One pot synthesis of pyrrolidines type 3,7-diazabicyclo [3.3.0] octane and biological activity

Abstract

Pyrrolidines type 2,4-disubstituted (alkyl, aryl or heteroaryl)-6,8-dioxo-3,7-diazabicyclo [3.3.0] octanes (8a-d) were successfully synthesized by an efficient one pot 1,3-dipolar cycloaddition of azomethine ylides (in situ generated from the reaction of aromatic aldehydes and methyl ester of alpha-amino acids) with dipolarophile (N-phenylmaleimide). The reaction of compounds 8a-d with hydrazine in ethanol at room temperature took place under nucleophilic substitution which furnished 5-amino-4,6-dioxo-octahydropyrrolo [3,4-b] pyrrole-3-carboxylic acid phenylamides (12a-d). Structures of the products were confirmed by IR and 1H NMR. The compounds (8b and 12a) were evaluated for antimicrobial (agar dilution method) and antioxidative (DPPH; 2,2-diphenyl-1-picrylhydrazyl and SOD; superoxide dismutase assays) activities. The results showed that at concentrations of 4-256 µg/mL, the tested compounds exhibited non-significant antimicrobial growth, whereas the 12a at 200 µg/mL began to exert some antioxidative activity.