CN117126087A - Compounds for preparing amino acid supplements and methods for preparing same - Google Patents

Abstract

The invention belongs to the technical field of feed additives, and specifically relates to a compound for preparing amino acid supplements and a preparation method thereof. The present invention uses methionine hydroxyl analogues as raw materials, first undergoes a methyl esterification reaction, and is purified to obtain 2-hydroxy-4-methylthiobutyric acid methyl ester; 2-hydroxy-4-methylthiobutyric acid methyl ester is then mixed with amino acids. An amidation reaction is carried out under the action of a catalyst to obtain a methionine hydroxyl analog-amino acid dipeptide compound. The development of the methionine hydroxyl analogue-amino acid dipeptide compound disclosed in the present invention has expanded the types of amino acid dipeptides. The methionine hydroxyl analogue will be used as a base fragment to replace amino acids. Since the more polar hydroxyl group in the molecule forms intramolecular hydrogen bond, its water solubility is greatly lower than that of a single crystalline amino acid, overcoming the shortcomings of crystalline amino acids in aquaculture. The methionine hydroxyl analog-amino acid dipeptide compound can be used in amino acid supplements, feed additives and aquatic feeds.

Description

Compounds for preparing amino acid supplements and methods for their preparation

Technical field

The invention belongs to the technical field of feed additives, and specifically relates to a compound for preparing amino acid supplements and a preparation method thereof.

Background technique

Fishmeal, as a protein source, is the main factor affecting feed costs for farmers. Supplementing amino acids can greatly reduce the proportion of fishmeal in feeds. Among them, methionine, lysine, and threonine are the main ones. These essential amino acids The supplement can greatly improve the production level and growth rate of aquatic products.

At present, commercial amino acid additives are mainly crystalline amino acids, including DL-methionine, L-methionine, DL-methionine hydroxy analog (MHA), DL-methionine hydroxy analog calcium salt (MHA-Ca) and N-hydroxymethylmethionine calcium , glycine, L-lysine salt (hydrochloride or sulfate), L-threonine, L-alanine, L-glutamic acid monosodium salt, etc., some of which are essential amino acids and some are non-essential amino acids As a food attractant. Among them, DL-methionine and L-lysine salts (hydrochloride or sulfate) are the most common. However, crystalline amino acids in feed cannot be absorbed simultaneously with bound amino acids. At the same time, the use of crystalline amino acids will change the pH of the feed and affect the utilization of feed by aquatic animals. In addition, due to the high solubility of crystalline amino acids in water, the crystalline amino acids in the feed are prone to dissolution and loss in the water environment, reducing the utilization rate of the feed and causing eutrophication of the water body. These factors have resulted in crystalline amino acids still not being widely used in aquatic feeds so far.

Therefore, solving problems such as unsynchronized amino acid absorption, feed pH and dissolution loss is crucial to promoting the application of amino acids in aquatic feeds and improving the production level and growth rate of aquatic products. For poultry animals, a large number of studies have shown that dietary protein entering the small intestine is digested by pepsin and trypsin to generate a mixture of amino acids and small peptides. The absorption of protein digestion products in the small intestine is mainly in the form of small peptides rather than amino acids. . Compared with the amino acid transport system, because the peptide transport system consumes less energy and is not easily saturated, animals absorb amino acid residues in polypeptides faster than free amino acids, and the absorption efficiency is also higher. On the other hand, Absorbing amino acids in the form of small peptides can avoid competition for the transport system from certain free amino acids during absorption, thereby improving transport efficiency. The nutritional significance of small peptides is mainly reflected in: (1) its role in protein nutrition; (2) improving the absorption of mineral elements; (3) improving the immunity of the animal body; (4) improving the production performance of animals; (5) Promote the development of intestinal mucosal structure and function, stimulate the secretion and activity of digestive enzymes; (6) improve the flavor and palatability of feed, etc., and can be added to feed as a flavoring agent. There are also studies showing that amino acids in peptide form can reduce the toxic effects of certain amino acids at high concentrations.

In order to solve the problems existing in the addition of free amino acids, researchers developed methionine dipeptide. Methionine dipeptide can be decomposed in the digestive tract of aquatic products and continuously provide methionine for protein synthesis. Compared with crystalline methionine, methionine dipeptide has much lower water solubility. In aquaculture, it can not only provide the amino acids needed for aquatic products, but also prevent the methionine in the feed from dissolving in the water environment and avoid water pollution. Among them, the methionine-methionine dipeptide developed by Evonik has been registered as a legal feed additive in many countries and has achieved good results.

