Abstract Zofenopril as an ACE inhibitor expired recently was found to have a favourable safety profile in comparison with other ACE inhibitors in treating high blood pressure, congestive heart failure, and acute myocardial infarction. It can be synthesised from the key building blocks of (S)-3-benzoylthio-2-methylpropanoic acid and (4S)-phenylthio-L-proline. In this report, an efficient hydrolytic resolution via Candida antarctic lipase B (CALB) for preparing the former block in isopropyl ether (IPE) containing (RS)-3-benzoylthio-2-methylpropyl pyrazolide (1) and water was developed. Quantitative improvements of the enzyme activity and enantioselectivity in terms of k2SKmS−1 = 5.726 L h−1 g−1 and E = 217 at 45 °C were found from the kinetic analysis. Insights into the CALB performance via thermodynamic analysis were then addressed and compared with those by using (RS)-3-benzoylthio-2-methylpropyl 1,2,4-triazolide (2) as the substrate. A putative thermodynamic model was moreover hypothesised for elucidating the more enthalpy reduction of 68.92-70.86 kJ mol−1 from the acyl part of (S)-1 and (S)-2 as well as that of 23.69-25.63 kJ mol−1 from the triad imidazolium to Ser105 and leaving 1,2,4-triazole moiety of (R)-2 and (S)-2 on stabilising the corresponding transition states.

中文翻译：

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CALB 催化的 (RS)-3-benzoylthio-2-methylpropyl azolides 的动力学拆分：动力学和热力学分析

摘要 佐芬普利作为一种最近过期的 ACE 抑制剂被发现在治疗高血压、充血性心力衰竭和急性心肌梗塞方面与其他 ACE 抑制剂相比具有良好的安全性。它可以由 (S)-3-苯甲酰硫基-2-甲基丙酸和 (4S)-苯硫基-L-脯氨酸的关键结构单元合成。在本报告中，开发了一种通过念珠菌南极脂肪酶 B (CALB) 在​​含有 (RS)-3-苯甲酰硫基-2-甲基丙基吡唑啉 (1) 和水的异丙基醚 (IPE) 中制备前块的有效水解拆分。从动力学分析中发现，在 45°C 下，酶活性和对映选择性在 k2SKmS-1 = 5.726 L h-1 g-1 和 E = 217 方面的定量改进。然后通过热力学分析深入了解 CALB 性能，并将其与使用 (RS)-3-苯甲酰硫基-2-甲基丙基 1,2,4-三唑化物 (2) 作为底物的那些进行比较。此外，还假设了一个推定的热力学模型，用于阐明 (S)-1 和 (S)-2 的酰基部分的 68.92-70.86 kJ mol-1 的更多焓减少以及来自 (S)-2 的 23.69-25.63 kJ mol-1将三联咪唑鎓转化为 Ser105，并留下 (R)-2 和 (S)-2 的 1,2,4-三唑部分以稳定相应的过渡态。