• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Molecular design to develop a novel tool for the elucidation of the function of glutamates

Research Project

Project/Area Number 05557110
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 医薬分子機能学
Research InstitutionTOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY

Principal Investigator

KOIZUMI Toru  Toyama Medical & Pharmaceutical University Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (40012611)

Co-Investigator(Kenkyū-buntansha) KAMATA Susumu  Shionogi Co. Ltd., Senior Researcher, 創薬第二研究所, 部長
TAKAHASHI Tamiko  Toyama Medical & Pharmaceutical University Faculty of Pharmaceutical Sciences, A, 薬学部, 助手 (10115181)
伊比井 信広  塩野義製薬, 新薬研究所, 主任研究員
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1993: ¥3,300,000 (Direct Cost: ¥3,300,000)
KeywordsGlutamate agonist / Glutamate antagonist / Phosphoglutamate / Sulfinylmaleimide / Acyliminium addition / Bicyclo [2.2.1] octane / Aminophosphonic acid / Conformation control / アシルイミニウム付加 / グルタミン酸受容体 / アゴニスト / アンタゴニスト / 機能分子 / 分子設計 / 不斉合成 / 環化付加反応 / キラルジエノフィル
Research Abstract

Chiral sulfinylmaleimides, a typical sulfinylethene-type dienophiles, react with various dienes to give the corresponding cycloadducts in highly diastereoselective manner. The aim of this research project is to develop a new tool to clarify the fucntion and the molecular understanding of glutamates in the human brain. For that purpose the chiral synthesis of glutamate and phosphoglutamate derivatives having the bicyclo [2.2.1] heptane ring system have been investigated and the following results were obtained.
1) The chiral synthesis of glutamate and phosphoglutamate derivatives having the bicyclo [2.2.1] heptane ring system : Asymmetric Diels-Alder reaction of the sulfinylmaleimides with cyclopentadiene afforded the single diastereomeric cycloadduct. The reduction of the cycloadduct followed by the N-acyliminium cyanation afforded the key intermediate for the glutamate synthesis. After several conversion process, the objective glutamate derivatives were obtained as dimethylammonium salt … More , whose bioassay show the NMDA antagonistic activity. These glutamate could be good lead compounds for further molecular design. The acyliminium addition of phosphorus nucleophiles afforded the corresponding phosphorus esters. The hydrolytic cleavage of the phosphorus esters was very difficult to give the objective phosphoglutamate derivatives.
2) Asymmetric Diels-Alder Cycloaddition of the Sulfinylethenes under Ultrahigh Pressure : In order to extend the scope of the above Diels-Alder reaction, the reaction of various sulfinylethenes with low-reactive dienes have been systematically studied. It was turned out that under the ultrahigh pressure conidition the low reactive dienes react with sulfinylethenes to give the corresponding cycloadducts highly diastereoselectively. The steric course of the reaction turned out to be the same as that was established under atmospheric pressure. So, the ultrahigh pressure methodology is quite useful for the molecular design of the glutamate receptor antagonists (or agonists) having the bicyclo [2.2.1] -heptane and-octane system. Less

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] T.Takahashi.: "Synthesis of Thioaldehydes Having Optically Active Alkoxy Moiety and Their Aasymmetric Hetero Diels-Alder Reaction" Heterocycles. 36. 1601-1616 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Arai: "Chiral Sulfinylethenes as Efficient Dienophiles for Asymmetric Diels-Alder Reactions" Sulfur Reports. 15. 41-65 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Arai: "Enantioselective Synthesis of (+)-Indolizidine,(+)-Laburnine and (+)-Elaeokanines A and C Using the Diels-Alder Reaction of α-(2-exo-hydroxy-10-bornylsulfinyl) maleimides" J.Chem.Soc.Perkin 1. 15-24 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Arai: "Asymmetric Diels-Alder Reaction of Optically Active α-(2-exo-hydroxy-10-bornylsulfinyl)-maleimides and Its Application to Optically Active 5-Functionalized Pyrrolines via Retro Diels-Alder Reaction" J.Chem.Soc.Perkin 1. 25-39 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Nakajima: "High Pressure Mediated Asymmetric Diels-Alder Reaction of Chiral sulfinylacrylate Derivatives with Furan and 2-Methoxyfuran" Heterocycles. 42. 129-133 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Takahashi, N.Kurose, and T.Koizumi: "Synthesis of Thioaldehydes Having Optically Active Alkoxy Moiety and Their Asymmetric Hetero Diels-Alder Reactions" Heterocycles. 36-No7. 1601-1616 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Arai, and T.Koizumi: "Chiral Sulfinylethenes as Efficient Dienophiles for Asymmetric Diels-Alder Reactions" Sulfur Reports. 15-No1. 41-65 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Kimura, I.Kimura, M.Muroi, K.Tanaka, H.Nojima, T.Uwano, and T.Koizumi: "The Structure Activity Relationship between PhenylenepolymethyleneBis-Ammonium Derivatives and Their Neuromuscular Blocking Action" Biol. Pharm. Bull. 17-No9. 1224-1231 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Takahashi, J.Sugita, T.Hirano, and T.Koizumi: "Synthesis of Optically Active 9-Methoxy-9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboxamide Derivatives via Asymmetric Diels-Alder Reaction of a Chiral Sulfinylmaleimide" Heterocycles. 39-No1. 305-314 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Arai, T.Kontani, and T.Koizumi: "Enantioselective Synthesis of (+)-Indolizidine, (+)-Laburnine and (+)-Elaeokanines A and C Using the Diels-Alder Reaction of alpha-(2-exohydroxy-10-bornylsulfinyl) maleimides" J.Chem. Soc. Perkin 1. No1. 15-24 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Arai, M.Matsui, A.Fujii, T.Kontani, T.Ohno, T.Koizumi, M.Shiro: "Asymmetric Diels-Alder Reaction of Optically Active alpha-(2-exo-hydroxy-10-bornylsulfinyl)-maleimides and Its Application to Optically Active 5-Functionalized Pyrrolines via Retro Diels-Alder Reaction" J.Chem. Soc. Perkin 1. No1. 25-39 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Takahashi, N.Kurose, S.Kawanami, A.Nojiri, T.Arai, T.Koizumi, and M.Shiro: "Nucleophilic Substitution Reaction of Optically Pure Chloroselenurane with Active Methylene Compounds." Chemistry Letters. No5. 379-389 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Y.Nakajima, W-Y Ge, J.Sugita, K.Okayama, T.Takahashi, and T.Koizumi: "High Pressure Mediated Asymmetric Diels-Alder Reaction of Chiral sulfinylacrylate Derivativeswith Furan and 2-Methoxyfuran" Heterocycles. 42-No1. 129-133 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Takahashi: "Synthesis of Thioaldehydes Having Optically Active Alkoxy Moiety and Their Aasymmetric Hetero Diels-Alder Reaction" Heterocycles. 36. 1601-1616 (1993)

