Synthesis of novel di- and tricationic carbapenems with potent anti-MRSA activity.

Abstract A new series of 1β-methyl carbapenems possessing a 6,7-disubstituted imidazo[5,1- b ]thiazol-2-yl group directly attached to the C-2 position of the carbapenem nucleus was prepared, and their activities against methicillin-resistant Staphylococcus aureus (MRSA) were evaluated. First, a benzyl moiety was introduced at the C-6 position of imidazo[5,1- b ]thiazole attached to the carbapenem. These benzylated molecules showed potent anti-MRSA activity, but poor water solubility. In order to overcome this drawback, we designed and synthesized di- and tricationic carbapenems and finally discovered a novel carbapenem ( 15i ), which exhibited excellent anti-MRSA activity and good water solubility.