化学酶法合成盐酸度洛西汀的研究进展

Research progresses in chemoenzymatic synthesis of Duloxetine hydrochloride

抑郁症的发病率在全球呈现明显上升趋势。盐酸度洛西汀是较好的抗抑郁药物,目前工业上采用全化学合成方法存在着一定的缺陷,而酶催化反应条件温和、环境友好,尤其对手性化合物的合成有极高的对映选择性,引入酶法能弥补化学合成的不足。本文针对化学法和酶法相结合制备手性药物盐酸度洛西汀的研究进展进行了综述,重点介绍了酶法拆分和生物催化不对称合成技术制备盐酸度洛西汀关键单一对映中间体:(S)-1-(噻吩-2-基)-1-仲醇衍生物的策略,分析了它们的优缺点,展望了发展前景,指出筛选高催化性能和高稳定性的微生物是实现酶催化技术工业化应用的主要方向。

The incidence of depression showed a clear upward trend in the global. Duloxetine is the better antidepressant drugs,there are some disadvantages on the industry for the full chemical synthesis. Enzyme catalysis has mild reaction condition,environmental friendly and synthetic chiral compounds with high enantioselectivity. Introduction of enzymatic can make up for the chemical synthesis. A review of the progress made in this article,we focused on the enzymatic resolution and bio-catalytic asymmetric synthesis critical enantiomer ： 1-（tetrahydrothioph-en-2-yl）propan-1-ol derivatives. Meanwhile we summarized their advantages and disadvantages and saw the rosy application prospect. Point out that screening high catalytic and high stability of microorganisms is the main direction of enzymatic technology to achieve industrial application.