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一种利用离子液体稳定的固定化酶拆分3-羟基-3-苯基丙腈的生物催化方法。

A biocatalytic approach for resolution of 3-hydroxy-3-phenylpropanonitrile with the use of immobilized enzymes stabilized with ionic liquids.

作者信息

Degórska Oliwia, Szada Daria, Jesionowski Teofil, Zdarta Jakub

机构信息

Faculty of Chemical Technology, Institute of Chemical Technology and Engineering, Poznan University of Technology, Berdychowo 4, 60965 Poznan, Poland.

出版信息

Comput Struct Biotechnol J. 2023 Feb 15;21:1593-1597. doi: 10.1016/j.csbj.2023.02.026. eCollection 2023.

Abstract

Due to the growing importance of synthesizing active pharmaceutical ingredients (APIs) in enantiomerically pure form, new methods of asymmetric synthesis are being sought. Biocatalysis is a promising technique that can lead to enantiomerically pure products. In this study, lipase from , immobilized on modified silica nanoparticles, was used for the kinetic resolution (via transesterification) of a racemic mixture of 3-hydroxy-3-phenylpropanonitrile (3H3P), where the obtaining of a pure (S)-enantiomer of 3H3P is a crucial step in the fluoxetine synthesis pathway. For additional stabilization of the enzyme and enhanced process efficiency, ionic liquids (ILs) were used. It was found that the most suitable IL was [BMIM]Cl; a process efficiency of 97.4 % and an enantiomeric excess (ee%) of 79.5 % were obtained when 1 % (w/v) of that IL in hexane was applied and the process was catalyzed by lipase immobilized on amine-modified silica.

摘要

由于以对映体纯形式合成活性药物成分(API)的重要性日益增加,人们正在寻找新的不对称合成方法。生物催化是一种有前途的技术,可产生对映体纯的产物。在本研究中,固定在改性二氧化硅纳米颗粒上的来自[具体来源未提及]的脂肪酶用于外消旋3-羟基-3-苯基丙腈(3H3P)混合物的动力学拆分(通过酯交换反应),其中获得纯的(S)-3H3P对映体是氟西汀合成途径中的关键步骤。为了进一步稳定酶并提高过程效率,使用了离子液体(IL)。发现最合适的IL是[BMIM]Cl;当在己烷中使用1%(w/v)的该IL并由固定在胺改性二氧化硅上的脂肪酶催化该过程时,获得了97.4%的过程效率和79.5%的对映体过量(ee%)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40d6/9974985/0efb3ca83b43/gr1.jpg

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