School of Pharmacy, Queen's University Belfast , Belfast BT9 7BL, N. Ireland, U.K.
Almac , Department of Biocatalysis & Isotope Chemistry, 20 Seagoe Industrial Estate, Craigavon BT63 5QD, N. Ireland, U.K.
Chem Rev. 2018 Jan 10;118(1):349-367. doi: 10.1021/acs.chemrev.7b00437. Epub 2017 Dec 18.
Chiral amines are valuable building blocks for the pharmaceutical industry. ω-TAms have emerged as an exciting option for their synthesis, offering a potential "green alternative" to overcome the drawbacks associated with conventional chemical methods. In this review, we explore the application of ω-TAms for pharmaceutical production. We discuss the diverse array of reactions available involving ω-TAms and process considerations of their use in both kinetic resolution and asymmetric synthesis. With the aid of specific drug intermediates and APIs, we chart the development of ω-TAms using protein engineering and their contribution to elegant one-pot cascades with other enzymes, including carbonyl reductases (CREDs), hydrolases and monoamine oxidases (MAOs), providing a comprehensive overview of their uses, beginning with initial applications through to the present day.
手性胺是制药工业的重要构建模块。ω-TAms 的出现为其合成提供了一个令人兴奋的选择,为克服与传统化学方法相关的缺点提供了一种潜在的“绿色替代方案”。在这篇综述中,我们探讨了 ω-TAms 在制药生产中的应用。我们讨论了涉及 ω-TAms 的各种反应,以及它们在动力学拆分和不对称合成中的使用的工艺考虑因素。借助特定的药物中间体和 API,我们通过蛋白质工程绘制了 ω-TAms 的发展情况,并探讨了它们在手性 1,2-二醇和其他酶(包括羰基还原酶 (CREDs)、水解酶和单胺氧化酶 (MAOs))的一锅法级联反应中的作用,提供了它们的使用情况的全面概述,从最初的应用到今天。