CN110878029A - Preparation method of D-serine - Google Patents
Preparation method of D-serine Download PDFInfo
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- CN110878029A CN110878029A CN201911106628.9A CN201911106628A CN110878029A CN 110878029 A CN110878029 A CN 110878029A CN 201911106628 A CN201911106628 A CN 201911106628A CN 110878029 A CN110878029 A CN 110878029A
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- MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 title claims abstract description 57
- 229930195711 D-Serine Natural products 0.000 title claims abstract description 57
- 238000002360 preparation method Methods 0.000 title claims abstract description 36
- MTCFGRXMJLQNBG-UHFFFAOYSA-N serine Chemical compound OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims abstract description 52
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims abstract description 45
- 238000000034 method Methods 0.000 claims abstract description 43
- 238000001035 drying Methods 0.000 claims abstract description 30
- 238000002425 crystallisation Methods 0.000 claims abstract description 29
- 230000008025 crystallization Effects 0.000 claims abstract description 29
- 238000012360 testing method Methods 0.000 claims abstract description 26
- 239000003054 catalyst Substances 0.000 claims abstract description 20
- 229960001153 serine Drugs 0.000 claims abstract description 19
- 238000004806 packaging method and process Methods 0.000 claims abstract description 17
- 238000011282 treatment Methods 0.000 claims abstract description 14
- 230000007062 hydrolysis Effects 0.000 claims abstract description 13
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 13
- 238000006243 chemical reaction Methods 0.000 claims abstract description 8
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 7
- 238000000967 suction filtration Methods 0.000 claims abstract description 7
- 102000006534 Amino Acid Isomerases Human genes 0.000 claims description 6
- 108010008830 Amino Acid Isomerases Proteins 0.000 claims description 6
- 108010008292 L-Amino Acid Oxidase Proteins 0.000 claims description 6
- 102000007070 L-amino-acid oxidase Human genes 0.000 claims description 6
- 230000006340 racemization Effects 0.000 claims description 6
- 238000005070 sampling Methods 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 5
- 239000012141 concentrate Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 230000003287 optical effect Effects 0.000 abstract description 16
- 238000009776 industrial production Methods 0.000 abstract description 4
- 238000011161 development Methods 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 239000000543 intermediate Substances 0.000 abstract description 3
- 229910052799 carbon Inorganic materials 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 9
- 230000003301 hydrolyzing effect Effects 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- 150000003863 ammonium salts Chemical class 0.000 description 3
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical class [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 3
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical class C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 3
- 229910001385 heavy metal Inorganic materials 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 102400000739 Corticotropin Human genes 0.000 description 2
- 101800000414 Corticotropin Proteins 0.000 description 2
- 229960000258 corticotropin Drugs 0.000 description 2
- 150000002505 iron Chemical class 0.000 description 2
- 238000002834 transmittance Methods 0.000 description 2
- 241000976983 Anoxia Species 0.000 description 1
- 208000002381 Brain Hypoxia Diseases 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- DYDCUQKUCUHJBH-UWTATZPHSA-N D-Cycloserine Chemical compound N[C@@H]1CONC1=O DYDCUQKUCUHJBH-UWTATZPHSA-N 0.000 description 1
- DYDCUQKUCUHJBH-UHFFFAOYSA-N D-Cycloserine Natural products NC1CONC1=O DYDCUQKUCUHJBH-UHFFFAOYSA-N 0.000 description 1
- 208000007465 Giant cell arteritis Diseases 0.000 description 1
- 230000007953 anoxia Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 239000003997 corticotropin derivative Substances 0.000 description 1
- 229960003077 cycloserine Drugs 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- VPPJLAIAVCUEMN-GFCCVEGCSA-N lacosamide Chemical compound COC[C@@H](NC(C)=O)C(=O)NCC1=CC=CC=C1 VPPJLAIAVCUEMN-GFCCVEGCSA-N 0.000 description 1
- 229960002623 lacosamide Drugs 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 206010043207 temporal arteritis Diseases 0.000 description 1
- 239000003104 tissue culture media Substances 0.000 description 1
Classifications
-
- 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
- C07C227/38—Separation; Purification; Stabilisation; Use of additives
- C07C227/40—Separation; Purification
