Enantioselective synthesis of 3-hydroxytetradecanoic acid and its methyl ester enantiomers as new antioxidants and enzyme inhibitors

Abstract

Optically pure R and S enantiomers of 3-hydroxytetradecanoic acid and its methyl esters were synthesised by porcine pancreas lipase catalysed hydrolysis of racemic methyl 3-hydroxytetradecanoate in aqueous medium, with the aim of determining their antioxidant, antielastase and antiurease activities. The effects of the weight ratio of substrate/lipase and the reaction time were investigated. Optimum reaction conditions were determined. The resolution reaction with porcine pancreas lipase afforded (R)-3-hydroxytetradecanoic acid, which is a component of bacterially important lipid A, with greater than 99 % ee in excellent enantiomeric ratio (> 900) after 7 h incubation with a substrate/lipase weight ratio of 3:1 and 43 % conversion of the substrate. Methyl (S)-3-hydroxytetradecanoate, which is the unreacted enantiomer of the racemic substrate, could be recovered with 98 % ee after 7 h resolution with a substrate/lipase weight ratio of 1:1 and 60 % conversion. (R)-3-Hydroxytetradecanoic acid was converted to its ester and the S methyl ester to its acid. This biocatalytic enantioselective resolution in aqueous medium presents an environmentally friendly and green chemistry method for the synthesis of R and S enantiomers of 3-hydroxytetradecanoic acid and its methyl esters.