Study On The Synthesis,Separation And Purification Of N~ε,N~ε,N~ε-Trimethyllysine

N^ε,N^ε,N^ε-trimethyllysine is a natural amino acid derivative derived from kelp.It has an excellent antihypertensive effect with few side effects.It also has the effects of lowering cholesterol,lowering blood lipids,and anti-platelet aggregation.At present,it is mainly prepared by chemical synthesis,but the yield of the product is low.At the same time,it also lacks an efficient large-scale separation and purification method,and the purity of the product cannot meet the requirements for medicinal use.Therefore,the development of green and efficient synthesis,separation and purification processes for N^ε,N^ε,N^ε-trimethyllysine is of great significance to industrial production.This thesis mainly forcus the optimization research on the synthesis process of N^ε,N^ε,N^ε-trimethyllysine,and carried out the research on the separation and purification process of elution crystallization for the first time.The synthesis process research mainly includes the synthesis of N^α-protected lysine and the study of the trimethylation reaction conditions.Using nickel chloride as a chelating agent,the influence of the molar ratio of lysine to nickel chloride,reaction temperature,p H,reaction time and other factors on the complexation of lysine N^α-Ni ions was studied,and the synthesized N^αprotected lysine was obtained.The best solution for acid is:p H 10,heating in a water bath at 60℃for 2 hours,and the yield of complexation can reach 87.81%.On the basis of the above research,using dimethyl carbonate as the methylation reagent,the reaction conditions for the trimethylation of N^α-protected lysine were explored.The optimal conditions for the synthesis of N^ε,N^ε,N^ε-trimethyllysine are finally determined as follows:the system temperature is 130℃,the molar ratio of dimethyl carbonate to N^α-protected lysine is 10:1,the reaction time is 8 h,and sodium carbonate as catalyst.The product is separated and purified by elution crystallization method.The effects of temperature,anti-solvent type,time,addition amount of seed crystals,volume ratio of anti-solvent to solvent,stirring speed and anti-solvent addition speed on the product purity and yield were investigated.The process conditions for the crystallization of N^ε,N^ε,N^ε-trimethyllysine are preliminarily determined:the crystallization temperature is15℃,the anti-solvent type is isobutanol,the crystallization time is 9 hours,the amount of seed crystals added is 3%,the anti-solvent and the The volume ratio of the solvent is4:7,the stirring speed is 200 r·min^-1,and the anti-solvent addition speed is 0.6 m L·min^-1.The response surface method was used to optimize the key parameters（crystallization temperature,crystallization time,anti-solvent to solvent volume ratio）that affect the crystallization of N^ε,N^ε,N^ε-trimethyllysine.In the experiment we found,the optimal reaction time was 10.69 h,the crystallization temperature was 14.91℃,and the volume ratio of anti-solvent to solvent was 1.77.Under the above conditions,the highest purity can reach 91.1%,and the yield is 74.7%.The synthesis,separation and purification process of N^ε,N^ε,N^ε-trimethyllysine established in this study can provide support for the large-scale production of N^ε,N^ε,N^ε-trimethyllysine.