The β-Lactam (Azetidin-2-one) as a Privileged Ring in Medicinal Chemistry
Within the realm of medicinal chemistry the “β-lactam” structure is closely associated with the discovery of Penicillin. Over the past seventy years, this association has been reinforced by the countless lives saved from bacterial infection by generations of structurally diverse β-lactam antibacterials. While the medical importance of these antibacterial β-lactams is undiminished, several developments over the past decade have both broadened and intensified the relevance of the β-lactam structure to medicinal chemistry. One of these developments is the realization that simple β-lactam structures have excellent chemical stability and, when incorporated into exploratory drug structures, they access a new and useful chemical space. A second development is the increasing ability of pathogenic bacteria to acquire resistance mechanisms against even the most recent generations of β-lactam antibacterials. These developments coincide with new methods for β-lactam synthesis. Each of these developments underlies resurgent interest in the β-lactam as a privileged ring in medicinal chemistry.