Abstract
To obtain derivatives of ursolic acid with improved water solubility and antioxidant activity, new ester-linked hybrids of ursolic acid and gallic acid were synthesized. In the reaction of methyl gallate with ursoloyl chloride acetate, both mono- and diacylation products were obtained. To prepare mono-alkylated and mono-acylated derivatives of gallic acid, 4,5-O-methoxymethylene-protected methyl gallate was used. It was found that ursolic-gallic acid hybrids containing phenolic ester linkage readily underwent hydrolysis at C-28 of triterpenoid. The dioxolane protection allowed selective hydrolysis of the methyl ester at the aromatic moiety of the hybrid compound leaving intact the labile C-28 ester at the triterpenoid moiety. The hybrids possessing an ester–ether linker (terpenoid-COO–CH2CH2–O-aryl) are stable to the hydrolysis. The majority of the obtained ursolic–gallic acid hybrids containing free phenolic hydroxyl groups possess excellent antioxidant activity. Notable water solubilities (∼0.5 mg/mL) of novel hybrids containing both carboxyl group and hydroxyls at aromatic moiety were found.
Graphical abstract
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Acknowledgments
This work was performed within the framework of the international project ERA.Net RUS Plus project # RUS_ST2017-139 “AnticancerBet”. According to the rules of this international project, funding was provided by RFBR national fund (Foundation of Basic Research Grant 18-53-76001). In accordance with the rules of the international project, it is necessary to indicate the number of ERA.Net RUS Plus project # RUS_ST2017-139 “AnticancerBet” and the number of the grant for which the funding is being carried out. Additionally two state Russian Federal programs should be mentioned.