Synthesis And Process Optimization Of L-Selenomethionine

L-Selenomethionine（L-SeMet）widely exists in plants,animals and fungus,but it can not meet people’s increasing demand for selenium because of its low content.Chemical synthesis of L-Selenomethionine is the most effective method to solve the current selenium supplement gap,but the reported synthesis process only stays in the laboratory stage because of environmental protection or synthesis efficiency.Therefore,it is urgent to explore the process route suitable for the industrial production of L-SeMet.Based on the investigation of the existing synthetic methods,a preparation project suitable for the industrial production of L-SeMet was optimized:1)Sulfonium salt was obtained by the reaction of Methyl iodide/Dimethyl sulfate with L-Methionine,and then L-Homoserine was obtained by thermal cracking of Sodium bicarbonate.The optimized process conditions are as follows:（1）Iodomethane synthesis method:n（L-Methionine）∶n（Iodomethane）∶n（Sodium bicarbonate）=5∶10∶8,with water as solvent,the reaction temperature was 90℃and the reaction time was 10 h.（2）Dimethyl sulfat synthesis method:n（L-Methionine）∶n（Dimethyl sulfate）∶n（Sodium bicarbonate）=10∶19∶18,with water as solvent,the reaction temperature was 90℃and the reaction time was 10 h.The highest yields were 71.61%and 66.83%respectively.2)L-Bromohomoserine was obtained by reacting L-Homoserine hydrochloride with Acetic hydrobromate.The optimized process conditions are as follows:L-Homoserine synthesis process was:n（L-Homoserine）∶n（Hydrobromide）=1.0∶3.1,the reaction temperature was 90℃,the reaction time was 12 h,and the maximum yield was 77.72%.3)Disodium diselenide was obtained by the reaction of selenium with Sodium triacetoxyborohydride/Sodium bisulfate formaldehyde,and then reacted with L-Bromohomoserine to obtain L-Selehypercysteine.The optimized process conditions are as follows:（1）Sodium triacetoxyborohydride method:n（Se）∶n（NaOH）∶n（Sodium triacetoxyborohydride）∶n（L-Bromohomoserine）=27∶52∶13∶10,the reaction temperature was 25℃,and the reaction time was 40 min;（2）Sodium bisulfate formaldehyde method:n（Se）∶n（NaOH）∶n（Sodium bisulfate formaldehyde）∶n（L-Bromohomoserine）=18∶50∶11∶10.The reaction temperature was60℃and the reaction time was 1 h.The final yields were 62.42%and 43.33%respectively.4)L-Selenomethionine was obtained by the reaction of L-Selehypercysteine with sodium triacetoxyborohydride at room temperature and then methylated with iodomethane.The optimized process conditions are as follows:n（L-Selehypercysteine）∶n（NaOH）∶n（Sodium triacetoxyborohydride）∶n（CH₃I）=10∶92∶34∶20,using aqueous solution as solvent and the reaction temperature was 25℃.Idimethane ethanol solution was added after adding sodium triacetoxyborohydride and stirring for 10 min,then precipitating solid in water bath for 5 min.Finally,the highest yield was 79.50%.