L-threonine factory direct sales, chemical synthesis method

The main chemical synthesis methods of L-threonine are as follows:

I. Aldol Condensation Method

Reaction Principle

Using acetaldehyde and glycine as raw materials, an aldol condensation reaction occurs under alkaline conditions to produce α-amino-β-hydroxybutyric acid, which is then processed through reduction, resolution and other steps to obtain L-threonine.

Reaction Steps

Glycine and acetaldehyde undergo a condensation reaction under the action of an alkaline catalyst such as sodium hydroxide to form α-amino-β-hydroxybutyraldehyde.

A reducing agent such as sodium borohydride is used to reduce the aldehyde group to a hydroxyl group, resulting in α-amino-β-hydroxybutyric acid. Since the resulting product is a DL-type mixture, a resolution method is required. For example, an optically active acid or base is used to form a diastereoisomeric salt with DL-threonine, and then they are separated based on the differences in their solubilities to obtain L-threonine.

Advantages and Disadvantages

Advantages: The raw materials are relatively easy to obtain, and the reaction steps are relatively clear.

Disadvantages: Harsh reaction conditions such as the use of strong bases are required during the reaction process, which places high requirements on the equipment. Moreover, the resolution process is relatively complex, and the yield may be affected to some extent.

II. Hydantoin Method

Reaction Principle

Starting with glycine, it reacts with urea to form 5-methylenehydantoin, which then undergoes a condensation reaction with acetaldehyde under alkaline conditions, followed by hydrolysis, decarboxylation and other steps to obtain L-threonine.

Reaction Steps

Glycine reacts with urea under heating conditions to form 5-methylenehydantoin.

5-methylenehydantoin undergoes a condensation reaction with acetaldehyde in a sodium hydroxide solution to form the corresponding hydantoin derivative.

The hydantoin ring is opened through a hydrolysis reaction to obtain α-amino-β-hydroxy-δ-ureidobutyric acid.

Finally, a decarboxylation reaction is carried out under acidic conditions to remove the ureido group and generate L-threonine. Similarly, the product obtained from the reaction may be of the DL type, and resolution is required to obtain L-threonine.

Advantages and Disadvantages

Advantages: The reaction route is relatively mature, and the intermediate products are relatively stable and easy to operate.

Disadvantages: There are many reaction steps, and the overall yield may not be high. Moreover, the reaction conditions need to be well controlled in steps such as hydrolysis and decarboxylation; otherwise, side reactions are likely to occur.

III. Asymmetric Synthesis Method

Reaction Principle

Using a chiral catalyst or a chiral reagent, the reaction selectively produces L-threonine, avoiding the cumbersome resolution steps in traditional methods.

Reaction Steps

For example, using a chiral oxazaborolidine as a catalyst, sodium borohydride is used to reduce the α-ketoester to obtain an optically active α-hydroxyester, which is then processed through ammonolysis, hydrolysis and other reactions to obtain L-threonine. The specific process is as follows:

First, the α-ketoester is mixed with the chiral oxazaborolidine catalyst, and then sodium borohydride is added for a reduction reaction to generate a chiral α-hydroxyester.

Then, the ester group is converted into an amino group through an ammonolysis reaction to obtain α-amino-β-hydroxyester.

Finally, L-threonine is obtained through a hydrolysis reaction.

Advantages and Disadvantages

Advantages: It can directly synthesize optically active L-threonine, avoiding the resolution process and improving the synthesis efficiency and product purity.

Disadvantages: Chiral catalysts or reagents are usually expensive, the reaction conditions are relatively harsh, and high requirements are placed on the reaction equipment and operation techniques.