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Synthetic Studies on Poison-frog Alkaloids As Antagonists on nicotinic Acetylcholine Receptors

Research Project

Project/Area Number 17590004
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical pharmacy
Research InstitutionUniversity of Toyama

Principal Investigator

TOYOOKA Naoki  University of Toyama, 大学院・医学薬学研究部, 准教授 (10217565)

Co-Investigator(Kenkyū-buntansha) TSUNEKI Hiroshi  富山大学, 大学院・医学薬学研究部, 准教授 (20332661)
SASAOKA Toshiyasu  富山大学, 大学院・医学薬学研究部, 教授 (00272906)
Project Period (FY) 2005 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,100,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥600,000)
Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
Keywords毒ガエルアルカロイド / ニコチン受容体 / 179 / 207E / ヒドロキシインドリチジン / monomorine I / 231C / 221I / epi-193E / 233A / 235U / 251AA / インドリチジン / 251N / 221K / NIH / 5,8位置換インドリチジン
Research Abstract

毒ガエルアルカロイド類の柔軟で効率的な合成研究を実施し、5, 8位置換インドリチジン、1, 4位置換キノリチジンおよび5, 8位置換6, 7-デヒドロインドリチジンの合成を達成した。これにより、数種のアルカロイドの絶対配置、相対配置を確定した。また、提出構造の誤りを指摘し、訂正構造式の提案を行った。さらに、脳内主要ニコチン受容体に対して、これら毒ガエルアルカロイド類がサブタイプ選択的に抑制作用を示すことも明らかにした。

Report

(5 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (38 results)

All 2009 2008 2007 2006 Other

All Journal Article (24 results) (of which Peer Reviewed: 20 results) Presentation (13 results) Remarks (1 results)

  • [Journal Article] Synthesis, Determination of the Absolute Stereochemistry, and Evaluations at the Nicotinic Acetylcholine Receptors of a Hydroxy-indolizidine Alkaloid from the Ant2009

    • Author(s)
      Zhou, D. ; Toyooka, N.* ; Nemoto, H. ; Yamaguchi, K. ; Tsuneki, H. ; Wada, T. ; Sasaoka, T. ; Sakai, H. ; Tezuka, Y. ; Kadota, S. ; Jones, T.H. ; Garraffo, H.M. ; Spande, T.F. ; Daly, J.W.
    • Journal Title

      Myrmicaria melanogaster Heterocycles 79

      Pages: 565-571

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] First Enantioselective Synthesis of a Hydroxyindolizidine Alkaloid from the Ant2009

    • Author(s)
      Toyooka, N.* ; Zhou, D. ; Nemoto, H. ; Tezuka, Y. ; Kadota, S. ; Jones, T.H. ; Garraffo, H.M. ; Spande, T.F. ; Daly, J.W.
    • Journal Title

      Myrmicaria melanogaster Synlett

      Pages: 1894-1896

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis, Determination of the Absolute Stereochemistry, and Evaluations at the Nicotinic Acetylcholine Receptors of a Hydroxyindolizidine Alkaloid from the Ant Myrmicaria melanogaster2009

    • Author(s)
      Zhou, D., Tovooka. N., Nemoto, H., Yamaguchi, K., Tsuneki, H., Wada, T., Sasaoka, T., Sakai, H., Tezuka, Y., Kadota, S., Jones, T. H., Garraffo, H. M., Spande, T. F., Daly, J. W.
    • Journal Title

      Heterocycles 79

      Pages: 565-571

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nemoto, H Enantioselective Syntheses of(-)-and(+)-Monomorine I2008

    • Author(s)
      Toyooka, N.* ; Zhou, D.
    • Journal Title

      J. Org. Chem 73

      Pages: 4575-4577

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of the Proposed Structure of Poison-Frog Alkaloids 179 and 207Eand Their Inhibitory Effects on Neuronal Nicotinic Acetylcholine Receptors2008

    • Author(s)
      Toyooka, N.* ; Zhou, D. ; Kobayashi, S. ; Tsuneki, H. ; Wada, T. ; Sakai, H. ; Nemoto, H. ; Sasaoka, T. ; Tezuka, Y. ; Subehan ; Kadota, S. ; Garraffo, H.M. ; Spande, T.F. ; Daly, J.W.
    • Journal Title

      Synlett

      Pages: 61-64

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of the Proposed Structure of Poison-Frog Alkaloids 179 and 207E and Their Inhibitory Effects on Neuronal Nicotinic Acetylcholine Receptors2008

    • Author(s)
      Toyooka, N., Zhou, D., Kobaya shi, S., Tsuneki, H., Wada, T., Sakai, H., Nemoto, H., Sasaoka, T., Tezuka, Y., Subehan, Kadota, S., Garraffo, H. M., Spande, T. F., Daly, J. W.
    • Journal Title

