Study On The Catalytic Promiscuity Of Hydrolase And Tandem Reaction

Enzyme catalysis in organic synthesis has drawn an increasing number of chemist's attention. By exploring of the new function; regulating the enzymatic reaction and designing of a new tandem reaction base on the promiscuity of enzyme, enzyme catalysis provide more valuable new ideas and new technologies for green chemistry.Lipase was firstly found to catalyze the Friedel-Craft reaction in water. After screening the reaction time, enzyme sources, reaction media, the molar ratio of substrate, temperature and the structure of substrates, the Friedel-Craft reactions of indole derivative andα,β-unsaturated compounds with lipase from porcine pancreas, TypeⅡ(PPL) as catalysis were founded.13 Fridel-Craft adducts were synthesized. The control experiments proved that the active site of PPL were responsible for those enzymatic reaction. The mechanisms for the Friedel-Craft reaction and tandem reaction catalyzed by PPL were also proposed.The tandem Nucleophilic addition/dehydration/Michael addition of aldehyde and indole with lipase (from porcine pancreas, TypeⅡ) as catalysis was screened. The enzyme sources, reaction media, temperature, the structure of substrate that affects this tandem reaction were investigated systemly. In solvent mixture (water/dioxane=4/1), lipase (from porcine pancreas, TypeⅡ) can catalyze the tandem Nucleophilic addition/dehydration/Michael addition between aldehydes and indole derivatives. After the stepwise process were optimized,26 bis(indolyl)alkanes were prepared in moderate to excellent yields by using PPL as catalyst.The influence of N-heterocyclic compounds on the enzymatic reaction was investigated. Though investigating enzyme sources, solvent, additive, the ratio of imidazole and acylase, we founded that D-aminoacylase and imidazole could be used as co-catalyze to catalyze the Claisen-Schmidt reaction. When the ratio of D-aminoacylase and imidazole is 2/1, the activity of D-aminoacylase was improved obviously. And 18 tandems Aldol condensation/dehydration adducts were obtained via this method. The control experiments demonstrated that the active site of D-aminoacylase was responsible for the enzymatic reaction. The mechanism for the Claisen-Schmidt reaction catalyzed by D-aminoacylase and imidazole was also proposed.A single enzyme can catalyze the cascade Aldol condensation-elimination-Michael-intromolecular Aldol condensation-elimination for synthesis of conjugate cyclohexanone-2-ene reaction with imidazole in octane. By investigating enzyme sources, solvent, additive, the ratio of imidazole and acylase, we found that D-aminoacylase and imidazole can co-catalyze this tandem reaction. After the stepwise process was optimized,15 conjugate cyclohexanone-2-enes were prepared. Some control experiments were designed to prove that the enzyme can co-catalyze this cascade reaction with imidazole in octane. The mechanism for the tandem reaction catalyzed by D-aminoacylase and imidazole was also proposed.In this thesis,72 compounds were synthesized and these compounds were characterized by IR,1H NMR,13C NMR, GC-MS and HRMS.