Esomeprazole is the most popular proton pump inhibitor (PPI) for treating gastroesophageal reflux disease. Enzymatic asymmetric sulfoxidation is a green approach to produce chiral sulfoxides. In this report, we focused on optimizing asymmetric sulfoxidation catalyzed by prazole sulfide monooxygenase (AcPSMO). The costly redox cofactor NADPH utilized by AcPSMO was regenerated by formate dehydrogenase with CO₂ as the coproduct, which can be removed easily. During the scale-up process, oxygen supply was found to be the main limiting factor during the early phase of the reaction, while the instability of AcPSMO and the lack of the cofactor NADPH hindered progress during the middle and late phases of the 0.6 L reaction. Finally, by adjusting oxygen mass transfer and increasing the dissolved oxygen, the enzymatic reaction was stepwise amplified to a 120 L scale using a 300 L thermostatic stirred reactor, affording 95.9% conversion and 99.9% enantiomeric excess after 12 h. Extraction and refinement of the product resulted in 0.39 kg of the isolated esomeprazole (sodium salt), with 57.8% overall yield (73.4% before the salt-forming reaction) and 99.1% purity. Thus, a green-by-design system was constructed for the efficient and precise oxidation of omeprazole sulfide into esomeprazole with molecular O₂ as the green cosubstrate and CO₂ and H₂O as byproducts.

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手性（酶法制备小号） -亚砜药物埃索美拉唑在试规模水平

埃索美拉唑是用于治疗胃食管反流疾病的最受欢迎的质子泵抑制剂（PPI）。酶促不对称亚砜氧化是生产手性亚砜的绿色方法。在本报告中，我们专注于优化由吡唑硫醚单加氧酶（Ac PSMO）催化的不对称硫氧化。Ac PSMO使用的昂贵的氧化还原辅助因子NADPH通过甲酸脱氢酶以CO ₂作为副产物进行再生，可以很容易地去除。在放大过程中，发现氧气供应是反应早期的主要限制因素，而Ac的不稳定性PSMO和辅因子NADPH的缺乏阻碍了0.6 L反应中期和后期的进展。最后，通过调节氧气的质量转移并增加溶解的氧气，使用300 L恒温搅拌反应器将酶促反应逐步放大至120 L规模，在12小时后转化率为95.9％，对映体过量为99.9％。产物的提取和精制产生0.39kg的分离的埃索美拉唑（钠盐），总收率为57.8％（成盐反应之前为73.4％）和99.1％的纯度。因此，设计了一种绿色设计系统，用于将奥美拉唑硫化物高效，精确地氧化为埃索美拉唑，其中分子O ₂为绿色共底物，CO ₂和H ₂ O为副产物。