Use of lipases for the kinetic resolution of lactic acid esters in heptane or in a solvent free system

• Lactate esters are only resolved when used as acyl acceptors.
• Only the d enantiomer is acylated whatever the donor/acceptor used.
• The best acylating agent is butyric anhydride.
• Lipase B from Candida antarctica is the most efficient enantioselective lipase.
• The resolution is complete within a few hours in heptane or a solvent free system.

Kinetic resolution of d,l-ethyl lactate (d,l-LA-Et) and d,l-butyl lactate (d,l-LA-Bu) was accomplished in the presence of lipases. Transesterification of the lactate esters with alcohols was shown to be poorly enantioselective, with a very low preference toward the l enantiomer. However, esterification of the free hydroxyl function of the lactate esters was much more enantioselective, with an opposite preference toward the d form. Among the 200 combinations screened (substrates and lipases), only two reactions fulfilled the required criteria for an efficient resolution (fast reaction, enantioselectivity ratio higher than 100). The best resolution was obtained by esterification of d,l-LA-Bu with butyric anhydride in the presence of lipase B from Candida antarctica (CAL-B) in heptane (at 30 °C): LA-Bu was resolved in 6 h with an initial esterification rate of d-LA-BU of 1.5 g L−1 h−1 gEZ−1, an enantioselectivity ratio higher than 100, a l substrate consumption lower than 1%, and a final substrate enantiomeric excess superior to 99%. After having demonstrated that neither LA-Bu nor BuAn were inhibitors of CAL-B, the reaction was further improved by carrying it out in a solvent free system, at an elevated temperature (60 °C), and at a higher lipase concentration. LA-Bu was resolved in 6 h with an initial rate of 7.6 g L−1 h−1 gEZ−1, an enantioselectivity ratio higher than 100, and a final substrate enantiomeric excess of 95%.

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