CN1594283A - Process for preparing N-acetyl-L-tyrosine - Google Patents
Process for preparing N-acetyl-L-tyrosine Download PDFInfo
- Publication number
- CN1594283A CN1594283A CN 200410013353 CN200410013353A CN1594283A CN 1594283 A CN1594283 A CN 1594283A CN 200410013353 CN200410013353 CN 200410013353 CN 200410013353 A CN200410013353 A CN 200410013353A CN 1594283 A CN1594283 A CN 1594283A
- Authority
- CN
- China
- Prior art keywords
- tyrosine
- acetyl
- crude product
- diacetyl oxide
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- CAHKINHBCWCHCF-JTQLQIEISA-N N-acetyl-L-tyrosine Chemical compound CC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 CAHKINHBCWCHCF-JTQLQIEISA-N 0.000 title claims abstract description 17
- 229960001682 n-acetyltyrosine Drugs 0.000 title claims abstract description 16
- 238000004519 manufacturing process Methods 0.000 title abstract description 11
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims abstract description 15
- 239000012043 crude product Substances 0.000 claims abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229960004441 tyrosine Drugs 0.000 claims abstract description 9
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims description 9
- CAHKINHBCWCHCF-UHFFFAOYSA-N N-acetyltyrosine Chemical compound CC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 CAHKINHBCWCHCF-UHFFFAOYSA-N 0.000 claims description 6
- 238000002425 crystallisation Methods 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- 239000013078 crystal Substances 0.000 claims description 4
- 230000008025 crystallization Effects 0.000 claims description 4
- 239000012141 concentrate Substances 0.000 claims description 3
- 238000001914 filtration Methods 0.000 abstract description 2
- 239000012736 aqueous medium Substances 0.000 abstract 1
- 238000001035 drying Methods 0.000 abstract 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000005917 acylation reaction Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 229940024606 amino acid Drugs 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 238000007670 refining Methods 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 241000233855 Orchidaceae Species 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000006389 diacetylation reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- -1 filters Chemical compound 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000007738 vacuum evaporation Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a process for preparing N-acetyl-L-tyrosine which comprises the steps of, dissolving L-tyrosine into aqueous medium, conducting acetylization 45-75 minutes at 50-80 deg. C by using acetic anhydride as acylating agent, obtaining crude product through concentration, dissolving dried crude product into 75-80 deg C hot water, decolorizing, filtering, concentrating, crystallizing and drying.
Description
Technical field
The invention belongs to amino acid whose preparation method, be specifically related to the preparation method of N-acetyl-L-tyrosine.
Background technology
It mainly is 20 basic kinds that China produces the amino acid starting material that the amino acid infusion solutions uses, and only contains in a kind of transfusion of 17 seed amino acids regulation and uses N-acetyl-L-tyrosine to replace tyrosine, and only this item estimates that annual use N-acetyl-L-tyrosine is more than 8 tons.Because the solubleness of tyrosine is too small, is unfavorable for that it absorbs, external transfusion is produced and has been shown the impetus of using N-acetyl-L-tyrosine to substitute tyrosine.About 100 tons of the tyrosine usage quantity of China's production transfusion also will be substituted by N-acetyl-L-tyrosine as can be seen successively.The present domestic manufacturer production N-acetyl-L-tyrosine that still do not have, the method for producing N-acetyl-L-tyrosine abroad is:
At first use Acetyl Chloride 98Min. acidylate in NaOH solution, temperature maintenance is kept the pH value at 9-10 at 5 degree, after acidylate is finished, is acidified to the Congo red stain orchid with concentrated hydrochloric acid.Vacuum-evaporation gets gluey residue (Acetyl tyrosine crude product) to doing.With ebullient acetone extracting crude product, repeat several, merging acetone extract filters, and is evaporated near dry, gets crystalloid Acetyl tyrosine behind the adding sherwood oil.Be dissolved in hot ethyl acetate, be evaporated to small volume, add sherwood oil, get crystallization.Use petroleum ether, the dry Acetyl tyrosine that gets.Then,, obtain the diacetylation thing, add concentrated hydrochloric acidization, must precipitate, add sodium hydroxide solution dissolving, the hydrolysis of 2N with the acetylize in the sodium hydroxide solution of the 2.5N of 17.6 times (V/W) of 1: 4 mole diacetyl oxide.Add the neutralization of 2N sulfuric acid, be evaporated to dried.Last residue repeats to merge the acetone extract for several times with the extracting of ebullient acetone, filters, and acetone evaporated is fallen, and last syrupy shape material absorbs with minimum water, and crystallisation by cooling gets N-acetyl-L-tyrosine.This method acylation process can produce the acetic acid sodium salt, and crude product purity is low, and solvent load is big, has the problem of solvent recuperation, drops into bigger; Solvent does not reclaim, and then can cause the pollution to environment.
