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Development of practical methods for the synthesis of taxane diterpenoids

Research Project

Project/Area Number 09555286
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Synthetic chemistry
Research InstitutionOkayama University

Principal Investigator

SAITO Seiki  Okayama University, Faculty of Engineering, Professor, 工学部, 教授 (60033239)

Co-Investigator(Kenkyū-buntansha) ISHIKAWA Teruhiko  Okayama University, Faculty of Engineering, Instructor, 工学部, 助手 (10263617)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1998: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥9,000,000 (Direct Cost: ¥9,000,000)
KeywordsTaxol / cyclohexane-1,3-dione / consecutive Michael-Claisen reaction / ビナコール環化 / タキソ-ル / 8員環合成 / 分子内[3+2]環化付加反応
Research Abstract

We have revisited the traditional consecutive Michael-Claisen [3 + 3] process (MC-[3+3]) promising for the synthesis of a cyclohexane-1, 3-dione derivatives from non-activated simple ketones and enoates, and evaluated its potential in modern organic synthesis. The reaction conditions employing the ketones (1.2 equiv), enoate (1.0 equiv), and t-BuOK (1.2 equiv) in THF as a solvent at temperature range of 0℃ to 40℃ have been established. Twenty to thirty examples were demonstrated to be effective under such conditions including the synthesis of a taxol A, C-ring synthons available in multi-gram quantities. The reactions exhibited remarkable regioselectivity that the Michael addition proceeded through nucleophilic attack by more hindered site of the ketones without exceptions, which, in turn, means that Claisen condensation resulted in the formation of carbon-carbon bonds between less hindered site of the ketones and acyl carbon of the enoates. In addition, taking advantages of the MC- [3+3] process, a few useful methods for the synthesis of six membered carbocyclic compounds have also been developed. A number of control experiments have been conducted to provide strong supporting information for the mechanism of this MC-[3+3] process.

