文献类型：期刊文献

英文题名：Carica papaya Lipase Catalysed Resolution of β-Amino Esters for the Highly Enantioselective Synthesis of (S)-Dapoxetine

作者：You, Pengyong[1];Qiu, Jian[1];Su, Erzheng[1];Wei, Dongzhi[1]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, New World Inst Biotechnol, Shanghai 200237, Peoples R China

年份：2013

卷号：2013

期号：3

起止页码：557

外文期刊名：EUROPEAN JOURNAL OF ORGANIC CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000316191600017)，CCR-EXPANDED(收录号:WOS:000316191600017)】；

基金：This work was supported by the Open Funding Project of the State Key Laboratory of Bioreactor Engineering, the Fundamental Research Funds for the Central Universities, and the Specialized Research Fund for the Doctoral Program (New Teachers) of Higher Education (20090074120015).

语种：英文

外文关键词：Amino acids; Natural products; Enzyme catalysis; Regioselectivity; Enantioselectivity

摘要：An efficient synthesis of the (S)-3-amino-3-phenylpropanoic acid enantiomer has been achieved by Carica papaya lipase (CPL) catalysed enantioselective alcoholysis of the corresponding racemic N-protected 2,2,2-trifluoroethyl esters in an organic solvent. A high enantioselectivity (E > 200) was achieved by two strategies that involved engineering of the substrates and optimization of the reaction conditions. Based on the resolution of a series of amino acids, it was found that the structure of the substrate has a profound effect on the CPL-catalysed resolution. The enantioselectivity and reaction rate were significantly enhanced by switching the conventional methyl ester to an activated trifluoroethyl ester. When considering steric effects, the substituted phenyl and amino groups should not both be large for the CPL-catalysed resolution. The mechanism of the CPL-catalysed enantioselective alcoholoysis of the amino acids is discussed to delineate the substrate requirements for CPL-catalysed resolution. Finally, the reaction was scaled up, and the products were separated and obtained in good yields (>= 80%). The (S)-3-amino-3-phenylpropanoic acid obtained was used as a key chiral intermediate in the synthesis of (S)-dapoxetine with very high enantiomeric excess (> 99%).