Synthetic studies of polyfunctionalized natural products with highly-fused ring systems

• Project/Area Number: 26713001
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Chemical pharmacy
• Research Institution: Nagoya University
• Principal Investigator: Satoshi Yokoshima 名古屋大学, 創薬科学研究科, 教授 (10376593)
• Research Collaborator: KITABAYASHI Yusuke ; YAMADA Ryosuke ; OCHI Yuji
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000); Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
• Keywords: アルカロイド / 天然物 / 全合成 / 複素環 / 環化付加反応 / 天然有機化合物 / 医薬品 / 縮環構造 / 多官能性

Outline of Final Research Achievements

Synthetic studies of polyfunctionalized natural products with highly-fused ring systems were conducted, and total syntheses of daphenylline and lycopalhine A were accomplished. The synthesis of daphenylline features intramolecular cycloaddition of an azomethine ylide as well as a Claisen rearrangement. In these reactions, the stereochemistries were remotely controlled by the characteristic conformation of the DEF tricyclic core. The synthesis of lydopalhine A features construction of the tricyclic system via cleavage of a cyclopropane ring and a subsequent intramolecular Michael addition. We also carried out synthetic studies of yuzurimine and obtained a key intermediate for the total synthesis, which has a tetrasubstituted C-C double bond in the [5-5] bicyclic system.

Research Products

• [Journal Article] Total Synthesis of Lycopalhine A (2017)
  • Author(s): Yuji Ochi, Satoshi Yokoshima, Tohru Fukuyama
  • Journal Title: Synthesis Volume: 49 Issue: 01 Pages: 96-114
  • DOI: 10.1055/s-0036-1588878
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Total Synthesis of (-)-Daphenylline (2016)
  • Author(s): Ryosuke Yamada, Yohei Adachi, Satoshi Yokoshima, Tohru Fukuyama
  • Journal Title: Angewandte Chemie International Edition Volume: 55 Issue: 20 Pages: 6067-6070
  • DOI: 10.1002/anie.201601958
  • NAID: 130007490838
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Chemical Transformation of an Intermediate in the Synthesis of Huperzine A, Leading to a Diverse Array of Molecules (2016)
  • Author(s): Satoshi Yokoshima, Masatsugu Ishikawa, Youko Beniyama, Tohru Fukuyama
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 64 Issue: 10 Pages: 1528-1531
  • DOI: 10.1248/cpb.c16-00507
  • NAID: 130005598027
  • ISSN: 0009-2363, 1347-5223
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Total Synthesis of (－)-Cardiopetaline (2016)
  • Author(s): Yoshitake Nishiyama, Satoshi Yokoshima, Tohru Fukuyama
  • Journal Title: Org. Lett. Volume: 18 Issue: 10 Pages: 2359-2362
  • DOI: 10.1021/acs.orglett.6b00789
  • NAID: 120005866818
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Total Synthesis of Lycpalhine A (2016)
  • Author(s): Yuji Ochi, Satoshi Yokoshima, Tohru Fukuyama
  • Journal Title: Organic Letters Volume: 18 Issue: 6 Pages: 1494-1496
  • DOI: 10.1021/acs.orglett.6b00338
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Total synthesis of Daphenylline (2016)
  • Author(s): Ryosuke Yamada, Yohei Adachi, Yokoshima Satoshi, Tohru Fukuyama
  • Organizer: 21st International Conference on Organic Synthesis
  • Place of Presentation: Bombay, India
  • Year and Date: 2016-12-11
  • Int'l Joint Research
• [Presentation] Synthetic Studies on Haliclonin A (2016)
  • Author(s): 折原 賢祐、河岸 文希、横島 聡、福山 透
  • Organizer: 21st International Conference on Organic Synthesis
  • Place of Presentation: Bombay, India
  • Year and Date: 2016-12-11
  • Int'l Joint Research
• [Presentation] 高度縮環構造をもつ天然物の合成研究 (2016)
  • Author(s): 横島 聡
  • Organizer: 平成28年度後期（秋季）有機合成化学講習会
  • Place of Presentation: 東京
  • Year and Date: 2016-11-16
  • Invited
• [Presentation] Synthesis of Heterocyclic Natural Products (2016)
  • Author(s): Satoshi Yokoshima
  • Organizer: The 1st M&M SYNTECH Unit International Meeting 2016
  • Place of Presentation: Nagoya, Japan
  • Int'l Joint Research / Invited
• [Presentation] 含窒素多環式天然物の合成研究 (2016)
  • Author(s): 横島 聡
  • Organizer: 第74回パネル討論会 次世代を切り拓く全合成研究の若い力
  • Place of Presentation: 徳島
  • Invited
• [Presentation] リコパルヒンAの合成研究 (2015)
  • Author(s): 越智祐司 横島聡 福山透
  • Organizer: 第４１回反応と合成の進歩シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2015-10-26
• [Presentation] ダフェニリンの全合成 (2015)
  • Author(s): 山田諒介、安立庸平、横島聡、福山透
  • Organizer: 第57回天然有機化合物討論会
  • Place of Presentation: 横浜
  • Year and Date: 2015-09-09
• [Presentation] Huperzine R の合成研究 (2015)
  • Author(s): 野村俊宗、横島聡、福山透
  • Organizer: 第61回日本薬学会東海支部大会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-07-04
• [Remarks] 名古屋大学大学院創薬科学研究科 天然物化学分野
  • URL: http://www.ps.nagoya-u.ac.jp/lab_pages/natural_products/index.html
• [Remarks] 名古屋大学大学院 創薬科学研究科 天然物化学分野
  • URL: http://www.ps.nagoya-u.ac.jp/lab_pages/natural_products/index.html