β-内酰胺的N-亚磺酰化：通过TEMPO催化的α-溴代氮杂环丁烷酮的自由基反应。

N-Sulfenylation of β-Lactams: Radical Reaction of -Bromo-azetidinones by TEMPO Catalysis.

作者信息

Giraldi Valentina, Giunchino Francesco, Casacchia Maria Edith, Cantelli Andrea, Lucarini Marco, Giacomini Daria

机构信息

Department of Chemistry a "Giacomo Ciamician", University of Bologna, Via Piero Gobetti, 87, Bologna 40129, Italy.

Department of Physical and Chemical Sciences, University of Aquila, Via Vetoio, Coppito, L'Aquila 67100, Italy.

出版信息

J Org Chem. 2023 Oct 20;88(20):14728-14735. doi: 10.1021/acs.joc.3c01759. Epub 2023 Sep 28.

DOI:10.1021/acs.joc.3c01759

PMID:37769169

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10594653/

Abstract

Azetidinones with a sulfenyl group on the β-lactam nitrogen atom show interesting biological activities as antimicrobial agents and enzyme inhibitors. We report in the present study a versatile synthesis of -sulfenylated azetidinones starting from the corresponding -bromo derivatives by means of the (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) radical as the catalyst and disulfides. Preparation of -halo-azetidinones was studied and optimized. The reactivity of -bromo-azetidinone as a model compound in the presence of TEMPO radical was investigated by NMR and electron paramagnetic resonance (EPR) spectroscopy studies. Optimization of the reaction conditions allowed the access of -alkylthio- or -arylthio-azetidinones from 55 to 92% yields, and the method exhibited a good substrate scope.

摘要

在β-内酰胺氮原子上带有亚磺酰基的氮杂环丁烷酮作为抗菌剂和酶抑制剂显示出有趣的生物活性。在本研究中，我们报道了一种通用的合成方法，以相应的α-溴代衍生物为起始原料，借助（2,2,6,6-四甲基哌啶-1-基）氧基（TEMPO）自由基作为催化剂和二硫化物来合成α-亚磺酰化氮杂环丁烷酮。对α-卤代氮杂环丁烷酮的制备进行了研究和优化。通过核磁共振（NMR）和电子顺磁共振（EPR）光谱研究，考察了α-溴代氮杂环丁烷酮作为模型化合物在TEMPO自由基存在下的反应活性。反应条件的优化使得α-烷硫基或α-芳硫基氮杂环丁烷酮的产率达到55%至92%，并且该方法具有良好的底物适用范围。