Synthesis and evaluation of 3-(carboxymethylidene)- and 3-(carboxymethyl)penicillinates as inhibitors of β-lactamase

Penicillin-resistant bacteria can often be treated through the co-administration of an antibiotic and a β-lactamase inhibitor. Current inhibitors target only class A β-lactamases. We report two new series of C3-modified penicillin sulfones, having either a simple methylene group (i.e., a homologue) or exocyclic unsaturation between the thiazolidine ring and the C3 carboxylate. The homologue has 10-fold better activity against a class C β-lactamase than does sulbactam itself. By contrast, the exocyclic C3 unsaturated compounds are less active.