Lipase-catalyzed Synthesis of C-6 Saturated and Unsaturated Fatty Acid Esters of L-Ascorbic Acid

L-Ascorbic acid (AsA) was reacted at 55°C for 5-7 h with 5 eq of palmitic, stearic, oleic, linoleic, linolenic and conjugated linoleic acids in 2-methyl-2-butanol (tertiary amyl alcohol, TAA) under catalysis by immobilized lipase (Candida antarctica) to give 3755% of pure 6-esters of AsA. The esters were isolated in elemental-pure form without chromatography. The esterification reaction also proceeded in acetonitrile and dimethyl sulfoxide, but not in nitromethane nor dimethylformamide. Adding drying salts and waterconsuming reagents or adding a low level of water to reaction mixtures in TAA gave reduced yields of Lascorbyl 6-palmitate. When the 6-oleate ester was stirred with lipase and oleic acid in TAA under the conditions used in esterification, about 44% of the ester was found in equilibrium with 56% of free AsA. t-Amyl palmitate was synthesized chemically; that ester was not detected in the lipase-catalyzed esterification. Those data show that primary hydroxyls were acylated selectively by the lipase, and that yields were optimum when the water in a reaction mixture was controlled.