Design and synthesis of bridged γ-lactams as analogues of β-lactam antibiotics

Anti-Bredt bridged bicyclo[3.2.1] γ-lactams were designed as inhibitors of penicillin binding proteins (PBPs). The compounds were prepared by a carbenoid insertion into a lactam N–H bond. Their weak antibacterial activity could either be explained by a poor chemical stability or by unfavorable steric interactions of the methylene bridge of the γ-lactam with the targeted enzymes.