Structure–activity relationships of trans-3,5-disubstituted pyrrolidinylthio-1β-methylcarbapenems. Part 1: J-111,347 and related compounds

1β-Methylcarbapenems having various 3,5-disubstituted pyrrolidinylthio-side chains at C-2 were designed and synthesized. Evaluation of their antibacterial activities indicated that J-111,347 (Scheme 1 ;  Figure FX15 Scheme 1.  Synthesis of carbapenem derivatives. Reagents: (a) 3a–n, i-Pr2NEt, CH3CN, 0 °C, (b) (i) Pd(PPh3)2Cl2, n-Bu3SnH, CH2Cl2, H2O; (ii) RP-18 column chromatography. Figure options Download full-size image Download high-quality image (75 K) Download as PowerPoint slide ) is the first example of an extremely broad spectrum antibiotic showing activity against methicillin-resistant Staphylococcus aureus (MRSA) as well as Pseudomonas aeruginosa.