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Enantioselective total syntheses of bioactive natural products via the enolate intermediate with dynamic chirality

Research Project

Project/Area Number 26460006
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Chemical pharmacy
Research InstitutionKanazawa University (2015-2016)
Kyoto University (2014)

Principal Investigator

Tomoyuki Yoshimura  金沢大学, 薬学系, 准教授 (20432320)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords天然物全合成 / 不斉合成 / 不斉記憶 / キラルエノラート / NHCカルベン触媒 / 不斉アルドール反応 / 不斉反応 / α-アリール化 / 全合成
Outline of Final Research Achievements

Enantioselective total syntheses of bioactive natural products were carried out. 1) Metachromin J and K, 2) epiliolide and its hydrate, and 3) altemicidin were chosen as target molecules because of their unique bioacitivites. In metachromin derivative synthesis, the precursor for asymmetric reaction via C-O axially chiral enolate was invesitigated. The preparation of substrate for synthesizing epiliolides through intramolecular cyclization using NHC catalyst and asymmetric aldol reaction has been accomplished. Investigation of alpha-arylation reaciton with C-N axially chiral enolate and benzyne, which is supposed as key reaction in altemicidin synthesis, resulted in giving benzocyclobutenone derivative bearing tetrasubstituted carbon in high enantioselectivity.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (22 results)

All 2017 2016 2015 2014 Other

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Acknowledgement Compliant: 1 results) Presentation (17 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (1 results)

  • [Journal Article] α-Arylation of α-Amino Acid Derivatives with Arynes via Memory of Chirality: Asymmetric Synthesis of Benzocy-clobutenones with Tetrasubstituted Carbon2017

    • Author(s)
      Kasamatsu, K., Yoshimura, T., Mandi, A., Taniguchi, T., Monde, K., Furuta, T., Kawabata, T.
    • Journal Title

      Org. Lett.

      Volume: 19 Issue: 2 Pages: 352-355

    • DOI

      10.1021/acs.orglett.6b03533

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Asymmetric Synthesis of Multisubstituted Dihydrobenzofurans by Intramolecular Conjugate Addition of Short-Lived C–O Axially Chiral Enolates2016

    • Author(s)
      Tomohara, K.; Kasamatsu, K.; Yoshimura, T.; Furuta, T.; Kawabata, T.
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 64 Issue: 7 Pages: 899-906

    • DOI

      10.1248/cpb.c16-00272

    • NAID

      130005160045

    • ISSN
      0009-2363, 1347-5223
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Catalyst-controlled regiodivergent vinylogous aza-Morita-Baylis-Hillman reactions2016

    • Author(s)
      Hyakutake, R.; Gondo, N.; Ueda, Y.; Yoshimura, T.; Furuta, T.; Kawabata, T.
    • Journal Title

      Tetrahedron Lett.

      Volume: 57 Issue: 12 Pages: 1321-1324

    • DOI

      10.1016/j.tetlet.2016.02.029

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Catalytic Asymmetric Reactions in Alkaloids and Terpenoids Syntheses2014

    • Author(s)
      Tomoyuki Yoshimura
    • Journal Title

      Tetrahedron Lett.

      Volume: 55 Issue: 37 Pages: 5019-5118

    • DOI

      10.1016/j.tetlet.2014.07.075

    • NAID

      120005512259

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] ルイス酸活性化によるシクロブタノンとニトロソベンゼンとの反応2017

    • Author(s)
      嶋佑介、五十嵐笑子、吉村智之、松尾淳一
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台(東北大学川内キャンパス)
    • Year and Date
      2017-03-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] ジペプチドを用いる不斉記憶型αーフッ素化の開発2017

    • Author(s)
      高嶋恵美、笠松幸司、吉村智之、川端猛夫
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台(東北大学川内キャンパス)
    • Year and Date
      2017-03-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] シクロブタノンと芳香環化合物との Friedel-Crafts 反応の開発2017

    • Author(s)
      蟹江真悠、吉村智之、松尾淳一
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台(東北大学川内キャンパス)
    • Year and Date
      2017-03-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] αーフッ素化アミノ酸誘導体の不斉記憶型合成2016

    • Author(s)
      笠松幸司、吉村智之、川場猛夫
    • 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
      茨城、つくば国際会議場
    • Year and Date
      2016-12-01
    • Related Report
      2016 Annual Research Report
  • [Presentation] αーハローγーヒドロキシエナミドの新しい合成法の開発とその有用性2016

    • Author(s)
      藪内優斗、葛口岳生、吉村智之、松尾淳一
    • Organizer
      日本薬学会北陸支部平成29年度総会及び第128回例会
    • Place of Presentation
      金沢、北陸大学薬学部
    • Year and Date
      2016-11-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] 不斉記憶型分子内アルキル化における立体保持・反転の要因について2016

