Quercetin (Q1) is a naturally occurring polyphenolic compound having potent nutritional and medicinal value. In this study, commercially available quercetin was used to synthesize various acyl, methyl, benzyl and methylbenzyl derivatives. Quercetin on simple acylation with different stoichiometry of the reagents gave quercetin-3,3’,4’,5,7-pentaacetate (Q2) and quercetin-3,3’,4’,7-tetraacetate (Q4). Quercetin-3,3’,4’,5,7-pentaacetate (Q2) on selective deacylation using imidazole yielded quercetin-3,3’,4’,5-tetraacetate(Q3). Benzylation of quercetin afforded quercetin-3,4’,7-tribenzylether (Q5) and quercetin-3,3’,4’,7-tetrabenzylether (Q6), which were separated by silica gel column chromatography. Following with alkylation then gave three methylbenzyl derivatives, namely, quercetin-3,4’,7-tribenzyl-3’-methylether (Q7), quercetin-3,3’,4’,7-tetrabenzyl-5-methylether (Q8) and quercetin-3,4’,7-tribenzyl-3’,5-dimethylether (Q9). Debenzylation of Q7, Q8 and Q9 was carried out to obtain three methyl derivatives quercetin-3’-methylether (Q10), quercetin-5-methylether (Q11) and quercetin-3’,5-dimethylether (Q12). Quercetin-3,4’,7-trimethylether (Q13), quercetin-3,3’,4’,7-tetramethylether (Q14) and quercetin-3,3’,4’,5,7-pentamethylether (Q15) were obtained using alkylations.
The structure of derivatives synthesized was established using UV-Vis shift reagent study and recording of melting point. Antioxidant activity was evaluated using DPPH free radical scavenging assay, and IC50 values of quercetin and its derivatives were calculated. Dihedral angles α of C3-C2-C1’-C6’ chain and β of O1-C2-C-1’-C2’ chain between AC and B rings of quercetin (Q1) and its derivatives (Q2-15) were calculated from energy minimized structures using Chem3D pro software. Quercetin (Q1) having dihedral angles α 11.5º and β 6.6º showed a high antioxidant property (IC50 = 47.20 µM). Quercetin-3’-methyl ether (Q10) (α 11.1º and β 6.3º) (IC50 = 52.54 µM), quercetin-5-methyl ether (Q11) (α 11.2º and β 6.4º) (IC50 = 52.24 µM) and quercetin-3’,5-dimethyl ether (Q12) (α 11.2º and β 6.3º) (IC50 = 119.27 µM) showed comparable antioxidant property. Further variations in dihedral angles α and β caused decrease in the antioxidant property as shown by quercetin-3,3’,4’,5,7-pentaacetate (Q2) (α 7.3º and β 3.9º) (IC50 = 790.57 µM) and quercetin-3,3’,4’,5-tertaacetate (Q3) (α 9.2º and β 4.6º) (IC50 = 516.26 µM).