Summary of the invention
The object of the present invention is to provide the preparation method of a kind of N-acetyl-L-tyrosine, to overcome the defective that above-mentioned preparation method exists.
Technical scheme of the present invention is: the preparation method of N-acetyl-L-tyrosine; it be with L-tyrosine in water medium; utilize the acylating agent diacetyl oxide; in acetylize under 50～80 ℃ the temperature condition after 45～75 minutes; concentrating catches up with acid crystal to get the Acetyl tyrosine crude product; the exsiccant crude product is dissolved in 75～80 ℃ of hot water, decolouring, filters, concentrate post crystallization, dry.
It is medium that present method adopts water to substitute dilute alkaline soln in acylation reaction, and acylation process is not supervened the acetic acid sodium salt, and the purity height of the N-that is generated acetyl-L-tyrosine crude product helps the refining of back, and its acidylate rate reaches 95%.Treating process utilizes refining the changing into of machine solvent acetone dissolving to utilize the hot water dissolving refining with original, and production process does not pollute environment, and is harmless; Owing to got rid of inflammable and explosive deleterious organism, improved production security.Total yield of products reaches 78-80%.Present method has raw and auxiliary material and is easy to get, and is inexpensive; Simple and safe operation; Technical process is short; Do not produce salt in the production; The three wastes are easy advantage such as processing less.
Description of drawings
Preparation technology's schema of accompanying drawing N-acetyl-L-tyrosine
Embodiment
Because L-Tyr has α-NH
2With two acylable groups of virtue nuclear-OH, the former electronegativity than the latter a little less than, be easy to acetylize, the N-Ac key of formation is more more firm than O-Ac key.In the acylation reaction process, for the least possible acidylate virtue nuclear-OH group, can the formed O-Ac key of hydrolysis in the technological process afterwards.For this reason, we are acylating agent with medium tenacity acetylation reagent-diacetyl oxide preferably.
With weight ratio is that 1: 3～5 L-tyrosine and diacetyl oxide carry out acylation reaction in water medium, and temperature of reaction is controlled between 50-80 ℃, and the reaction times was controlled between 45～75 minutes; generally after 60 minutes; reclaim solvent, centrifugal oven dry, i.e. reaction solution after the acidylate; vacuum is caught up with acid; control vacuum tightness and temperature well, vacuum tightness is 80～100mmhg, and temperature is 75～80 ℃; can accomplish the O-Ac that generates when catching up with hydrolysis acidylate in the sour process again.Concentrate and to catch up with acid crystal to get the Acetyl tyrosine crude product to be dissolved in 75～80 ℃ of hot water, add activated carbon decolorizing, filtration, vacuum concentration post crystallization, centrifugal oven dry.
The total yield of products of aforesaid method production reaches 78-80%.The more existing process recovery ratio of yield of the present invention exceeds nearly 8～10%; The more existing production cost of production cost reduces by 34～50%; The product of producing is through the check of Hubei Province medicine inspecting institute, and quality product has reached the requirement of Japanese aginomoto 92 editions comprehensively.And the transmitance of finished product and optically-active and crystal formation quality standard are higher.