Report

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

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Teruhiko Ishikawa, Keita Nagai, Mami Senzaki, Akiko Tatsukawa and Seiki Saito: "Hemiaminal Generated by Hydration of Ketone-based Nitrone as an N,O-Centered Nucleophile in Organic Synthesis"Tetrahedron. 54. 2433-2448 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Teruhiko Ishikawa, Shushiro Ikeda, Masataka Ibe and Seiki Saito: "Synthesis of A-Ring Fragments of 1α,25-Dihydroxyvitamin D, and Taxane Diterpenoids : Effective Construction of Conjugated Formylcyclohexene Framework from isoxazolines"Tetrahedron. 54. 5869-5882 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Teruhiko Ishikawa, Keita Nagai, Takayuki Kudoh and Seiki Saito: "Chiral Lewis Acid-Hydroxylamine Hybrid Reagent for Enantioselective Michael Addition Reaction Directed toward β-Amino Acids Synthesis"Synlett. 1291-1293 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 斎藤清機,石川彰彦: "隣接ジオール制御素子による不斉空間の構築とニトロン-オレフィン[3+2]環化付加反応の立体制御への応用"有機合成化学協会誌. 56. 86-95 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Teruhiko Ishikawa, Eiji Uedo, Siho Okada, Seiki Saito: "Pyrrolidine-Catalyzed Homo-Aldol Condensation Reactions of Aldehydes"Synlett. 450-452 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishikawa,T., Kudoh,T., Shigemori,K., Saito,S.: "Application of the Silicon-Tether Strategy for Controlling the Regioselectivity and Diastereoselectivity of Intramolecular Nitrone Cycloadditions for Aminopolyol Synthesis."J.Am.Chem.Soc.. 112. 7633-7637 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Teruhiko Ishikawa, Eiji Uedo, Rie Tani, Seiki Saito: "Aromatization of Enamines Promoted by a Stoichiometric Amount of Palladium (II) Salts : A Novel Method for the Synthesis of Aromatic Amines"J.Org.Chem.. 66. 186-191 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Teruhiko Ishikawa, Mami Senzaki, Ryuuichirou Kadoya, Takashi Morimoto, Naoki Miyake, Miyoko Izawa, and Seiki Saito: "Hydroxamate-tethered Intramolecular Diels-Alder Reactions Employing Hydroxamate Tethers The First Example and Promising prospects"J.Am.Chem.Soc.. (in press.). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Teruhiko Ishikawa, Kazuo Shimizu, Hirokazu Ishii, Shushiro Ikeda, and Seiki Saito: "Simultaneous Discrimination of Diastereotopic Group and Faces : The first Example in Intramolecular [3+2] and [2+2+1] Cycloaddition Reactions"J.Org.Chem.. (in press.). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Teruhiko Ishikawa, Masamitu Okano, Toshiaki Aikawa, and Seiki Saito: "Novel Carbon-Carbon Bond Forming Reactions Using Carbocations produced from Substituted Propargyl Silyl Ethers by the Action of TMSOTf"J.Org.Chem.. (in press.). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Teruhiko Ishikawa, Ryuichiro Kadoya, Massaki Arai, Haruka Takahashi, Yumi Kaisi, Tomohiro Mizuta, Kazusa Yoshikai and Seiki Saito: "Revisiting [3+3] Route to 1,3-Cyclohexanedione Frameworks : Missing Opportunity in Organic Synthesis for Sixty Years and Hidden Aspect of Thermodynamically Controlled Enolates"J.Org.Chem.. (submitted for publication.). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Teruhiko Ishikawa, Keita Nagai, Mami Senzaki, Akiko Tatsukawa and Seiki Saito: "Hemiaminal Generated by Hydration of Ketone-based Nitrone as an N, O-Centered Nucleophile in Organic Synthesis"Tetrahedron. 54. 2433-2448 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Teruhiko Ishikawa, Shushiro Ikeda, Masataka Ibe and Seiki Saito: "Synthesis of A-Ring Fragments of 1α, 25-Dihydroxyvitamin D_3 and Taxane Diterpenoids : Effective Construction of Conjugated Formylcyclohexene Framework from Isoxazolines"Tetrahedron. 54. 5869-5882 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Teruhido Ishikawa, Keita Nagai, Takayuki Kudoh and Seiki Saito: "Chiral Lewis Acid-Hydroxylamine Hybrid Reagent for Enantioselective Michael Addition Reaction Directed toward β-Amino Acids Synthesis"Synlett. 1291-1293 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Seiki Saito and Teruhiko Ishikawa: "Asymmetric Bias Generated by Protected Vicinal Diol Controller and Its application to Asymmetric Nitrone-Olefin Cyycloaddition Reactions"J.Syn.Org.Chem.Jpn.. 56. 86-95 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Teruhiko Ishikawa, Eiji Uedo, Siho Okada, Seiki Saito: "Pyrrolidine-Catalyzed Homo-Aldol Condensation Reactions of Aldehydes"Synlett. 450-452 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishikawa, T. ; Kudoh, T. ; Shigemori, K. ; Saito, S.: "Application of the Silicon-Tether Strategy for Controlling the Regioselectivity and Diastereoselectivity of Intramolecular Nitrone Cycloadditions for Aminopolyol Synthesis."J.Am.Chem.Soc.. 112. 7633-7637 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Teruhiko Ishikawa, Eiji Uedo, Rie Tani, Seiki Saito: "Aromatization of Enamines Promoted by a Stoichiometric Amount of Palladium (II) Salts : A Novel Method for the Synthesis of Aromatic Amines"J.Org.Chem.. 186-191 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Teruhiko Ishikawa, Mami Senzaki, Ryuuichirou Kadoya, Takashi Morimoto, Naoki Miyake, Miyoko Izawa, and Seiki Saito: "Hydorxamate-tethered Intramolecular Diels-Alder Reactions Employing Hydroxamate Tethers The First Example and Promising Prospects"J.Am.Chem.Soc.. (in press.). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Teruhiko Ishikawa, Kazuo Shimizu, Hirokazu Ishii, Shushiro Ikeda, and Seiki Saito: "Simultaneous Discrimination of Diastereotopic Groups and Faces : The first Example in Intramolecular [3+2] and [2+2+1] Cycloaddition Reactions"J.Org.Chem.. (in press.). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Teruhiko Ishikawa, Masamitu Okano, Toshiaki Aikawa, and Seiki Saito: "Novel Carbon-Carbon Bond Forming Reactions Using Carbocations Produced from Substituted Propargyl Silyl Ethers by the Action of TMSOTf"J.Org.Chem.. (in press.). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Teruhiko Ishikawa, Ryuichiro Kadoya, Masaki Arai, Haruka Takahashi, Yumi Kaisi, Tomohiro Mizuta, Kazusa Yoshikai and Seiki Saito: "Revisiting [3+3] Route to 1,3-Cyclohexanedione Frameworks : Missing Opportunity in Organic Synthesis for Sixty Years and Hidden Aspect of Thermodynamically Controlled Enolates"J.Org.Chem.. (submitted for publication.). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Teruhiko Ishikawa,Keita Nagai,Mami Senzaki,Akiko Tatsukawa,and Seiki Saito: "Hemiaminal Generated by Hydration of Ketone-Based Mitroneas an N.O-Centered Nucleophile in Organic Synthesis" Tetrahedron. 54. 2433-2448 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Teruhiko Ishikawa,Shushiro Ikeda,Masataka Ibe,and Seiki Saito: "Synthesis of A-Ring Fragments of 1α,25-Dihydroxyvitamin D_3 and Texane Diterpenoids:Effective Construction of Conjugated Formicyclohexene Framework from Isoxazolines" Tetrahedron. 54. 5869-5882 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 斎藤清機, 石川彰彦: "隣接ジオール制御素子による不斉空間の構築とニトロン-オレフィン[3+2]環化付加反応の立体制御への応用" 有機合成協会誌. 56・2. 16-25 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ishikawa,T;Nagai,K;Senzaki,M;Tatsukawa,A;Saito,S.: "Hemiaminal Generated by Hydration of Ketone-Based Nitrone as an N.O^Centered Nucleophile in Oroanic Synthesis" Tetrahedron. (in press). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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