3-O-alkylascorbic acids as free-radical quenchers: synthesis and inhibitory effect on lipid peroxidation

A novel series of 3-O-alkylascorbic acids (3-RASA, 3a-n) was synthesized to act as radical scavengers for active oxygen species and free radicals, and their redox potentials and inhibitory effects on lipid peroxidation in rat liver microsomes were evaluated. The redox potentials of the 3-RASA compounds were increased by the substituent group to 90-190 mV above the potential for ascorbic acid (i.e., 3-RASA compounds were harder to oxidize). Although 3-O-dodecylascorbic acid (3c) and 3-O-(decylcarbomethyl)ascorbic acid (3i) differed in their redox potentials, they both markedly inhibited lipid peroxidation in rat liver microsomes to a similar extent (IC50 = 3.1 and 3.3 X 10(-6) M, respectively). Structure-activity relationship studies demonstrated that the anti lipid peroxidation activity of the 3-RASA compounds was markedly dependent upon their hydrophobicity.