Studies on isolation, total syntheses and structure-activity relationship of plants alkaloids with AChE inhibitory activity

• Project/Area Number: 23790124
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Drug development chemistry
• Research Institution: Chiba University
• Principal Investigator: KOGURE Noriyuki 千葉大学, 大学院・薬学研究院, 助教 (80396689)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: アルカロイド / アセチルコリンエステラーゼ / リコポジウム / ヒガンバナ / 不斉全合成 / 構造決定

Research Abstract

This research was aimed for the search of plant alkaloids which has AChE inhibitory activity by separation from Lycopodium and Amaryllidaceae plants, chemical total synthesis of natural alkaloids. As a result, we succeeded in the isolation and structure elucidation of many new alkaloids and achieved the total syntheses of several kinds of natural alkaloids.

Research Products

• [Journal Article] Chemical Conversion of Strychnine into Kopsiyunnanine-I, a New Hexacyclic Indole Alkaloid from Yunnan Kopsia arborea (2012)
  • Author(s): N. Kogure, Y. Suzuki, Y. Wu, M.Kitajima, R. Zhang, and H. Takayama
  • Journal Title: Tetrahedron Lett Volume: 53(48) Issue: 48 Pages: 6523-6526
  • DOI: 10.1016/j.tetlet.2012.09.078
  • Peer Reviewed
• [Journal Article] Synthesis and Biological Evaluation of 4-Chlorocolchicine Derivatives as Potent Anticancer Agents with Broad Effective Dosage Ranges (2012)
  • Author(s): H. Nishiyama, M. Ono, T. Sugimoto, T.Sasai, N. Asakawa, T. Matsumoto, T. Yaegashi, M. Nagaoka, T. Matsuzaki, N. Kogure, M. Kitajima, and H. Takayama
  • Journal Title: Med. Chem. Comm Volume: 3(12) Issue: 12 Pages: 1500-1504
  • DOI: 10.1039/c2md20250f
  • Peer Reviewed
• [Journal Article] Lycopodium Alkaloids: Isolation and Asymmetric Synthesis. (2012)
  • Author(s): M. Kitajima
  • Journal Title: Topics in Current Chemistry Volume: 309 Pages: 1-32
  • Peer Reviewed
• [Journal Article] Syntheses of Fawcettimine-Type Lycopodium Alkaloids Utilizing the Pauson-Khand Reaction (2012)
  • Author(s): A. Nakayama
  • Journal Title: Synlett Volume: 23 Pages: 2014-2024
  • Peer Reviewed
• [Journal Article] Asymmetric Total Synthesis of a Pentacyclic Lycopodium Alkaloid, Huperzine-Q. Angew (2011)
  • Author(s): A. Nakayama, N. Kogure, M. Kitajima, and H. Takayama
  • Journal Title: Chem., Int. Ed. Volume: 50(35) Issue: 35 Pages: 8025-8028
  • DOI: 10.1002/anie.201103550
  • Peer Reviewed
• [Journal Article] Ten New Fawcettimine-related Alkaloids from Three Species of Lycopodium (2011)
  • Author(s): K. Katakawa, H. Mito, N. Kogure, M.Kitajima, S. Wongseripipatana, M. Arisawa, and H. Takayama
  • Journal Title: Tetrahedron Volume: 67(35) Issue: 35 Pages: 6561-6567
  • DOI: 10.1016/j.tet.2011.05.107
  • Peer Reviewed
• [Journal Article] Two New Alkaloids from Crinum asiaticum var. sinicum (2011)
  • Author(s): N. Kogure, N. Katsuta, M. Kitajima, and H. Takayama
