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Development of asymmetric synthetic method for organofluorine compounds of biological interests

Research Project

Project/Area Number 09672163
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical pharmacy
Research InstitutionTokyo University of Pharmacy and Life Science

Principal Investigator

TAGUCHI Takeo  Tokyo University of Pharmacy and Life Science, School of Pharmacy, Professor, 薬学部, 教授 (00016180)

Co-Investigator(Kenkyū-buntansha) ITO Hisanaka  Tokyo University of Pharmacy and Life Science, School of Pharmacy, Assistant (70287457)
KITAGAWA Osamu  Tokyo University of Pharmacy and Life Science, School of Pharmacy, Lecturer, 薬学部, 講師 (30214787)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
KeywordsDifluorocyclopropane / Glutamic acid / Cyclopropylglycine / Methylenecyclopropane / Clasen rearrangement / Asymmetric synthesis / Diels-Alder reaction / lodoaminocyclization / Atropisomers / メチレンジフルオロシクロプロパン / シクロプロパン / フルオロアクリル酸 / シクロプロピルアニオン / クライゼン転位反応 / ジフルオロケトン
Research Abstract

As our continuous studies on development of new synthetic methods for organofluorine compounds directed to the synthesis of fluoro analogs of biologicaly interesting substrates, we have focused develop asymmetric synthetic methods for organofluorine compounds during these three years with the financial support in part from the Ministry of Education, Science, Sports and Culture.
Our achievements are summarized as follows.
(1) We have synthesized fuctionalized difluorocyclopropane derivatives in optically active form from glyceraldehyde as a chiral precursor, which are used for the preparation of conformationlly restricted glutamate analogs (FィイD22ィエD2CCGs). Pharmacological evaluation of FィイD22ィエD2CCGs was also investigated.
(2) We have succeeded in establishing the efficient synthetic methods for methylenedifluorocyclopropanes, which are revealed to have unique properties such as highly reactive Michael acceptor.
(3) For the construction of a fluorine substituted chiral tertiary carbon in optically pure form, we have examined the asymmetric Diels-Alder reaction of 2-fluoroacrylate and we applied our results to the preparation of conformationally restricted glutamate analog having norbornane structure.
(4) We have found an efficient enantioselective Claisen rearrangement promoted by the chiral borane complex as a Lewis acid, which opened a new synthetic method for optically active functionalized difluoromenthylene compounds. We have also achieved N-selective iodocyclization reaction of amide derivatives controlled by metallic reagent. As a new class of asymmetric reactions, we have developed several reactions using atropisomeric anilide derivatives.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (46 results)

All Other

All Publications (46 results)

