Synthesis of Carbapenems Containing Peptidoglycan Mimetics and Inhibition of the Cross?Linking Activity of a Transpeptidase of <scp>l,d</scp> Specificity

The carbapenem class of ?-lactams has been optimized against Gram-negative bacteria producing extended-spectrum ?-lactamases by introducing substituents at position C2. Carbapenems are currently investigated for the treatment tuberculosis as these drugs potent covalent inhibitors l,d-transpeptidases involved in mycobacterial cell wall assembly. optimization carbapenems inactivation unusual targets is sought herein exploiting nucleophilicity C8 hydroxyl group to introduce chemical diversity. As structure analogs peptidoglycan precursors, were chosen increase similarity between drug and substrate. Fourteen peptido-carbapenems efficiently synthesized. They more effective than reference drug, meropenem, owing positive impact a phenethylthio substituent introduced C2 but peptidomimetics added did not further improve activity. Thus, can be modified modulate pharmacokinetic properties highly efficient carbapenems.