Combination of the Suzuki-Miyaura Cross-Coupling Reaction with Engineered Transaminases
Combination of the Suzuki-Miyaura Cross-Coupling Reaction with Engineered Transaminases
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DOI：
10.1002/chem.201804366
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发表时间：
2018-10-26
影响因子：
4.3
通讯作者：
Bornscheuer, Uwe T.
中科院分区：
文献类型：
--
作者：
Dawood, Ayad W. H.;Bassut, Jonathan;Bornscheuer, Uwe T.
酶与化学反应步骤的结合是有机合成的一个重要研究领域，为了提高总转化率和获得较高的操作稳定性，首选在一个锅内进行级联反应。在这里，结合Suzuki-Miyaura反应来合成联芳基化合物，然后进行转氨反应。仔细优化化学和生物催化反应所需的反应条件，实现了高效的两步一锅反应，以高达84%的总转化率产生具有优异光学纯度（bb0 - 99% ee）的最终手性胺。成功的关键是烟曲霉胺转氨酶（4CHI-TA）的蛋白质工程，其中单个丙氨酸突变可将转氨酶的转化率提高到2.3倍。最后，演示了最佳4CHI-TA变体固定化后向连续流系统的转移。
The combination of enzymatic and chemical reaction steps is one important area of research in organic synthesis, preferentially as cascade reactions in one-pot to improve total conversion and achieve high operational stability. Here, the combination of the Suzuki-Miyaura reaction is described to synthesize biaryl compounds followed by a transamination reaction. Careful optimization of the reaction conditions required for the chemo- and biocatalysis reaction enabled an efficient two-step-onepot reaction yielding the final chiral amines with excellent optical purity (>99% ee) in up to 84% total conversion. Key to the success was the protein engineering of the amine transaminases from Asperguillus fumigatus (4CHI-TA) where single alanine mutations increased the conversion up to 2.3-fold. Finally, the transfer to a continuous flow system after immobilization of the best 4CHI-TA variant is demonstrated.