CN109734575A - A method of preparing 3-hydroxybutyrate amino-acid salt compound - Google Patents
A method of preparing 3-hydroxybutyrate amino-acid salt compound Download PDFInfo
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- CN109734575A CN109734575A CN201910008534.1A CN201910008534A CN109734575A CN 109734575 A CN109734575 A CN 109734575A CN 201910008534 A CN201910008534 A CN 201910008534A CN 109734575 A CN109734575 A CN 109734575A
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- hydroxybutyrate
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- acid salt
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- -1 3-hydroxybutyrate amino-acid salt compound Chemical class 0.000 title claims abstract description 27
- 238000000034 method Methods 0.000 title claims abstract description 23
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- OMSUIQOIVADKIM-UHFFFAOYSA-N ethyl 3-hydroxybutyrate Chemical compound CCOC(=O)CC(C)O OMSUIQOIVADKIM-UHFFFAOYSA-N 0.000 claims abstract description 29
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/26—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having more than one amino group bound to the carbon skeleton, e.g. lysine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/01—Saturated compounds having only one carboxyl group and containing hydroxy or O-metal groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention provides a kind of methods for preparing 3-hydroxybutyrate amino-acid salt compound, it include: that ethyl 3-hydroxybutanoate or 3-hydroxybutyrate methyl esters is added in (1) in the reaction vessel, using water as solvent, then it is added base catalyst, ethyl 3-hydroxybutanoate or 3-hydroxybutyrate methyl esters obtain 3-hydroxybutyrate through alkali catalyzed hydrolysis；(2) 3-hydroxybutyrate is added in reaction vessel, ethyl alcohol is added as solvent, adds natural amino acid, 3- reacts 12-24 hours at a temperature of 30-80 DEG C, obtains 3-hydroxybutyrate amino-acid salt compound.Clipped purification process of the present invention, it is easy to operate, it can save material.The present invention using in ethyl alcohol at salt by the way of, make reaction carry out more thoroughly, not only save the reaction time, also reduce energy consumption and loss of material, improve product yield, production cost is greatly saved.
Description
Technical field
The present invention relates to chemical technology fields, and in particular to a kind of side for preparing 3-hydroxybutyrate amino-acid salt compound
Method.
Background technique
Beta-hydroxy-butanoic acid amino-acid salt can be absorbed into blood, it can decomposite free amino acid and β-hydroxyl there
Base butyric acid.Since beta-hydroxy-butanoic acid is a kind of group water solution, more ketones can be added in blood by eating the product, this can
To allow the body of eater to obtain better energy production.Very stable when beta-hydroxy-butanoic acid is in conjunction with amino acid, it passes through manufacture
Additional amino acid nutrient needed for ketone provides additional benefit.
Contain hydroxyl and carboxyl Liang Zhong functional group in 3-hydroxybutyrate molecule, the comprehensive performance with pure and mild carboxyl, is one
Kind important pharmaceutical raw material and pharmacological agents.Wherein (R) -3-hydroxybutyrate is the R- configuration in 3-hydroxybutyrate racemic modification
Isomers, be a kind of chipal compounds with optical activation, No. CAS is 625-72-9.(R) -3-hydroxybutyrate is lactation
The compound generated in animal body by the long-chain fat acid metabolic in liver, is present in blood plasma and periphery as main ketoboidies
In tissue, week tissue has good penetrating power and quick diffusivity out of the human body, may be used as body most tissues
In energy source.Generally, R-3-HB exists mostly in the form of various salt.(R) -3-hydroxybutyrate is in addition to trophic function
Except, also have the function of many diseases for the treatment of, comprising: can treat many diseases for having benefited from ketone body levels raising (as wrapped
Include the neurological disorders disease of epilepsy and myoclonia and the neurodegenerative disorders including A Erzimo disease and dementia etc.)；Pass through
Ubiquinone is aoxidized to reduce free radical injury (such as ischemic disease)；Reinforce metabolic efficiency (to improve training effectiveness and sports achievement, control
It treats and supports deficiency, angina pectoris, myocardial infarction etc.)；Treat such as relevant disease of the cancer especially cancer of the brain (such as astrocytoma)；It is right
It is had a good effect in carbohydrate metabolism disturbance (the low ketoboidies disease of such as type-1 diabetes mellitus, type-2 diabetes mellitus, hypoglycemia)；It can be used for
Prevent and treat sclerotin reduction, osteoporosis, serious osteoporosis and related fracture etc..Based on these functions, (R) -3- hydroxyl
Butyric acid and its salt may be used as food additives and drug, have huge health care and medical value.
