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2002 Fiscal Year Final Research Report Summary

Development of Tandem Cyclization Reactions Catalyzed by Cu(II) Salts and Its Applications toward Biologically Active Compounds

Research Project

Project/Area Number 13672206
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

KOU Hiroya  Tohoku University, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院・薬学研究科, 助教授 (70192721)

Project Period (FY) 2001 – 2002
KeywordsIndole Derivatives / Lewis Acid / Cu(II) Salts / Biologically Active Compounds / Cyclization Reactions / Hippadine / Duocarmycin SA / Arborescidine A
Research Abstract

At first, the relationships between the substrate(s) structure and the copper(II) catalyst(s) were studied with the aim of developing general methods for indole syntheses. As a result, it was shown that this reaction could be applied to the any substrates on the acetylene terminal, even if that had an electron withdrawing nature and the any functional groups did not affect for the reactions. Three Kinds of copper salts, namely, Cu(OTf)_2, Cu(OAc)_2, and Cu(OCHO)_2・xH_2O were found to be excellent catalysts for sulfonamide substrates. However, good catalysts had not been found for the substrates having carbamate functional group, yet. On the other hand, copper(II) catalyzed cyclization reaction could be also applied toward unsubstituted aniline derivatives. For this compounds, Cu(OCOCF_3)_2・xH_2O was a best catalyst and it was found that this salt could catalyze the cyclization reaction for wide variety substrates. During the investigation described above, it was also clarified that the nature of the bond between copper atom and oxygen atom was important for the catalytic activities, e.g. Cu(OTs)_2 and Cu(OMs)_2, those Cu-O bond is somewhat covalent bond nature did not have any catalytic activities toward any substrates, whereas Cu(OTf)_2, which seems to be an ionic salt was a good catalyst.
Next, tandem cyclization reactions were investigated. The tandem cyclization reactions could be realized by treating the substrates, which have the leaving group in the same molecules, first with KH, then heated with copper(II) salt.
Finally, these reactions were applied to the syntheses of biologically active compounds. The formal synthesis of hippadine and duocarmycin SA were succeeded by using the indole synthesis as key steps. Asymmetric synthesis of arborescidine A is in progress.

  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] Kou Hiroya: "Efficient Construction of Indole Rings from 2-Ethynylaniline Derivatives Catalyzed by Copper(II) Salts and Its Application to the Tandem Cyclization Reactions"Tetrahedron Letters. 43・7. 1227-1280 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kou Hiroya: "Synthesis of Betulin Derivatives and Their Protective Effects against the Cytotoxicity of Cadmium"Bioorganic & Medicinal Chemistry. 10・10. 3229-3236 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kou Hiroya: "Cyclization reaction of 2-alkynylbenzyl alcohol and 2-alkynylbenzylamine derivatives promoted by tetrabutylammonium fluoride"Tetrahedron. 57・48. 9697-9710 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kou Hiroya: "Efficient Construction of Indole Rings from 2-EthynyIaniline Derivatives Catalyzed by Copper(II) Salts and Its Application to the Tandem Cyclization Reactions"Tetrahedron Letters. 43-7. 1227-1280 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kou Hiroya: "Synthesis of Betulin Derivatives and Their Protective Effects against the Cytotoxicity of Cadmium"Bioorganic & Medicinal Chemistry. 10-10. 3229-3236 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kou Hiroya: "Cyclization reaction of 2-alkynyIbenzyl alcohol and 2-alkynylbenzylamine derivatives promoted by tetrabutylammonium fluoride"Tetrahedron. 57-48. 9697-9710 (2001)

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

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Published: 2004-04-14  

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