Optimization of enzymatic esterification of dihydrocaffeic acid with hexanol in ionic liquid using response surface methodology.

BACKGROUND: Developing an efficient lipophilization reaction system for phenolic derivatives could enhance their applications in food processing. Low solubility of phenolic acids reduces the efficiency of phenolic derivatives in most benign enzyme solvents. The conversion of phenolic acids through esterification alters their solubility and enhances their use as food antioxidant additives as well as their application in cosmetics. RESULTS: This study has shown that lipase-catalyzed esterification of dihydrocaffeic acid with hexanol in ionic liquid (1-butyl-3-methylimidazoliumbis (trifluoromethylsulfonyl) imide) was the best approach for esterification reaction. In order to achieve the maximum yield, the process was optimized by response surface methodology (RSM) based on a five-level and four independent variables such as: dosage of enzyme; hexanol/dihydrocaffeic acid mole ratio; temperature and reaction time. The optimum esterification condition (Y = 84.4%) was predicted to be obtained at temperature of 39.4 °C, time of 77.5 h dosage of enzyme at 41.6% and hexanol/dihydrocaffeic acid mole ratio of 2.1. CONCLUSION: Finally, this study has produced an efficient enzymatic esterification method for the preparation of hexyl dihydrocaffeate in vitro using a lipase in an ionic liquid system. Concentration of hexanol was the most significant (p < 0.05) independent variable that influenced the yield of hexyl dihydrocaffeate. Graphical abstract Synthesis of different Hexyl dihydrocaffeates in ionic liquid.

Comparative study of the antioxidant activities of some lipase-catalyzed alkyl dihydrocaffeates synthesized in ionic liquid.

The solubility limitations of phenolic acids in many lipidic environments are now greatly improved by their enzymatic esterification in ionic liquids (ILs). Herein, four different ILs were tested for the esterification of dihydrocaffeic acid with hexanol and the best IL was selected for the synthesis of four other n-alkyl esters with different chain-lengths. The effect of alkyl chain length on the anti-oxidative properties of the resulted purified esters was investigated using ß-carotene bleaching (BCB) and free radical scavenging method DPPH and compared with butylated hydroxytoluene (BHT) as reference compound. All four esters (methyl, hexyl, dodecyl and octadecyl dihydrocaffeates) exhibited relatively strong radical scavenging abilities. The scavenging activity of the test compounds was in the following order: methyl ester>hexyl ester⩾dodecyl ester>octadecyl ester>BHT while the order for the BCB anti-oxidative activity was; BHT>octadecyl ester>dodecyl ester>hexyl ester>methyl ester.

Inhibition of prostaglandin E(2) production by synthetic minor prenylated chalcones and flavonoids: synthesis, biological activity, crystal structure, and in silico evaluation.

The discovery of potent inhibitors of prostaglandin E2 (PGE2) synthesis in recent years has been proven to be an important game changer in pharmaceutical industry. It is known that excessive production of PGE2 triggers a vast array of biological signals and physiological events that contributes to inflammatory diseases such as rheumatoid arthritis, atherosclerosis, cancer, and pain. In this Letter, we report the synthesis of a series of minor prenylated chalcones and flavonoids which was found to be significantly active in suppressing the PGE2 production secreted by lipopolysaccharide-induced mouse macrophage cells (RAW 264.7). Among the compounds tested, 14b showed a dose-response inhibition of PGE2 production with an IC50 value of 2.1 µM. The suppression upon PGE2 secretion was not due to cell death since 14b did not reduce the cell viability in close proximity to the PGE2 inhibition concentration. The obtained atomic coordinates for the single-crystal XRD of 14b was then applied in the docking simulation to determine the potential important binding interactions with murine COX-2 and mPGES-1 putative binding sites.