化工进展2025，Vol.44Issue(9)：5224-5233,10.DOI:10.16085/j.issn.1000-6613.2024-1151
瑞来巴坦及其中间体的合成研究进展
Progress on synthesis of relebactam and its key intermediates
摘要
Abstract
Relebactam is a new class of β-lactamase inhibitors that can restore or enhance the activity of β-lactam antibiotics,thereby mitigating the threat to public health posed by bacterial resistance globally.In this paper,the seven marketed β-lactamase inhibitors are introduced,and relebactam is analysed by retrosynthetic analysis,taking relebactam as an example to introduce the difficulties in the synthesis of such active pharmaceutical ingredients(APIs).Depending on the starting materials,there are four process routes to synthesize the key intermediate 11-PG of relebactam,and the advantages and disadvantages of using L-pyroglutamic acid,(2S,5S)-5-hydroxypiperidine-2-carboxylic acid,L-glutamic acid,and 4-hydroxy-2-butanone as the starting materials are illustrated.The process improvement strategies of the original researcher Merck&Co.for the synthesis of relebactam from 11-PG are emphasized to achieve the concept of large-scale preparation of relebactam.Simultaneously,it is pointed out that the construction of the double chirality and urea ring of such compounds is the key.The efficient design and construction of chiral piperidine are the most effective manner for shortening the synthetic route of relebactam.The formation of the urea ring and the deprotection of Boc under mild conditions and in a clean and efficient manner will become the research direction in the future.关键词
瑞来巴坦/逆合成工艺/β-内酰胺酶抑制剂/手性哌啶/成脲环/脱BocKey words
relebactam/retrosynthetic process/β-Lactamase inhibitor/chiral piperidine/formation of the urea ring/deprotection of Boc分类
化学化工引用本文复制引用
王帅,张得意,李超,乔仁忠..瑞来巴坦及其中间体的合成研究进展[J].化工进展,2025,44(9):5224-5233,10.基金项目
国家自然科学基金(22177011,21977012,21672021). （22177011,21977012,21672021）
