Synthesis Of Three N-heterocyclic Compounds Catalyzed By Protease

Heterocyclic compounds are a class of organic compounds with biological activity and pharmacological activity.The study of their synthesis method has always been one of the hot topics for chemical synthesis workers.However,N-heterocyclic compounds as an important branch of heterocyclic compounds have also attracted chemists’ s wide attention.Although the reported synthesis method has achieved a good catalytic yield,there are more or less problems such as complicated synthesis of catalysts or catalysts causing environmental pollution,cumbersome operations,harsh reaction conditions,etc.,which do not fully meet the requirements of “green chemistry”.Therefore,this paper will study three types of nitrogen-containing heterocyclic compounds catalyzed by protease.The main tasks are:(1)The synthesis of dipyrromethane and its derivatives catalyzed by α-chymotrypsin: Method for synthesizing dipyrromethane and its derivatives catalyzed by α-chymotrypsin had been achieved.The optimal catalyst was determined by screening the enzyme source as α-chymotrypsin,and the effects of solvent,temperature,enzyme amount,and solvent on the reaction were examined.Finally,the reaction was performed in a 40% aqueous ethanol solution(v/v)at 50°C.The dipyrromethene and its derivatives were synthesized through Friedel-Crafts reaction by the reaction of pyrrole and aromatic aldehydes catalyzed by 20 mg α-chymotrypsin.The reaction yield reached 69%.Compared with traditional catalysts,this method has the advantages of mild reaction conditions,environmental friendliness,and good substrate adaptability.(2)α-Chymotrypsin catalyzes the synthesis of 2-substituted benzimidazole derivatives: A method for synthesising 2-substituted benzimidazole derivatives catalyzed by α-chymotrypsin was obtained.After selection of the reaction conditions such as enzyme type,solvent,temperature,and enzyme amount,the optimum reaction conditions were determined as follows: α-chymotrypsin catalyzed the model reaction of o-phenylenediamine with ethyl acetoacetate at 50°C in ethanol,and the yield up to 93%.Expanded 16 products with a maximum yield of 96%.The method is green,safe and efficient,and has positive significance for the development of green chemistry.(3)Synthesis of quinazolinone derivatives catalyticed by alkaline protease: A method for synthesising quinazolinone derivatives catalyzed by alkaline proteases had been obtained.After selection of the reaction conditions such as the type of enzyme,the solvent,the temperature,the amount of the enzyme and the like,the final determined optimal reaction conditions are: alkaline protease was used as a catalyst to synthesize quinazolinone at 50°C in ethanol.This reaction achieved a high yield of 95% and extended 10 products with 72-95% yields.This method has mild reaction conditions and high yields,can be a reference for synthetic quinazolinone.