Optimization of Synthesis of (S)-Omeprazole Catalyzed by Soybean Pod Peroxidase in Water-in-Oil Microemulsions Using RSM

Response surface methodology (RSM) was used to optimize the oxidizing the omeprazole sulfide to (S)-omeprazole catalyzed by environmentally friendly catalyst soybean pod peroxidase (SPP) in cetyltrimethylammonium bromide (CTAB)/isooctane/n-butyl alcohol/water water-in-oil microemulsions. With the initial concentration of SPP of 3200 U ml −1 , the conversion of the omeprazole sulfide, the (S)-omeprazole yield and ee were 93.75%, 91.56% and 96.08%, respectively, under the optimal conditions: Wo of 15.85, the concentration of H 2 O 2 of 22.44 mM and reaction temperature of 49.68 °C, respectively. The proposed mechanism of asymmetric sulfoxidations catalyzed by SPP involves three concomitant mechanisms as follows: (1) a two-electron reduction of SPP-I, (2) a single-electron transfer to SPP-I and (3) nonenzymatic reactions. Based on the proposed mechanism which is reasonable and can express the oxidations, the reaction system includes five enzymatic and two nonenzymatic reactions. With 5.44% of the average relative error, a kinetic model based on the mechanisms fitting observed data very well was established, and the SPP-catalyzed reactions including both the two-electron reduction and the single-electron transfer mechanisms obey ping-pong mechanism with substrate and product inhibition, while nonenzymatic reactions follow a power law. This study has also demonstrated the feasibility of SPP as a substitute with low cost, excellent enantioselectivity and better thermal stability. Graphic Abstract