Development of Lipase-Catalyzed Domino-Type Asymmetric Syntheses

脂肪酶催化多米诺骨牌型不对称合成的发展

基本信息

  • 批准号:
    15590005
  • 负责人:
  • 金额:
    $ 2.3万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2003
  • 资助国家:
    日本
  • 起止时间:
    2003 至 2004
  • 项目状态:
    已结题

项目摘要

The lipase catalyzed organic syntheses have been gaining increased attention as environmentally benign processes. However, their application has been limited mainly to the preparation of optically active compounds via the kinetic resolution of racemic carboxylic acid derivatives or the alcohols. Recently, we disclosed the first domino type asymmetric synthesis, in which the lipase catalyzed kinetic resolution of racemic alcohols with ethoxyvinyl esters (EVEs) bearing reactive functional moieties was followed by the intramolecular Diels-Alder reaction of the resulting optically active esters to directly give polycyclic compounds. This project has aimed at the practical expansion of this domino type synthesis methodology. The followings are summary of the results :1. Some ruthenium complexes were discovered to effectively catalyze the racemization of optically active alcohols at room temperature and have no inhibition of the lipase-catalyzed reactions. By the combined use of these comple … More xes and lipases, we have achieved the first domino-type synthesis accompanied by a dynamic kinetic resolution. Thus, in this process, the kinetic resolution of 3-vinylcyclohexen-1-ols, the racemization of the remaining optically active alcohols, and the intramolecular Diels-Alder reaction concurrently took place to directly afford multi-substituted decalines (90-95% ee, 69.83% yields).2. The lipase catalyzed domino type synthesis was applied to racemic acyclic and cyclicα-hydroxynitrones, and the kinetic resolution and the intramolecular dipolar cycloaddition reactions continuously proceeded to give isoxazolidine derivatives (>90% ee) as a single diastereomer in each case. This protocol was used for the first catalytic asymmetric total synthesis of (-)-rosmarinecine, a natural pyrrolizidine alkaloid, from commercially available racemic 3-hydroxypyrrolidine.3. Systematic investigation on the ruthenium-catalyzed racemization of optically active alcohols has found that the substituents of the benzene-ligands of the ruthenium complexes had significant affect on their catalytic reactivity. Less
脂肪酶催化的有机合成作为一种对环境无害的工艺,越来越受到人们的关注。然而,它们的应用主要局限于通过外消旋羧酸衍生物或醇的动力学拆分制备光学活性化合物。最近,我们发现了第一个多米诺骨牌型不对称合成,其中脂肪酶催化外消旋醇与具有活性功能的乙氧基乙烯酯(EVEs)的动力学分解,然后由旋光性酯的分子内Diels-Alder反应直接生成多环化合物。该项目旨在实际扩展这种多米诺骨牌类型的综合方法。结果总结如下:1。一些钌配合物在室温下能有效地催化旋光性醇的外消旋,而对脂肪酶催化的反应无抑制作用。通过结合使用这些复杂的x酶和脂肪酶,我们实现了第一个伴随着动态动力学分辨率的多米诺骨牌型合成。因此,在此过程中,3-乙烯基环己烯-1-醇的动力学分解、剩余旋光性醇的外消旋化和分子内Diels-Alder反应同时发生,直接产生了多取代下降(90-95% ee,产率69.83%)。将脂肪酶催化的多米诺骨牌型合成应用于外消旋无环和环α-羟基硝基酮,动力学分解和分子内偶极环加成反应连续进行,得到异恶唑烷衍生物(> - 90% ee)作为单个非对映体。该方案首次用于催化不对称全合成(-)-迷迭香碱,天然吡咯利西啶生物碱,从市售的消旋3-羟基吡咯利啶。系统研究了钌催化旋光性醇的外消旋反应,发现钌配合物的苯配体取代基对其催化活性有显著影响。少

