Design And Synthesis Of A Novel Class Of Constrained Tricyclic Pyrrolizidinone Carboxylic Acids As Carbapenem Mimics

A series of tricyclic pyrrolizidinone carboxylic acids harboring an angular methano group were synthesized as mimics of carbapenems and carbapenams, A key reaction involved a novel intramolecular cyclopropanation mediated by a trimethylstannylmethyl group and an adjacent iminium ion. Enolate chemistry on a tricyclic lactam ring unit allowed the introduction of various substituents. Further elaboration afforded tricyclic pyrrolidinone carboxylic acids, which were found to be inactive as inhibitors against a panel of bacterial strains. However, the antibacterial activity of ceftazidine was enhanced in the presence of the tricyclic analogues.