(R) preparation of -3-hydroxybutyrate is mainly chemical method and microbial method.The shortcomings that chemical synthesis of the prior art
The optical purity of mainly product is relatively low, i.e., enantiomeric excess value (ee value) is relatively low.Microbe fermentation method can be direct
Obtain R-3-HB；Or the poly- R-3-HB of Microbe synthesis is first used, the polymer of then degrading obtains R-3-HB, microbial method
Product ee value is higher, but since technique is more complex, production investment is big, causes the cost and price of R-3-HB high.
Summary of the invention
The purpose of the invention is to provide a kind of method for preparing 3-hydroxybutyrate amino-acid salt compound, can reduce
Cost, and high income.
The purpose of the present invention is what is be achieved through the following technical solutions:
A method of preparing 3-hydroxybutyrate amino-acid salt compound, comprising:
(1) ethyl 3-hydroxybutanoate or 3-hydroxybutyrate methyl esters are added in the reaction vessel, and water is added as solvent, so
After the molar ratio of base catalyst, ethyl 3-hydroxybutanoate or 3-hydroxybutyrate methyl esters and base catalyst is added is 1:2.5~4.5；
Ethyl 3-hydroxybutanoate or the reaction of 3-hydroxybutyrate methyl esters and base catalyst, ethyl 3-hydroxybutanoate or 3-hydroxybutyrate methyl esters warp
Alkali catalyzed hydrolysis obtains 3-hydroxybutyrate；
(2) 3-hydroxybutyrate obtained in step (1) is added in reaction vessel, ethyl alcohol is added as solvent, adds
The molar ratio of natural amino acid, 3-hydroxybutyrate and natural amino acid is 1~1.1:1.5；3-hydroxybutyrate and natural amino acid
At a temperature of 30-80 DEG C, reacts 12-24 hours, obtain 3-hydroxybutyrate amino-acid salt compound.
Further, in step (1), the base catalyst be selected from one of sodium hydroxide, potassium hydroxide, lithium hydroxide or
It is a variety of.
Further, in step (1), the time that ethyl 3-hydroxybutanoate or 3-hydroxybutyrate methyl esters are reacted with base catalyst is
3-12 hours.
Further, in step (1), further includes: ethyl 3-hydroxybutanoate or 3-hydroxybutyrate methyl esters are reacted with base catalyst
Afterwards, water is removed through vacuum distillation；It adds ethyl alcohol dispersion is sufficiently stirred and be cooled to 0 DEG C or less crystallization, and protected between 0 DEG C -5 DEG C
Temperature 12 hours or more, suction filtration isolated solid, with ethanol washing solid, dried to get 3-hydroxybutyrate is arrived.
Further, in step (2), the natural amino acid is selected from alanine, valine, leucine, isoleucine, dried meat ammonia
Acid, phenylalanine, tryptophan, methionine, glycine, serine, threonine, cysteine, tyrosine, asparagine, paddy ammonia
One of amide, lysine, arginine, histidine, aspartic acid, glutamic acid are a variety of.
Further, in step (2), further includes: 3-hydroxybutyrate and natural amino acid after completion of the reaction, are filtered,
Active carbon is added in filtrate to decolourize, after refiltering, removes ethyl alcohol through vacuum distillation；Isopropanol is added to be sufficiently stirred point
It dissipates, is cooled to 0 DEG C or less crystallization, and keep the temperature to filter for 24 hours or more between 0 DEG C -5 DEG C and isolate solid, obtained after dry
3-hydroxybutyrate amino-acid salt compound.
Further, the weight of the active carbon is the 20% of 3-hydroxybutyrate weight.
