Discovery of novel trans-3,5-disubstituted pyrrolidinylthio-1β-methylcarbapenems

Novel trans-3,5-disubstituted pyrrolidinylthio-1β-methylcarbapenems were designed and synthesized to provide J-111,347 (1a) as the first example of an exceptionally broad-spectrum antibiotic, showing activity against methicillin-resistant Staphyloccocus aureus (MRSA) as well as Pseudomonas aeruginosa. Further derivation of 1a afforded J-111,225 (2a), J-114,870 (3a), and J-114,871 (3b), which showed improved safety profiles and retained broad-spectrum antibacterial activities.