Contents of the invention

The methionine hydroxyl analogue-amino acid dipeptide compound provided by the invention expands the types of amino acid dipeptides, and adjusts one amino acid into a methionine hydroxyl analogue. The methionine hydroxyl analogue is used as the basic fragment of the dipeptide compound. Due to its relatively low intramolecular polarity The large hydroxyl group forms intramolecular hydrogen bonds, and its water solubility is lower than that of traditional amino acid dipeptides.

One of the objects of the present invention is to provide a compound for preparing amino acid supplements.

In order to achieve the above objects, the present invention adopts the following technical solutions:

The structural formula of the compound is as formula III:

Among them, M is any one of H, Na, K, and Ca, and R is H, CH ₃ , CH ₃ SCH ₂ CH ₂ , CH ₃ CH(OH), HOOCCH ₂ CH ₂ , NH ₂ CH ₂ CH ₂ CH ₂ Any of CH ₂ .

The second object of the present invention is to provide a method for preparing the above compound.

In order to achieve the above objects, the present invention adopts the following technical solutions:

The preparation method specifically includes: 1) methionine hydroxyl analogue and methanol generate 2-hydroxy-4-methylthiobutyric acid methyl ester compound under the action of solvent 1 and catalyst 1;

2) The 2-hydroxy-4-methylthiobutyric acid methyl ester compound generates a methionine hydroxyl analogue-amino acid dipeptide compound salt with amino acids under the action of solvent 2 and catalyst;

3) The salt of the methionine hydroxyl analogue-amino acid dipeptide compound is then acidified and neutralized to form a methionine hydroxyl analogue-amino acid dipeptide compound;

The catalyst 1 is selected from one or more of sulfuric acid, phosphoric acid, sodium hydrogen sulfate, calcium dihydrogen phosphate, sodium tungstate, and tin dichloride; the catalyst 2 includes inorganic base sodium hydroxide, hydrogen oxidizing agent, carbonic acid Sodium, potassium carbonate or organic base sodium methoxide, triethylamine, pyridine; the solvent 1 is selected from one or more of toluene, benzene, and xylene; the solvent 2 is selected from methanol, ethanol, isopropyl alcohol, One or more of acetonitrile, methylene chloride, chloroform, and toluene; the amino acids are glycine, L-alanine, L-threonine, D,L-methionine, L-methionine, and L-glutamine One or more of amino acid monosodium salt and L-lysine; the methionine hydroxyl analogue is as formula I; the 2-hydroxy-4-methylthiobutyric acid methyl ester compound is as formula II:

Further, the molar ratio of the methionine hydroxyl analogue to methanol is 1:4-10.

Further, the molar ratio of methyl 2-hydroxy-4-methylthiobutyrate to amino acid is 1.0-1.1:1.0.

Furthermore, the mass of the catalyst 1 is 5% to 20% of the mass of the methionine hydroxyl analogue.

Further, the mass of the catalyst 2 is 1% to 2% of the mass of the amino acid.

Further, as a preference, the solvent 2 is ethanol.

Further, the reaction temperature in step 1) is 60°C to 110°C.

Further, as a preference, the reaction temperature in step 1) is 70°C to 110°C.

Furthermore, as a more preferred method, the reaction temperature in step 1) is 85°C to 100°C.

Further, the reaction temperature in step 2) is 65°C to 120°C.

Furthermore, as a preference, the reaction temperature in step 2) is preferably 70°C to 90°C.

Furthermore, as a more preferred method, the reaction temperature in step 2) is 70°C to 80°C.

The third object of the present invention is to provide a composition for preparing an amino acid supplement.

In order to achieve the above objects, the present invention adopts the following technical solutions:

The composition is composed of the above-mentioned compound and auxiliary materials in a mass ratio of 1:100 to 1000.

The fourth object of the present invention is to provide an amino acid supplement containing the above composition.

The fifth object of the present invention is to provide an application of the above-mentioned amino acid supplement in the preparation of poultry feed additives and aquatic feed additives.

The sixth object of the present invention is to provide a method for increasing the amino acid content in poultry feed and aquatic feed.

In order to achieve the above objects, the present invention adopts the following technical solutions:

The method is to add the above-mentioned amino acid supplement to poultry feed and aquatic feed.