      Synlett

      Pages: 61-64

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enantioselective Syntheses of (-)-and (+)-Monomorine I2008

    • Author(s)
      Toyooka, N., Zhou D., Nemoto, H.
    • Journal Title

      J. Org. Chem. 73

      Pages: 4575-4577

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] First Enantioselective Synthesis of a Hydroxyindolizidine Alkaloid from the Ant Myrmicaria melanogaster2008

    • Author(s)
      Toyooka. N., Zhou, D., Nemot, H., Tezuka, Y., Kadota, S., Jones, T. H., Garraffo, H. M., Spande, T. F., Daly, J. W.
    • Journal Title

      Synlett

      Pages: 1894-1896

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of Poison-frog Alkaloids and Their Pharmacological Effects at Neuronal Nicotinic Acetylcholine Receptors2007

    • Author(s)
      Toyooka, N.* ; Tsuneki, H. ; Kobayashi, S. ; Dejun, Z. ; Kawasaki, M. ; Kimura, K. ; Sasaoka, T. ; Nemoto, H.
    • Journal Title

      Current Chemical Biology 1

      Pages: 97-114

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Flexible Synthesis of Poison-frog Alkaloids of the 5, 8-Disubstituted Indolizidine-class. II: Synthesis of(-)-209B, (-)-231C, (-)-233D, (-)-235B', (-)-221I, and an Epimer of 193E and Pharmacological Effects at Neuronal Nicotinic Acetylcholine Receptors2007

    • Author(s)
      Kobayashi, S. ; Toyooka, N.* ; Zhou, D. ; Tsuneki, H.* ; Wada, T. ; Sasaoka, T. ; Sakai, H. ; Nemoto, H. ; Garraffo, H.M. ; Spande, T.F. ; Daly, J.W.
    • Journal Title

      Beilstein J. Org. Chem 3

      Pages: 30-30

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Flexible Synthetic Routes to Poison-frog Alkaloids of the 5,8- Disubstituted Indolizidine-class. I.: Synthesis of Common Lactam Chiral Building Blocks and Application to the Synthesis of(-)-203A, (-)-205A, and(-)-219F2007

    • Author(s)
      Toyooka, N.* ; Zhou, D. ; Nemoto, H. ; Garraffo, H.M. ; Spande, T.F. ; Daly, J.W.
    • Journal Title

      Beilstein J. Org. Chem 3

      Pages: 29-29

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of Poison-frog Alkaloids 233A, 235U, and 251AA and Their Inhibitory Effects on Neuronal Nicotinic Acetylcholine Receptors2007

    • Author(s)
      Toyooka, N.* ; Kobayashi, S. ; Zhou, D. ; Tsuneki, H. ; Wada, T. ; Sakai, H. ; Nemoto, H. ; Sasaoka, T. ; Garraffo, H.M. ; Spande, T.F. ; Daly, J.W.
    • Journal Title

      Bioorg. Med. Chem. Lett 17

      Pages: 5872-5875

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of Poison-frog Alkaloids 233A,235U, and 251AA and Their Inhibitory Effbcts on Neuronal Nicotinic Acetyicholine Receptors2007

    • Author(s)
      Toyooka, N.^*; Kobayashi, S.; Zhou, D.; Tsuneki, H.; Wada, T.; Sakai, H.; Nemoto, H.; Sasaoka, T.; Garraffo, H. M.; Spande, T. F, ; Daly, J. W.
    • Journal Title

      Bioorg. Med. Chem. Lett 17

      Pages: 5872-5875

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Flexlble Synthetic Routes to Poison-frog Alkaloids of the 5,8-Disubsti tuted Indolizidine-class. I.: Synthesis of Common Lactam Chlrai Building Blocks and Applicatlon to the Synthesis of(-)-203A,(-)-205A, and(-)-219F2007

    • Author(s)
      Tovooka, N.^*; Zhou, D.; Nemo to, H.; Garraffo, H. M.; Spande, T. F.; Daly, J. W.
    • Journal Title

      Beilstein J. Org. Chem 3(online journal)

      Pages: 29-29

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rexlble Synthesis of Poison-frog Aikaloids of the 5,8-Disubstituted Indolizidine-class. II: Synthesis of(-)-209B, (-)-231C, (-)-233D, (-)-235B'',(-)-221I, and an Epimer of 193E and Pharmacological Effects at Neuronal Nicotinlc Acetylcholine Receptors2007

    • Author(s)
      Kobayashl, S.; Toyooka, N.^*; Zhou, D.; Tsuneki, H.; Wada, T.; Sasaoka, T.; Sakai, H.; Nemoto, H.; Garraffo, H. M.; Spande, T. F.; Daly, J. W.
    • Journal Title