  • [Publications] 北川理: "Regio-controlled Iodcaminocycligation Reaction of an Ambident Nucleophile Mediated by Li Al (Ot-Bu) 4"Tetrahedron Lett.. 38. 615-618 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 岡田みどり: "Fluorolactonization of 4-Alkenoic Acid Derivatives with N-Fluoropentachloro pyridinium Trifoliate"J. Fluorine Chem.. 82. 157-161 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 伊藤久央: "Enantioselective Aromatic Claisen Rearrangement"Tetrahedron Lett.. 38. 4815-4818 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 田口武夫: "Preparation of methyllene-gem-difluorocyclopropanes aut Its Reactivity as Michael Acceptor"Tetrahedron. 53. 9497-9508 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 渋谷彰: "Generation and Reactions of Difluorocyclopropyl Anion"Tetrahedron Lett.. 38. 5537-5540 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 藤田征夫: "Regiocontrolled Iodoaminocyclization Reaction of an Ambident Nucleophile Mediated by basic Metallic Reagent"J, Org. chem.. 62. 7330-7335 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 伊藤久央: "Asymmetric Diels-Alder Reactions of 2-Fluoroacrylic Acid Derivatives. Part1 :"Tetrahedron : Asymmetry. 9. 1979-1987 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 伊藤久央: "Asymmetric Diels-Alder Reactions of 2-Fluoroacrylic Acid Derivatives. Part2 :"Tetrahedron : Asymmetry. 9. 1989-1994 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 伊藤久央: "Enantioselective Claisen Rearrangement of Difluorovinyl Allyl Ethers"Chem. Commun.. 2441-2442 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 北川理: "Optically Active Axially Chiral Anilide and Maleimide Deniatives as New chiral Reagent"J, Org. Chem.. 63. 2634-2640 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 渋谷彰: "Preparation of Difluoro Analogs of CCGS and their Pharmacological Evaluations"Bicorg. Med. Chem. Lett.. 8. 1979-1984 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 田口武夫: "Preparation of F_2MCPGs via Selenoxide Elimination"J, Fluorine Chem.. 97. 157-159 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 藤田征夫: "Stereo selective Synthesis of an Optically Active Axially Chirol Lactam and Its Reaction with some Electrophiles"Tetrahedron Lett.. 40. 1949-1952 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 北川理: "Efficient Synthesis of Various Atropisomeric Amides in Optically Pure Forms and their Application to Asymmetric Reations"Tetrahedron Lett.. 40. 8827-8831 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 渋谷彰: "Preparation of Methylenedifuorocyclopropanes via Cyclopropyl Aston promoted B-Elimination"Tetrahedron. 55. 10325-10340 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 伊藤久央: "Synthesis of 2-Fluoro Analog of G Aminonorbornane-2.6-dicarboxylic Acid"Tetrahedron. 55. 12741-12750 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kitagawa, O.: "Regio-controlled lodoaminocyclization Reaction of an Ambident Nucleophile Mediated by LiAl (Ot-Bu)ィイD24°ィエD2."Tetrahedron Lett.. 38(4). 615-618 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okada, M.: "Fluorolactonization of 4-Alkenoic Acid Derivatives with N-Fluoropentachloropyridinium Triflate."J. Fluorine Chem.. 82. 157-161 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ito, H.: "Enantioselective Aromatic Claisen Rearrangement."Tetrahedron Lett.. 38(27). 4815-4818 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Taguchi, T.: "Preparation of Methylene-gem-difluorocyclopropanes and Its Reactivity as Michael Acceptor."Tetrahedron. 53(28). 9497-9508 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shibuya, A.: "Generation and Reactions of Difluorocyclopropyl Anion."Tetrahedron Lett.. 38(31). 5537-5540 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fujita, M.: "Regiocontrolled lodoaminocyclization Reaction of an Ambident Nucleophile Mediated by Basic Metallic Reagent."J. Org. Chem.. 62(21). 7330-7335 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ito, H.: "Asymmetric Diels-Alder Reactions of 2-Fluoroacrylic Acid Derivatives. Part 1 : The Construction of Fluorine Substituted Chiral Tertiary Carbon."Tetrahedron : Asymmetry. 9. 1979-1987 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ito, H.: "Asymmetric Diels-Alder Reactions of 2-Fluoroacrylic Acid Derivatives. Part 2 : A Remarkable Effect of Fluorine Substituent on the Diastereoselectivity."Tetrahedron : Asymmetry. 9. 1989-1994 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ito, H.: "Enantioselective Claisen Rearrangement of Difluorovinyl Allyl Ethers."Chem. Commun.. 2441-2442 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kitagawa, O.: "Optically Active Axially Chiral Anilide and Maleimide Derivatives as New Chiral Reagents ; Synthesis and Application to Asymmetric Diels-Alder Reaction."J. Org. Chem.. 63. 2634-2640 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shibuya, A.: "Preparation of Difluoro Analogs of CCGs and their Pharmacological Evaluations."Bioorg. Med. Chem. Lett.. 8. 1979-1984 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Taguchi, T.: "Preparation of F2MCPGs via Selenoxide Eliminaton."J. Fluorine Chem.. 97. 157-159 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fujita, M.: "Stereoselective Synthesis of an ptically Active Axially Chiral Lactam and Its Reaction with Some Electrophiles."Tetrahedron Lett.. 40(10). 1949-1952 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kitagawa, O.: "Efficient Synthesis of Various Atropisomeric Amides in Optically Pure Forms and their Application to Asymmetric Reactions."Tetrahedron Lett.. 40(50). 8827-8831 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shibuya, A.: "Preparation of Methylenedifluorocyclopropanes via Cyclopropyl Anion Promoted β-Elimination."Tetrahedron. 55. 10325-10340 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ito, H.: "Synthesis of 2-Fluoro Analog of 6-Aminonorbornane-2, 6-dicarboxylic Acid ; A Conformationally Rigid Glutamic Acid Derivative."Tetrahedron. 55. 12741-2750 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 田口武夫: "Preparation of F_2MCPGs via selenoxide elimination"J.Fluorine Chene.. 97. 157-159 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 渋谷彰: "Preparation of Methybene difluero yclopropanes via cyclopropyl Anion Promoted B-Eltmination"Tetrahedron. 55. 10325-10340 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 伊藤久央: "Synthesis of 2-Fluore Analog of 6-Ayinororbornane-2.6-chi carboxylic Acid:A Conformationally Ridiy Glutamic acid"Tetrahedron. 55. 12741-12750 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 藤田征夫: "Stereoselective Synthesis of an Optically Active Axially Chiral Lactom and Its Reution with Some Electrophiles"Tetrahedron Lett.. 40. 1949-1952 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 北川理: "Effictent Syuthesis of Various Atropisomeric Amides in Optically Pure Forms and ther Application to A symmatric Reactions"Tetrahedron Lett.. 40. 8827-8831 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 渋谷 彰: "Preparation of Difluovc Analogs of CCGs and Their, Pharmacological Evaluations" Bioorg. Med, Chem, Lett.8・15. 1979-1984 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 伊藤久央: "Asymmetric Diels-Alder Reaction of 2-Fluoroacrylic Acid Derivatives. Part 1." Tetrahedron Asymmotry. 9・11. 1979-1987 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 伊藤久央: "Asymmetric Diels-Alder Reaction of 2-Fluoroacrylic Acid Derivatives. Part 2." Tetrahodron Asymmetry. 9・11. 1989-1994 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 伊藤久央: "Enantioselective Claisen Rearrangoment of Difluorovimyl Allyl Ethers" J, Chem. Soc., Chem, Commun.2441-2442 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 岡田みどり: "Fluoro-lactonization of 4-Alkenoic Acid Derivatives with N-Fluoropentachloropyridinium Triflate" J.Fluorine Chem.82・2. 157-161 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 田口武夫: "Preparation of Methylene-gem-difluorocyclopropanes and Its Reactivity as Michael Acceptor" Tetrahedron. 53・28. 9497-9508 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 伊藤久央: "Enantioselective Aromatc Claisen Rearrangement" Tetrahedron Lett.38・27. 4815-4818 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 渋谷彰: "Generation and Reactions of Difluorocyclopropyl Anion" Tetrahedron Lett.38・31. 5537-5540 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 藤田征夫: "Regiocontrolled Iodoaminocyclization Reaction of an Ambident Nucleophile Mediated by Basic Metallic Reagent" J.Org.Chem.62・21. 7330-7335 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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