Improvement In The Synthesis Of N(2)-L-alanyl-L-glutamine

Glutamine is a rich amino acid in the human body which is participated in human metabolism,under normal circumstances,It are able to meet the metabolic needs which are synthesized inthe body, when the state of emergency and high decompose such as strenuous exercise、trauma、infection、the require of L-glutamine greatly exceeds the capacity of the body’ssynthesis, will need to supplement glutamine in vitro.The use of glutamine in potentialnutrition is limited because of its unstable chemical property、poor water solubility、maybreak down toxic substance and so on, so we need to find a suitable substitute.N(2)-L-Albany acryl-L-glutamine dipeptide which is short for proglumetacin dipeptide,candecomposition for glutamine to meet the needs of human metabolic in vivo and it have moreadvantage such as stable chemical properties、 good water solubility、 non-toxic,soproglumetacin dipeptide can be used as parenteral nutrition agent.Proglumetacin dipeptide arewidely used in foreign countries,its market demand is more and more big. since ourintroduction,the market prospect is broad.Existing synthesis methods of proglumetacin dipeptide are DCC couping method、organicphosphorus reagent method、NCA method、Glutamic acid method,etc.This article is a studyon the synthesis route and synthesis process, aimed at improving the production processwhich started from L-methyl lactate,thionyl chloride and glutamine for the synthesis ofproglumetacin dipeptide to enhance the product’s yield and reduce production costs. Thereaction factors of each step were examined to determine the optimum condition.The experiment results showed as following: L-methyl lactate first react with thionylchloride in the condition of using pyridine as catalyst,reflux temperature70℃,n(L-methyllactate):n(thionyl chloride)=1:1.1,almost quantitatively obtain the crude product of D-2-chlo-rine methyl propionate.D-2-chlorine methyl propionates were hydrolyzed in the condition ofpH10,D-2-chloropropionic acid’s yield reached73%,and purity up to97.6%.D-2-chloropropio-nic acid react with thionyl chloride in the condition of using DMF as catalyst,reflux temper-ature70℃,n(D-2-chloropropionic acid):n(thionyl chloride)=1:1.2,D-2-chloropropionyl chlori-de’s yield reached90%,and purity is more than99%.The total yield of D-2-chloropropionylchloride synthesized by L-methyl lactate up to65.7%(reported in the literature was54%). D-2-chloropropionyl chloride react with glutamine in the condition of using sodium hyd-roxide as acid binding agent,toluene/water as two-phase solvent,low temperature,n(glutamine):n(D-2-chloropropionyl chloride react):n(NaOH)=1:1.2:2.4.N-(D-2-chlorinated propyl acyl)-L-glutamine’s yield reached89%,and purity up to96%.N-(D-2-chlorinated propyl acyl)-L-glutamine react with28%aqueous ammonia to synthesize proglumetacin dipeptide, the reac-tion temperature was60℃,the crude product’s yield reached78%,and the purity was97.8%.The product’s yield reached90%,and the purity up to99.6%after refining.The improved synthesis route has the advantages of the following: the reaction cond iti-ons is mild, the raw materials are cheap and easy to get,low costs,the reaction process issimple,easy to operate,the product’s yield was improved,suitable for industrial production.