Title of article :
Structure–activity relationships of trans-3,5-disubstituted pyrrolidinylthio-1β-methylcarbapenems. Part 1: J-111,347 and related compounds
Author/Authors :
Hideaki Imamura، نويسنده , , Norikazu Ohtake، نويسنده , , Aya Shimizu، نويسنده , , Hideki Jona، نويسنده , , Hiroki Sato، نويسنده , , Rie Nagano، نويسنده , , Ryosuke Ushijima، نويسنده , , Koji Yamada، نويسنده , , Terutaka Hashizume، نويسنده , , Hajime Morishima، نويسنده ,
Abstract :
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 and ) is the first example of an extremely broad spectrum antibiotic showing activity against methicillin-resistant Staphylococcus aureus (MRSA) as well as Pseudomonas aeruginosa.
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.
