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Development of new synthetic methods for organofluorine compounds of biomedical interest

Research Project

Project/Area Number 13672231
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, Lecturer, 生命科学部, 講師 (70287457)
KITAGAWA Osamu  Tokyo University of Pharmacy and Life Science, School of Pharmacy, Lecturer, 薬学部, 講師 (30214787)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsFluorinated olefins / Dipeptide isostere / carbocyclization / Cyclopropane derivative / Radical cycloaddition / Homoally radical / アミノ酪酸 / シクロペンタン誘導体 / ピロリジン誘導体
Research Abstract

As our continuous studies on development of new synthetic methods for organofluorine compounds directed to the synthesis of fluoro analogs of biomedically interesting compounds, we have focused to develop efficient methods for stereoselective construction of fluorinated olefins, carbocyclic compounds and cyclopropane carboxylic acid derivatives during these three years with the financial support in part from the Ministry of Education, Science, Sports and Culture. Our achievements in fluorine chemistry are summarized as follows. (1)Stereoselective construction of (Z)-fluoroolefin derivatives having an appropriate functional groups and substituents, which can be applied as dipeptide isosteres can be established. (2)We have developed carbocyclization reaction of terminally difluorinated alkenyl active methine compounds leading to fluorinated functionalized five membered carbocylic compounds. (3)A two step stereoselective synthesis of fluorocyclopropane carboxylic acid derivatives was successfully established. Moreover, development of highly efficient synthetic methods for nonfluorinated organic compounds, which, due to their generality, could be applied to the preparation of fluorinated compounds in the future is also involved in our research project. These are radical [3+2] cycloaddition reactions of homoallyl active methine radical species and azahomoallyl radical species with various alkenes leading to the coresponding cyclic compounds, and zirconium mediated olefin-carbonyl coupling reaction of N-alkenylcarbamate derivatives for the preparation of amino acids and nitrogen containing heterocyclic compounds.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] 田口 武夫: "Carbocyclization reactions of terminally difluorinated alkenyl active methine compounds mediated by SnCl_4 and amine"J.Fluorine Chem.. 123. 75-80 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 田口 武夫: "Iodine Atom Transfer [3+2] Cycloaddition Reaction with Electron-Rich Alkenes Using N-Tosyliodoaziridine Derivatives as Novel Azahomoallyl Radical Precursors"J.Org.Chem.. 68. 3184-3189 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 田口 武夫: "Synthesis of Optically Active Atropisomeric Anilide Derivatives through Diastereoselective W-Allylation with Chiral Pd-π-Allyl Catalyst"J.Org.Chem.. 68. 9851-9853 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 田口 武夫: "Construction or nitrogen-heterocyclic comopunds through zirconium mediated intramolecular alkene-carbonyl coupling reaction of N-(ο-alkenylaryl)carbamate derivatives"Tetrahedron. 60. 1385-1392 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakamura, Y., Okada, M., Horikawa, H., Taguchi, T.: "Preparation of γ-fluorinated homoallylic alcohol derivatives via regioselective hydride reduction of allylic alcohol dervaives."J.Fluorine Chem.. 117. 143-148 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okada, M., Nakamura, Y., Saito, A., Sato, A., Horikawa, H., Taguchi, T.: "Synthesis of α-Alkylated (Z)-γ-Fluoro-β,γ-enoates through Organocopper Mediated Reaction of γ,γ-Difluoro-α,β-enoates : A Different Reactivity of R_3Al-Cu(I) and Me_2CuLi."Chem.Lett.. 28-29 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okada, M., Nakamura, Y., Saito, A., Sato, A., Horikawa, H., Taguchi, T.: "Stereoselective construction of functionalized (Z)-fluoroalkenes directed to depsipeptide isosteres."Tetrahedron Lett.. 43. 5845-5847 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Saito, A., Okada, M., Nakamura, Y., Kitagawa, O., Horikawa, H., Taguchi, T.: "Carbocyclization reactions of terminally difluorinated alkenyl active methine compounds mediated by SnCl_4 and amine."J.Fluorine Chem.. 123. 75-80 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Saito, A., Ito, H., Taguchi, T.: "A stereoselective preparation of 1-fluorocyclopropane-1-carboxylate derivatives through radical addition of fluoroiodoacetate to alkenes followed by intramolecular substitution reaction."Tetrahedron. 57. 7487-7493 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kitagawa, O., Fujiwara, H., Taguchi, T.: "Radical [3+2]-cycloaddition reaction with alkenes using dimethyl 2-(iodomethyl)-cyclopropane-1,1-dicarboxylate as a new homoallyl radical precursor."Tetrahedron. 42. 2165-2167 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kitagawa, O., Yamada, Y., Fujiwara, H., Taguchi, T.: "Radical Cascade Reaction with 1,4-Dienes and 1,4-Enynes Using 2-(lodomethyl)cyclopropane-1,1-dicarboxylate as a Homoallyl Radical Precursor : One-Step Synthesis of Bicyclo[3.3.0]octane Derivatives."J.Org.Chem.. 67. 