    • Author(s)
      大津寄悠、川上晋平、松田誠司、吉村智之、尾谷優子、谷紀彦、大和田智彦、川端猛夫
    • Organizer
      第110回有機合成シンポジウム
    • Place of Presentation
      東京、早稲田大学国際会議場
    • Year and Date
      2016-11-11
    • Related Report
      2016 Annual Research Report
  • [Presentation] キラルエノラートの長寿命化:アミノ酸誘導体の不斉αーフッ素化への応用2016

    • Author(s)
      笠松幸司、木下智彦、吉村智之、川端猛夫
    • Organizer
      第42回反応と合成の進歩シンポジウム
    • Place of Presentation
      静岡、静岡市清水文化会館
    • Year and Date
      2016-11-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] 不斉記憶型分子内アルキル化における反応機構解析 ー立体保持・立体反転の要因についてー2016

    • Author(s)
      大津寄悠、川上晋平、松田誠司、吉村智之、尾谷優子、谷紀彦、大和田智彦、川端猛夫
    • Organizer
      第66回日本薬学会近畿支部総会・大会
    • Place of Presentation
      大阪、大阪薬科大学
    • Year and Date
      2016-10-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] ベンザインを求電子剤としたC-N軸不斉エノラートを経由するアミノ酸誘導体の不斉α-アリール化2015

    • Author(s)
      笠松幸司、吉村智之、川端猛夫
    • Organizer
      第65回 日本薬学会近畿支部総会・大会
    • Place of Presentation
      大阪大谷大学
    • Year and Date
      2015-10-17
    • Related Report
      2015 Research-status Report
  • [Presentation] Asymmetric alpha-Fluorination of Amino Acid Derivatives via Memory of Chirality2015

    • Author(s)
      Koji Kasamatsu, Tomoyuki Yoshimura, Takeo Kawabata
    • Organizer
      The 3rd International Symposium on Process Chemistry
    • Place of Presentation
      Kyoto International Conference Center, KYOTO, JAPAN
    • Year and Date
      2015-07-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Elongation of Life-Time of Chiral Enolate Intermediate: Asymmetric alpha-Fluorination of Amino Acid Derivatives via Memory of Chirality2015

    • Author(s)
      Koji Kasamatsu, Tomoyuki Yoshimura, Takeo Kawabata
    • Organizer
      27th International symposium on chiral discrimination (ISCD27)
    • Place of Presentation
      Boston park plaza hotel, USA
    • Year and Date
      2015-06-29
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] エノラートを反応中間体とする不斉記憶型反応の新展開2015

    • Author(s)
      吉村智之
    • Organizer
      第1回 近畿薬学シンポジウム:化学系の若い力
    • Place of Presentation
      京都大学薬学部記念講堂
    • Year and Date
      2015-06-27
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 不斉記憶型 Dieckmann 縮合の開発とメカニズム解析2015

    • Author(s)
      木下智彦、吉村智之、川端猛夫
    • Organizer
      シンポジウム モレキュラー・キラリティー2015
    • Place of Presentation
      早稲田大学
    • Year and Date
      2015-06-12
    • Related Report
      2015 Research-status Report
  • [Presentation] 長寿命化現象を利用するアミノ酸誘導体の不斉記憶型α-フッ素化2015

    • Author(s)
      笠松幸司、吉村智之、川端猛夫
    • Organizer
      シンポジウム モレキュラー・キラリティー2015
    • Place of Presentation
      早稲田大学
    • Year and Date
      2015-06-12
    • Related Report
      2015 Research-status Report
  • [Presentation] ベンザインを用いるアミノ酸誘導体の不斉記憶型α―アリール化2014

    • Author(s)
      笠松 幸司,吉村 智之,川端 猛夫
    • Organizer
      第44回複素環化学討論会
    • Place of Presentation
      札幌市民ホール,札幌
    • Year and Date
      2014-09-11
    • Related Report
      2014 Research-status Report
  • [Presentation] α―アミノ酸を唯一の不斉源として用いるα―アリールアミノ酸誘導体の不斉合成2014

    • Author(s)
      笠松 幸司,吉村 智之,川端 猛夫
    • Organizer
      日本プロセス化学会2014サマーシンポジウム
    • Place of Presentation
      タワーホール船堀,東京
    • Year and Date
      2014-08-01
    • Related Report
      2014 Research-status Report
  • [Presentation] C-N 軸性不斉エノラートを経るアミノ酸誘導体の不斉記憶型α―アリール化の開発2014

    • Author(s)
      笠松 幸司,友原 啓介,百武 龍一,楊 畔,吉村 智之,川端 猛夫
    • Organizer
      シンポジウム モレキュラー・キラリティー2014
    • Place of Presentation
      仙台,仙台国際センター
    • Year and Date
      2014-06-07
    • Related Report
      2014 Research-status Report
  • [Remarks] 川端研究室

    • URL

      http://www.fos.kuicr.kyoto-u.ac.jp/index.html

    • Related Report
      2015 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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