Enzyme/Ionic Liquid-Catalyzed Addition Reactions And Their Cascade Reactions

The development of green synthetic method is a hot research topic in organic chemistry. The employment of ionic liquid as green catalyst or using enzyme as efficient catalyst is green synthetic routes. In addition, the combination of multi-enzyme, single-enzyme, chemo-enzymatic system for the synthesis of bioactive compounds widened the application of enzyme in organic synthesis. The exploration of enzyme/ionic liquid-catalyzed new reactions and the cascade reactions attracted the research interest of chemists.D-aminoacylase was firstly found to catalyze the Michael addition to form carbon-carbon bond in organic media. The experiment results demonstrated that the active site of D-aminoacylase was responsible for the enzymatic Michael addition reaction. The mechanism for the Michael addition reaction catalyzed by D-aminoacylase was proposed.Ionic liquid was firstly found to catalyze the Markovnikov addition reaction to form the carbon-nitrogen bond. Bothe the ionic liquids [BMIm]BF₄ and [BMIm]OH could catalyze the Markovnikov addition of N-heterocycles such as imidazole, triazole, pyrazole, pyrimidine, purine with vinyl ester of carboxylic acid. Comparing the different catalytic behavior of [BMIm]BF₄ and [BMIm]OH, we found that ionic liquid [BMIm]OH could improve the reaction efficiency largely. In the reaction process, ionic liquid was functionalized as the catalyst. A mechanism for the ionic liquid [BMIm]OH-catalyze Markovnikov addition reaction was proposed and some experiemts demonstrated the validation of the mechanism.The new reaction catalyzed by ionic liquid [BMIm]OH to form the carbon -nitrogen bond was explored. The influences of the structures of amines, N-heterocycles,α,β-unsaturated carbonyl compounds and the reaction conditions on the Michael addition catalyzed by [BMIm]OH were systematically investigated. A new strategy for the fast forming of carbon-nitrogen bond at room temperature was developed and the catalytic mechanism was studied.A new method for the cascade reaction was investigated. Multi-enzyme catalysis, single enzyme catalysis and chemo-enzymatic method for the cascade reaction of Michael addition and acylation reaction was used to synthesize a series of pyrimidine derivatives containing a sugar branch. The influence of reaction conditions, substarte structure and acceptor structure on the cascade reaction was investigated. It was found that the structure of Michael acceptor has great influence on the cascade reaction. For vinyl 3-propenoyloxy propionate, two-enzymatic system was used to synthesize the pyrimidine derivatives containing a sugar branch. For vinyl acrylate, single-mediated cascade reaction in one pot was employed. For vinyl methacryalte or vinyl coronate, the exployment of chemo-enzymatic method in two steps was preferred.In this thesis, 97 compounds were synthesized including 7 vinyl esters, 22 Markovnikov adducts, 52 Michael adducts, 16 pyrimidine derivatives containing a sugar branch. These compounds were characterized by ¹H NMR, ¹³C NMR, FTIR and ESI-MS and 54 compounds have been confirmed to be new compounds.