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2005 Fiscal Year Final Research Report Summary

Development of novel protein phosphatase inhibitors based on fostriecin

Research Project

Project/Area Number 16590083
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Drug development chemistry
Research InstitutionOsaka University

Principal Investigator

MIYASHITA Kazuyuki  Osaka University, Graduate School of Pharmaceutical Sciences, Associate Professor, 薬学研究科, 助教授 (10166168)

Co-Investigator(Kenkyū-buntansha) IMANISHI Takeshi  Osaka University, Graduate School of Pharmaceutical Sciences, Professor, 薬学研究科, 教授 (40028866)
Project Period (FY) 2004 – 2005
KeywordsFostriecin / Leustroducsin / Protein phosphatase / Total synthesis / Structure-activity relationship
Research Abstract

We have already succeeded to synthesize an antitumor antibiotic, fostriecin, stereoselectively. A characteristic feature of our synthesis is highly convergent, in which fostriecin was separated into three segments A (an unsaturated lactone moiety), B (a polyalcohol moiety containing a series of stereogenic centers) and C (a triene moiety). Because of the characteristic feature, this synthetic strategy is highly versatile and would be applicable to synthesize not only fostriecin but also other fostriecin family natural products and various unnatural analogues. Applying our synthesis, we planned to synthesize leustroducsin B which shows protein phosphatase 2A specific inhibitory activity, like fostriecin, and some analogues such as a hybrid of fostriecin and leustroducsin, and also planned to study a structure-activity relationship of protein phosphatase inhibition.
Regarding the total synthesis of leustroducsin B, we have successfully synthesized a key intermediate having a carbon skeleton of leustroducsin B. Some analogues focusing on the triene moiety of fostriecin and on the aminoethyl substituent of leustroducsin B were also synthesized stereoselectively, and employed to study structure-activity relationship of protein phosphatase inhibition. As a consequence, it was found that the aminoethyl moiety of leustroducsin was not in relation with the activity, but the triene moiety was suggested to play a significant role in specific inhibition against protein phosphatase 2A.

  • Research Products

    (4 results)

All 2004

All Journal Article (4 results)

  • [Journal Article] A novel and efficient method for inside selective esterification of terminal vic-diols2004

    • Author(s)
      M.Ikejiri
    • Journal Title

      Tetrahedron Lett. 45・6

      Pages: 1243-1246

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] サイトカイン誘導活性天然物Leustroducsin Bの全合成研究2004

    • Author(s)
      宮下 和之
    • Journal Title

      第30回反応と合成の進歩シンポジウム講演要旨集

      Pages: 254-255

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A novel and efficient method for inside selective esterification of terminal vic-diols2004

    • Author(s)
      M.Ikejiri, K.Miyashita, T.Tsunemi, T.Imanishi
    • Journal Title

      Tetrahedron Lett. 45(6)

      Pages: 1243-1246

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Synthetic study on leustroducsin B having a cytokine induction activity2004

    • Author(s)
      K.Miyashita, T.Tsunemi, M.Ikejiri, T.Imanishi
    • Journal Title

      30th Symposium on Progress in Organic Reactions and Syntheses-Application in the Life Sciences-

      Pages: 254-255

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2007-12-13  

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