ESTERIFICATION OF NATURAL COMPOUNDS WITH FATTY ACIDS

Abstract

In this PhD project we dealt with β-sitosterol, resveratrol and quercetin, three natural substances featuring ascertained biological activities. These compounds are characterized by a limited bioavailability and a low stability: these features reduce their application in pharmaceutical, nutraceutical and dermocosmetic areas. In order to improve the above mentioned properties, we synthesized esters of these compounds, following either a chemical approach (resveratrol, quercetin, and β-sitosterol) and a enzymatic approach (resveratrol and β-sitosterol). The esterification was performed with saturated (palmitic and stearic) and unsaturated (oleic, linoleic and linolenic) fatty acids: this synthesis introduced in a single molecule (prodrug) two moieties both pharmacologically active. Chemical synthesis was used to obtain resveratrol triesters, but failed with diesters: so these derivatives were synthesized by enzymatic approach. 1 H-NMR and C-NMR analyses allowed to define the structure of these derivatives. The synthesis of quercetin penta, tetra and triesters was obtained by modulating the acid/quercetin molar ratio; monoand bi-dimensional NMR techniques were used to determine the structure of all quercetin esters, while for triester computational studies were needed. In addition, for resveratrol and quercetin esters the antioxidant activity was evaluated: this property was not increased by esterification. Also the bioavailability was studied for resveratrol and its trioleoyl ester, but the resveratrol resulted more bioavailable in comparison with its ester. In order to improve drug topical delivery, quercetin and its derivatives were also incorporated in liposome formulations.