Résumé
Due to their multiple biological properties, heterocycles have a central place in medicinal chemistry. Amongst all, the indole is one of the most important and attractive heterocycles, often reported as privileged scaffolds for the development of new therapeutic agents. The synthesis of polycyclic indole derivatives creates a broad structural diversity by varying the cyclic junction and the nature of the fused rings. Indoles and their fused derivatives have many interesting pharmacological properties, including anti-inflammatory, antituberculous, and antidiabetic.We have been particularly interested in indole-fused lactones since the combination of these two pharmacophores should offer scaffolds of interest in medicinal chemistry. Thus, we present the synthesis of 1,2-, 1,7- and 3,4-indole-fused lactones via a simple and efficient reaction sequence. The functionalization of these "oxazino-indole", "oxazepino-indole" and "oxepino-indole" tricycles is carried out by palladocatalyzed C-C coupling, nucleophilic substitution or 1,3-dipolar cycloaddition. The evaluation of their activity against Mycobacterium tuberculosis shows that the “oxazino-indole” and "oxazepino-indole” structures are new inhibitors of M. tuberculosis growth in vitro.