- C07C227/42—Crystallisation
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P13/00—Preparation of nitrogen-containing organic compounds
- C12P13/04—Alpha- or beta- amino acids
- C12P13/06—Alanine; Leucine; Isoleucine; Serine; Homoserine
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
- C12P41/002—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by oxidation/reduction reactions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Analytical Chemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of D-serine, relating to the field of preparation of drug intermediates and comprising the following steps: the method comprises the following steps: l-serine hydrolysis; step two: preparing DL-serine; step three: preparing D-serine; step four: crystallization treatment; step five: drying, testing and packaging, wherein the specific process in the first step is to hydrolyze 0.15-0.6 mol/L L-serine under the catalysis of a catalyst for 6-32h at 15-45 ℃ and at the pH of 7-9, and after the reaction is finished, performing suction filtration to remove the catalyst. According to the invention, through the processes of L-serine hydrolysis, DL-serine preparation, D-serine preparation, crystallization treatment, drying, test packaging and the like, the optical purity and yield of the prepared D-serine are effectively improved, the high optical activity of the D-serine is ensured, the process flow is simple, the process cost is greatly reduced, the method is suitable for large-scale industrial production, and the method has a wide economic development prospect.
Description
Technical Field
The invention relates to the field of preparation of drug intermediates, in particular to a preparation method of D-serine.
Background
D-serine is an endogenous brain information synergic substance, can be used for preventing or treating brain injury caused by cerebral ischemia or anoxia, D-serine is also an important intermediate of some chiral drugs such as cycloserine, lacosamide and the like, a 25-peptide corticotropin analogue artificially synthesized by D-serine has 6 times stronger action than natural corticotropin and corticotropin 24 peptide and longer maintenance time, intravenous injection can last for 8 hours, is used for treating inflammatory patients such as temporal arteritis, multiple rheumatism and the like, and can also be used for biochemical research, preparation of tissue culture medium, reaction by taking DL-serine and chloroacetyl chloride as raw materials under alkaline condition, extraction by ethyl acetate after reduced pressure evaporation, and products are obtained after activated carbon treatment and acylase resolution, the optical purity and the yield in the preparation process of D-serine in the prior art are lower, and the high optical activity of the D-serine is difficult to ensure, the process flow is complex, the production process cost is high, and the method is not suitable for large-scale industrial production.
Disclosure of Invention
The invention aims to solve the defects in the prior art and provides a preparation method of D-serine.
In order to achieve the purpose, the invention adopts the following technical scheme:
a preparation method of D-serine comprises the following steps:
the method comprises the following steps: l-serine hydrolysis;
step two: preparing DL-serine;
step three: preparing D-serine;
step four: crystallization treatment;
step five: drying, testing and packaging.
Preferably, the specific process of the first step is that 0.15-0.6 mol/L L-serine is hydrolyzed under the catalysis of a catalyst for 6-32 hours at 15-45 ℃ and at the pH of 7-9, and after the reaction is finished, the catalyst is removed by suction filtration.
Preferably, the specific process of the second step is to add amino acid racemase to the product of the first step, and obtain DL-serine through racemization.
Preferably, the specific process of the third step is to add L-amino acid oxidase to the product DL-serine in the second step, and obtain D-serine through splitting.
Preferably, the specific process of the step four is to inject the concentrated solution in the step three into a crystallization tank, heat the temperature of the crystallization tank, and crystallize.
Preferably, the specific process of the fifth step is that the wet sample in the fourth step is put into a dryer for drying, then a sampling test is carried out, and after the test is qualified, a qualified product is packaged.
Preferably, the mass ratio of the catalyst to the L-serine is 1: 3 to 10.
Preferably, the crystallization time in the fourth step is 15-50 min.
Preferably, the temperature of the crystallization tank in the fourth step is heated to 110-200 ℃.
Preferably, the drying time in the step five is 10-60min, and the drying temperature in the step five is 100-170 ℃.