      Beilstein J. Org. Chem 3(online journal)

      Pages: 30-30

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of Poison-frog Alkaloids and Their Pharmacolo gical Effects at Neuronal Nicotinic Acetylcholine Receptors2007

    • Author(s)
      Toyooka, N.^*; Tsuneki, H.; Kobayashi, S.; Dejun, Z.; Kawasaki, M.; Kimura, K.; Sasaoka, T.; Nemoto H.
    • Journal Title

      Current Chemical Biology 1

      Pages: 97-114

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 毒ガエルアルカロイドの合成とニコチン受容体に対する活性評価2006

    • Author(s)
      豊岡尚樹*、根本英雄、恒枝宏史
    • Journal Title

      有機合成化学協会誌 64

      Pages: 49-60

    • NAID

      10016925229

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chiral Synthesis of Poison-Frog Alkaloids 251N2006

    • Author(s)
      Toyooka, N.* ; Dejun, Z. ; Nemoto, H.* ; Garraffo, H.M. ; Spande, T.F. ; Daly, J.W.
    • Journal Title

      and 221K Heterocycles 70

      Pages: 541-548

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enantioselective Syntheses of Poison-Frog Alkaloids : 219F and 221I and an Epimer of 193E2006

    • Author(s)
      Toyooka, N.* ; Dejun, Z. ; Nemoto, H.* ; Garraffo, H.M. ; Spande, T.F. ; Daly, J.W.
    • Journal Title

      Tetrahedron Lett 47

      Pages: 581-582

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] The Enantioselective Synthesis of Poison-Frog Alkaloids(-)-203A, (-)-209B,(-)-231C, (-)-233D, and(-)-235B2006

    • Author(s)
      Toyooka, N.* ; Dejun, Z. ; Nemoto, H.* ; Garraffo, H.M. ; Spande, T.F. ; Daly, J.W.
    • Journal Title

      Tetrahedron Lett 47

      Pages: 577-580

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chiral Synthesis of Poison-frog Alkaloids 251N and 221K2006

    • Author(s)
      Toyooka, N., Zhou, d., Nemoto, H., Garraffo, H.M., Spande, T.F., Daly, J.W.
    • Journal Title

      Heterocycle 70

      Pages: 541-8

    • NAID

      40015208578

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 毒ガエルアルカロイドの合成とニコチン受容体に対する活性評価2006

    • Author(s)
      豊岡 尚樹, 根本 英雄, 恒枝 宏史
    • Journal Title

      有機合成化学協会誌 64

      Pages: 49-60

    • NAID

      10016925229

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The enantioselective synthesis of poison-frog alkaloids (-)-203A, (-)-209B, (-)-231C, (-)-233D, and (-)-235B"2006

    • Author(s)
      Toyooka, N., Dejun, Z., Nemoto, H., Garraffo, H.M., Spande, T.F., Daly, J.W.
    • Journal Title

      Tetrahedron Lett. 47

      Pages: 577-580

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Enantioselective syntheses of poison-frog alkaloids : 219F and 221I and an epimer of 193E2006

    • Author(s)
      Toyooka, N., Dejun, Z., Nemoto, H., Garraffo, H.M., Spande, T.F., Daly, J.W.
    • Journal Title

      Tetrahedron Lett. 47

      Pages: 581-582

    • Related Report
      2005 Annual Research Report
  • [Presentation] Monomorine I 両対掌体の短工程合成2008

    • Author(s)
      周 徳軍, 豊岡尚樹, 根本英雄
    • Organizer
      日本薬学会北陸支部第118回例会
    • Place of Presentation
      富山
    • Year and Date
      2008-07-05
    • Related Report
      2008 Annual Research Report
  • [Presentation] アリから単離されたヒドロキシインドリチジンアルカロイドの合成2008

    • Author(s)
      豊岡尚樹, 周徳軍, 根本英雄, 山口薫, 恒枝宏史, 和田努, 笹岡利安, 手塚康弘, 門田重利, H. Martin Garraffo, Thomas F. Spande, John W. Daly
    • Organizer
      第38回複素環化学討論会
    • Place of Presentation
      Fukuyama
    • Related Report
      2008 Final Research Report
  • [Presentation] ピロリチジン型毒ガエルアルカロイドの合成研究2008

    • Author(s)
      周徳軍, 豊岡尚樹, 根本英雄, 手塚康弘, 門田重利, H. Martin Garraffo, Thomas F. Spande, John W. Daly
    • Organizer
      第34回反応と合成の進歩シンポジウム
    • Place of Presentation
      Kyoto
    • Related Report
      2008 Final Research Report
  • [Presentation] 毒ガエルアルカロイド179, 207Eの合成2008

