Insight into microwave assisted immobilized Candida antarctica lipase B catalyzed kinetic resolution of RS-(±)-ketorolac
•Synergistic effect of microwave irradiation and lipase catalysis.•Kinetic resolution of ketorolac with 1.5 fold increase in initial rate.•50% conversion with 98% ee(s), >99% ee(p) and >200 enantiospecificity in 3 h.•Ping Pong bi–bi mechanism with dead-end complex of n-octanol.
Microwave assisted biocatalytic transformation is a green process for chiral drug resolution. Different immobilized enzymes such as Novozym 435, Lipozyme TL IM, Lipozyme RM IM, Lipase Amano AS and Lipase AYS amino were screened for the kinetic resolution of RS-(±)-ketorolac under microwave irradiation. To study kinetics and mechanism, the effect of different parameters on the conversion, initial rates and enantiomeric excess of substrate were studied. Under microwave synergism, an increase in initial rates up to 1.5-fold was observed. Novozym 435 effectively catalyzed the enantioselective esterification of RS-(±)-ketorolac, showing excellent conversion (50%) and enantiomeric excess (>99%) in 3 h at 50 °C and 300 rpm. Based on initial rate and progress curve data, the reaction was found to follow the Ping Pong bi–bi mechanism with inhibition by n-octanol.
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Journal: Process Biochemistry - Volume 50, Issue 2, February 2015, Pages 230–236