The invention has the beneficial effects that:
according to the invention, through the processes of L-serine hydrolysis, DL-serine preparation, D-serine preparation, crystallization treatment, drying, test packaging and the like, the optical purity and yield of the prepared D-serine are effectively improved, the high optical activity of the D-serine is ensured, the process flow is simple, the process cost is greatly reduced, the method is suitable for large-scale industrial production, and the method has a wide economic development prospect.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments.
Example 1
A preparation method of D-serine comprises the following steps:
the method comprises the following steps: l-serine hydrolysis: hydrolyzing 0.15mol/L L-serine under the catalysis of a catalyst for 6 hours at 15 ℃ and pH7, after the reaction is finished, performing suction filtration to remove the catalyst, wherein the mass ratio of the catalyst to L-serine is 1: 3;
step two: preparation of DL-serine: adding amino acid racemase into the product obtained in the step one, and obtaining DL-serine through racemization;
step three: preparation of D-serine: adding L-amino acid oxidase into the product DL-serine in the step two, and splitting to obtain D-serine;
step four: and (3) crystallization treatment: injecting the concentrated solution in the third step into a crystallization tank, heating the temperature of the crystallization tank to 110 ℃, and crystallizing for 15 min;
step five: drying, testing and packaging: and (2) drying the wet sample in the fourth step in a dryer at the drying temperature of 100 ℃ for 10min, then performing a sampling test, packaging qualified products after passing the test, and effectively improving the optical purity and yield of the prepared D-serine and ensuring the high optical activity of the D-serine through the processes of L-serine hydrolysis, DL-serine preparation, D-serine preparation, crystallization treatment, drying, test packaging and the like.
The indices for D-serine were obtained according to the above examples and were experimentally determined as shown in the following table:
| index (I) | Product regulation | Example 1 |
| Appearance of the product | White crystalline or crystalline powder | White crystalline or crystalline powder |
| Smell(s) | Slight odor | Slight odor |
| Content (%) | ≥98.5 | 98.7 |
| Specific rotation | －30.0°～－32.5° | -31.1° |
| Clear acidity (pH value) | 5.4～6.4 | 5.6 |
| Chloride (%) | ≤0.02 | 0.015 |
| Sulfate (%) | ≤0.02 | 0.013 |
| Ammonium salt (%) | ≤0.02 | 0.014 |
| Transmittance of solution | ≥95.0 | 97 |
| Loss on drying (%) | ≤0.2 | 0.14 |
| Burning residue (%) | ≤0.1 | 0.04 |
| Iron salt (%) | ≤0.002 | 0.001 |
| Heavy metals | ≤10 | 7 |
| Arsenic salt | ≤0.0001 | 0.00006 |
Example 2
A preparation method of D-serine comprises the following steps:
the method comprises the following steps: l-serine hydrolysis: hydrolyzing 0.6mol/L L-serine under the catalysis of a catalyst for 32 hours at 45 ℃ and pH9, after the reaction is finished, performing suction filtration to remove the catalyst, wherein the mass ratio of the catalyst to L-serine is 1: 10;
step two: preparation of DL-serine: adding amino acid racemase into the product obtained in the step one, and obtaining DL-serine through racemization;
step three: preparation of D-serine: adding L-amino acid oxidase into the product DL-serine in the step two, and splitting to obtain D-serine;
step four: and (3) crystallization treatment: injecting the concentrated solution in the third step into a crystallization tank, heating the temperature of the crystallization tank to 200 ℃, and crystallizing for 50 min;
step five: drying, testing and packaging: and (2) drying the wet sample in the fourth step in a dryer at the drying temperature of 170 ℃ for 60min, then performing a sampling test, packaging qualified products after passing the test, and effectively improving the optical purity and yield of the prepared D-serine and ensuring the high optical activity of the D-serine through the processes of L-serine hydrolysis, DL-serine preparation, D-serine preparation, crystallization treatment, drying, test packaging and the like.
