MANY pathogenic bacteria secrete penicillinases (β-lactamases, EC 3.5.2.6) as a defence mechanism against β-lactam antibiotics1. Inhibitors of penicillinase are therefore of potential clinical importance, and interest in this area has been stimulated by the discovery of effective naturally occurring enzyme inactivators2–4. We have studied the interaction of one of these, clavulanic acid (I) with the exocellular enzyme from Staphylococcus aureus, and we report here the synthesis of a novel penicillinase inhibitor whose design was based on the mechanism postulated for the inactivation by clavulanate.