Synthesis and Antiradical Activity of Isoquercitrin Esters with Aromatic Acids and Their Homologues

Int J Mol Sci. 2017 May 17;18(5):1074. doi: 10.3390/ijms18051074.


Isoquercitrin, (IQ, quercetin-3-O-β-d-glucopyranoside) is known for strong chemoprotectant activities. Acylation of flavonoid glucosides with carboxylic acids containing an aromatic ring brings entirely new properties to these compounds. Here, we describe the chemical and enzymatic synthesis of a series of IQ derivatives at the C-6″. IQ benzoate, phenylacetate, phenylpropanoate and cinnamate were prepared from respective vinyl esters using Novozym 435 (Lipase B from Candida antarctica immobilized on acrylic resin). The enzymatic procedure gave no products with "hydroxyaromatic" acids, their vinyl esters nor with their benzyl-protected forms. A chemical protection/deprotection method using Steglich reaction yielded IQ 4-hydroxybenzoate, vanillate and gallate. In case of p-coumaric, caffeic, and ferulic acid, the deprotection lead to the saturation of the double bonds at the phenylpropanoic moiety and yielded 4-hydroxy-, 3,4-dihydroxy- and 3-methoxy-4-hydroxy-phenylpropanoates. Reducing capacity of the cinnamate, gallate and 4-hydroxyphenylpropanoate towards Folin-Ciocalteau reagent was significantly lower than that of IQ, while other derivatives displayed slightly better or comparable capacity. Compared to isoquercitrin, most derivatives were less active in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, but they showed significantly better 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid, ABTS) scavenging activity and were substantially more active in the inhibition of tert-butylhydroperoxide induced lipid peroxidation of rat liver microsomes. The most active compounds were the hydroxyphenylpropanoates.

Keywords: DPPH; Novozym 435; antioxidant activity; aromatic acid; cinnamic acid; gallic acid; isoquercitrin; lipase; lipoperoxidation.

MeSH terms

  • Chromatography, High Pressure Liquid
  • Esters* / chemistry
  • Free Radical Scavengers / analysis
  • Free Radical Scavengers / chemical synthesis*
  • Free Radical Scavengers / pharmacology*
  • Lipid Peroxidation / drug effects
  • Mass Spectrometry
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Quercetin / analogs & derivatives*
  • Quercetin / analysis
  • Quercetin / chemical synthesis
  • Quercetin / pharmacology


  • Esters
  • Free Radical Scavengers
  • isoquercitrin
  • Quercetin