The indices for D-serine were obtained according to the above examples and were experimentally determined as shown in the following table:
example 3
A preparation method of D-serine comprises the following steps:
the method comprises the following steps: l-serine hydrolysis: hydrolyzing 0.4mol/L L-serine under the catalysis of a catalyst for 19 hours at the temperature of 30 ℃ and the pH value of 8, after the reaction is finished, performing suction filtration to remove the catalyst, wherein the mass ratio of the catalyst to L-serine is 1: 6;
step two: preparation of DL-serine: adding amino acid racemase into the product obtained in the step one, and obtaining DL-serine through racemization;
step three: preparation of D-serine: adding L-amino acid oxidase into the product DL-serine in the step two, and splitting to obtain D-serine;
step four: and (3) crystallization treatment: injecting the concentrated solution in the third step into a crystallization tank, heating the temperature of the crystallization tank to 155 ℃, and crystallizing for 35 min;
step five: drying, testing and packaging: and (2) drying the wet sample in the fourth step in a dryer, wherein the drying temperature is 135 ℃, the drying time is 35min, then carrying out a sampling test, packaging qualified products after the test is qualified, and effectively improving the optical purity and yield of the prepared D-serine and ensuring the high optical activity of the D-serine through the processes of L-serine hydrolysis, DL-serine preparation, D-serine preparation, crystallization treatment, drying, test packaging and the like.
The indices for D-serine were obtained according to the above examples and were experimentally determined as shown in the following table:
example 4
A preparation method of D-serine comprises the following steps:
the method comprises the following steps: l-serine hydrolysis: hydrolyzing 0.3mol/L L-serine under the catalysis of a catalyst for 15 hours at 22 ℃ and pH7.5, after the reaction is finished, performing suction filtration to remove the catalyst, wherein the mass ratio of the catalyst to the L-serine is 1: 5;
step two: preparation of DL-serine: adding amino acid racemase into the product obtained in the step one, and obtaining DL-serine through racemization;
step three: preparation of D-serine: adding L-amino acid oxidase into the product DL-serine in the step two, and splitting to obtain D-serine;
step four: and (3) crystallization treatment: injecting the concentrated solution obtained in the third step into a crystallization tank, heating the temperature of the crystallization tank to 145 ℃, and crystallizing for 12 min;
step five: drying, testing and packaging: and (2) drying the wet sample in the fourth step in a dryer at the drying temperature of 115 ℃ for 15min, then performing a sampling test, packaging qualified products after the test is qualified, and effectively improving the optical purity and yield of the prepared D-serine and ensuring the high optical activity of the D-serine through the processes of L-serine hydrolysis, DL-serine preparation, D-serine preparation, crystallization treatment, drying, test packaging and the like.
The indices for D-serine were obtained according to the above examples and were experimentally determined as shown in the following table:
| index (I) | Product regulation | Example 4 |
| Appearance of the product | White crystalline or crystalline powder | White crystalline or crystalline powder |
| Smell(s) | Slight odor | Slight odor |
| Content (%) | ≥98.5 | 98.8 |
| Specific rotation | －30.0°～－32.5° | -31.5° |
| Clear acidity (pH value) | 5.4～6.4 | 5.8 |
| Chloride (%) | ≤0.02 | 0.0155 |
| Sulfate (%) | ≤0.02 | 0.014 |
| Ammonium salt (%) | ≤0.02 | 0.017 |
| Transmittance of solution | ≥95.0 | 97.3 |
| Loss on drying (%) | ≤0.2 | 0.145 |
| Burning residue (%) | ≤0.1 | 0.045 |
| Iron salt (%) | ≤0.002 | 0.0012 |
| Heavy metals | ≤10 | 7.5 |
| Arsenic salt | ≤0.0001 | 0.000065 |
By combining the experimental test data of the embodiment 1, the embodiment 2, the embodiment 3 and the embodiment 4, the contents of chloride, sulfate, ammonium salt, ferric salt, heavy metal, arsenic salt and the like in the D-serine product are low, the optical purity and the yield of the prepared D-serine are effectively improved, the high optical activity of the D-serine is ensured, the process flow is simple, the process cost is greatly reduced, the method is suitable for large-scale industrial production, and the method has a wide economic development prospect.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention should be equivalent or changed within the scope of the present invention.