In conclusion by adopting the above-described technical solution, compared with prior art, the present invention having the advantage that
The present invention provides a kind of new methods for preparing 3-hydroxybutyrate amino-acid salt compound, with ethyl 3-hydroxybutanoate
Or 3-hydroxybutyrate methyl esters is raw material and catalyst reaction, prepares after 3-hydroxybutyrate with natural amino acid into salt, obtains 3- hydroxyl
Base butyric acid amino-acid salt compound.Clipped purification process, it is easy to operate, it can save material.The present invention uses ethyl alcohol
The middle mode at salt carries out reaction more thorough, not only saves the reaction time, also reduce energy consumption and loss of material, mention
High product yield, is greatly saved production cost.
Present invention omits the concentrated water processes and 3-hydroxybutyrate of the preparation of 3-hydroxybutyrate amino-acid salt compound crude product
The anhydrous isopropyl alcohol refining and concentrating of amino-acid salt compound finished product plus acetone crystallization such as are filtered, washed, dry at a series of processes,
Organic solvent-acetone is not only eliminated, but also has saved the loss of material and energy consumption of respective process, considerably reduces 3-
Hydroxybutyric acid at amino acid complex production cost.Reduce in the crude of 3-hydroxybutyrate propylhomoserin acid complex and purification
Thermal histories, ensure that 3- at the problem of also avoiding the easy moisture absorption of 3-hydroxybutyrate complex compound finished product at amino acid complex in water
The quality of hydroxybutyric acid propylhomoserin acid complex.
Specific embodiment
A specific embodiment of the invention is further described in detail below.
Embodiment 1
200 grams of water are added in reaction vessel, 130 grams of ethyl 3-hydroxybutanoates are added with stirring, to 3-hydroxybutyrate second
After ester thoroughly dissolves, 166 grams of addition lithium hydroxides then heat to 35 DEG C, isothermal reaction 24 hours.After completion of the reaction, it depressurizes
Water is distilled off；It is cooled to 0 DEG C, ethyl alcohol is added, dispersion 2 hours is sufficiently stirred, is cooled to 0 DEG C or less crystallization, and at 0 DEG C -5 DEG C
Between keep the temperature 12 hours or more, filter separation, it is dry at 35 DEG C with ethanol washing solid, that is, obtain 147 grams of 3-hydroxybutyrates
Finished product, yield 90.1%.
It takes 147 grams of 3-hydroxybutyrate finished products to be added in reaction vessel, adds ethyl alcohol, stirring and dissolving is added 75 grams of L- and relies
Propylhomoserin then heats to 45 DEG C of isothermal reactions 12 hours.After completion of the reaction, ethyl alcohol is distilled off below temperature 70 C, is cooled to 0
DEG C, isopropanol is added, dispersion is sufficiently stirred, be cooled to 0 DEG C or less crystallization, and keep the temperature 24 hours or more between 0 DEG C -5 DEG C, takes out
Filter separation washs solid with isopropanol, drying at 35 DEG C obtains 165 grams of 3-hydroxybutyrate lysine salt compound finished products, receives
Rate is 92%.
Embodiment 2
200 grams of water are added in reaction vessel, 130 grams of 3-hydroxybutyrate methyl esters are added with stirring, to 3-hydroxybutyrate first
After ester thoroughly dissolves, 166 grams of addition lithium hydroxides then heat to 35 DEG C, isothermal reaction 24 hours.After completion of the reaction, it depressurizes
Water is distilled off；It is cooled to 0 DEG C, ethyl alcohol is added, dispersion 2 hours is sufficiently stirred, is cooled to 0 DEG C or less crystallization, and at 0 DEG C -5 DEG C
Between keep the temperature 12 hours or more, filter separation, it is dry at 35 DEG C with ethanol washing solid, that is, obtain 147 grams of 3-hydroxybutyrates
Finished product, yield 90.1%.
It takes 147 grams of 3-hydroxybutyrate finished products to be added in reaction vessel, adds ethyl alcohol, stirring and dissolving is added 75 grams of L- and relies
Propylhomoserin then heats to 45 DEG C of isothermal reactions 12 hours.After completion of the reaction, ethyl alcohol is distilled off below temperature 70 C, is cooled to 0
DEG C, isopropanol is added, dispersion is sufficiently stirred, be cooled to 0 DEG C or less crystallization, and keep the temperature 24 hours or more between 0 DEG C -5 DEG C, takes out
Filter separation washs solid with isopropanol, drying at 35 DEG C obtains 165 grams of 3-hydroxybutyrate lysine salt compound finished products, receives
Rate is 92%.
