Experimental design of the kinetic resolution of a key precursor of high‐value bioactive myo ‐inositols by an immobilized lipase

BACKGROUND: The response surface methodology was successfully applied to the optimization of the reaction variables for the kinetic resolution of a precursor of high‐value myo ‐inositols, ( ± )‐1,2‐ O ‐isopropylidene‐3,6‐di‐ O ‐benzyl‐ myo ‐inositol (( ± )‐1), by Novozym 435. The resolutions were run separately, with two acylating agents, ethyl acetate and vinyl acetate, in a solvent‐free system. The variables analyzed were reaction temperature, substrate concentration, water concentration and enzyme activity. A statistical model was employed for the evaluation of the influence of the variables on conversion and enantiomeric excess ( ee ). RESULTS: The optimal conditions for this resolution using vinyl acetate as acylating agent were 45 °C, 5 mg mL −1 of substrate, 71 U of enzyme activity and 0%w/w of water concentration. The high conversion (49.2 %) and ee (>99%) reached in the chemoenzymatic synthesis of acylated product, L‐(−)‐5‐ O ‐Acetyl‐3,6‐di‐ O ‐benzyl‐1,2‐ O ‐isopropylidene‐ myo ‐inositol, secure the efficient synthesis of the D enantiomorph present in the original racemic mixture (( ± )‐1) as well. CONCLUSIONS: The use of the experimental design strategy was productive, leading to a 14‐fold increase in the productivity of the reaction compared with the non‐optimized conditions. Both derivative L‐(−)‐2 and remaining substrate D‐(+)‐1 were obtained at high ee . © 2012 Society of Chemical Industry