The synthesis of 6,6-dibromo-2β-(heterocyclylthiomethyl)penam esters 4 and their conversion into compounds 7 and 10, analogs of the β-lactamase inhibitors brobactam and sulbactam having a thio-substituted 2β-methyl group, is described. Biological activities of the new compounds are presented. The successful clinical application of β-lactam antibiotic combinations incorporating clavulanic acid or sulbactam has firmly established that β-lactamase inhibitors can play an important role in the treatment of infections caused by β-lactamase producing organisms. The continuing search for more potent β-lactamase inhibitors has led to the synthesis of a variety of structurally modified β-lactam derivatives. Recent publications have highlighted the discovery of potent β-lactamase inhibitors by modification of the 2β-methyl group in sulbactam. Similar modification of brobactam, another effective β-lactamase inhibitor, has been less successful in providing compounds of superior activity. Our renewed interest in this area arose from a recent paper by Alpegiani et al. who had discovered that selected azetidinyl benzothiazolyl disulfides directly rearranged to the corresponding 2β-(benzothiazolylthiomethyl)penams upon thermolysis in refluxing toluene in the presence of an acid catalyst. We adopted this methodology and report herein on the synthesis of a series of 6,6-dibromo-2β-(heterocyclylthiomethyl)penam esters which, in turn, could be converted into analogs of sulbactam and brobactam having a heterocyclylthiosubstituted 2β-methyl group. Comparative data on the β-lactamase inhibitory properties of the modified derivatives and their parent compounds are presented.