The first synthesis and antioxidant and anticholinergic activities of 1-(4,5-dihydroxyb enzyl)pyrrolidin-2-one derivative bromophenols including natural products

Abstract

We report herein the first synthesis of biologically active natural bromophenols, namely 1-(2,3,6-tribromo-4,5-dihydroxybenzyl)pyrrolidin-2-one (2), 2RS-1-(2,3-dibromo-4,5-dihydroxybenzyl)-5-oxopyrrolidine-2-carboxylic acid(3), and 2RS-methyl 1-(2,3-dibromo-4,5-dihydroxybenzyl)-5-oxopyrrolidine-2-carboxylate (4), along with their differentderivatives (6 and 8–18). Among the synthesized compounds, 3, 4, and their derivatives (8 and 9) are yielded inracemic form. Radical scavenging assays of the synthesized molecules were investigated using various bioanalyticalantioxidant methods including 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS • +) and 2,2-diphenyl-1-picrylhydrazyl (DPPH • ). In addition, the reducing power of the novel bromophenols was investigated by Cu 2+ –Cu + reducing, Fe 3+ –Fe 2+ reducing, and [Fe 3+ –(TPTZ) 2 ] 3+ –[Fe 2+ –(TPTZ) 2 ] 2+ reducing capacity and ferrous ions(Fe 2+) chelating abilities. The molecules demonstrated powerful antioxidant activities when compared to standardantioxidant compounds of α -tocopherol, trolox, butylated hydroxyanisole (BHA), and butylated hydroxytoluene (BHT).Moreover, novel bromophenols were tested against cholinergic enzymes including acetylcholinesterase (AChE) andbutyrylcholinesterase (BChE) enzymes in the last part of this study. The presented novel bromophenols showed Kivalues in the range of 2.60 ± 0.75–16.36 ± 2.67 nM against AChE and 13.10 ± 3.33–54.47 ± 13.53 nM against BChE.