Lipase Mediated Oxidation Reaction And Its Application In Organic Synthesis

Enzymes are macromolecules with biocatalytic functions,and possess the intrinsic advantages such as high catalytic efficiency,mild reaction conditions,environmental friendliness,nontoxicity,etc..Enzyme catalytic promiscuity,which refers to the ability of catalyzing completely different types of reactions relative to the natural reaction,has been explored recently with the development of enzymology.The exploration of enzyme catalytic promiscuities is significant and challenging which provides a new pathway for green chemistry.In this area,lipase is the most used enzyme due to its broad specificity and excellent stability in various media.As part of our ongoing research in developing new applications of lipase in this new area,lipase mediated oxidation and the applications in organic synthesis were investigated in this work.The main research contents and results are as follows:A novel chemoenzymatic process for the synthesis of ?-cyano epoxides through a tandem Knoevenagel-epoxidation reaction was studied.The reaction conditions were optimized,including enzyme sources,amount of enzyme and reaction media.Under the optimal reaction conditions(ethanenitrile derivative(1 mmol),the aromatic aldehyde(1 mmol),Novozym 435(300U)in DMF/ethyl acetate(2/3)stirred at 50 °C),a series of ?-cyanoepoxides could be obtained in high yields.Azoxybenzene and its derivatives are key compounds as a result of their broad application as reducing agents,chemical stabilizers,therapeutic medicines,polymer inhibitors,and dyes.In this chapter,an efficient chemoenzymatic process for the synthesis of azoxybenzenes was developed.A peracid was generated in situ by Novozym 435,and then a range of anilines were oxidized by the produced peracid to afford azoxybenzenes in yields ranging from 63.1% to 94.1%.The experimental results indicate that the electronic effects of the substituents have little influence on the production of the corresponding azoxybenzenes.However,steric effects of the substituents did affect the reaction,because ortho-substituted anilines were less active than meta-substituted and para-substituted anilines.A lipase-glucose oxidase system has been designed for the oxidation of N-heteroaromatic compounds and tertiary amines.This reaction conditions,such as the ratio of glucose oxidase and lipase,the ratio of phosphate buffer and ethyl acetate,the amount of enzymes and reaction temperature had been optimized.This dual-enzyme system can work well with different N-heteroaromatic compounds and tertiary amines in this oxidation,and this green method can be easily scaled up.Therefore,this dual-enzyme system not only displays environmental friendliness,but also demonstrates its huge potential in industrial applications.