A one-pot five component reaction for the synthesis of tetrazol-benzofuran hybrids and their inhibitory activity against

• Published in: Organic & biomolecular chemistry 2024-09, Vol.22 (35), p.724-7244
• Main Authors: Aguilar-Morales, Cesia M, Alejandre-Castañeda, Viridiana, Contreras-Celedón, Claudia, Ramírez-Díaz, Martha Isela, Islas-Jácome, Alejandro, Meza-Carmen, Victor, Chacón-García, Luis, Cortés-García, Carlos J
• Format: Article
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/d4ob00995a

A synthetic strategy for obtaining a new series of 1,5-disubstituted tetrazole-benzofuran hybrid systems via a one-pot five-component reaction is described. This process involves a Ugi-azide multicomponent reaction coupled to an intramolecular cyclization catalyzed by Pd/Cu, resulting in low to moderate yields from 21 to 67%. This protocol allowed the synthesis of highly substituted benzofurans at the 2-position through an operationally simple process under mild reaction conditions and with high bond forming efficiency due to the formation of six new bonds (two C-C, two C-N, one N-N, and one C-O). Besides, to evaluate the antifungal activity of 1,5-disubstituted tetrazole-benzofurans 9a-n , in vitro studies against Mucor lusitanicus were performed, finding that compound 9b exhibits bioactivity comparable to the commercial antifungal drug Amphotericin B. These results suggest potential for use in controlling mucormycosis infections in animal models, highlighting the importance of these findings given the limited antifungal drug options and high mortality rates associated with this infection. The synthesis of a novel 1,5-disubstituted tetrazole-benzofuran hybrid system by a high-order multicomponent reaction with promising antifungal activity against mucormycosis is reported.