The benefits of the present invention are:

1) The methionine hydroxyl analogue-amino acid dipeptide compound disclosed in the present invention has a new structure. Compared with the monomer free amino acid, the water solubility is significantly reduced, which can avoid the dissolution and loss of amino acids added to the feed in the water environment. water pollution.

2) The methionine hydroxyl analog-amino acid dipeptide compound disclosed in the present invention can be used not only as a methionine supplement, but also as a supplement for other amino acids, and can be flexibly matched. Especially when used in aquatic feed and poultry feed, it can greatly reduce the amount of fish meal. The use reduces feed costs.

3) The methionine hydroxyl analogue-amino acid dipeptide compound disclosed in the present invention can be used as an additive for aquatic feed and poultry feed. Compared with free amino acids, the usage amount of amino acids can be reduced by more than 50%; the solubility can be reduced by more than 50% compared with amino acids.

4) The methionine hydroxyl analog-amino acid dipeptide compound disclosed in the present invention can reduce the usage of methionine by 50% compared to traditional methionine dipeptide products, and using the methionine hydroxyl analog as a base fragment can be flexibly combined with other amino acids Flexible compatibility and simple synthesis.

Detailed ways

Preferred embodiments of the present invention will be described in detail below. Experimental methods without specifying specific conditions in the preferred embodiments usually follow conventional conditions. The examples are given to better illustrate the content of the present invention, but the content of the present invention is not limited to the examples. Therefore, those skilled in the art can make non-essential improvements and adjustments to the embodiments based on the above-mentioned content of the invention, which still fall within the protection scope of the present invention.

Example 1. Preparation of methyl 2-hydroxy-4-methylthiobutyrate sample 1

In a three-necked round-bottomed flask with a liquid separator, add 375.0 g (1.0 mol) of methionine hydroxyl analogue with a mass percentage of 40%, 323.63 g (10.0 mol) of methanol with a mass percentage of 99%, and the mass of the catalyst. 30 grams of sulfuric acid with a percentage content of 98%, then add 300 grams of toluene, raise the temperature to 90°C, keep it slightly boiling, and maintain the reflux state for 6 hours. After the reaction is completed, separate the upper organic layer and then concentrate under reduced pressure to obtain 159.19 grams of colorless methyl 2-hydroxy-4-methylthiobutyrate liquid, with a yield of 95% and a purity of 98%. .

Example 2. Preparation of methyl 2-hydroxy-4-methylthiobutyrate sample 2

In a three-necked round-bottomed flask with a liquid separator, add 151.52 grams (1.0 mol) of methionine hydroxyl analogue with a mass percentage of 99%, 129.42 grams (4.0 mol) of methanol with a mass percentage of 99%, and the mass of the catalyst. 7.5 grams of phosphoric acid with a percentage content of 85%, then add 900 grams of toluene, raise the temperature to 100°C, and maintain the reflux state for 6 hours. After the reaction is completed, separate the upper organic layer and then concentrate under reduced pressure to obtain 159.24 grams of colorless methyl 2-hydroxy-4-methylthiobutyrate liquid, with a yield of 96% and a purity of 99%. .

Example 3. Preparation of methyl 2-hydroxy-4-methylthiobutyrate sample 3

In a three-necked round-bottomed flask with a liquid separator, add 170.46 grams (1.0 mol) of methionine hydroxyl analogue with a mass percentage of 88%, 190.12 grams (6.0 mol) of methanol with a mass percentage of 99%, and the mass of the catalyst. 15 grams of calcium dihydrogen phosphate with a percentage content of 99%, then add 600 grams of toluene, raise the temperature to 85°C, and maintain the reflux state for 6 hours. After the reaction is completed, the mixture is statically separated, and the upper organic layer is separated, and then concentrated under reduced pressure to obtain 155.84 grams of colorless methyl 2-hydroxy-4-methylthiobutyrate liquid, with a yield of 93% and a purity of 98%. .

Example 4. Preparation of methyl 2-hydroxy-4-methylthiobutyrate sample 4

In a three-necked round-bottomed flask with a liquid separator, add 200.0 g (1.0 mol) of methionine hydroxyl analogue with a mass percentage of 75%, 190.12 g (6.0 mol) of methanol with a mass percentage of 99%, and the mass of the catalyst. 30 grams of sodium bisulfate with a percentage content of 99% was added, then 600 grams of toluene was added, the temperature was raised to 90°C, and the reaction was maintained in the reflux state for 6 hours. After the reaction is completed, separate the upper organic layer and then concentrate under reduced pressure to obtain 155.93 grams of colorless methyl 2-hydroxy-4-methylthiobutyrate liquid, with a yield of 94% and a purity of 99%. .