    • Related Report
      1995 Annual Research Report
  • [Publications] Y.Arai: "Chiral Sulfinylethenes as Efficient Dienophiles for Asymmetric Diels-Alder Reactions" Sulfur Reports. 15. 41-65 (1993)

    • Related Report
      1995 Annual Research Report
  • [Publications] Y.Arai: "Enantioselective Synthesis of(+)-Indolizidine, (+)-Laburnine and(+)-Elaeokanines A and C Using the Diels-Alder Reaction of α-(2-exo-hydroxy-10-bornylsulfinyl)maleimides" J. Chem. Soc.Perkin 1. 15-24 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Y.Arai: "Asymmetric Diels-Alder Reaction of Optically Active α-(2-exo-hydroxy-10-bornylsulfinyl)-maleimides and Its Application to Optically Active 5-Functionalized Pyrrolines via Retro Diels-Aeaction" J. Chem. Soc. Perkin 1. 25-39 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Y.Nakajima: "High Pressure Mediated Asymmetric Diels-Alder Reaction of Chiral sulfinylacrylate Derivatives with Furan and 2-Methoxyfuran" Heterocycles. 42. 129-133 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] T.Takahashi: "Synthesis of Thioaldehydes Having Optically Active Alkoxy Moiety and Their Aasymmetric Hetero Diels-Alder Reaction" Heterocycles. 36. 1601-1616 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Takeuchi: "Application of CFPA method to the Enantiomeric Excess Determination of Some Hindered Alcohols in Asymmetric and Natural Product Synthesis" Tetrahedron. 49. 1861-1870 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Arai: "Chiral Sulfinylethenes as Efficient Dienophiles for Asymmetric Diels-Alder Reactions" Sulfur Reports. 15. 41-65 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] M.Kimura: "The Structure Activity Relationship between Phenylenepolymethylene Bis-Ammonium Derivatives and Their Neuromuscular Blocking Action" Biol.Pharm.Bull.17. 1224-1231 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Takahashi: "Synthesis of Optically Active 9-Methoxy-9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboxamide Derivatives via Asymmetric Diels-Alder Reaction of a Chiral Sulfinylmaleimide" Heterocycles. 39. 305-314 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Arai: "Enantioselective Synthesis of(+)-Indolizidine,(+)-Laburmine and(+)-Elaeokanines A and C Using the Diels-Alder Reaction of α-(2-exo-hydroxy-10-bornylsulfinyl)maleimides" J.Chem.Soc.Perkin 1. 15-24 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Arai: "Asymmetric Diels-Alder Reaction of Optically Active α-(2-exo-hydroxy-10-bornylsulfinyl)-maleimides and Its Application to Optically Active 5-Functionalized Pyrrolines" J.Chem.Soc.Perkin 1. 25-39 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Arai: "Enantioselective Synthesis of (+)-Indolizidine,(+)-Laburnine and (+)-Elaeokanines a and C using the Diels-Alder Reaction" J.Chem.Soc.Perkin Trans.1. 15-24 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Y.Arai: "Asymmetric Diels-Alder Reaction of Optically Active alpha-(2-exo-Hydroxy-10-bornyl)sulfinylmaleimides and its Application" J.Chem.Soc.Perkin Trans.1. 25-39 (1994)

    • Related Report
      1993 Annual Research Report

URL: 

Published: 1993-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi