Synthesis Of Functionalized Chromenes Catalyzed By Immobilized Lipase Via A Multicomponent Reaction In Ionic Liquid

With the development of enzymology research,many enzymes have been reported to catalyze many types of reactions,which are called enzyme catalytic promiscuity.This property makes it possible to promote multi-step reactions in a multi-component reaction.Lipase can catalyze multi-component reaction to synthesize a series of active skeleton small molecules with mild reaction conditions and high yield.This study mainly explores the immobilization materials and conditions of lipase,and uses the catalytic promiscuity of enzyme to design multi-component series reaction in ionic liquid,which provides an effective new way for the development of green chemistry.The main research contents and results are as follows:Synthesis of indolyl 4H-chromenes via a three-component reaction catalyzed by lipase in ionic liquids is reported here for the first time.We use ionic liquids as the reaction solvent,and optimize and screen the reaction conditions: including enzyme source,enzyme dosage,ionic liquid screening,and then determine the optimal system of the reaction.This study shows that at 60?C,only 60 mg of Mucor miehei lipase(MML)is required to achieve optimal yield in a system that catalyzes 1 mmol of substrate in 5 ml of [EMIM] [BF4].Furthermore,[EMIM][BF4] exhibited good reusability in this enzymatic reaction.It is noteworthy that the salicylaldehydes or indoles with electron donating groups provided higher yields than those substrates with electron withdrawing groups.The magnetic nanoparticle immobilized enzyme was used to catalyze the multicomponent reaction to synthesize 4H-chromenes derivatives.In order to increase the stability and recyclability of the enzyme,Mucor miehei lipase(MML)was covalently immobilized on cyanuric chloride(TCT)-modified magnetic nanoparticles.The functionalized 4H-chromenes is then synthesized by a multicomponent series reaction using immobilized MML.The optimal system for this reaction was also determined.Immobilized MML has high catalytic activity,good recyclability and substrate suitability.When the ionic liquid acts as a solvent,the rate and yield of the reaction are increased,further illustrating the industrial value of the ionic liquid.