Studies On Asymmetric Etherification And Halogenation Reactions Catalyzed By Vanadium-dependent Chloroperoxidase

Conventional chemical synthesis of ethers and thioether compounds relies on time-consuming and energy-consuming heavy metal catalytic techniques.Vanadium-dependent chloroperoxidase（VCPO）is a promising catalyst for organic synthesis due to its wide availability,stability and high catalytic activity.To date,there are few reports related to enzyme-catalyzed methods,especially VCPO-catalyzed synthesis of ethers and thioether compounds.In this study,VCPO-catalyzed intermolecular reactions of olefins with alcohols or thiols were investigated to give a series of haloether and thioether compounds.In addition,the catalytic activity of VCPO in three deep eutectic solvents（DES）was explored using thymol halogenation reaction as a model reaction.In the first part,VCPO-catalyzed intermolecular addition reactions of olefins and alcohols were investigated to obtain a series of ethers under the conditions of additional addition of hydrogen peroxide and halide ions.The optimal reaction conditions were obtained by optimizing the conditions of buffer p H,hydrogen peroxide and potassium bromide concentrations,enzyme concentration,and alcohol volume fraction.The results showed that the reaction could proceed smoothly,however the competitive addition of solvent water and alcohols limited the yields.Then,a substrate spectroscopy study was performed and 29 haloether compounds were successfully reacted and isolated on a semi-preparative scale.The structures of all the products were confirmed by ~1H NMR,¹³C NMR.Finally,six of the compounds were reductively dehalogenated to obtain conventional ethers,and the structures of the products were confirmed by GC-MS.In conclusion,a new method for the synthesis of ethers with high catalytic efficiency catalyzed by bioenzymes under mild conditions was investigated.In the second part,VCPO-catalyzed synthesis of thioether andβ-hydroxythioether compounds from olefins and thiols in aqueous solution without any additives was investigated.Controlled experiments,enzyme concentration screening,and buffer p H screening showed that the bioenzyme plays a crucial role in the reaction,but it was not the enzyme active center that catalyzes the formation of the product.Several other enzymes could also catalyze the reaction to proceed,indicating the universality of bioenzymes catalyzing the formation of thioether compounds.Finally,a substrate spectroscopy study was performed to scale up the reaction to a semi-preparative scale,and 14 thioether andβ-hydroxy thioether compounds were isolated,and the structures of all products were confirmed by ~1H NMR and ¹³C NMR.In the third part,the catalytic activity of VCPO in DES system was investigated using thymol halogenation as a model reaction.Firstly,three different DES-buffer and ratios were screened to determine the best reaction system to catalyze this reaction.Then hydrogen peroxide concentration,buffer p H,and VCPO concentration screening were carried out to find out the best reaction conditions.The results showed that VCPO could still maintain good catalytic activity in DES containing a certain proportion of buffer.In summary,a series of ether and thioether compounds were synthesized under milder,more efficient and greener conditions through organic reactions catalyzed by VCPO in aqueous solution.The halogenation of thymol in the DES system confirmed that VCPO still has catalytic activity in the DES system.This study has certain reference significance for the reaction types and reaction systems catalyzed by VCPO.