Theoretical study of the reaction from 6-methylidene penem to seven-membered ring intermediates.

A sort of beta-lactamase inhibitor, 6-methylidene penem can inhibit both class A and class C serine beta-lactamase. Its inhibition mechanism involves yielding a seven-membered ring intermediate after acylation of the serine. Density functional theory (DFT) method was used on the molecular model to determine the mechanism of producing the seven-membered ring intermediate. Solvent effects were considered via polarizable continuum model (PCM). Moreover, a water-assisted process was considered in the hydrogen transfer process. The results show that the seven-membered ring intermediate can be obtained via two possible mechanisms, namely, concerted mechanism and stepwise mechanism. In stepwise mechanism, a new thiirane intermediate which has never been reported was found. The product of stepwise mechanism, e, has five tautomerics, and they can be tautomerized by hydrogen transfer.