L-Methionine CAS 63-68-3

The production methods of methionine are divided into two categories: chemical methods and biological methods; chemical methods are divided into acrolein method, amino lactone method, malonate method, casein hydrolysis method, solid-liquid phase transfer catalysis method, etc. The world’s major methionine production companies have developed their own methionine production processes based on the acrolein method. The rest of the chemical methods are far behind the acrolein method in terms of process route and product yield, and are now basically abandoned.

1. Acrolein method: The acrolein method is a methionine production process developed in the 1960s. The acrolein method is further divided into the hydantoin method and the cyanohydrin method.
   • Hydantoin method: acrolein and methyl mercaptan undergo an addition reaction under the action of a catalyst to form methylthiopropionaldehyde; methylthiopropionaldehyde undergoes condensation reaction with NaCN or HCN, NH4HCO3 to obtain methylthioethylacetate. urea (hydantoin); then methylthioethyl hydantoin is hydrolyzed under the action of NaOH or K2CO3 to generate methionine sodium/potassium salt; further use H2SO4, HCl or CO2 acidification to obtain DL-methionine, and finally concentrate, crystallize, The methionine product was obtained by separation.
   • Cyanohydrin method: The products of the cyanohydrin process are mainly liquid DL-methionine hydroxy analogs or solid DL-methionine hydroxy analogs calcium salts. Acrolein and methyl mercaptan undergo addition reaction under the action of catalyst to generate methylthiopropionaldehyde; methylthiopropionaldehyde reacts with NaCN or HCN to generate 2-hydroxy-4-methylthiobutyronitrile; hydrolyzed with concentrated sulfuric acid 2 -Hydroxy-4-methylthiobutyronitrile can obtain methionine hydroxyl analog (MHA); 2-hydroxy-4-methylthiobutyric acid can be further reacted with Ca(OH)2 or CaO to obtain methionine hydroxyl analog ( MHA-Ca).
2. Aminolactone method
   The amino lactone method, also known as the γ-butyrolactone method, mainly uses γ-butyl lactone as the raw material to synthesize methionine.
3. Malonate method
   The malonate method mainly uses 2-methylthio ethane chloride and phthalimidoethyl malonate sodium salt, ethylacetamidocyanoacetate, diethylacetamidopropyl One of the diacid salts and ethyl acetoacetate was used as the raw material to prepare methionine, and the yields were 58%, 48%, 60.5%, and 70%, respectively. ester was reacted to obtain β-methylthioethyl acetoacetate, which was then reacted with NH3, followed by hydrolysis with NaOH to obtain methionine sulfoxide. The reduction of methionine sulfoxide with calcium sulfate was equivalent to DL-methionine, and the yield reached 70%.
4. Solid-liquid phase transfer catalysis
   The catalyst triethylamine was added dropwise to the mixture of glycine ethyl ester hydrochloride, benzaldehyde, anhydrous magnesium sulfate and dichloromethane to prepare ethyl benzylideneaminoacetate, ethyl benzylideneaminoacetate and 2-chloroethyl acetate Ethyl methyl sulfide was synthesized under the saponification of potassium hydroxide and anhydrous potassium carbonate to synthesize benzylidene aminomethyl ethyl sulfide ethyl acetate, and finally methionine was obtained by hydrolysis with concentrated hydrochloric acid, and the yield reached 59%.

In recent years, biological methods have developed rapidly in the production of pharmaceuticals and fine chemicals, and many companies have also conducted vigorous research on the production of methionine by biological methods.

1. Preparation of L-methionine by enzymatic resolution
   L-methionine is directly absorbed and utilized by the body without enzymatic conversion in animals. It is mainly used in the pharmaceutical industry, such as the preparation of compound amino acid infusions, nutritional supplements; adjuvant therapy for pneumonia, cirrhosis, fatty liver, gastric ulcer, etc. Wait. The enzymatic splitting method is to split the chemically synthesized DL-methionine into L-methionine by optical splitting. First, DL-methionine was acetylated to N-acetyl-DL-methionine, then N-acetyl-DL-methionine was separated by amino acid acylase, and finally L-methionine was obtained by decolorization, concentration, crystallization and other processes.
2. Production of methionine by fermentation
   The methionine produced by fermentation method is all L-type, which mainly relies on the ability of microorganisms to synthesize various amino acids. Through the mutagenesis of the strains, various auxotrophic and resistant mutants are selected to relieve the feedback in the metabolic regulation. And repression, to achieve the purpose of excessive synthesis of amino acids. The metabolic regulation mechanism of methionine biosynthesis is complex, and the production metabolic pathway is strictly feedback-inhibited. In the methionine biosynthesis pathway, not only the key enzyme aspartokinase is cooperatively feedback-inhibited by lysine and threonine, homoserine dehydrogenation The enzyme is feedback-inhibited by threonine, which is repressed by methionine, and in the synthesis of methionine from homoserine, S-adenosylmethionine has a stronger feedback inhibition effect on homoserine-O-transacetylase.
3. Chemical-enzymatic production of methionine
   The chemical method is to use chemical methods to synthesize hydantoin, cyanohydrin or methionine, and then use chemical hydrolysis to obtain solid methionine or liquid methionine hydroxyl analogs. The chemical-enzymatic method is to chemically synthesize cyanohydrin or methionine. As a substrate, methionine is prepared by hydrolysis with nitrile invertase. The chemical method and enzymatic method are combined to prepare methionine to achieve the purpose of reducing reaction steps, improving efficiency, reducing by-products, reducing three wastes and reducing costs.