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1990 Fiscal Year Final Research Report Summary

Synthetic Studies on Forskolin and Its Related Compounds

Research Project

Project/Area Number 01571164
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Chemical pharmacy
Research InstitutionTeikyo University

Principal Investigator

HASHIMOTO Shun-ichi  Teikyo University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (80107391)

Co-Investigator(Kenkyū-buntansha) YANAGIYA Yuki  Teikyo University, Faculty of Pharmaceutical Sciences, Research Associate, 薬学部, 助手 (10200544)
Project Period (FY) 1989 – 1990
KeywordsForskolin / Adenylate Cyclase / Structure-activity Relatioship / Total Synthesis / Labane diterpene / Butenolide / Intramolecular Diels-Alder Reaction
Research Abstract

The labane diterpene forskolin, isolated from the roots of the Indian herb Coleus forskolii, has been shown to be hypotensive agent with spasmolytic, cardiotonic, and platelet aggregation inhibitory activity, and also demonstrated to be a unique and potent stimulator of the enzyme adenylate cyclase in various tissues. Owing to its therapeutic potential for glaucoma, congestive heart failure and bronchial asthma coupled with a substantial structural challenge, forskolin has elicited considerable synthetic attention. There have been synthesized more than 100 analogues from forskolin and its congeners, and through structure-activity relationships of them the region involving 1alpha-OH, 9alpha-OH, and 11-carbonyl has been suggested to be responsible for the above biological activities. We embarked upon an investigation directed towards the total synthesis of forskolin and its analogues otherwise difficult to prepare from natural forskolin with an aim to gain more information of structure-a … More citivity relationships and to differentiate a variety of activities forskolin exhibits. The activitiy of (<plus-minus>)-forskolin obtained by our total synthesis for adenylate cyclase in rat cerebral cortical membranes was half as potent as of natural forskolin, while (<plus-minus>)-1, 6, 7-trideoxyforskolin was totally inactive as we expected. Our attention was focused on the activity of (<plus-minus>)-6, 7-dideoxyforskolin, since it was not determined whether the presence of 6beta-OH and 7beta-OH is important or not for the activity. The result obtained with the synthesized molecule showed total inactivity, and so the presence of 6betaーOH and/or 7betaーOH was proposed to be crucial for the activity. With the above results in hand, we then directed our efforts to the total synthesis of (-)-forskol in natural form and the synthesis of its derivatives from the homochiral,versatile tricyclic lactone intermediate constructed by salient intramolecular DielsーAlder reaction of the butenolide. We have now found that the homochiral lactone with four asymmetric centers was efficiently constructe starting with the (S)-propargyl alcohol obtainable through (S)-BINAL-H reduction of the corresponding acetylenic ketone and successive recrystallization. The project on this line is goi Less

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] 橋本 俊一: "A Stereocontrolled Synthesis of(±)ー1,6,7ーTrideoxyforskolin" J.Chem.Soc.,Chem.Commun.24-25 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 橋本 俊一: "A Total Synthesis of(±)ーForskolin" J.Am.Chem.Soc.110. 3670-3672 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 橋本 俊一: "A Rapid and Efficient Synthesis of 1,2ーtransーβーLinked Glycosides via Benzyl or BenzoylーProtected Glycopyranosyl Pyosphates" J.Chem.Soc.,Chem.Commun.685-687 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 橋本 俊一: "A Mild and Rapid 1,2ーTransーGlycosidation Method via BenzoylーProtected Glycopyranosyl P,PーDiphenylーNー(pーToluenesulfonyl)phosphinimidates" Heterocycles. 30. 775-778 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 橋本 俊一: "An Extremely Mild and General Method for the Stereocontrolled Construction of 1,2ーCisーGlycosidic Linkages via SーGlycopyranosy Phosphorodiamidimidothioates" Tetrahedron Letters. 31. 4769-4772 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 橋本 俊一: "A Stereocontrolled Synthesis of(±)ー6,7ーDideoxyforskolin"

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shun-ichi Hashimoto: "A Stereocontrolled Synthesis of (<plus-minus>)-1, 6, 7-Trideoxyforskol " J. Chem. Soc., Chem. Commun. 24-25 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shun-ichi Hashimoto: "A Total Synthesis of (<plus-minus>)-Forskol " J. Am. Chem. Soc. 110. 3670-3672 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shun-ichi Hashimoto: "A Rapid and Efficient Synthesis of 1, 2-trans-beta-Linked Glycosides via Benzyl or Benzoyl-Protected Glycopyranosyl Phosphates" J. Chem. Soc., Chem. Commun. 685-687 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shun-ichi Hashimoto: "A Mild and Rapid 1, 2-Trans-Glycosidation Method via Benzoyl-Protected Glycopyranosyl P, P-Diphenyl-N-(p-Toluenesulfonyl) phosphinimidates" Heterocycles. 30. 775-778 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shunーichi Hashimoto: "An Extremely Mild and General Method for the Stereocontrolled Construction of 1, 2-Cis-Glycosidic Linkages via S-Glycopyranosyl Phosphorodiamidimidothioates" Tetrahedron Letters. 31. 4769-4772 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shun-ichi Hashimoto: "A Stereocontrolled Synthesis of (<plus-minus>)-6, 7-Dideoxyforskol "

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

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Published: 1993-08-12  

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