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DEVELOPMENT OF ASYMMETRIC RADICAL REACTIONS AND APPLICATION TO THE SYNTHESIS OF BIO-ACTIVE COMPOUNDS

Research Project

Project/Area Number08672441
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical pharmacy
Research InstitutionCHIBA UNIVERSITY

Principal Investigator

NISHIDA Atsushi  CHIBA UNIVERSITY,FACULTY OF PHARMACEUTICAL SCIENCES,ASSOCIATE PROFESSOR, 薬学部, 助教授 (80130029)

Project Period (FY) 1996 – 1998
Project Status Completed(Fiscal Year 1998)
Budget Amount *help
¥2,300,000 (Direct Cost : ¥2,300,000)
Fiscal Year 1998 : ¥400,000 (Direct Cost : ¥400,000)
Fiscal Year 1997 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1996 : ¥1,100,000 (Direct Cost : ¥1,100,000)
KeywordsRadical Cyclization / Diastereoselectivity / Chiral Auxiliary / Lewis Acid / Alkoxy Radical / beta-Cleavage / Chiral Cyclopropane / Enantioselectivity / trans-2-アミノシクロヘキサノール / 2-シクロペンテニル酢酸 / アルキルスタニルエステル / スズラジカル / アセタール
Research Abstract

1. DIASTEREOSELECTIVE RADICAL CYCLIZATION
1) New chiral auxiliaries, trans-2-(N-benzenesulfonyl-N-benzylamino)cyclohexanol and its derivatives were developed and used for diastereoselective radical cyclization. When trans-2-(N- benzenesulfonyl-N-benzylamino)cyclohexyl 7-iodo-2,6-heptadienoate was reacted with nBu_3SnH in the presence of Et_3B and bulky Lewis acid, such as MAD, a diastereo mixture of (2- cyclopentenyl)acetate was obtained in 92% yield. After standard hydrolysis, (2-cyclopentenyl)acetic acid was obtained (53% ee) and the chiral auxiliary was recovered. Optically active (2- cyclopentenyl)acetic acid is a starting material for many biologically active compounds, such as coriolin, hirsutic acid C, and alepraic acid (a member of cyclopentenyl fatty acids).
Optically active (2-cyclohexenyl)acetic acid (38% ee) was also obtained using the same auxiliary.
2) Diastereoselective addition of tri-n-butyltin radical to chiral alpha, beta-unsaturated esters, having 8- phenylmenthyl grou … More p as a chiral auxiliary, was achieved in the presence of Lewis acid. Thus obtained beta-stannylester was converted to a chiral cyclopropane derivative.
3) Chiral hydroxythiols, which were prepared from (R)-(+)-pulegone, were converted to chiral acetals, When the chiral acetals were irradiated using UV lamp in the presence of benzophenone, carbon radicals were generated and cyclized to chiral cyclopentane derivatives. Although diastereoselectivity was low, the reaction is a new method for the synthesis of chiral 2-substituted cyclopentanones.
2. ENANTIOSELECTIVE RADICAL CYCLIZATION
When cyclohexyl 8-iodonona-2,8-dienoate was reacted with nBu_3SnH and Et_3B in the presence of chiral aluminum reagent, chiral (2-methylenecyclohexyl)acetate was obtained in 46% ee, This is the first example of enantioselective radical cyclization.
3. NEW RADICAL SKELETAL REARRANGEMENT VIA ALKOXY RADICAL
The radical reaction of epoxydecalin thiocarbonylimidazolide afforded rearranged bicyclic cyclooctanes. The reaction proceeded via ten-membered ring carbon radicals, which was generated by beta-cleavage of alkoxy radicals. This reaction is useful for some terpene synthesis having a cyclooctane ring. Less

Report

(4results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report

Research Products

(16results)

