Regioselective synthesis of diacylglycerol rosmarinates and evaluation of their antioxidant activity in fibroblasts

Abstract

A series of new model of lipophilized phenolic compound derived from the rosmarinic acid was synthesized: 1,2-diacylglycerol rosmarinate (RDAG) with different alkyl chain lengths from five to eighteen carbons. These RDAG were obtained through a chemo-enzymatic synthesis: A chemical esterification based on the Mitsunobu reaction, followed by a lipase-catalyzed transesterification to link the different lipophilic moieties. The antioxidant abilities of these molecules were assessed on reactive oxygen species (ROS) overexpressing fibroblasts. The RDAG12 displayed the best antioxidant activity of the series. Lengthening of the lipid chain beyond twelve carbon atoms leads to a decrease in the antioxidant activity, thus confirming the occurrence of a cut-off effect. Antioxidant RDAG12 activity was then compared with that of vitamins C and E, rosmarinic acid and decyl rosmarinate (R10). The order of activity was R10>RDAG12>RDAG5>rosmarinic acid ~ vitamin C ~ vitamin E. At 5μM, R10 exhibited an even better antioxidant activity than the combination of vitamins C and E at 5μM each. These results confirm, firstly, that catechol structure is very effective in terms of antioxidant activity and secondly, that linking an appropriate hydrophobic domain is a powerful strategy to synthesize effective antioxidants.