New Antiradical Clusters Synthesized Using the First Green Biginelli Reactions of Calix[4]Arene

Abstract

Oxidative stress causes many diseases in humans, therefore antioxidants have a special position in the medicinal chemistry. There are many strategies such as clustering single drug units in order to develop new drugs. Four dihydropyrimidine moieties were grafted at the upper rim of calix[4]arene by facial green Biginelli reaction in good yield, giving two novel clusters of calix[4]arene-based dihydropyrimidines possessing amplified antiradical activity in comparison to the corresponding monomers. In fact, a monomer dihydropyrimidine can be considered as 1/4 of the corresponding cluster. Antiradical tests carried out with 2,2-diphenyl-1-picrylhydrazyl radicals in methanol showed enhanced antiradical activity of calixarene structures in comparison to monomers. Presumably, this is attributed to tethering and arraying of four impacted dihydropyrimidine units, which make a synergistic effect in interactions with radicals for developing effective radical scavenging activity (clustering effect).