All Other

All Publications

  • [Publications] Mayumi Nishida: "Enantioselective Radical Cyclization Controlled by the Chiral Aluminum Reagent" The Journal of the Chemical Society, Chemical Communications. 579-580 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Atsushi Nishida: "Radical Cyclization Using a Thioacetal Group for Radical Generation" Tetrahedron. 52巻. 9713-9734 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mayumi Nishida: "Diastereoselective 1,4-Addition of Stannyl Radical in the Presence of Lewis Acid : A Novel Synthetic Route to Optically Active β-Stannyl Esters" The Journal of Organic Chemistry. 61巻. 3574-3575 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 西田 篤司: "新規ラジカル反応の開発-アルコキシラジカルを経る骨格変換反応及びルイス酸存在下における不斉ラジカル環化反応-" 有機合成化学協会誌. 54巻. 27-35 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Atsushi Nishida: "Skeletal Rearrangement via Alkoxy Radical : Conversion of Epoxydecalin Thiocarbonylimidazolide to Bicyclo 〔6.3.0〕 undecanone and Bicyclo 〔5.3.1〕 undecanone" Tetrahedron Letters. 38巻. 5519-5522 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Atsushi Nishida: "Development of New Radical Reactions : Skeletal Rearrangement via Alkoxy Radical and Asymmetric Radical Cyclization" Reviews on Heteroatom Chemistry. 16巻. 287-311 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mayumi Nishida, Hiroshi Hayashi, Atsushi Nishida, Norio Kawahara: "Enantioselective Radical Cyclization Controlled by the Chiral Aluminum Reagent" Journal of Chemical Society, Chemical Communications. 5. 579-580 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Atsushi Nishida, Norio Kawahara, Mayumi Nishida, Osamu Yonemitsu: "Radical Cyclization Using a Thioacetal Group for Radical Generation" Tetrahedron. 5. 9713-9734 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mayumi Nishida, Atsushi Nishida, Norio Kawahara: "Diastereoselective 1,4-Addition of Stannyl Radical in the Presence of Lewis Acid : A Noble Synthetic Route to Optically Active beta-Stannyl Esters" The Journal of Organic Chemistry. 61. 3574-3575 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Atsushi Nishida, Mayumi Nishida: "Development of New Radical Reactions-Skeletal Rearrangement via Alkoxy Radical and Asymmetric Radical Cyclization in the Presence of Lewis Acid-" Journal of Synthetic Organic Chemistry, Japan. 54. 27-35 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Atsushi Nishida, You-Ichirou Kakimoto, Yukie Ogasawara, Norio Kawahara, Mayumi Nishida, Hiroaki Takayanagi: "Skeletal Rearrangement via Alkoxy Radical : Conversion of Epoxydecalin Thiocarbonylimidazolide to Bicyclo[6.3.0]undecanone and Bicyclo[5.3.1]undecanone" Tetrahedron Letters. 38. 5519-5522 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Atsushi Nishida, Mayumi Nishida: "Development of New Radical Reactions : Skeletal Rearrangement via Alkoxy Radical and Asymmetric Radical Cyclization" Reviews on Heteroatom Chemistry. 16. 287-311 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Atsushi Nishida: "Skeletal Rearrangement via Alkoxy Radical:Conversion of Epoxydecalin Thiocarbonylimidazolide to Bicyclo[6.3.0]undecanone and Bicyclo[5.3.1]undecanone" Tetrahedron Letters. 38巻31号. 5519-5522 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Atsushi Nishida: "Development of New Radical Reactions:Skeletal Rearrangement via Alkoxy Radical and Asymmetric Radical Cyclization" Reviews on Heteroatom Chemistry. 16巻. 287-311 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] A.Nishida: "Radical Cyclization Using a Thioacetal Group for Radical Generation" Tetrahedron. 52巻11号. 9713-9734 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M.Nishida: "Diastereoselective 1,4-Addition of Stannyl Radical in the Presence of Lewis Acid : Novel Synthetic Route to Optically Active β-Stannyl Esters" The Journal of Organic Chemistry. 61巻29号. 3574-3575 (1996)

    • Related Report
      1996 Annual Research Report

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Published : 1996-04-01   Modified : 2016-04-21  

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