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Alkaloid Synthesis and Its Middle Molecular Strategy Based on Reaction Integration

Publicly Offered Research

Project AreaMiddle molecular strategy: Creation of higher bio-functional molecules by integrated synthesis.
Project/Area Number 18H04408
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Research InstitutionKyoto University

Principal Investigator

大野 浩章  京都大学, 薬学研究科, 教授 (30322192)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsアルカロイド / 金触媒 / 連続反応 / 反応集積化 / 中分子
Outline of Annual Research Achievements

(1) アクアミリンアルカロイドの全合成研究
我々はこれまでに、金触媒連続環化反応を基盤としたストリクタミンの形式全合成を達成している。しかしながら、既知のストリクタミン前駆体からストリクタミンに変換する反応を再現できない問題があった。そこで今年度は、新たな合成戦略を用いたアクアミリンアルカロイド骨格の構築を試みた。最初に、アミド型の求核部位を有する環化前駆体の不斉合成を行い、金触媒環化反応を検討したところ、目的の環化体を得ることはできなかった。次に、ニトリル部位を有する基質の環化反応を検討したが、この場合も目的の反応は進行しなかった。一方で、求核部位をカルボン酸に変換した環化前駆体を用いて反応を行ったところ、目的のラクトン体が効率よく得られた。さらに、生じたラクトン部をラクタムに変換にも成功している。ラクタムの還元と分子内アミノ化による窒素官能基の導入を行うことにより、アクアミリンアルカロイドの合成が可能となる。
(2) アスピドスペルマアルカロイドの全合成研究
前年度までに、アスピドスペルミジンおよびマラガシャノール類の基本骨格を一挙に構築する連続環化反応条件の最適化を行った。今年度は本反応の不斉化について検討を行い、リガンドとしてDTBM-SEGPHOS、金触媒のカウンターイオンとしてNaBARFを用いた際に、良好な不斉収率で目的の四環性化合物が得られることを見出した。引き続き、得られた環化生成物を既知のビンドロシン合成中間体に導き、形式全合成を完了した。

Research Progress Status

令和元年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和元年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (29 results)

All 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (19 results) (of which Int'l Joint Research: 12 results,  Invited: 6 results) Remarks (2 results)

  • [Int'l Joint Research] ハイデルベルク大学(ドイツ)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Gold(I)-Catalyzed Cascade Cyclization of Anilines with Diynes: Controllable Formation of Eight-Membered Ring-Fused Indoles and Propellane-Type Indolines2020

    • Author(s)
      A. Yamaguchi, S. Inuki, Y. Tokimizu, S. Oishi, H. Ohno
    • Journal Title

      J. Org. Chem.

      Volume: 85 Issue: 4 Pages: 2543-2559

    • DOI

      10.1021/acs.joc.9b03256

    • NAID

      120006817609

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gold(I)-Catalyzed Cascade Cyclization Reactions of Allenynes for the Synthesis of Fused Cyclopropanes and Acenaphthenes2019

    • Author(s)
      T. Ikeuchi, S. Inuki, S. Oishi, H. Ohno
    • Journal Title

      Angew. Chem. Int. Ed.

      Volume: 58 Issue: 23 Pages: 7792-7796

    • DOI

      10.1002/anie.201903384

    • NAID

      120006634622

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Construction of the Pyrrolo[2,3-d]carbazole Core of Spiroindoline Alkaloids by Gold-Catalyzed Cascade Cyclization of Ynamide2019

    • Author(s)
      J. Matsuoka, H. Kumagai, S. Inuki, S. Oishi, H. Ohno
    • Journal Title

      J. Org. Chem.

      Volume: 84 Issue: 14 Pages: 9358-9363

    • DOI

      10.1021/acs.joc.9b01149

    • NAID

      120006708241

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Introduction of a Polar Functional Group to the Lipid Tail of 4-<i>epi</i>-Jaspine B Affects Sphingosine Kinase Isoform Selectivity2018

    • Author(s)
      S. Inuki, T. Miyagawa, S. Oishi, H. Ohno
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 66 Issue: 9 Pages: 866-872

    • DOI

      10.1248/cpb.c18-00366

    • NAID

      130007479591

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2018-09-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of Jaspine B Regioisomers through Palladium-Catalyzed Stereoselective Tetrahydrofuran Formation: Insight into the Ligand Recognition of Sphingosine Kinases2018

    • Author(s)
      Miyagawa, S. Inuki, M. Honda, S. Nakamura, I. Nakanishi, N. Fujii, S. Oishi, H. Ohno
    • Journal Title

      Tetrahdron

      Volume: 74 Issue: 15 Pages: 1802-1809

    • DOI

      10.1016/j.tet.2018.02.042

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gold(I)-Catalyzed Oxidative Cascade Cyclization of 1,4-Diyn-3-ones for the Construction of Tropone-Fused Furan Scaffolds2018

    • Author(s)
      N. Hamada, A. Yamaguchi, S. Inuki, S. Oishi, H. Ohno
    • Journal Title

      Org. Lett.

      Volume: 20 Issue: 15 Pages: 4401-4405

    • DOI

      10.1021/acs.orglett.8b01524

    • NAID

      120006634623

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Direct Synthesis of Aryl-Annulated [c]Carbazoles by Gold(I)-Catalysed Cascade Reaction of Azide-Diynes and Arenes2018

    • Author(s)
      Y. Kawada, S. Ohmura, M. Kobayashi, W. Nojo, M. Kondo, Y. Matsuda, J. Matsuoka, S. Inuki, S. Oishi, C. Wang, T. Saito, M. Uchiyama, T. Suzuki, H. Ohno
    • Journal Title

      Chem. Sci.