933-927 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kitagawa O., Yamada, Y., Sugawara, A., Taguchi, T.: "Radical Cascade Reaction with 1,4-Dienes and 1,4-Enynes Using 2-(lodomethyl)cyclopropane-1,1-dicarboxylate as a Homoallyl Radical Precursor : One-Step Synthesis of Bicyclo[3.3.0]octane Derivatives."Org.Lett.. 4. 1011-1013 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kitagawa, O., Yamada, Y., Fujiwara, H., Taguchi, T.: "Iodoaziridine Derivatives as Novel Azahomoally Radical Precursors for [3+2] Cycloaddition Reactions with Alkenes."Angew.Chem.Int.Ed.. 40. 3865-3867 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kitagawa, O., Miyaji, S., Yamada, Y., Fujiwara, H., Taguchi, T.: "Iodine Atom Transfer [3+2] Cycloaddition Reaction with Electron-rich Alkenes using N-Tosyl lodoaziridine Derivatives as Novel Azahomoallyl Radical Precursors."J.Org.Chem.. 68. 3184-3189 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ito, H., Omodera, K., Takigawa, Y., Taguchi, T.: "Zirconium-Mediated Intramolecular Ester Transfer Reaction : Synthesis of α-Substituted γ-Aminobutyric Acid (GABA) Derivatives."Org.Lett.. 4. 1499-1501 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takigawa, Y., Ito, H., Omodera, K., Ito, M., Taguchi, T.: "Construction of Nitrogen-heterocyclic Compounds through Zirconium Mediated Intramolecular Alkene-Carbonyl Coupling Reaction of N-(2-alkenylaryl)carbamate Derivatives."Tetrahedron. 60. 1385-1392 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Saito, A., Ito, H., Taguchi, T.: "Intramolecular Diels-Alder Reactions of Ester-Tethered 1,7,9-Decatrienoates : Bis[chloro-(methyl)aluminum]trifluoromethanesulfonamide as a Catalyst."Org.Lett.. 4. 4619-4621 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 田口 武夫: "Carbocyclization reactions of terminally difluorinated alkenyl active methine compounds mediated by SnCl4 and amine"J.Fluorine Chem.. 123. 75-80 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 田口 武夫: "Iodine Atom Transfer [3+2] Cycloaddition Reaction with Electron-Rich Alkenes Using N-Tosyliodoaziridine Derivatives as Novel Azahomoallyl Radical Precursors"J.Org.Chem.. 68. 3184-3189 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 田口 武夫: "Synthesis of Optically Active Atropisomeric Anilide Derivatives through Diastereoselective N-Allylation with Chiral Pd-π-Allyl Catalyst"J.Org.Chem.. 68. 9851-9853 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 田口 武夫: "Construction of nitrogen-heterocyclic compounds through zirconium mediated intramolecular alkene-carbonyl coupling reaction of N-(o-alkenylaryl) carbamate derivatives"Tetrahedron. 60. 1385-1392 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 中村裕子: "Preparation of δ-fluorinated homoallylic alcohol derivatives via regioselective hydride reduction of allylic alcohol derivatives"J. Fluorine Chem.. 117. 143-148 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 岡田みどり: "Stereoselective construction of functionalized (Z)-fluoroalkenes directed to depsipeptide isosteres"Tetrahedron Lett.. 43. 5845-5847 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 伊藤久央: "Zirconium-Mediated Intramolecular Ester Transfer Reaction : Synthesis of α-Substituted γ-Aminobutyric Acid (GABA) Derivatives"Org. Lett.. 4. 1499-1501 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 斉藤亜紀夫: "Intramolecular Diels-Alder Reactions of Ester-Tethered 1,7,9-Decatrienoates : Bis[chloro(methyl)aluminum]trifluoromethanesufonamide as a Catalyst"Org. Lett.. 4. 4619-4621 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 北川 理: "Radical Cascade Reaction with 1,4-Dienes and 1,4-Enynes Using 2-(iodomethyl)cyclopropane-1,1-dicarboxylate as a Homoallyl radical precursor : One-step Synthesis bicyclo[3.3.0]octane Derivatives"Org. Lett.. 4. 1011-1031 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 北川 理: "Radical [3+2]cycloaddition reaction with alkenes using dimethyl 2-(iodomethyl)cyclopropane-1,1-dicarboxylate as a new homoallyl radical precursor"Tetrahedron Lett.. 42. 2165-2167 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 斉藤亜紀夫: "A stereoselective preparation of 1-fluorocyclopripane-1-carboxylate derivatives through radical addition of fluoroiodoacetated followed by intramolecular subustition reaction"Tetrahedron. 57. 7487-7493 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 北川 理: "Iodoaziridine Derivatives as Novel Azahomoallyl Radical Precursors for [3+2]Cycloaddition Reactions with Alkenes"Angew. Chem. Int. Ed.. 40. 3865-3867 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 岡田みどり: "Synthesis of α-alkylated (Z)-γ-fluoro-b,g-enoates through organocopper mediated reaction of γ,γ-difluoro-α,β-enoates"Chem. Lett.. (1). 28-29 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 北川 理: "Radical [3+2]cycloaddition reaction with various alkenes using iodomethyl cyclopropane derivatives as new homoallyl radical precursors"J. Org. Chem.. 67. 922-927 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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