azetidin2ones

Azetidin-2-ones, also called 2-azetidinones, are chemical compounds that feature a four-membered lactam ring in which a carbonyl group sits adjacent to a nitrogen atom. The ring comprises three carbon atoms and one nitrogen, giving a rigid, highly strained framework. Substituents can be introduced on the nitrogen (N-substituted azetidin-2-ones) or at other ring positions, producing a wide range of derivatives with varying stability and reactivity.

The ring strain of the azetidinone core drives notable chemical reactivity, including susceptibility to nucleophilic attack and ring opening, especially under acidic or basic conditions. This reactivity makes azetidin-2-ones useful as synthetic intermediates in organic chemistry and as scaffolds in medicinal chemistry. They can be further functionalized to tune properties such as lipophilicity, electrophilicity, and metabolic stability.

In medicinal chemistry, the azetidinone moiety is best known as the core of beta-lactam antibiotics. While many clinically important beta-lactams are bicyclic or contain additional fused rings, all share the essential four-membered beta-lactam ring that includes an azetidinone substructure. These compounds typically act by inhibiting penicillin-binding proteins and disrupting bacterial cell wall synthesis. Not all azetidin-2-ones are antibiotics, but their core is a common starting point for designing antimicrobial agents and other pharmacophores.

Synthesis of azetidin-2-ones commonly involves the Staudinger [2+2] cycloaddition between ketenes and imines, yielding substituted beta-lactams. Other approaches include cyclization of N-acylaminoketones or aminoacyl derivatives, as well as newer catalytic methods that enable diverse substitution patterns on the ring.