Study On The Catalytic Resolution Of Lipase Novozyme 435 For The Preparation Of Chiral Alcohol Building Blocks

Chiral secondary alcohols are important compounds in organic synthesis,which can be used as chiral blocks or intermediates in the synthesis and preparation of drugs,natural products and fine chemicals.Asymmetric reduction of carbonyl compounds(including asymmetric hydrogenation and asymmetric transfer hydrogenation)is an important method for the preparation of chiral secondary alcohols in the established strategies.But,this kind of method shortcomings,such as transition metal catalysts are expensive and difficult to recycle,in the air and moisture stability problems,toxicity is not friendly to the environment,looking for a highly efficient organic small molecular catalysts also takes a lot of effort and time,so people hope to find a simple and efficient method of preparation of chiral alcohols.At present,biocatalysts,as a new generation of catalysts,have been widely used in organic synthesis,and have shown advantages that cannot be replaced by traditional chemical catalysis,providing a new direction for the development of organic synthesis.The preparation of chiral secondary alcohols by enzymatic separation of racemic alcohols has been reported in many literatures.The lipase Novozyme 435 is a nonspecific lipase produced by Candida Antarctic B,which is immobilized on a hydrophobic carrier acrylic resin.Novozyme 435 can show catalytic activity in organic solvents,is has certain resistance to acid and alkali,in a wide PH range will remain stable,ability of high temperature,under the reaction conditions of 110℃,the activity of enzyme was not significantly affected,as a kind of immobilized enzyme,convenient recycling use,Novozyme 435 itself has this advantage makes it a priority to choose in the study object.In this study,we used vinyl acetate as acyl donor and catalyzed the enantioselective acylation of racemic alcohol by lipase Novozyme 435 to separate racemic alcohol and prepare chiral secondary alcohol blocks used in the synthesis of natural products and drugs.In the experiment,we use 1HNMR to monitor the reaction and determine the stop time of the reaction.Through experiments,we found that lipase Novozyme 435 showed high enantioselectivity in the catalytic resolution of various secondary alcohols,and obtained chiral alcohol blocks with high EE value.Finally,we carried out the amplification experiment and found that the catalytic activity of lipase Novozyme 435 was not affected in a large scale of reactions.Therefore,the lipase Novozyme 435 can be used in industrial preparation and can bring great economic benefits.