Highly efficient azido-Ugi multicomponent reactions for the synthesis of bioactive tetrazoles bearing sulfonamide scaffolds

Recent studies revealed that the contribution of the different bioactive scaffolds in one structure creates modern drugs/compounds with unique synergistic biological properties. In this regard, thanks to the interesting biological and medicinal properties of sulfonamide and tetrazole skeletons, this study describes the engagement of sulfonamides in the Ugi tetrazole reaction to access a library of tetrazole bearing sulfonamide. This four-component reaction was performed in a one-pot among available starting material, i.e., an isocyanide, a sulfonamide, an aldehyde and sodium azide in MeOH at 45 degrees C using ZnCl2 as a catalyst, for the synthesis of very versatile products with high atom economy and yields. The key point in this strategy is the formation of an intermediate Schiff base and its activation in the azido-Ugi reaction by a Lewis acid catalyst. Importantly, all products are purified through the group-assisted purification (GAP) chemistry, which can avoid traditional purification such as recrystallization and chromatography methods. Also, the docking study between the synthesized compounds and human serum albumin (HSA) was stimulated to theoretically rationalize their biological activity and potential binding interactions. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

Recent studies have shown that the combination of different bioactive scaffolds in a structure can create modern drugs/compounds with unique synergistic biological properties. This study describes the synthesis of tetrazole bearing sulfonamide compounds through the engagement of sulfonamides in the Ugi tetrazole reaction, with high atom economy and product yields. The use of group-assisted purification (GAP) chemistry avoids traditional purification methods, and theoretical docking studies provide insights into the potential biological activity and binding interactions of the synthesized compounds with human serum albumin.