Optimization Of Synthesis Process Of L-Selenium-Methylselenocysteine

L-Se-Methylselenocysteine（L-Se Mc）is a new type of food nutrition fortifier and the only organic selenium compound approved as a food additive.However,domestic industrial production has not yet been realized,and the synthetic routes are only applicable to laboratories.In large-scale production,it is mainly restricted by the methods used expensive reagents which lead to high costs（such as enzyme）or flammable and explosive reagents（such as Na BH₄,and so on）.Because of these problems,based on the investigation of the existing synthetic methods,the preparation scheme of L-Se Mc was optimized,and the reasonable technological route was obtained:1)With SOCl₂,1,4-Dioxane and H₂O at low temperatures for solvent of SOCl₂with L-serine to obtain 3-chloro-L-alanine hydrochloride in one step,and the total yield was 89.7%;2)L-selenocystine（L-Se C₂）was obtained by reacting 3-chloro-L-alanine hydrochloride with Na₂Se₂produced by the reaction between Se and（CH₃COO）₃BHNa/CH₂（OH）SO₂,and the total yield was 73.0%and 58.0%,respectively;3)Selenocysteine（Se C）was obtained by the reaction between L-Se C₂and（CH₃COO）₃BHNa at room temperature,and then L-Se Mc was obtained by methylation with CH₃I,and the total yield was 84.0%.The various process conditions in the route,such as reaction temperature,reaction time,feeding method,material ratio,p H,etc,were optimized and verified through the single factor experiments.The final optimized three-step synthesis process was as follows:（1）The optimized synthesis process of 3-chloro-L-alanine hydrochloride was:Preparation of compound solvent system mixing time is 9 h and n（H₂O）:n（SOCl₂）=2:1,n（SOCl₂）:n（L-serine）=29:20,the reaction temperature 35℃,the reaction time 30 h.（2）The optimized synthesis process of L-Se C₂was:（1）Sodium triacetoxyborohydride method:n（CH₃COO）₃BHNa):n（Na OH）:n（Se）=5:22:9,water as olvent,the reaction temperature for preparing Na₂Se₂was 25℃and the reaction time was 40 min.（2）Sodium formaldehyde sulfoxylate method:n（CH₂（OH）SO₂Na）:n（Na OH）:n（Se）=10:20:13,water as solvent,the reaction temperature for preparing Na₂Se₂was 60℃and the reaction time was 1 h,the p H of the 3-chloro-L-alanine hydrochloride solution was 8.（3）The optimized synthesis process of L-Se Mc was:n（（CH₃COO）₃BHNa）:n（CH₃I）:n（L-Se C₂）=157:200:50,water as solvent,the reaction temperature was normal,the reaction time of the two steps was 20min,n（L-Se C₂）:n（ethanol）=1:85.In this paper,the synthesis of L-Se Mc has the advantages of fewer side reactions,high raw material utilization,good safety,greener process,lower cost and higher yield,which is more suitable for industrial production than the previous synthesis route.