Claims (2)
1, the preparation method of a kind of N-acetyl-L-tyrosine; it is characterized in that L-tyrosine in water medium; utilize the acylating agent diacetyl oxide; in acetylize under 50～80 ℃ the temperature condition after 45～75 minutes; concentrating catches up with acid crystal to get the Acetyl tyrosine crude product; the exsiccant crude product is dissolved in 75～80 ℃ of hot water, decolouring, filters, concentrate post crystallization, dry.
2, the preparation method of N-acetyl-L-tyrosine according to claim 1 is characterized in that the preferential diacetyl oxide of acylating agent, and the consumption weight ratio of L-tyrosine and diacetyl oxide is 1: 3～5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410013353 CN1262534C (en) | 2004-06-24 | 2004-06-24 | Process for preparing N-acetyl-L-tyrosine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410013353 CN1262534C (en) | 2004-06-24 | 2004-06-24 | Process for preparing N-acetyl-L-tyrosine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1594283A true CN1594283A (en) | 2005-03-16 |
| CN1262534C CN1262534C (en) | 2006-07-05 |
Family
ID=34662918
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410013353 Expired - Lifetime CN1262534C (en) | 2004-06-24 | 2004-06-24 | Process for preparing N-acetyl-L-tyrosine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1262534C (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102219706A (en) * | 2011-04-21 | 2011-10-19 | 宁波市镇海海德生化科技有限公司 | Method for preparing acetyl tyrosine ethyl ester monohydrate and product of acetyl tyrosine ethyl ester monohydrate |
| CN111153829A (en) * | 2019-12-26 | 2020-05-15 | 烟台鲁银药业有限公司 | Preparation method of N-acetyl-L-tyrosine |
| CN114716335A (en) * | 2020-12-22 | 2022-07-08 | 武汉远大弘元股份有限公司 | Process for preparing N-acetyl-L-tyrosine |
-
2004
- 2004-06-24 CN CN 200410013353 patent/CN1262534C/en not_active Expired - Lifetime
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102219706A (en) * | 2011-04-21 | 2011-10-19 | 宁波市镇海海德生化科技有限公司 | Method for preparing acetyl tyrosine ethyl ester monohydrate and product of acetyl tyrosine ethyl ester monohydrate |
| CN102219706B (en) * | 2011-04-21 | 2013-08-21 | 宁波市镇海海德生化科技有限公司 | Method for preparing acetyl tyrosine ethyl ester monohydrate and product of acetyl tyrosine ethyl ester monohydrate |
| CN111153829A (en) * | 2019-12-26 | 2020-05-15 | 烟台鲁银药业有限公司 | Preparation method of N-acetyl-L-tyrosine |
| CN114716335A (en) * | 2020-12-22 | 2022-07-08 | 武汉远大弘元股份有限公司 | Process for preparing N-acetyl-L-tyrosine |
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| Publication number | Publication date |
|---|---|
| CN1262534C (en) | 2006-07-05 |
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Address after: 430070 Hubei city of Wuhan province Wuchang Luo Yu Road, No. 399 Patentee after: WUHAN GRAND HOYO PHARMACEUTICAL Co.,Ltd. Address before: 430070 Hubei city of Wuhan province Wuchang Luo Yu Road, No. 399 Patentee before: WUHAN University HOYO PHARMACE |
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Owner name: WUHAN GRAND HOYO CO., LTD. Free format text: FORMER OWNER: WUHAN GRAND HOYO PHARMACEUTICAL CO., LTD. Effective date: 20141203 |
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Effective date of registration: 20141203 Address after: 430000 Hubei city of Wuhan Province, East Lake New Technology Development Zone Road No. two international business center 30 building 6 layer 1 Patentee after: WUHAN GRAND HOYO Co.,Ltd. Address before: 430070 Hubei city of Wuhan province Wuchang Luo Yu Road, No. 399 Patentee before: WUHAN GRAND HOYO PHARMACEUTICAL Co.,Ltd. |
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Granted publication date: 20060705 |
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