• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of Lipase-Catalyzed, Effective, Asymmetric Synthetic Methods

Research Project

Project/Area Number 11672102
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

AKAI Shuji  Osaka University ; Graduate School of Pharmaceutical Sciences ; Research Associate, 薬学研究科, 助手 (60192457)

Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywordslipase / ethoxyvinyl esters / asymmetric synthesis / enantioselective desymmetrization / diol / kinetic resolution / Diels-Alder reaction / tandem reaction / エトキシビニル 2-フロアート / 不斉四級炭素 / 非対称化 / 光学活性アルコール / 酵素触媒エステル交換反応
Research Abstract

Nowadays, lipase-catalyzed asymmetric transesterification of alcohols has been widely employed as one of the most efficient asymmetric synthetic methods. For this kind of reactions, we have recently developed a novel class of acyl donor, 1-ethoxyvinyl esters (EVEs), which are superior to the currently-best acyl donors, vinyl esters (VEs). Their advantages involve solution of the deactivation of lipases by the side-product derived from VEs, high reactivity and enantioselectivity, and easy preparation of EVEs having various acyl moieties. By the use of EVEs, this project aims at developing novel asymmetric synthetic methods that could hardly be attained by the previous methods using VEs. The followings are summary of the results :
1. 1-Ethoxyvinyl 2-furoate 1 was developed as a highly effective acyl donor for the lipase-catalyzed desymmetrization of prochiral 2,2-disubstituted 1,3-propanediols. The method using 1 features high reactivity and enantiotopic selectivity, applicability for wid … More e range of the substrates, increase of the optical purity of the products through kinetic amplification, and stability of the products under various conditions. 1 was also found to be effective for the desymmetrization of meso-1,2-cycloalkanediols. This protocol was successfully applied for the construction of the pivotal optically active spiro quaternary carbon center of the antitumor antibiotic, fredericamycin A, and thereby a divergent asymmetric synthesis of both enantiomers of its ABCDE-analog was established.
2. A novel lipase-catalyzed tandem asymmetric synthesis has been developed, which involves in situ preparation of a 1-ethoxyvinyl acrylate having an electron-withdrawing substituent at the β-position, lipase-catalyzed kinetic resolution of (2-furyl)carbinols, and intramolecular Diels-Alder reaction of thus introduced acyl moiety. This one-pot procedure provides 7-oxabicyclo[2.2.1]heptenes with up to 99% ee. Unprecedented phenomena of the lipase ; viz., catalysis of the Diels-Alder reaction to amplify the enantioselectivity through kinetic resolution was discovered. Less

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Akai,Shuji: "Studies on Total Synthesis of Antitumor Antibiotic, Fredericamycin A"薬学研究の進歩. 15. 21-29 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kita,Yasuyuki: "Asymmetric Total Synthesis of Fredericamycin A"Angewandte Chemie, International Edition. 38. 683-686 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kita,Yasuyuki: "Convenient Enzymatic Resolution of Alcohols Using Highly Reactive, Nonharmful Acyl Donors, 1-Ethoxyvinyl Ester"Journal of Organic Chemistry. 65. 83-88 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akai,Shuji: "1-Ethoxyvinyl 2-furoate, an efficient acyl donor for the lipase-catalyzed enantioselective desymmetrization of prochiral 2, 2-disubstituted 1, 3-propanediols and meso 1, 2-diols"Chemical Communications. 1461-1462 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 北泰行: "フレデリカマイシンAの全合成"現代化学 増刊. 36. 102-116 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akai,Shuji: "Lipase-Catalyzed Asymmetric Desymmetrization of Prochiral 2, 2-Disubstituted 1,3-Propanediols Using 1-Ethoxyvinyl Benzoate"Chemical Pharmaceutical Bulletin. 48. 1519-1523 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akai, Shuji: "Studies on Total Synthesis of Antitumor Antibiotic, Fredericamycin A"Advances in Pharmaceutical Sciences. 15. 21-29 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kita, Yasuyuki: "Asymmetric Total Synthesis of Fredericamycin A"Angewandte Chemie, International Edition. 38. 683-686 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kita, Yasuyuki: "Convenient Enzymatic Resolution of Alcohols Using Highly Reactive, Nonharmful Acyl Donors, 1-Ethoxyvinyl Ester"Journal of Organic Chemistry. 65. 83-88 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akai, Shuji: "1-Ethoxyvinyl 2-furoate, an efficient acyl donor for the lipase-catalyzed enantioselective desymmetrization of prochiral 2,2-disubstituted 1,3-propanediols and meso 1,2-diols"Chemical Communications. 1461-1462 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kita, Yasuyuki: "Asymmetric Total Synthesis of Fredericamycin A"Gendai Kagaku Zokan. 36. 102-116 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akai, Shuji: "Lipase-Catalyzed Asymmetric Desymmetrization of Prochiral 2,2-Disubstituted 1,3-Propanediols Using 1-Ethoxyvinyl Benzoate"Chemical Pharmaceutical Bulletin. 48. 1519-1523 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Akai,Shuji: "1-Ethoxyvinyl 2-furoate, an efficient acyl donor for the lipase-catalyzed enantioselective desymmetrization of prochiral 2,2-disubstituted 1,3-propanediols and meso 1,2-diols"Chemical Communications. 1461-1462 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Akai,Shuji: "Lipase-Catalyzed Asymmetric Desymmetrization of Prochiral 2,2-Disubstituted 1,3-Propanediols Using 1-Ethoxyvinyl Benzoate"Chemical Pharmaceutical Bulletin. 48. 1519-1523 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 北泰行: "フレデリカマイシンAの全合成"現代化学 増刊. 36. 102-116 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Akai Shuji: "Studies on Total Synthesis of Antitumor Antibiotic, Fredericamycin A"薬学研究の進歩. 15. 21-29 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kita Yasuyuki: "Convenient Enzymatic Resolution of Alcohols Using Highly Reactive, Nonharmful Acyl Donors, 1-Ethoxyvinyl Esters"J. Org. Chem.. 65. 83-88 (2000)

    • Related Report
      1999 Annual Research Report

URL: 

Published: 2000-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi