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Green chemistry oriented synthesis of biologically active natural products and structure-activity relationships

Research Project

Project/Area Number 17590014
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 Sciences

Principal Investigator

AOYAGI Yutaka  Tokyo University of Pharmacy & Life Sciences, School of Pharmacy, Lecturer, 薬学部, 講師 (70212389)

Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2005: ¥2,800,000 (Direct Cost: ¥2,800,000)
KeywordsGreen chemistry / biologically active natural products / diterpene / cytotoxicity / structure-activity relationship / 生理活性 / NF-κB / リパーゼTL / マイクロウェーブ / 環状ヘキサデプシペプチドGE3 / grandione / ent-kaurene / triptolide
Research Abstract

The results in this project aimed at 'Green Chemistry' are as follows :
1. To discover new biologically active natural products, we explored chemical constituents from higher plants (Labiatae, Coriaceae, Rubiaceae, and Podocarpaceae) using HPLC attached with reversed phase column and aqueous solvent systems. As a results, Some new sesqui-and diterpenes were isolated.
2. Some cytotoxic analogues were synthesized from natural products, isolated from Rabdosia excisa, Perovskia abrotanoides, Coriaria japonica, Tricalysia dubia, and Tripterygium wilfordii. The structure-activity relationships (SAR) between the structures of ent-kaurene type, isetexane type, and abietane type natural products and their semisynthetic analogues and cytotoxic activity were discussed. The microwave oven was used for preparation of semisynthetic analogues aimed at 'Green Chemistry'.
3. The kinetic resolution of secondary alcohols with lipase TL were carried out to produce optically pure secondary alcohols. One of the secondary alcohols was converted to piperazic acids in semi-large scale. Now we are trying to synthesize a natural hexadepsipeptide GE3, which includes both enatiomers of piperazic acids.
4. The facile palladium-catalyzed synthesis of pyrroles and indoles, which are important medicinal molecule skeletons, was developed.
5. The nonproteogenic amino acids were synthesized from Garner aldehydes as a chiral pool.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (25 results)

All 2007 2006 2005

All Journal Article (25 results)

  • [Journal Article] Three New Diterpenoids, Tricalysiolide H and Tricalysiones A and B, from Tricalysia dubia2007

    • Author(s)
      Koichi Nishimura
    • Journal Title

      Tetrahedron 63

      Pages: 4558-4562

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Tricalysiolide A-F, New Rearranged ent-Kaurene Diterpenes from Tricalysia dubia2006

    • Author(s)
      Koichi Nishimura
    • Journal Title

      Tetrahedron 62

      Pages: 1512-1519

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Semisynthesis of C-ring Modified Triptolide Analogues and their Cytotoxic Activities2006

    • Author(s)
      Yutaka Aoyagi
    • Journal Title

      Bioorganic Medicinal Chemistry Letters 16

      Pages: 1947-1949

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cytotoxicity of Abietane Diterpenoids from Perovskia abrotanoides and of their Semisynthetic Analogues2006

    • Author(s)
      Yutaka Aoyagi
    • Journal Title

      Bioorganic Medicinal Chemistry 14

      Pages: 5285-5291

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Semisynthesis of 1-O-Monoacyl or 12-O-monoacyl, 1,12-O-Diacyl, and 11,12-Dehydrated Excisanin A 7,14-Acetonides and their Cytotoxic Activity2006

    • Author(s)
      Yutaka Aoyagi
    • Journal Title

      Bioorganic Medicinal Chemistry 14

      Pages: 5802-5811

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Efficient Synthesis of Pyrroles and 4,5,6,7-Tetrahydroindoles via Palladium-Catalyzed Oxidation of Hydroxy-enamines2006

    • Author(s)
      Yutaka Aoyagi
    • Journal Title

      Tetrahedron 62

      Pages: 8533-8538

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Semisynthesis of Isetexane Diterpenoid Analogues and their Cytotoxic Activity2006

    • Author(s)
      Yutaka Aoyagi
    • Journal Title

      Chemical Pharmaceutical Bulletin 54

      Pages: 1602-1604

    • NAID

      110004836485

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Semisynthesis of 1-O-Monoacyl or 12-0-monoacyl, 1,12-O-Diacyl, and 11, 12-Dehydrated Excisanin A 7,14-Acetonides and their Cytotoxic Activity2006

    • Author(s)
      Yutaka Aoyagi
    • Journal Title

      Bioorganic Medicinal Chemistry 14

      Pages: 5802-5811

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Efficient Synthesis of Pyrroles and 4,5,6,7-Tetrahydro- indoles via Palladium-Catalyzed Oxidation of Hydroxy-examines2006

    • Author(s)
      Yutaka Aoyagi
    • Journal Title

      Tetrahedron 62

      Pages: 8533-8538

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Semisynthesis of Isetexane Diterpenoid Analogues and their Cytotoxic Activity2006

