Continuous kinetic resolution of aliphatic and aromatic secondary alcohols by sol-gel entrapped lipases in packed bed bioreactors

Abstract The efficiency of tailored sol-gel entrapment using a ternary mixture of silane precursors was demonstrated for the continuous-flow kinetic resolution of aliphatic and aromatic secondary alcohols catalyzed by lipases. The main factors (temperature, substrate concentration, flow rate) influencing the enantioselective acylation of two model compounds, rac -2-octanol ( rac - 1 ) and rac -1-phenylethanol ( rac - 2 ), catalyzed by Candida antarctica B lipase in a packed-bed reactor were optimized by experimental design. The optimal values resulted for the rac - 1 , 0.5 M substrate concentration, 50 °C reaction temperature and 0.8 ml/min flow rate, were validated by long-term processing (144 h) in the continuous mode, resulting a productivity of about 145 μmol min −1  g −1 and enantiomeric ratio E higher than 280. For rac - 2 , the optimal parameter values were calculated as 40 °C reaction temperature, 0.45 ml/min flow rate and 0.2 M substrate concentration, yielding a productivity of about 40 μmole min −1  g −1 and enantiomeric ratio above 200. For both substrates, the productivity was considerably higher compared to data reported by other authors, demonstrating the robustness, efficiency, and stability of the selected biocatalyst. The kinetic resolution of the third substrate, rac -2-chloromandelic acid ( rac - 3 ) was first studied in batch mode, selecting the best lipase ( Candida antarctica A), immobilization method (sol-gel entrapment with a ternary silane mixture combined with adsorption on Celite 545), temperature (40 °C), and reaction medium (diisopropylether). These optimal parameters were successfully upgraded to the continuous-flow process, resulting a productivity of 1.7 μmol min −1  g −1 .