  • Journal Title: Chem. Pharm. Bull Volume: 59 (12) Pages: 1545-1548
  • NAID: 130001852130
  • URL: https://www.jstage.jst.go.jp/article/cpb
  • Peer Reviewed
• [Journal Article] Two New Alkaloids from Crinum asiaticum var. sinicum. (2011)
  • Author(s): N. Kogure
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 59 Pages: 1545-1548
  • NAID: 130001852130
  • Peer Reviewed
• [Presentation] 新規骨格LycopodiumアルカロイドLycoposerramine-Rの不斉全合成研究 (2013)
  • Author(s): 石田寛明、木村真也、小暮紀行、北島満里子、高山廣光
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-30
• [Presentation] Lycopodium nummularifoliumのアルカロイド成分の探索 (2013)
  • Author(s): 岡部慧、小暮紀行、北島満里子、高山廣光
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-28
• [Presentation] Pauson-Khand反応を基盤としたFawcettimineの不斉全合成研究 (2012)
  • Author(s): 中山淳、小暮紀行、北島満里子、高山廣光
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-31
• [Presentation] 栃木県産Lycopodium serratum含有アルカロイドの成分探索 (2012)
  • Author(s): 池城沙耶子、北島満里子、小暮紀行、片川和明、高山廣光
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-30
• [Presentation] Lycoposerramine-Rの全合成研究 (2012)
  • Author(s): 木村 真也
  • Organizer: 日本薬学会第132回年会
  • Place of Presentation: 北海道大学
• [Presentation] 栃木県産Lycopodium serratum含有アルカロイドの成分探索 (2012)
  • Author(s): 池城 沙耶子
  • Organizer: 日本薬学会第132回年会
  • Place of Presentation: 北海道大学
• [Presentation] Synthetic Studies of Fawcettimine-type Lycopodium Alkaloids, Potential Seed Molecules for Drug Development (2011)
  • Author(s): A. Nakayama, N. Kogure, M. Kitajima and H. Takayama
  • Organizer: 8^<th> AFMC International Medicinal Chemistry Symposium (AIMECS11)
  • Place of Presentation: Tokyo
  • Year and Date: 2011-12-30
• [Presentation] Synthetic Study of Lycoposerramine-R, A Novel Skeletal Type of Lycopodium Alkaloids (2011)
  • Author(s): S. Kimura, N. Kogure, M. Kitajima and H. Takayama
  • Organizer: 8^<th> AFMC International Medicinal Chemistry Symposium (AIMECS11)
  • Place of Presentation: Tokyo
  • Year and Date: 2011-12-30
• [Presentation] アセチルコリンエステラーゼ阻害活性を有する植物アルカロイドに関する化学的研究 (2011)
  • Author(s): 小暮紀行
  • Organizer: 第4回食品薬学シンポジウム生薬天然物部会奨励研究講演(受賞講演)
  • Place of Presentation: 東京
  • Year and Date: 2011-10-28
• [Presentation] Fawcettimine型リコポジウムアルカロイド類の不斉全合成研究 (2011)
  • Author(s): 中山淳、小暮紀行、北島満里子、高山廣光
  • Organizer: 第99回有機合成シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2011-06-15
• [Presentation] アセチルコリンエステラーゼ阻害活性を有する植物アルカロイドに関する化学的研究 (2011)
  • Author(s): 小暮 紀行
  • Organizer: 第４回食品薬学シンポジウム
  • Place of Presentation: 慶應義塾大学薬学部
• [Presentation] Lycopodium nummularifoliumのアルカロイド成分の探索
  • Author(s): 岡部慧
  • Organizer: 日本薬学会第133回年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 新規骨格LycopodiumアルカロイドLycoposerramine-Rの不斉全合成研究
  • Author(s): 石田寛明
  • Organizer: 日本薬学会第133回年会
  • Place of Presentation: パシフィコ横浜
• [Remarks]
  • URL: http://www.p.chiba-u.ac.jp/lab/seitai/index.html
• [Remarks] 千葉大学大学院薬学研究院 生体機能性分子研究室
  • URL: http://www.p.chiba-u.ac.jp/lab/seitai/index.html