The Synthesis And Process Research Of L-5-Methyl Tetrahydrofolate Calcium

L-5-methyl tetrahydrofolic acid(L-5-MTHF)is a new type of folic acid drugs.It was known that it can serve as food additives,dietary supplement,etc.With important pharmacological effects,it can take participate in a lot of important physiological and biochemical body reactions,in which it can pass through the blood-brain barrier to prevent Alzheimer's disease,cell anemia,etc.L-5-MTHF has more advantages compared with other folate drug,which has a good curative effect and function,less side effects.So it will become the common focus of the medical and pharmaceutical research.The process of L-5-MTHF and intermediate product tetrahydrofolate(THF)were researched.The reaction used folic acid as raw material,sodium borohydride as reducing agent,sodium hyposulfite as antioxidant,and in order to control reaction solution's pH,we employed citric acid-disodium hydrogen phosphate buffer solution.Finally,the high purity and high yield target product was obtained.A reasonable and feasible High performance liquid chromatography(HPLC)detection was set up to check the reative process.The influential factors of the reaction were studied,such as the material molar ratio,reaction temperature,buffer concentration,pH values,etc.Through contrast experiment,THF's optimal synthesis condition was determined.When the molrate of folic acid: sodium borohydride: sodium hyposulfite was 1:17.5:1.3,reaction temperature was 30 ?,buffer concentration was 0.2 M,buffer pH value was 4.5,the purity of THF was 90.1% and the yield was 81.1%.The purity of 5-MTHF was 88.9%and the yield was 70.4%,While the molrate of folic acid:sodium borohydride was 1:38,the reaction temperature was 50?,the concentration of the buffer was 0.2 M,pH value was 6.5 and the addition of formaldehyde was 0.4 mL.Finally,we used organic?-phenethylamine to resolve 5-MTHF,and then crystallized,the optical purity of L-5-MTHF was 98.5%.The product was characterized by1H-NMR,FT-IR and UV-spectrum.This synthetic route is a simple method,its reaction time is short and easy to control and the reaction is environment friendly.This method provides a scalable to get high yield high purity L-5-MTHF for the future.