Synthesis of alkyl quercetin derivatives

Series of alkyl quercetin derivatives were synthesized from the reactions between quercetin (1) and the corresponding alkyl halides. Three methyl quercetin derivatives, 5,3′-dihydroxy-3,7,4′-trimethoxyflavone (2), 5-hydroxy-3,7,3′,4′-tetramethoxyflavone (3), 3,5,7,3′,4′-pentamethoxyflavone (4), three ethyl quercetin derivatives, 5,3′-dihydroxy-3,7,4′-triethoxyflavone (5), 5-hydroxy-3,7,3′,4′-tetraethoxyflavone (6), 3,5,7,3′,4′-pentaethoxyflavone (7), two propyl quercetin derivatives, 5,3′-dihydroxy-3,7,4′-tripropoxyflavone (8) and 5-hydroxy-3,7,3′,4′-tetrapropoxyflavone (9), two butyl quercetin derivatives, 5,3′-dihydroxy-3,7,4′-tributoxyflavone (10), 2-(3,4-dibutyoxybenzoyloxy)-4-butoxy-6-hydroxybenzoic acid (11), and two benzyl quercetin derivatives, 5,3′-dihydroxy-3,7,4′-tribenzoxyflavone (12), 5-hydroxy-3,7,3′,4′-tetrabenzoxyflavone (13), were purified by column chromatography. Among these, synthesis and physical properties of 5, 8, 9, 10, and 11 were reported for the first time. The chemical structures were determined by spectroscopy, including NMR, MS, and IR, and the physical properties of the quercetin derivatives were also characterized. Formation of 11 from the alkylation was of a great interest, and it was rationalized by the singlet oxygen-mediated product decomposition. Antioxidant and anti-bacterial activities of the synthesized alkyl quercetin derivatives were measured and found less active than 1.