Synthesis Of ?-ketoamide And Application In Double Enzyme System Catalyzed By ?-transaminase

a-ketoamide compounds is a class of dicarbonyl amide compounds,which has very important biological activity because of the special dicarbonyl structure in its molecular structure,thus is widely used in various biological enzyme inhibitors and biological tissue proteins.Most importantly,?-ketoamide compounds are precursor compounds for the synthesis of a range of complex drugs.Due to its broad applicability,how to synthesize?-ketoamide has received widespread attention of scientists.However,there are some disadvantages exist in synthesis methods,such as use transition metal catalysts,a large amount of solvent,limitation of substrate range,harsh reaction conditions and low conversion.Therefore,the development of a relatively green synthesis method is very necessary.?-transaminase is a kind of green pollution-free and efficient catalyst in the conversion of chiral amine.Therefore,co-transaminase is widely used in the synthesis of chiral amines.However,?-transaminase has a reaction equilibrium problem in the process of catalysis,large number of researchers choose to convert by-products into other substances to promote the reaction to forward moving,but the by-products are generally converted into unusable substances,resulting in waste of raw materials.Therefore,finding a new method to apply green transaminase is an urgent problem to be solved.In this paper,a relatively green,inexpensive,easily prepared aromatic ketones and ammonium hydrochloride were used as raw materials to synthesize aromatic?-ketoamide by using non-metallic catalyst nBu4NI.This method is the first time in the same way synthesis of three primary-,secondary-,and tertiary-a-ketoamides.Compared to other methods,the method is simple,the reaction conditions are relatively mild,the yield is high and only a small amount of solvent is needed.This method provides us with a new method for the synthesis of a-ketoamide,and at the same time,we think this method is very practical and has the potential for further industrial production.This paper also proposed that a-ketoamides were applied to cascade reaction system catalysised by the co-transaminase and carbonyl reductase.On the one hand,by the virtue of ?-transaminase,racemic phenethylamine was kinetic resoluted to obtain the chiral amine of high optical purity(from the amino donor,chiral compound 1),and a-ketoamide was converted to the target chiral 2-aminoamide(chiral compound 3),on the other hand,by use of carbonyl reductase,by-product acetophenoneis reduced to chiral alcohol(chiral compound 2),thus promoting the forward reaction,resulting in high conversion and high ee value of this enzyme reaction system.This reaction greatly increases the added value of the product,simultaneously synthesizes three chiral compounds with high optical purity.