Claims (10)
1. A preparation method of D-serine is characterized by comprising the following steps:
the method comprises the following steps: l-serine hydrolysis;
step two: preparing DL-serine;
step three: preparing D-serine;
step four: crystallization treatment;
step five: drying, testing and packaging.
2. The preparation method of D-serine according to claim 1, wherein the specific process of the first step is to hydrolyze 0.15-0.6 mol/L L-serine under the catalysis of a catalyst for 6-32h at 15-45 ℃ and pH 7-9, and after the reaction is completed, suction filtration is performed to remove the catalyst.
3. The process according to claim 1, wherein the step two comprises adding an amino acid racemase to the product obtained in the step one, followed by racemization to obtain DL-serine.
4. The method according to claim 1, wherein the step three comprises adding L-amino acid oxidase to the product DL-serine of the step two, and cleaving the mixture to obtain D-serine.
5. The method according to claim 1, wherein the step four comprises the specific step of injecting the concentrate from the step three into a crystallization tank, and heating the crystallization tank to crystallize the D-serine.
6. The method for preparing D-serine according to claim 1, wherein the specific process of the fifth step is that the wet sample obtained in the fourth step is placed into a dryer for drying, then a sampling test is carried out, and after the test is passed, a qualified product is packaged.
7. The method according to claim 1, wherein the mass ratio of the catalyst to the L-serine is 1: 3 to 10.
8. The process according to claim 1, wherein the crystallization time in step four is 15-50 min.
9. The method as claimed in claim 1, wherein the temperature of the crystallization tank in the fourth step is increased to 110-200 ℃.
10. The method as claimed in claim 1, wherein the drying time in the step five is 10-60min, and the drying temperature in the step five is 100-170 ℃.
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3546070A (en) * | 1965-11-02 | 1970-12-08 | Ajinomoto Kk | Fermentative method of producing l-serine from dl-serine |
| US4335209A (en) * | 1979-05-09 | 1982-06-15 | Mitsui Toatsu Chemicals, Inc. | Process for preparation of L-tryptophan by enzyme |
| US20030212262A1 (en) * | 2000-04-04 | 2003-11-13 | Connolly Thomas M | Human serine racemase |
| CN101717810A (en) * | 2009-10-26 | 2010-06-02 | 南京大学 | Preparation method of D-serine by enzymatic conversion |
| CN101735085A (en) * | 2009-12-17 | 2010-06-16 | 上海化学试剂研究所 | Method for preparing D-serine by kinetic resolution |
| CN109251923A (en) * | 2018-10-22 | 2019-01-22 | 天津博瑞威生物医药科技有限公司 | Serine racemase enzyme mutant |
| US20220040226A1 (en) * | 2020-06-01 | 2022-02-10 | Celagenex Research (India) Pvt. Ltd. | Synergistic medicinal compositions for treating dysfunctional d-serine signaling |
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- 2019-11-13 CN CN201911106628.9A patent/CN110878029A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3546070A (en) * | 1965-11-02 | 1970-12-08 | Ajinomoto Kk | Fermentative method of producing l-serine from dl-serine |
| US4335209A (en) * | 1979-05-09 | 1982-06-15 | Mitsui Toatsu Chemicals, Inc. | Process for preparation of L-tryptophan by enzyme |
| US20030212262A1 (en) * | 2000-04-04 | 2003-11-13 | Connolly Thomas M | Human serine racemase |
| CN101717810A (en) * | 2009-10-26 | 2010-06-02 | 南京大学 | Preparation method of D-serine by enzymatic conversion |
| CN101735085A (en) * | 2009-12-17 | 2010-06-16 | 上海化学试剂研究所 | Method for preparing D-serine by kinetic resolution |
| CN109251923A (en) * | 2018-10-22 | 2019-01-22 | 天津博瑞威生物医药科技有限公司 | Serine racemase enzyme mutant |
| US20220040226A1 (en) * | 2020-06-01 | 2022-02-10 | Celagenex Research (India) Pvt. Ltd. | Synergistic medicinal compositions for treating dysfunctional d-serine signaling |
Non-Patent Citations (1)
| Title |
|---|
| 于荣华等: "化学酶法制备D-丝氨酸", 《精细化工》 * |
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