Vacuum-driven lipase-catalysed direct condensation of l-ascorbic acid and fatty acids in ionic liquids: synthesis of a natural surface active antioxidant

Abstract

L-Ascorbic acid (vitamin C) is a useful natural antioxidant, but is highly polar and does not dissolve in fats and oils. One solution is the synthesis of 6-O-L-ascorbyl fatty acid esters, which are surface-active and protect fats and oils from oxidation. Previous syntheses of 6-O-L-ascorbyl fatty acid esters by Candida antarctica lipase B (CAL-B)-catalysed esterification were inefficient due to either the poor solubility of L-ascorbic acid in nonpolar organic solvents or poor lipase activity in polar organic solvents. We report that replacing organic solvents with ionic liquids such as 1-alkyl-3-methylimidazolium tetrafluoroborates makes this synthesis more efficient and greener for three reasons. First, like polar organic solvents, ionic liquids dissolve polar substrates such as ascorbic acid (e.g., ∼130 mg mL⁻¹ in sBMIM·BF₄ at 60 °C), but unlike polar organic solvents, ionic liquids do not inactivate CAL-B. For this reason, using an ionic liquid as the solvent gave a faster reaction and a higher yield of product. Second, it eliminates toxic organic solvents that easily evaporate. Third, since ionic liquids are not volatile, we could use vacuum to drive the equilibrium toward product formation. This ability eliminated the need to use an excess of acyl donor or an activated acyl donor. One problem we encountered was product inhibition due to its precipitation on the immobilized lipase particles. To avoid this inhibition, we added a hydrophobic phase such as hexane or polypropylene beads. A CAL-B-catalysed direct esterification of stoichiometric amounts of ascorbic acid and oleic acid gave a high conversion (83%). The product 6-O-L-ascorbyl oleate was isolated as a mixture with oleic acid using only water and ethanol or methanol in 61% yield.