Embodiment described above is merely to illustrate technical idea and feature of the invention, in the art its object is to make
Technical staff can understand the content of the present invention and implement it accordingly, patent model of the invention only cannot be limited with the present embodiment
It encloses, i.e., it is all according to same changes or modifications made by disclosed spirit, it still falls in the scope of the patents of the invention.
Claims (7)
1. a kind of method for preparing 3-hydroxybutyrate amino-acid salt compound characterized by comprising
(1) ethyl 3-hydroxybutanoate or 3-hydroxybutyrate methyl esters are added in the reaction vessel, and water is added as solvent, then plus
The molar ratio for entering base catalyst, ethyl 3-hydroxybutanoate or 3-hydroxybutyrate methyl esters and base catalyst is 1:2.5~4.5；3- hydroxyl
Base ethyl butyrate or 3-hydroxybutyrate methyl esters are reacted with base catalyst, and ethyl 3-hydroxybutanoate or 3-hydroxybutyrate methyl esters are urged through alkali
Change hydrolyzes to obtain 3-hydroxybutyrate；
(2) 3-hydroxybutyrate obtained in step (1) is added in reaction vessel, ethyl alcohol is added as solvent, added natural
The molar ratio of amino acid, 3-hydroxybutyrate and natural amino acid is 1~1.1:1.5；3-hydroxybutyrate and natural amino acid are in 30-
At a temperature of 80 DEG C, reacts 12-24 hours, obtain 3-hydroxybutyrate amino-acid salt compound.
2. a kind of method for preparing 3-hydroxybutyrate amino-acid salt compound according to claim 1, which is characterized in that step
Suddenly in (1), the base catalyst is selected from one of sodium hydroxide, potassium hydroxide, lithium hydroxide or a variety of.
3. a kind of method for preparing 3-hydroxybutyrate amino-acid salt compound according to claim 1, which is characterized in that step
Suddenly in (1), the time that ethyl 3-hydroxybutanoate or 3-hydroxybutyrate methyl esters are reacted with base catalyst is 3-12 hours.
4. a kind of method for preparing 3-hydroxybutyrate amino-acid salt compound according to claim 1, which is characterized in that step
Suddenly in (1), further includes: after ethyl 3-hydroxybutanoate or 3-hydroxybutyrate methyl esters are reacted with base catalyst, removed through vacuum distillation
Water；It adds ethyl alcohol dispersion is sufficiently stirred and be cooled to 0 DEG C or less crystallization, and keep the temperature 12 hours or more between 0 DEG C -5 DEG C, filter
Solid is isolated, with ethanol washing solid, is dried to get 3-hydroxybutyrate is arrived.
5. a kind of method for preparing 3-hydroxybutyrate amino-acid salt compound according to claim 1, which is characterized in that step
Suddenly in (2), the natural amino acid is selected from alanine, valine, leucine, isoleucine, proline, phenylalanine, color ammonia
Acid, methionine, glycine, serine, threonine, cysteine, tyrosine, asparagine, glutamine, lysine, smart ammonia
One of acid, histidine, aspartic acid, glutamic acid are a variety of.
6. a kind of method for preparing 3-hydroxybutyrate amino-acid salt compound according to claim 1, which is characterized in that step
Suddenly in (2), further includes: 3-hydroxybutyrate and natural amino acid after completion of the reaction, are filtered, be added in filtrate active carbon into
Row decoloration after refiltering, removes ethyl alcohol through vacuum distillation；It adds isopropanol and dispersion is sufficiently stirred, be cooled to 0 DEG C or less analysis
Crystalline substance, and keep the temperature to filter for 24 hours or more between 0 DEG C -5 DEG C and isolate solid, 3-hydroxybutyrate amino-acid salt is obtained after dry
Compound.
7. a kind of method for preparing 3-hydroxybutyrate amino-acid salt compound according to claim 6, which is characterized in that institute
The weight for stating active carbon is the 20% of 3-hydroxybutyrate weight.