    • Author(s)
      豊岡尚樹, 周徳軍, 古林創史, 恒枝宏史, 和田努, 酒井秀紀, 根本英雄, 笹岡利安, 手塚康弘, Subehan, 門田重利, H. Martin Garraffo, Thomas F. Spande, John W. Daly
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      Yokohama
    • Related Report
      2008 Final Research Report
  • [Presentation] ピロリチジン型毒ガエルアルカロイドの合成研究2008

    • Author(s)
      周 徳軍, 豊岡尚樹, 根本英雄, 山口 薫, 手塚康弘, 門田重利, Garraffo, H. M., Spande, T. F., Daly, J. W.
    • Organizer
      第34回反応と合成の進歩シンポジウム
    • Place of Presentation
      京都
    • Related Report
      2008 Annual Research Report
  • [Presentation] アリから単離されたヒドロキシインドリチジンアルカロイドの合成2008

    • Author(s)
      豊岡尚樹, 周 徳軍, 根本英雄, 山口 薫, 恒枝宏史, 和田 努, 笹岡利安, 手塚康弘, Garraffo, H. M., Spande, T. F., Daly, J. W., Jones, T. H.
    • Organizer
      第38回複素環化学討論会
    • Place of Presentation
      福山
    • Related Report
      2008 Annual Research Report
  • [Presentation] Synthesis of Proposed Structure of Poison-frog Alkaloids 207E and 179 and Their Inhibitory Effects on Nicotinic Acetylcholine Receptors2007

    • Author(s)
      Toyooka, N ; Zhou, D. ; Kobayashi, S. ; Tsuneki, H. ; Sasaoka, T. ; Nemoto, H. ; Garraffo, H. M. ; Spande, T. F. ; Daly, J. W.
    • Organizer
      the 19th French-Japanese Symposium on Medicinal and Fine Chemistry
    • Place of Presentation
      Toyama
    • Related Report
      2008 Final Research Report
  • [Presentation] Synthesis of Proposed Structure of Poison-frog Alkaloids207E and 179 and Their Inhibitory Effects on Nicotinic Acetylcholine Receptors2007

    • Author(s)
      Naoki TOYOOKA, Dejun ZHOU, Soushi KOBAYASHI, Hiroshi TSUNEKI, Toshiyasu SASAOKA, Hideo NBMOTO, H. Martin GARRAFFO, Thomas F. SPANDE and John W. DALY
    • Organizer
      The nineteenth French-Japanese Symposium on Medicinai and Fine Chemlstry (FJS 2007)
    • Place of Presentation
      富山
    • Related Report
      2007 Annual Research Report
  • [Presentation] Synthetic Studies on Biologically Active Alkaloids2006

    • Author(s)
      Toyooka, N.
    • Organizer
      Xiamen University
    • Place of Presentation
      Xiamen
    • Related Report
      2008 Final Research Report
  • [Presentation] Synthetic Studies on Biologically Active Alkaloids2006

    • Author(s)
      Toyooka, N.
    • Organizer
      Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences
    • Place of Presentation
      Shanghai
    • Related Report
      2008 Final Research Report
  • [Presentation] 毒ガエルアルカロイドの合成とそのニコチン受容体抑制活性評価2006

    • Author(s)
      周徳軍、豊岡尚樹、恒枝宏史、古林創史、笹岡利安、根本英雄、Daly, J.W. ; Spande, T.F. ; Garraffo, H.M.
    • Organizer
      第32回反応と合成の進歩シンポジウム
    • Place of Presentation
      Hiroshima
    • Related Report
      2008 Final Research Report
  • [Presentation] 毒ガエルアルカロイド233A, 251AA, 235Uのキラル合成2006

    • Author(s)
      周徳軍、豊岡尚樹、根本英雄、Garraffo, H.M. ; Spande, T.F. ; Daly, J.W.
    • Organizer
      日本薬学会北陸支部第114例会
    • Place of Presentation
      Kanazawa
    • Related Report
      2008 Final Research Report
  • [Presentation] Chiral Synthesis of 5, 8-Disubstituted Indolizidine Type Poison-frog Alkaloids2006

    • Author(s)
      Toyooka, N. ; Zhou, D. ; Nemoto, H. ; Garraffo, H.M. ; Spande, T.F. ; Daly, J W.
    • Organizer
      International Molecular Chirality Conference in Toyama
    • Place of Presentation
      Toyama
    • Related Report
      2008 Final Research Report
  • [Remarks]

    • URL

      http://www.pha.u-toyama.ac.jp/mediche2/index-j.html

    • Related Report
      2008 Final Research Report

URL: 

Published: 2005-04-01   Modified: 2016-04-21  

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