Pickering emulsion and method for preparing chiral alcohol compound based on enzyme catalysis of Pickering emulsion

Abstract

The invention relates to a method for efficiently preparing a chiral alcohol compound based on Pickering emulsion enzyme catalysis. According to the method, hydrophilic cofactors and ketoreductase are subjected to in-situ encapsulation through Pickering emulsion, enrichment of the cofactors on an emulsion droplet interface is achieved through the electrostatic interaction between a connecting agent and the cofactors, the ketoreductase can be combined with the cofactors more easily on the interface, and then the efficiency of preparing the chiral alcohol compounds through catalysis of the ketoreductase is improved. The reaction can be circulated for multiple times, the appearance of the emulsion is not obviously changed, the reaction conversion rate is maintained at 90% or above, and the coenzyme TTN can reach 40000 or above. Compared with a reaction system without addition of the connecting agent, the reaction system with addition of the connecting agent has the advantages that cofactors are enriched on an interface, so that the cofactors are more efficiently combined with ketoreductase on the interface, the reaction time is effectively shortened, the use amount of the cofactors is reduced, and more reaction cycles can be realized within the time of maintaining the activity of the ketoreductase.

Description

technical field [0001] The invention relates to enzyme catalysis, in particular to a method for efficiently preparing chiral alcohol compounds based on Pickering emulsion enzyme catalysis. Background technique [0002] Chiral alcohol compounds are important components of chiral drugs, such as (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxy-1-oxopentyl]-4- Phenyl-2-oxazolidinone is an important intermediate of lipid-lowering drug ezetimibe. At present, the industrial synthesis of chiral alcohol drug intermediates mainly consists of the following two methods: chemical synthesis and racemate resolution. The chemical synthesis method relies on noble metals such as rhodium and palladium and their compounds, which are costly, cumbersome, and have low selectivity. They also cause great pollution to the environment, and the conversion of complex substrates containing many substituents cannot be efficiently completed. Decomposition occurs and leads to the formation of by-products. Howev...

AI Technical Summary

Problems solved by technology

[0004] The present invention aims at the problem of ketoreductase activity loss in the existing immobilization method, the problem of cofactor cannot be recycled efficiently, the problem of cofactor loss in the reaction process, and the distance between ketone reductase and cofactor, etc., and provides a pickering-based emulsion enzyme catalyzed The method for efficiently preparing chiral alcohol compounds effectively avoids the problem of activity loss and loss in the process of enzyme immobilization, realizes the lossless encapsulation of cofactors, and at the same time promotes the enrichment of cofactors at the interface through the "linker" , realizing more efficient binding and synergistic catalysis of ketoreductase and cofactor at the interface, and then realizing the efficient synthesis of chiral alcohols at the emulsion droplet interface

Images