A dynamic kinetic resolution catalyzed by immobilized lipase coupled with a novel grinding immobilized oxovanadium：Kinetic model and performance

Abstract

A dual immobilized lipase and oxovanadium co-catalyzed dynamic kinetic resolution (DKR) system was established and successfully applied to synthesize (R)-1-(3-Methoxyphenyl) acetate in batch, resulting in a key chiral intermediate of (S)-rivastigmine with highly yield (97.6 %), e.e (99.01 %) and selectivity Sel (99.4 %). Herein, oxovanadium was immobilized onto diatomite via grinding immobilization for the first time to access a novel immobilized oxovanadium (V-D) used to catalyze an in situ racemization of undesired enantiomer substrate. The racemization rate of hydrated vanadyl sulfate was found for the first time to be much higher than that of vanadyl sulfate without crystalline water because water molecules in the former may form ion clusters of solvation membranes to disperses the charge density of positive carbon ions and promote their stability. This grinding immobilization approach may become a promising alternative for the immobilization of metals, especially precious metals due to its low cost, high efficiency, easily separated and large reaction interface. The kinetic model of the kinetic resolution catalyzed by LA-MR was developed, which may obey the sequential mechanism with both substrate and product inhibition, while the in-situ racemization reaction catalyzed by V-D may comply with power law.