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Synthesis of viridiofungins and zaragozic acids, cholesterol synthesis inhibitors

Research Project

Project/Area Number 09470487
Research Category

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

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical pharmacy
Research InstitutionNagasaki University

Principal Investigator

HATAKEYAMA Susumi  Nagasaki University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (20143000)

Project Period (FY) 1997 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1997: ¥3,600,000 (Direct Cost: ¥3,600,000)
Keywordsviridiofungin / zaragozic acid / sphingo lipid synthesis inhibition / antibacterial activity / squalene synthase inhibition / asymmetric synthesis / dialkenylcarbinol / dihydroxylation / ビリジオフンジン天然物 / ビリジオフンジンAエステル / キラル合成 / 絶対構造の決定
Research Abstract

Both viridiofungins and zaragogic acids have attracted much attention as leading compounds for developing an effective cholesterol lowering drug because of their potent squalene synthase inhibitory activity. In this research, we aimed to develop efficient methods for the syntheses of these families of compounds.
Viridiofungin A was isolated from a strain of Trichoderma viride Pers.(Fungi, Hyphomycetes) together with viridiofundin B and C.These viridiofungins have unique structures consisting of a common citric acid moiety having C-16 long chain and an aromatic amino acid residue such as tyrosine, phenylalanine, and tryptophane. However, the absolute structures of these compounds were not determined. In this research, we achieved the first synthesis of viridiofungin A trimethyl ester which allowed us to determine its absolute configuration to be 3S, 4S, 2'S.
For zaragozic acids, we envisaged a new strategy which relies on unprecedented double dihydroxylation of dialkenylcarbinols. We first examined double hydroxylation of various dialkenylcarbinols to check the diastereoselectivity. As a result, we found that this reaction took place with moderate to excellent diastereoselectivity and the major diastereoisomer possessed desirable configuration for the synthesis of zaragozic acids. Now we are carrying out the synthesis of zaragozic acid A based on the above-mentioned strategy.

Report

(5 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] 江角朋之: "Synthesis of Viridiofungin A Trimethyl Ester and Determination of the Absolute Structure of Viridiofungin A"Tetrahedron Letters. 39. 877-880 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tomoyuki Esumi: "Synthesis of viridiofungin A Trimetyl Ester and Determination of the Absolute Structure of Viridiofungin A"Tetrahedron Letters. 39. 877-880 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 江角朋之: "Synthesis of Viridiofungin A Trimethyl Ester and Determination of the Absolute Structure of Viridiofungin A" Tetrahedron Letters. 39. 877-880 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 江角朋之: "Synthesis of Viridiofungin A Trimethyl Ester and Detetmination of the Absolute Structure of Viridiofungin A" Tetrahedron Letters. 39(印刷中). (1998)

    • Related Report
      1997 Annual Research Report

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

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