Enantioselective Synthesis and Profiling of Two Novel Diazabicyclooctanone 尾-Lactamase Inhibitors

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• 作者：Hui Xiong ; Brendan Chen ; Thomas F. Durand-R茅ville ; Camil Joubran ; Yun W. Alelyunas ; Dedong Wu ; Hoan Huynh
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2014
• 出版时间：October 9, 2014
• 年：2014
• 卷：5
• 期：10
• 页码：1143-1147
• 全文大小：325K
• ISSN：1948-5875

文摘

The enantioselective synthesis of two novel cyclopropane-fused diazabicyclooctanones is reported here. Starting from butadiene monoxide, the key enone intermediate 7 was prepared in six steps. Subsequent stereoselective introduction of the cyclopropane group and further transformation led to compounds 1a and 1b as their corresponding sodium salt. The great disparity regarding their hydrolytic stability was rationalized by the steric interaction between the cyclopropyl methylene and urea carbonyl. These two novel 尾-lactamase inhibitors were active against class A, C, and D enzymes.

Keywords:

尾-lactamase inhibitor; asymmetric synthesis; hydrolytic stability