Synthesis and Antiradical Activity of Isoquercitrin Esters with Aromatic Acids and Their Homologues - PubMed (original) (raw)

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

Eva Heřmánková-Vavříková et al. Int J Mol Sci. 2017.

Abstract

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Figure 1

Isoquercitrin (1, quercetin 3-_O_-β-

d

-glucopyranoside).

Figure 2

Figure 2

Aromatic acids 12–15 and their activated forms 22–25 used in the enzymatic approach [22,23].

Scheme 1

Scheme 1

Preparation of isoquercitrin esters 2–5 by enzymatic methodology.

Figure 3

Figure 3

Aromatic acids 16–21 and their protected forms 26–31 used for the chemical approach.

Scheme 2

Scheme 2

Preparation of isoquercitrin esters 6–11 by chemical methodology. Reagents and conditions: (i) imidazole, _tert_-butyldimethylsilyl chloride, dimethylformamide (DMF), 25 °C, 24 h; (ii) NaH, BnBr, DMF, 25 °C, 24 h; (iii) tetrabutylammonium fluoride , tetrahydrofuran (THF) 25 °C, 24 h; (iv) perBn aromatic acids 26–31, 4-dimethylaminopyridine , N,_N_′-dicyclohexylcarbodiimide (DCC), 25 °C, 24 h; (v) H2-Pd/C, EtOH:THF 1:1, 25 °C, 12 h.

Figure 4

Figure 4

Proposed structures of the isoquercitrin esters 2–11.

Figure 5

Figure 5

MS-ESI spectra of the isoquercitrin esters 2–11.

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