Synthesis And Optimization Of Ala-Gln

L-glutamine occupied an irreplaceable position in clinical medicine,immunology,nutrition and other disciplines.However,due to the limitation of the source and application process,the scientists are focusing on looking for some replacement.Luckily,L-alanyl-L-glutamine(called two peptide for short)was proved to be a suitable replacement.So highly synthesis of it can be helpful for the theory and practical application.Based on the previous synthesis strategy,we associated the character of fine chemical industry with the condition of equipment and facility to screen the suitable synthetic process with L-methyl lactate and L-glutamine as the starting materials.Taking the cost and waste of the process into consideration,we optimized the technology to meet the production.This technology shows high competitiveness in the market.The works are as followed:1.D-2-chloropropionyl chloride is obtained from D-2-chlorine methyl propionate as the starting material via chlorination,ester solution and acylation steps,which will react with Lglutamine to give N-(D-2-Chloropropionyl chloride)-L-glutamine under low temperature by controlling certain p H.The intermediates undergo ammonolysis in concentrated ammonia,concentration,refined,and dechloridation to afford the product N(2)-L-alanyl-L-.glutamine in sequence.2.2-chloropropionic acid methyl ester can be obtained from L-methyl lactate and thionyl chloride,which will undergo transesterification reaction to give D-2-chloropropionic acid in the presence of formic acid.D-2-chloropropionic acid reacts with thionyl chloride to produce D-2-chloropropionyl chloride.3.By controlling the temperature below 10? and p H between 10-11,D-chloride propionyl-L-glutamine is synthesized from L-.glutamine in toluene and aqueous solution of sodium hydroxide and the D-2-chloropropionyl via adding dropwise.4.D-chloride propionyl-L-glutamine will undergo ammoniation in alomost 35% concentrated ammonia at 65?.The crude product proceeds crystallization in methanol and decolorization with NORIT activated carbon to give the N(2)-L-alanyl-L-glutamine.After the above optimization,the technology has competitiveness in market.