atsushi Toyoshima, Makoto Sasaki
    • Journal Title

      Tetrahedron Letters

      Volume: 57 Issue: 31 Pages: 3532-3534

    • DOI

      10.1016/j.tetlet.2016.06.107

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Diastereoselective Rong-Closing Metathesis as a Means to Construct Medium-Sized Cyclic Ethers: Application to the Synthesis of a Photoactivatable Gambierol Derivative2016

    • Author(s)
      Yu Onodera, Kazuaki Hirota, Yuto Suga, Keiichi Konoki, Mari Yotsu-Yamashita, Makoto Sasaki
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 81 Pages: 8234-8252

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Stereodivergent Synthesis and Configurational Assignment of the C1-C15 Segment of Amphirionin-52016

    • Author(s)
      Moemi Kanto, Sota Sato, Masashi Tsuda, Makoto Sasaki
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 81 Issue: 19 Pages: 9105-9121

    • DOI

      10.1021/acs.joc.6b01700

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Exploiting Ruthenium Cabene-Catalyzed Reactions in Total Synthesis of Marine Oxacycle Natural Products2016

    • Author(s)
      Haruhiko Fuwa, Makoto Sasaki
    • Journal Title

      Bulletin of the Chemical Society of Japan

      Volume: 89 Issue: 12 Pages: 1403-1415

    • DOI

      10.1246/bcsj.20160224

    • NAID

      130005316188

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] 海洋生物由来の生物機能大環状天然中分子の高効率全合成2018

    • Author(s)
      佐々木 誠
    • Organizer
      科研費・新学術領域研究「反応集積化が導く中分子戦略:高次生物機能分子の創製」第5回成果報告会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ゴニオドミンAの全合成研究2018

    • Author(s)
      川島悠岐、三好太朗、岩崎浩太郎、不破春彦、佐々木 誠
    • Organizer
      日本化学会第98春季年会
    • Related Report
      2018 Annual Research Report 2017 Research-status Report
  • [Presentation] エニグマゾールAの全合成研究2018

    • Author(s)
      櫻井敬祐、佐々木 誠、不破春彦
    • Organizer
      日本化学会第98春季年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] カリビアンシガトキシンの合成研究-MN環部の立体選択的合成法の開発-2017

    • Author(s)
      岩崎浩太郎、荒井啓介、佐々木 誠
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      東北大学(宮城県仙台市)
    • Year and Date
      2017-03-26
    • Related Report
      2016 Research-status Report
  • [Presentation] ポルチミンの合成研究2017

    • Author(s)
      三好太朗、齋藤真輝、岩崎浩太郎、佐々木 誠
    • Organizer
      日本化学会第97春季年会
    • Place of Presentation
      慶應義塾大学(神奈川県横浜市)
    • Year and Date
      2017-03-18
    • Related Report
      2016 Research-status Report
  • [Presentation] イリオモテオリド-2aの合成および構造研究2017

    • Author(s)
      坂本渓太、佐々木 誠、不破春彦
    • Organizer
      日本化学会第97春季年会
    • Place of Presentation
      慶應義塾大学(神奈川県横浜市)
    • Year and Date
      2017-03-18
    • Related Report
      2016 Research-status Report
  • [Presentation] エニグマゾールAの合成研究2017

    • Author(s)
      櫻井敬祐、佐々木 誠、不破春彦
    • Organizer
      日本化学会第97春季年会
    • Place of Presentation
      慶應義塾大学(神奈川県横浜市)
    • Year and Date
      2017-03-18
    • Related Report
      2016 Research-status Report
  • [Presentation] ネオペルトリドのAMCA標識アナログの合成と機能評価2017

    • Author(s)
      柳翔太、佐々木 誠、不破春彦
    • Organizer
      日本化学会第97春季年会
    • Place of Presentation
      慶應義塾大学(神奈川県横浜市)
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
  • [Presentation] ゴニオドミンAの全合成研究2017

    • Author(s)
      川島悠岐、三好太朗、岩崎浩太郎、不破春彦、佐々木 誠
    • Organizer
      第28回万有仙台シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] ゴニオドミンAの全合成研究2017

    • Author(s)
      川島悠岐、三好太朗、岩崎浩太郎、不破春彦、佐々木 誠
    • Organizer
      第59回天然有機化合物討論会
    • Related Report
      2017 Research-status Report
  • [Presentation] ゴニオドミンAの全合成研究2017

    • Author(s)
      川島悠岐、三好太朗、岩崎浩太郎、不破春彦、佐々木 誠
    • Organizer
      第112回有機合成シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] イリオモテオリド-2aの全合成研究2016

    • Author(s)
      坂本渓太、佐々木 誠、不破春彦
    • Organizer
      第63回トキシンシンポジム
    • Place of Presentation
      山形県天童温泉滝の湯(山形県天童市)
    • Year and Date
      2016-07-14
    • Related Report
      2016 Research-status Report
  • [Presentation] ガンビエロールの光感応性類縁体の合成と機能評価2016

    • Author(s)
      小野寺悠、佐々木 誠、不破春彦
    • Organizer
      第63回トキシンシンポジム
    • Place of Presentation
      山形県天童温泉滝の湯(山形県天童市)
    • Year and Date
      2016-07-14
    • Related Report
      2016 Research-status Report
  • [Presentation] ネオペルトリドの蛍光標識体の合成と機能解析2016

    • Author(s)
      柳 翔太、佐々木 誠、不破春彦
    • Organizer
      第63回トキシンシンポジム
    • Place of Presentation
      山形県天童温泉滝の湯(山形県天童市)
    • Year and Date
      2016-07-14
    • Related Report
      2016 Research-status Report
  • [Presentation] ネオペルトリド蛍光標識アナログの設計・合成・機能評価2016

    • Author(s)
      柳 翔太、野口拓真、川上雅人、佐々木 誠、不破春彦、丹羽伸介、杉 本亜紗子
    • Organizer
      日本ケミカルバイオロジー学会第11回年会
    • Place of Presentation
      京都テルサ(京都府京都市)
    • Year and Date
      2016-06-15
    • Related Report
      2016 Research-status Report
  • [Book] 理科年表 20192018

    • Author(s)
      佐々木 誠
    • Total Pages
      17
    • Publisher
      丸善出版株式会社
    • ISBN
      9784621303320
    • Related Report
      2018 Annual Research Report
  • [Book] 天然有機化合物の全合成 独創的なものづくりの反応と戦略2018

    • Author(s)
      不破春彦、佐々木 誠
    • Total Pages
      7
    • Publisher
      化学同人
    • ISBN
      9784759813876
    • Related Report
      2018 Annual Research Report 2017 Research-status Report
  • [Book] 理化年表 平成30年2017

    • Author(s)
      佐々木 誠
    • Total Pages
      17
    • Publisher
      丸善出版株式会社
    • ISBN
      9784621302187
    • Related Report
      2017 Research-status Report
  • [Book] 理科年表 平成29年2016

    • Author(s)
      佐々木 誠
    • Total Pages
      17
    • Publisher
      丸善株式会社
    • Related Report
      2016 Research-status Report
  • [Remarks] Sasaki Group Web Site

    • URL

      http://www.agri.tohoku.ac.jp/kanshoku

    • Related Report
      2018 Annual Research Report
  • [Remarks] Sasaki Group Web Site

    • URL

      http://www.agri.tohoku.ac.jp/kanshoku/index.html

    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2023-01-30  

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