      Volume: 9 Pages: 8416-8425

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] Total synthesis of dictyodendrins by the gold-catalyzed cascade cyclization of conjugated diynes with pyrroles2019

    • Author(s)
      Junpei Matsuoka, Yuka Matsuda, Yuiki Kawada, Shinsuke Inuki, Shinya Oishi, Hiroaki Ohno
    • Organizer
      The 11th Seoul-Kyoto-Osaka Joint Symposium on Pharmaceutical Sciences for Young Scientists
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Gold-Catalyzed Cascade Cyclization Reactions via C-H Bond Cleavage2019

    • Author(s)
      Hiroaki Ohno
    • Organizer
      The 47th Naito Conference
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Gold-Catalyzed C-C bond Formation and Its Application to Alkaloid Synthesis2019

    • Author(s)
      Hiroaki Ohno
    • Organizer
      Technische Universitat Wien Special Lecture
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 金触媒連続環化反応を基盤としたAspidophylline Aの全合成研究2019

    • Author(s)
      田口淳一, 奥村怜司, 大原礼子, 井貫晋輔, 大石真也, 大野浩章
    • Organizer
      第39回有機合成若手セミナー
    • Related Report
      2019 Annual Research Report
  • [Presentation] Gold-Catalyzed Cascade Cyclization of Anilines with Diynes: Controllable Formation of Eight-Membered Ring Fused Indoles and Propellane-Type Indolines2019

    • Author(s)
      Ayuta Yamaguchi, Shinsuke Inuki, Yusuke Tokimizu, Shinya Oishi, Hiroaki Ohno
    • Organizer
      27th International Society of Heterocyclic Chemistry Congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Synthetic Study of Aspidophylline A Based on Gold(I)-Catalyzed Cascade Cyclization2019

    • Author(s)
      Junichi Taguchi, Reiji Okumura, Ayako Ohara, Shinsuke Inuki, Shinya Oishi and Hiroaki Ohno
    • Organizer
      27th International Society of Heterocyclic Chemistry Congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Total Synthesis of Dictyodendrins by the Gold-Catalyzed Cascade Cyclization of Conjugated Diynes with Pyrroles2019

    • Author(s)
      Junpei Matsuoka, Yuka Matsuda, Yuiki Kawada, Shinsuke Inuki, Shinya Oishi, Hiroaki Ohno
    • Organizer
      27th International Society of Heterocyclic Chemistry Congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dictyodendrin 類の多様性志向型全合成2019

    • Author(s)
      松岡純平、松田優佳、川田惟樹、井貫晋輔、大石真也、大野浩章
    • Organizer
      第61回天然有機化合物討論会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Gold-Catalyzed Cascade Cyclization for Fused Ring Construction2019

    • Author(s)
      Hiroaki Ohno
    • Organizer
      The 8th Japanese-Sino Symposium on Organic Chemistry for Young Scientists
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Controllable Formation of Oxocine-Fused Indoles and Propellane-Type Indolines via Gold-Catalyzed Cascade Cyclization2019

    • Author(s)
      Ayuta Yamaguchi, Shinsuke Inuki, Yusuke Tokimizu, Shinya Oishi, Hiroaki Ohno
    • Organizer
      The 8th Japanese-Sino Symposium on Organic Chemistry for Young Scientists
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Gold-Catalyzed Cascade Cyclization of Alkynyl Tryptophol Derivatives: Synthetic Strategy for Aspidophylline A2019

    • Author(s)
      Junichi Taguchi, Reiji Okumura, Ayako Ohara, Shinsuke Inuki, Shinya Oishi, Hiroaki Ohno
    • Organizer
      The 8th Japanese-Sino Symposium on Organic Chemistry for Young Scientists
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dictyodendrin 類の多様性志向型全合成2019

    • Author(s)
      松岡純平、松田優佳、川田惟樹、井貫晋輔、大石真也、大野浩章
    • Organizer
      第69回日本薬学会関西支部総会・大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 金触媒連続環化反応を基盤としたAspidophylline Aの全合成研究2019

    • Author(s)
      田口淳一、奥村怜司、大原礼子、井貫晋輔、大石真也、大野浩章
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 金触媒を用いた複素環骨格の構築とアルカロイドの全合成2018

    • Author(s)
      大野浩章
    • Organizer
      第53回天然物化学談話会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Synthesis of Fused Cyclopropanes via Gold-Catalyzed Cascade Cyclization of Allenynes2018

    • Author(s)
      池内貴哉、井貫晋輔、大石真也、大野浩章
    • Organizer
      JGP Chem & ChemEn International Workshop: Sustainability-Oriented Organic Synthesis
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Synthetic Study of Akuammiline Alkaloids Based on Gold(I)-Catalyzed Cascade Cyclization2018

    • Author(s)
      田口淳一、奥村怜司、大原礼子、井貫晋輔、大石真也、大野浩章
    • Organizer
      JGP Chem & ChemEn International Workshop: Sustainability-Oriented Organic Synthesis
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 天然物骨格一挙構築法の開発と応用2018

    • Author(s)
      大野浩章
    • Organizer
      京大テックフォーラム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Dictyodendrin類の多様性志向型全合成2018

    • Author(s)
      松岡純平、松田優佳、川田惟樹、大石真也、大野浩章
    • Organizer
      「有機合成化学を起点とするものづくり戦略」 最終シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] Gold-Catalyzed C-C bond Formation and Its Application to Alkaloid Synthesis2018

    • Author(s)
      Hiroaki Ohno
    • Organizer
      1st NCTU Conference on Advanced Organic Synthesis
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] 研究室ホームページ

    • URL

      http://www.pharm.kyoto-u.ac.jp/seizo/index.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 研究室ホームページ

    • URL

      http://www.pharm.kyoto-u.ac.jp//seizo/

    • Related Report
      2018 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2021-01-27  

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