Spirocyclopropyl beta-lactams as mechanism-based inhibitors of serine beta-lactamases. Synthesis by rhodium-catalyzed cyclopropanation of 6-diazopenicillanate sulfone.

ABSTRACT

Class A-class C mechanism-based beta-lactamase inhibitors were designed on the basis of the intermediacy of an oxycarbenium species capable of cross-linking with amino acids residues in the active site. Penams 24 and 27 were very potent against AmpC in vitro. The MIC values of 24 in combination with piperacillin against class A and class C producing organisms showed improvement over clinically used tazobactam.