Study On The Synthesis Of Chiral N-Methyl-Alanine

N-methyl-L-alanine is an important modification of L-alanine, it can inhibit the proliferation of virus, inhibit tumor cell growth, improve immunity, it is an important medicine intermediate, N-methyl-L-alanine containing peptide natural products have been isolated from a variety of sources, and their secondary metabolites (e.g. vancomycin, cyclosporin) have found clinical use due in part to the physical properties and chemical stability conferred by the N-methyl-L-alanine present intheir structures. Therefore, it is particularly important for us to tudy on the synthesis and synthetic process of N-methyl-L-alanine.In this paper we use L-alanine as raw material, after esterification, acylation reaction of carboxyl and amino protection, then the methylation reaction, the final product after hydrolysis reaction. It provides a new technical route for the synthesis of N-methyl-L alanine.In this paper, to optimize the process conditions of esterification reaction, alcohol, catalyst, temperature, time and other factors, the factors of protection groups, acylation reaction solvents, temperature, time, substrate concentration, catalyst, solvent, time, temperature, substrate concentration, dropping the temperature and other factors of methylation reaction, temperature and other factors the hydrolysis reaction were optimized in detail, and finally discusses the research on the racemization of the methylation reaction, the influences of temperature, reaction time and methylation reaction of racemic.Through the experiment the optimum conditions are:(1) the esterification reaction of thionyl chloride as the catalyst, selection of raw materials, and the solvent is isopropyl alcohol, refluxing 5h, the yield reached 97.3%; (2) the acylation, selection of formamide as acylating agent, solvent is toluene, substrate concentration is 1.8mol/L, refluxing 4h, yield to 97.3%; (3) the methylation reaction, selection of sodium hydroxide as alkali, tetrahydrofuran as solvent, reaction time, molar ratio of substrate 4h, sodium hydroxide and sulfuric acid methyl ester was two 1:1.8:1.2, the reaction temperature is 15 DEG C, the yield reached 92.3%, and under this condition the product without racemization, the optical N-methyl-N-N-acyl alanine isopropyl pure; (4) the hydrolysis reaction, heating reflux in 3mol/L hydrochloric acid solution, the yield reached 53%, the total yield of the process is 46%.The new process developed in this paper, with the low price of raw materials, simple process, simple after treatment, no racemization, high product yield, and provides a reliable technique for the synthesis of N-methyl-L-alanine.