Study On Hydrolases Catayltic Two Kinds Of C-N Formation Reactions And Synethsis Of Omeprazole

The enzyme catalysis having greenness and high efficiency, and has been alwaysconsidered as a biocatalyst of rapid, specificity, it only for a certain reaction with highrecognition. Current studies suggests that many enzymes can catalyze the second reactionwith its active site that catalyze own reaction, namely catalytic promiscuity of enzyme, alsocalled non-specific of enzyme.Omeprazole was the first proton pump inhibitors pioneering developed by Astracompany of Sweden. Since listed, repeatedly occupy the top of world medicine sales due toits high efficiency and low toxicity, high cure rate, short course of treatment, well tolerability,having good curative effect for peptic ulcer disease.In this paper, we studied the hydrolase catalytic promiscuity on Mannich condensation,Markovnikov addition in organic solvent, meanwhile the synthetic process of omeprazole wasstudied and improved. Content is composed of four chapters:The first chapter introduces the application of enzyme catalysis in organic synthesis, theresearch progress of C-N bond formation reactions and the traditional synthesis method ofN-heterocyclic compound omeprazole.The second chapter explores the lipase from Candida rugosa catalyzed three-componentMannich condensation of aromatic aldehydes, ketones, N-heterocyclic compounds in microwater.16kinds of N-heterocyclic derivatives were synthetised. The control experimentsproved that the active site of lipase from Candida rugosa were responsible for those enzymaticreaction. The reaction conditions impact on the lipase catalyzed Mannich condensation wereinvestigated. The present method has many obvious advantages, compared to those reportedin the literature, including being environmentally more benign, the generality simplicity of themethodology, the ease of product isolation, the higher yield and potential for recycling oflipase.Markovnikov addition of vinyl compounds with N-heterocycle derivatives in organicsolvent catalyzed by protease was studied in the third chapter. The influences of reactionconditions including enzyme source, reaction media, enzyme dosage, reaction tempertature,reaction time, the molar ratio of substrate and the structures of substrates on enzymaticMarkovnikov addition were systematically investigated,16Markovnikov addition adductswere synthesized under the optimal conditions. Researches indicated that wide substrateapplication under mild reaction conditions, meanwhile, the protocol is conform to therequirements of the green chemistry in organic synthesis reaction. Synthetic process of omeprazole were researched in the fourth chapter, the studied focuson improving the nitrification and esterification reaction in the synthetic process of2-chlorinemethyl-4-methoxy-3,5-dimethyl pyridine hydrochloride. Concluding that thesuitable concentration of nitric acid is78%. Controling the temperature in90～95℃,4-methoxy-2,3,5-trimethyl pyridine-N-oxide: acetic anhydride=1:3.5, the dosage of DMAPis1.2g as per mole4-methoxy-2,3,5-trimethyl pyridine-N-oxide. Then the yield of2-methoxyl-4-methoxyl-3,5-dimethyl pyridine will increase5%. These conditons wouldshorten the reaction time, save production costs, reduce energy consumption, improveproduction efficiency, suitable for industrial production.