Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

Beilstein J Org Chem. 2024 Nov 26:20:3077-3084. doi: 10.3762/bjoc.20.256. eCollection 2024.

Abstract

A series of 1,5-disubstituted tetrazole-indole hybrids were synthesized via a high-order multicomponent reaction consisting of an Ugi-azide/Pd/Cu-catalyzed hetero-annulation cascade sequence. This operationally simple one-pot protocol allowed high bond-forming efficiency and creating six new bonds (two C-C, three C-N, and one N-N). Additionally, the products were evaluated against breast cancer MCF-7 cells, finding moderate activity in the compounds substituted with fluorine and chlorine.

Keywords: 1,5-disubstituted tetrazoles; MCF-7 cell line; Ugi-azide reaction; high-order multicomponent reaction; isocyanides; methanesulfonylindoles.

Grants and funding

C.M. A-M. (756225) and América A. Frías-López (833463) acknowledges the support of CONACHYT through a graduate scholarship. This work was financially supported by Instituto De Ciencia, Tecnología e Innovación del Estado de Michoacán de Ocampo (ICTI-PICIR23-024) and CIC-UMSNH (18104).