Example 5. Preparation of methionine hydroxyl analogue-glycine dipeptide

Add 83.79 grams (0.5 mol) of 2-hydroxy-4-methylthiobutyric acid methyl ester with a mass percentage of 98%, 331.76 grams of ethanol with a mass percentage of 99%, and The mixture was 34.45 grams (0.455 mol) of 99% glycine powder and 1.21 grams of 30% sodium hydroxide aqueous solution. The mixture was then heated to 85°C and stirred for 8 hours. After the reaction is completed, sulfuric acid is added to acidify the pH to 5.0, then the insoluble matter is filtered out, and the filtrate is concentrated under reduced pressure until there is no liquid, to obtain 87.50 grams of a white powdery methionine hydroxyl analogue-glycine dipeptide compound, with a yield of 90% (based on glycine ), the purity is 97%.

Example 6. Preparation of methionine hydroxyl analog-alanine dipeptide

Add 83.79 grams (0.5 mol) of 2-hydroxy-4-methylthiobutyric acid methyl ester with a mass percentage of 98%, 331.76 grams of ethanol with a mass percentage of 99%, and The mixture was 44.99 grams (0.5 mol) of 99% L-alanine powder and 0.67 grams of 30% sodium hydroxide aqueous solution. The mixture was then heated to 70°C and stirred for 8 hours. After the reaction, add sulfuric acid to acidify to pH 5.5, then filter out the insoluble matter, and concentrate the filtrate under reduced pressure until there is no liquid, to obtain 107.14 grams of white powdery methionine hydroxyl analogue-alanine dipeptide compound, with a yield of 92% ( Based on L-alanine), the purity is 95%.

Example 7. Preparation of methionine hydroxyl analog-methionine dipeptide

Add 82.94 grams (0.5 mol) of 2-hydroxy-4-methylthiobutyric acid methyl ester with a mass percentage of 99%, 829.4 grams of ethanol with a mass percentage of 99%, and 829.4 grams of ethanol with a mass percentage of 99% in a three-neck round bottom flask. The mixture was 75.36 grams (0.5 mol) of 99% D,L-methionine powder and 1.21 grams of 30% sodium hydroxide aqueous solution. The mixture was then heated to 80°C and stirred for 8 hours. After the reaction, add sulfuric acid to acidify to pH 5.6, then filter out the insoluble matter, and concentrate the filtrate under reduced pressure until there is no liquid, to obtain 133.37 grams of white powdery methionine hydroxyl analogue-methionine dipeptide compound, with a yield of 91% (D , L-methionine), the purity is 96%.

Example 8. Preparation of methionine hydroxyl analog-methionine dipeptide

Add 82.94 grams (0.5 mol) of 2-hydroxy-4-methylthiobutyric acid methyl ester with a mass percentage of 99%, 500.0 grams of ethanol with a mass percentage of 99%, and 500.0 grams of ethanol with a mass percentage of 99% in a three-neck round bottom flask. The mixture was 75.36 grams (0.5 mol) of 99% L-methionine powder and 1.21 grams of 30% sodium hydroxide aqueous solution, and then the temperature was raised to 85°C, and the reaction was stirred for 8 hours. After the reaction, add sulfuric acid to acidify to pH 5.5, then filter out the insoluble matter, and concentrate the filtrate under reduced pressure until there is no liquid, to obtain 136.30 grams of white powdery methionine hydroxyl analogue-methionine dipeptide compound, with a yield of 93% (in L -methionine), the purity is 96%.

Example 9. Preparation of methionine hydroxyl analog-methionine dipeptide

Add 82.94 grams (0.5 mol) of 2-hydroxy-4-methylthiobutyric acid methyl ester with a mass percentage of 99%, 600.0 grams of ethanol with a mass percentage of 99%, and The mixture was 80.53 grams (0.476 mol) of 99% monosodium L-glutamate powder and 1.21 grams of 30% sodium hydroxide aqueous solution, and then the temperature was raised to 90°C, and the reaction was stirred for 8 hours. After the reaction, add sulfuric acid to acidify to pH 6.0, then filter out the insoluble matter, and concentrate the filtrate under reduced pressure until there is no liquid, to obtain 131.71 grams of white powdery methionine hydroxyl analogue-glutamic acid dipeptide compound, with a yield of 90% ( Based on L-methionine), the purity is 98%.

