Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, China.
Chem Commun (Camb). 2022 Sep 27;58(77):10869-10872. doi: 10.1039/d2cc04006a.
A catalytic asymmetric total synthesis of avibactam and relebactam, two marketed diazabicyclooctane (DBO) β-lactamase inhibitors (BLIs), has been accomplished. An important feature of this study is the creation of a stereogenic center by using Rh-catalysed asymmetric hydrogenation, affording the crucial α-amino acid ester derivative with high-level enantiocontrol (99% ee). Furthermore, the adoption of flow technologies for the assembly of a majority of intermediates significantly achieves a faster preparation and greater synthetic efficiency than corresponding batch procedures.
已完成两种市售的二氮杂双环辛烷（DBO）β-内酰胺酶抑制剂（BLI）阿维巴坦和雷利巴坦的催化不对称全合成。这项研究的一个重要特点是通过使用 Rh 催化的不对称氢化反应创建一个手性中心，从而以高对映选择性（99%ee）获得关键的α-氨基酸酯衍生物。此外，采用流动技术组装大多数中间体可显著实现比相应的分批工艺更快的制备和更高的合成效率。
