合成β-内酰胺酶抑制剂阿维巴坦的关键中间体的研究进展

β-内酰胺类抗生素耐药性是对目前全球卫生、食品安全和发展的重大威胁之一。由于新型抗生素开发难度不断增加，采用复方型抗生素就成为解决这一难题的重要手段。阿维巴坦是一类β-内酰胺酶抑制剂，其抑酶谱广，与其他β-内酰胺类抗生素联用可有效恢复或增强其活性，极大地缓解了针对耐药菌无药可用的局面。在几乎所有的合成路线中，都经历了一个重要的中间体：顺式-5-羟基哌啶-2-甲酸，然后由其再进一步衍生化后获得目标化合物。本文对顺式-5-羟基哌啶-2-甲酸的化学合成和酶促合成两种方式的研究现状和发展前景进行概述和总结，从而对其在医药合成领域中的应用提供参考。

Research progress of key intermediates for the synthesis of β-lactamase inhibitor avibactam

Antibiotic resistance is one of the greatest threats to current global health and food safety. Due to the increasing difficulty in developing new antibiotics, the combination drugs containing antibiotic and β-lactamase inhibitor have become an acceptable choice to solve this problem. Avibactam, a kind of β-lactamase inhibitor with broad inhibition spectrum, can effectively restore or enhance the activity of many β-lactam antibiotics to greatly alleviate the situation that no drug is available for drug-resistant bacteria. In almost all synthetic routes, cis-5-hydroxy-L-pipecolic acid is the key intermediate for the synthesis of avibactam, and can directly deliver this target compound after a few transformations. In this paper, we summarize the chemical and enzymatic synthesis methods of cis-5-hydroxy-L-pipecolic from current literatures, and provide some suggestions for the manufacture of