Example 10. Preparation of methionine hydroxyl analog-lysine dipeptide

Add 83.79 grams (0.5 mol) of 2-hydroxy-4-methylthiobutyric acid methyl ester with a mass percentage of 98%, 331.76 grams of ethanol with a mass percentage of 99%, and The mixture was 76.12 grams (0.5 mol) of 98% L-lysine powder and 0.67 grams of 30% sodium hydroxide aqueous solution. The mixture was then heated to 85°C and stirred for 8 hours. After the reaction, add sulfuric acid to acidify to pH 6.5, then filter out the insoluble matter, and concentrate the filtrate under reduced pressure until there is no liquid, to obtain 133.32 grams of white powdery methionine hydroxyl analogue-lysine dipeptide compound, with a yield of 91% ( Based on L-alanine), the purity is 95%.

Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not limiting. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified. Modifications or equivalent substitutions without departing from the spirit and scope of the technical solution of the present invention shall be included in the scope of the claims of the present invention.

Claims (12)

1. Compounds for preparing amino acid supplements, characterized in that the structural formula of the compound is as formula III: Among them, M is any one of H, Na, K, and Ca, and R is H, CH ₃ , CH ₃ SCH ₂ CH ₂ , CH ₃ CH(OH), HOOCCH ₂ CH ₂ , NH ₂ CH ₂ CH ₂ CH ₂ Any of CH ₂ . 2. The preparation method of the compound according to claim 1, characterized in that the preparation method specifically includes: 1) Methionine hydroxyl analogue and methanol generate 2-hydroxy-4-methylthiobutyric acid methyl ester compound under the action of solvent 1 and catalyst 1; 2) The methyl 2-hydroxy-4-methylthiobutyrate compound reacts with amino acids under the action of solvent 2 and catalyst 2 to generate a methionine hydroxyl analogue-amino acid dipeptide compound salt; 3) The salt of the methionine hydroxyl analogue-amino acid dipeptide compound is then acidified and neutralized to form a methionine hydroxyl analogue-amino acid dipeptide compound; The catalyst 1 is selected from one or more of sulfuric acid, phosphoric acid, sodium hydrogen sulfate, calcium dihydrogen phosphate, sodium tungstate, and tin dichloride; the catalyst 2 includes inorganic base sodium hydroxide, hydrogen oxidizing agent, carbonic acid Sodium, potassium carbonate or organic base sodium methoxide, triethylamine, pyridine; the solvent 1 is selected from one or more of toluene, benzene, and xylene; the solvent 2 is selected from methanol, ethanol, isopropyl alcohol, One or more of acetonitrile, methylene chloride, chloroform, and toluene; the amino acids are glycine, L-alanine, L-threonine, D,L-methionine, L-methionine, and L-glutamine One or more of amino acid monosodium salt and L-lysine; the methionine hydroxyl analogue is as formula I; the 2-hydroxy-4-methylthiobutyric acid methyl ester compound is as formula II: 3. The preparation method according to claim 2, characterized in that the molar ratio of the methionine hydroxyl analogue to methanol is 1:4-10. 4. The preparation method according to claim 2, characterized in that the molar ratio of methyl 2-hydroxy-4-methylthiobutyrate to amino acid is 1.0 to 1.1:1.0. 5. The preparation method according to claim 2, characterized in that the mass of the catalyst is 5% to 20% of the mass of the methionine hydroxyl analogue. 6. The preparation method according to claim 2, characterized in that the mass of the catalyst 2 is 1% to 2% of the mass of the amino acid. 7. The preparation method according to claim 2, characterized in that the reaction temperature in step 1) is 60°C to 110°C. 8. The preparation method according to claim 2, characterized in that the reaction temperature in step 2) is 65°C to 120°C. 9. A composition for preparing an amino acid supplement, characterized in that the composition is composed of the compound according to claim 1 and auxiliary materials in a mass ratio of 1:100 to 1000. 10. An amino acid supplement containing the composition of claim 9. 11. Application of the amino acid supplement according to claim 10 in the preparation of poultry feed additives and aquatic feed additives. 12. A method for increasing the amino acid content in poultry feed and aquatic feed, characterized in that the method is to add the amino acid supplement of claim 10 to poultry feed and aquatic feed.