    • Author(s)
      Yutaka Aoyagi
    • Journal Title

      Chemical & Pharmaceutical Bulletin 54

      Pages: 1602-1604

    • NAID

      110004836485

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cytotoxicity of abietane diterpenoids from Perovskia abrotanoides and of their semisynthesis analogues2006

    • Author(s)
      Yutaka Aoyagi et al.
    • Journal Title

      Bioorganic & Medicinal Chemistry 14・15

      Pages: 5285-5291

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Synthesis of 1-0-monoacyl or 12-0-monoacyl, 1-,12-0-diacyl- and 11,12-dehydrated excisanin A 7,14-acetonides and their cytotoxic activity2006

    • Author(s)
      Yutaka Aoyagi et al.
    • Journal Title

      Bioorganic & Medicinal Chemistry 14・15

      Pages: 5802-5811

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effecient synthesis of pyrroles and 4,5,6,7-tetrahydroindoles via palladium-catalyzed oxidation of hydroxyl-enamines2006

    • Author(s)
      Yutaka Aoyagi et al.
    • Journal Title

      Tetrahedron 62・36

      Pages: 8533-8538

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Semisynthesis of icetexane diterpenoid analogues and their cytotoxic activity2006

    • Author(s)
      Yutaka Aoyagi et al.
    • Journal Title

      Chemical & Pharmaceutical Bulletin 54・11

      Pages: 1602-1604

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Tricalysiolide A-F, new rearranged ent-kaurene diterpenoids, from Tricalysia dubia2006

    • Author(s)
      Koichi Nishimura et al.
    • Journal Title

      Tetrahedron 62

      Pages: 1512-1519

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Semisynthesis and SAR study of C-ring modified cytotoxic triptolide analogues2006

    • Author(s)
      Yutaka Aoyagi et al.
    • Journal Title

      Bioorg.Med.Chem.Lett. 16

      Pages: 1947-1949

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Biomimetic Synthesis of Grandione from Demethylsalvicanol via Hetero-Diels-Alder Type Dimerization and Sructure Dvision of Grandione2005

    • Author(s)
      Yutaka Aoyagi
    • Journal Title

      Tetrahedron Letters 46

      Pages: 7885-7887

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The Isolation and Structure Elucidation of a New Sesquiterpene Lactone from the Poisonous Plant Coriaria japonica (Coriariaceae)2005

    • Author(s)
      Takeshi Kinoshita
    • Journal Title

      Chemical Pharmaceutical Bulletin 53

      Pages: 1040-1042

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Asymmetric Synthesis of (2R, 3R, 4R)-3-Hydroxy-4-methylproline via Chromium(II) Chloride-Mediated Coupling Reactions of (S)-Garner Aldehyde with Crotyl Bromide2005

    • Author(s)
      Haruko Inaba
    • Journal Title

      Heterocycles 65

      Pages: 2657-2665

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Biomimetic Synthesis of Grandione from De-methylsalvicanol via Hetero-Diels-Alder Type Dimerization and Structure Division of Grandione2005

    • Author(s)
      Yutaka Aoyagi
    • Journal Title

      Tetrahedron Letters 46

      Pages: 7885-7887

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The Isolation and Structure Elucidation of a New Sesquiterpene Lactone from the coriaria japonica (Coriariaceae)2005

    • Author(s)
      Takeshi Kinoshita
    • Journal Title

      Chemical Pharmaceutical Bulletin 53

      Pages: 1040-1042

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Asymmetric Synthesis of (2R, 3R, 4R)-3-Hydroxy- 4-methylproline via Chromium (II) Chloride-Mediated Coupling Reactions of (S)-Garner Aldehyde with Crotyl Bromide2005

    • Author(s)
      Haruko Inaba
    • Journal Title

      Heterocycles 65

      Pages: 2657-2665

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The isolation and structure elucidation of a new sesquiterpene lactone from a poisonous plant Coriaria japonica (Coriariaceae)2005

    • Author(s)
      Takeshi Kinoshita et al.
    • Journal Title

      Chem.Pharm.Bull. 53

      Pages: 1040-1042

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Asymmetric synthesis of (2R,3R,4R)-3-hydroxy-4-methylproline via chromium(II) chloride-mediated coupling reactions of (S)-Garner aldehyde with crotyl bromide2005

    • Author(s)
      Haruko Inaba et al.
    • Journal Title

      Heterocycles 65

      Pages: 2657-2665

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Biomimetic synthesis of grandione from demethylsalvicanol via hetero Diels-Alder type dimerization and structural revision of grandione2005

    • Author(s)
      Yutaka Aoyagi et al.
    • Journal Title

      Tetrahedron Lett. 46

      Pages: 7885-7887

    • Related Report
      2005 Annual Research Report

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

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