Emerging Trends in Chemistry and Pharmacology of b-Lactams

Abstract

The four-membered cyclic amides commonly known as 2-azetidinones or β-lactams occupy a prominent place in the realm of organic and medicinal chemistry since the structure elucidation of penicillin showed the presence of β-lactam ring in it and the antibacterial activity of penicillin was attributed to the presence of β-lactam ring. The early investigations in organic chemistry were focused on development of synthetic methodologies because of delicacies involved in construction of four-membered strained ring whereas the researches in medicinal chemistry focused on broadening the spectrum of antibacterial activity. These studies led to development of several novel methodologies for construction of the β-lactam ring and discovery of several β-lactam antibiotics such as monobactams, cephalosporins, carbapenams, trinems, etc [1-4]. With the advent of stereochemistry and knowledge of its significance in determining the bioactivity, synthetic efforts concentrated on development of stereoselective methodologies – both diastereoand enantioselective. The development of resistance in pathogens against this important class of antibiotics and the curiosity among pharmaceutical chemists to explore other biological properties of -lactams led to investigations in its alternative applications in medicinal chemistry which resulted into the discovery of novel β-lactams such as clavulanic acid, a β-lactamase inhibitor, and ezetimibe, a cholesterol absorption inhibitor. The β-lactams, to date, have been reported as inhibitors of several enzymes and anticancer agents as well.