Alkylidene Oxapenem ß-Lactamase Inhibitors Revisited: Potent Broad Spectrum Activity but New Stability Challenges.

We present a comprehensive study of C6-alkylidene containing oxapenems. We show that this class of ß-lactamase inhibitors possesses an unprecedented spectrum with activity against class A, C, and D enzymes. Surprisingly, this class of compounds displayed significant photolytic instability in addition to the known hydrolytic instability. Quantum mechanical calculations were used to develop models to predict the stability of new analogues.