Studies on Nonconventionally Fused Bicyclic β-Lactams.-A number of structurally novel [3.2.0]bicyclic β-lactam ring systems such as (IV), (IX), and (XIV) that have the lactam functionality arranged in alternative orientations within the four-membered ring are prepared. Semiempirical calculations indicate that the thermodynamic stabilities of the alternative isomeric ring systems are similar to that of the classical structure. The derivatives (Xb) and (XVI) show weak activity against Staphylococcus aureus or Vibrio cholerae.

The ability to affect eukaryotic and prokaryotic cellular growth, signaling and differentiation is a continuing focus in the pharmaceutical industry. The fundamental ability to affect these cellular processes is inherent in lactones. Lactones, which are ubiquitous in nature, reflect a broad phylogenetic diversity indicative of their ability to act as simple alkylating compounds, with their in situ activities falling into one of two categories, i.e., protect or conquer. Medically, their utility as pharmaceutical agents range from that of antimicrobial to anti-neoplastic agent depending on the functional groups attached.

The common practice in antibacterial drug development has been to rapidly make an attempt to find ever-more stable and broad-spectrum variants for a particular antibiotic, once a drug resistance for that antibiotic is detected. We are now facing bacterial resistance toward our clinically relevant antibiotics of such a magnitude that the conversation for antimicrobial drug development ought to include effective new antibiotics with alternative mechanisms of action. The electrophilic β-lactam ring is amenable for the inhibition of different enzyme classes by a suitable decoration of the core scaffold. Monocyclic β-lactams lacking an ionizable group at the lactam nitrogen exhibit target preferences toward bacterial enzymes important for resistance and virulence. The present review intends to draw attention to the versatility of the β-lactams as antimicrobials with “unusual” molecular targets.