项目成果

期刊论文数量(20)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Lipase-Catalyzed Domino Dynamic-Kinetic-Resolution of Racemic 3-Vinylcyclohex-2-en-1-ols/Intramolecular Diels-Alder Reaction
脂肪酶催化外消旋 3-Vinylcyclohex-2-en-1-ols/分子内 Diels-Alder 反应的多米诺动力学解析
  • DOI:
  • 发表时间:
    2004
  • 期刊:
  • 影响因子:
    0
  • 作者:
    S.Akai;K.Tanimoto;Y.Kita
  • 通讯作者:
    Y.Kita
Development of Novel Asymmetric Reactions Oriented to Next-Generation Enzymatic Organic Syntheses
面向下一代酶促有机合成的新型不对称反应的开发
  • DOI:
  • 发表时间:
    2003
  • 期刊:
  • 影响因子:
    0
  • 作者:
    福元康文;西村安代;Masaki KANAMORI et al.;赤井 周司;福元康文;福元康文;S.Akai
  • 通讯作者:
    S.Akai
Akai, Shuji: "Lipase-Catalyzed Domino Dynamic-Kinetic-Resolution of Racemic 3-Vinyl-cyclohex-2-en-1-ols/Intramolecular Diels-Alder Reaction"Angew.Chem.Int.Ed.. 43. 1407-1410 (2004)
Akai,Shuji:“外消旋 3-乙烯基-环己-2-en-1-醇/分子内 Diels-Alder 反应的脂肪酶催化多米诺动态动力学解析”Angew.Chem.Int.Ed. 43. 1407-1410
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
赤井 周司: "次世代型酵素触媒反応を志向する不斉合成反応の開発研究(日本薬学会学術振興賞受賞記念総説)"薬学雑誌. 123. 919-931 (2003)
赤井修二:“以下一代酶催化反应为目标的不对称合成反应的开发研究(日本药学会学术振兴奖纪念评论)”Pharmaceutical Journal 123. 919-931(2003)。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Enantiodivergent preparation of optically active oxindoles having a stereogenic quaternary carbon center at the C3 position via the lipase-catalyzed desymmetrization protocol: effective use of 2-furoates for either enzymatic esterification or hydrolysis.
  • DOI:
    10.1021/jo035749h
  • 发表时间:
    2004-03
  • 期刊:
  • 影响因子:
    0
  • 作者:
    S. Akai;Toshiaki Tsujino;Emi Akiyama;Kouichi Tanimoto;T. Naka;Y. Kita
  • 通讯作者:
    S. Akai;Toshiaki Tsujino;Emi Akiyama;Kouichi Tanimoto;T. Naka;Y. Kita
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AKAI Shuji其他文献

AKAI Shuji的其他文献

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{{ truncateString('AKAI Shuji', 18)}}的其他基金

Synthesis of PEGylated drug candidates for PET imaging
用于 PET 成像的聚乙二醇化候选药物的合成
  • 批准号:
    24659049
  • 财政年份:
    2012
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Nucleophilic deoxyfluorination of phenol derivatives and its application to drug discovery
苯酚衍生物的亲核脱氧氟化及其在药物发现中的应用
  • 批准号:
    24390005
  • 财政年份:
    2012
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
The development of innovative asy mmetric synthetic methods by the enzyme-metal combo catalysis
酶-金属组合催化创新不对称合成方法的发展
  • 批准号:
    21390005
  • 财政年份:
    2009
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Development of regioselective reactions of substituted benzynes and its application to synthesis of polysubstituted fused aromatic compounds
取代苯炔区域选择性反应的进展及其在多取代稠合芳香族化合物合成中的应用
  • 批准号:
    19590008
  • 财政年份:
    2007
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Construction of Carbon Skeleton via Lipase-Catalyzed Domino-Type Syntheses with Dynamic Kinetic Resolution
通过脂肪酶催化的多米诺骨牌动态分辨率合成碳骨架的构建
  • 批准号:
    17590006
  • 财政年份:
    2005
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Development of New Method for Construction of Chiral, Non-Racemic Quaternary Carbon Center by Enzymatic Acylation of Alcohols and Application Thereof
醇酶酰化构建手性非外消旋季碳中心新方法的开发及其应用
  • 批准号:
    13672214
  • 财政年份:
    2001
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Development of Lipase-Catalyzed, Effective, Asymmetric Synthetic Methods
脂肪酶催化、有效、不对称合成方法的开发
  • 批准号:
    11672102
  • 财政年份:
    1999
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
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