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| CN201910008534.1A CN109734575A (en) | 2019-01-04 | 2019-01-04 | A method of preparing 3-hydroxybutyrate amino-acid salt compound |
| PCT/CN2019/073448 WO2020140309A1 (en) | 2019-01-04 | 2019-01-28 | Method for preparing 3-hydroxybutyrate amino acid salt compound |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110862316A (en) * | 2018-08-27 | 2020-03-06 | 浙江华睿生物技术有限公司 | Crystal form of (R) -3-hydroxybutyric acid and application thereof |
| WO2020140309A1 (en) * | 2019-01-04 | 2020-07-09 | 上海欣海国际贸易有限公司 | Method for preparing 3-hydroxybutyrate amino acid salt compound |
| CN112341331A (en) * | 2019-08-07 | 2021-02-09 | 辽宁科硕营养科技股份有限公司 | 3-hydroxybutyrate and preparation method and application thereof |
| WO2024067626A1 (en) * | 2022-09-27 | 2024-04-04 | 南京纽邦生物科技有限公司 | Composite of acid and salt, and preparation method therefor |
| WO2024067584A1 (en) * | 2022-09-27 | 2024-04-04 | 南京纽邦生物科技有限公司 | Complex of 3-hydroxybutyric acid and sodium 3-hydroxybutyrate and preparation method therefor |
| WO2024153236A1 (en) * | 2023-01-19 | 2024-07-25 | 南京纽邦生物科技有限公司 | Complex of 3-hydroxy-3-methylbutyric acid and salt thereof, and preparation method therefor |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107162893A (en) * | 2017-07-11 | 2017-09-15 | 洛阳华荣生物技术有限公司 | (R) synthesis technique of 3 hydroxybutyric acids and its salt |
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| CN1560024A (en) * | 2004-03-02 | 2005-01-05 | 国家海洋局第一海洋研究所 | Functional fatty acid-amino acid complex and preparation method thereof |
| PE20151949A1 (en) * | 2013-03-19 | 2016-01-05 | Univ South Florida | COMPOSITIONS AND METHODS TO PRODUCE ELEVATED AND SUSTAINED KETOSIS |
| CN108017555B (en) * | 2017-11-28 | 2021-03-26 | 郑州海斯威生物技术有限公司 | Beta-hydroxybutyryl-amino acid compound and preparation method and application thereof |
| CN109734575A (en) * | 2019-01-04 | 2019-05-10 | 上海欣海国际贸易有限公司 | A method of preparing 3-hydroxybutyrate amino-acid salt compound |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107162893A (en) * | 2017-07-11 | 2017-09-15 | 洛阳华荣生物技术有限公司 | (R) synthesis technique of 3 hydroxybutyric acids and its salt |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110862316A (en) * | 2018-08-27 | 2020-03-06 | 浙江华睿生物技术有限公司 | Crystal form of (R) -3-hydroxybutyric acid and application thereof |
| WO2020140309A1 (en) * | 2019-01-04 | 2020-07-09 | 上海欣海国际贸易有限公司 | Method for preparing 3-hydroxybutyrate amino acid salt compound |
| CN112341331A (en) * | 2019-08-07 | 2021-02-09 | 辽宁科硕营养科技股份有限公司 | 3-hydroxybutyrate and preparation method and application thereof |
| CN112341331B (en) * | 2019-08-07 | 2023-04-07 | 辽宁科硕营养科技股份有限公司 | 3-hydroxybutyrate and preparation method and application thereof |
| WO2024067626A1 (en) * | 2022-09-27 | 2024-04-04 | 南京纽邦生物科技有限公司 | Composite of acid and salt, and preparation method therefor |
| WO2024067584A1 (en) * | 2022-09-27 | 2024-04-04 | 南京纽邦生物科技有限公司 | Complex of 3-hydroxybutyric acid and sodium 3-hydroxybutyrate and preparation method therefor |
| WO2024153236A1 (en) * | 2023-01-19 | 2024-07-25 | 南京纽邦生物科技有限公司 | Complex of 3-hydroxy-3-methylbutyric acid and salt thereof, and preparation method therefor |
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