Syntheses and biological activities of new penem derivatives with side chains derived from 4-hydroxyproline

New penem derivatives with various substituted, enantiomerically pure pyrrolidine-thio side chains at the C-2 position were synthesized and their chemotherapeutic potentials assessed in comparison with Sch 29482. The following criteria were used for preliminary evaluation: Antibacterial activity in vitro, beta-lactamase inhibition and apparent hydrolysis rates by crude murine and human kidney enzyme preparations. The most active compounds, 16e, 16f and 18 exhibit properties typical of this substance class with a tendency towards greater antibacterial potency in comparison with Sch 29482, especially against Pseudomonas aeruginosa. No clear-cut structure-activity relationships could be found with respect to beta-lactamase inhibition and stability against degrading renal enzymes.