Résumé
Since the introduction of penicillin in 1941, the use of antibiotics significantly decreased the death rate associated with bacterial infections. Today, 60% of prescribed antibacterial drugs belong to the β-lactam family, characterized by a crucial four membered β-lactam ring (e.g., cephalosporin, monobactam). However, their intensive use leads to the emergence of bacterial resistance especially in Gram-negative bacteria through the expression of β-lactamases. Faced with this deadly threat, the WHO draw up a list of priority pathogens and the first priority concerns Gram-negative β-lactamase producers. Nowadays, the main therapeutic class of antibiotics available remains the β-lactam derivatives and their development is a real challenge. Indeed, substituents at C-3, C-4, and C-7 of cephalosporins as well as at N-1 of monobactams are key positions for antimicrobial activity, and their chemical modifications are tricky. The last developments are well illustrated by the chemical structure of the recently marketed cephalosporin: Cefiderocol. Our group is also working in this area for many years with the development of β-lactam analogs. The modification of lateral chains generally requires long synthetic routes, low overall yields and toxic reagents. Here, we propose a simple way to functionalize cephalosporin at C-3 position through an optimized palladium-catalyzed cross-coupling reaction between a vinyl triflate and an aromatic boronic acid. We also exposed a functionalization of monobactam at N-1 using a Buchwald-Hartwig cross-coupling reaction between the nitrogen atom of the β-lactam ring and bromo derivatives. These pallado-catalyzed reactions involved the use of commercially available base, ligands, catalysts and β-lactam intermediates and are therefore a promising pathway to easily access novel β-lactam structures.