CN101759767A - Method for synthesizing glycylglycine - Google Patents
Method for synthesizing glycylglycine Download PDFInfo
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- CN101759767A CN101759767A CN200810121715A CN200810121715A CN101759767A CN 101759767 A CN101759767 A CN 101759767A CN 200810121715 A CN200810121715 A CN 200810121715A CN 200810121715 A CN200810121715 A CN 200810121715A CN 101759767 A CN101759767 A CN 101759767A
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- glycylglycine
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Abstract
The invention discloses a method for synthesizing glycylglycine, which comprises the following steps of: taking glycine as a raw material, adding glycerol to perform reflux reaction with stirring at the temperature of between 175 and 180 DEG C, and adding distilled water after cooling and putting the mixture into a refrigerator to stay overnight; performing filtration and washing the mixture with ethanol to prepare an intermediate product, namely 2,5-diketopiperazine; hydrolyzing the 2,5-diketopiperazine in the presence of NaOH, adding hydrochloric acid and regulating the pH to 6.0, and then adding the ethanol to stay overnight in the refrigerator; and finally performing filtration and washing the mixture with the ethanol until no chloridion exists to prepare the glycylglycine, wherein the yield of the glycylglycine is 81 percent. The method has the advantages of simpleness, difficult cause of environmental pollution, and suitability for industrialized production.
Description
Technical field
The invention relates to a kind of synthetic method of glycylglycine, belong to chemical pharmacy field.
Background technology
Glycylglycine (L-Glycylglycine) has another name called N-glycylglycine, contract diamino-acetic acid, glycylglycine or sweet victory, structural formula:
Molecular formula: C
4H
8N
2O
3, CAS number: 556-50-3.Glycylglycine is white lobate crystallization, and fusing point is 260～262 ℃ (decomposition).In the time of 25 ℃ in the water solubleness be 13.4g/100mL, be soluble in hot water, be insoluble in alcohol, be insoluble to ether.
Glycylglycine is a kind of biochemical reagents, in biological study and pharmaceutically as the stablizer of blood preservation and pharmaceutical grade protein cytochrome C aqueous injection, can be used to measure the substrate of glycylglycine pepx, and synthetic polypeptide.And glycylglycine is as a kind of small peptide, and the interaction of itself and transition metal has critical effect in fields such as many biotechnology and pharmaceutical chemistry.
Also few for the synthetic method of glycylglycine at present.Because amino acid and polypeptide is synthetic comparatively complicated; require active a-amino acid; couple together in certain sequence; keep opticity constant again; and have peptide bond to exist in the polypeptide; various reactions easily taking place, separate etc. as hydrolysis, ammonia, therefore needs to introduce protecting group and protect amino acid whose carbon teminal or nitrogen end.
Summary of the invention
One of purpose of the present invention provides a kind of synthetic method of glycylglycine.
Technical solution of the present invention is as follows:
1, intermediate 2, the preparation of 5-piperazinedione.
30mL glycerine is added in the flask that people 100mL is equipped with reflux exchanger, under agitation add the glycine 12g of porphyrize, stir 50min in 175～180 ℃.Be cooled to room temperature, add people 12mL distilled water, put people's refrigerator overnight.Suction filtration is used 50% washing with alcohol, gets crude product 2, the 5-piperazinedione.The water recrystallization promptly gets pure product.M.p.300～302 ℃, productive rate 89%.
2, generate glycylglycine.
In the 250mL round-bottomed flask, add the sodium hydroxide solution of people 50mL 1mol/L, under agitation add people 5g2, the 5-piperazinedione, stirring at room to 2, the 5-piperazinedione all dissolves, add 2mol/L hydrochloric acid 25mL then, regulating pH is 6.0, is evaporated to about 20mL, add people 30mL 95% ethanol, in refrigerator, place and spend the night suction filtration, washing with alcohol with 70%, in washings till the no chlorion, glycylglycine .m.p.258～260 ℃, productive rate 81%.
The method applied in the present invention is simple and easy to do, and productive rate is higher.By utilizing glycerine is a kind of high boiling point (boiling point is 290 ℃) solvent, can form very strong hydrogen bond with water molecules, so have the intensive water-absorbent.Utilize this character, glycine is easy to dehydration condensation in 175～180 ℃ in glycerine, generate corresponding intermediate product 2, the 5-piperazinedione, and then effectively protected the nitrogen end of glycine.Material reagent required for the present invention is inexpensive and be easy to get, and operational path is short, the yield height, and be difficult for contaminate environment, be suitable for suitability for industrialized production.
Claims (8)
1. the synthetic method of a glycylglycine is characterized in that may further comprise the steps:
(1) glycerine is added the people and be equipped with in the flask of reflux exchanger, under agitation add the glycine of porphyrize.Be cooled to room temperature, add an amount of distilled water of people, put people's refrigerator overnight.Suction filtration is used washing with alcohol, gets crude product 2, the 5-piperazinedione.The water recrystallization promptly gets pure product.
(2) in the 250mL round-bottomed flask, add people's sodium hydroxide solution, under agitation add people 2, the 5-piperazinedione is stirred to 2, and the 5-piperazinedione all dissolves, add hydrochloric acid then, regulate pH, behind the concentrating under reduced pressure, add people's ethanol, place in refrigerator and spend the night, suction filtration is used washing with alcohol, in washings, till the no chlorion, get glycylglycine.
2. according to the said stirring and refluxing reaction of claim 1 (1), it is characterized in that the glycerine volume: glycine quality=5mL: 2g, the temperature of reaction is 175～180 ℃, the stirring reaction time is 50min.
3. according to the said washing composition of claim 1 (1), it is characterized in that used solution is 50% ethanol
4. according to the said hydrolysis reaction of claim 1 (2), it is characterized in that concentration of sodium hydroxide solution is 1mol/L, and the sodium hydroxide solution volume: 2,5-piperazinedione quality=10mL: 1g, temperature of reaction is a room temperature.
5. according to the said hydrochloric acid soln of claim 1 (2), it is characterized in that concentration is 2mol/L, and the sodium hydroxide solution volume: hydrochloric acid soln volume=2: 1
6. according to the said pH regulator of claim 1 (2), it is characterized in that pH regulator to 6.0.
7. according to the reaction of the said concentrating under reduced pressure of claim 1 (2), it is characterized in that volume ratio is 15: 4 before and after the decompression, and with 95% ethanol removal of impurities, and the liquor capacity behind the concentrating under reduced pressure: volumes of aqueous ethanol=2: 3.
8. according to the said washing composition of claim 1 (2), it is characterized in that used solution is 70% ethanol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810121715A CN101759767A (en) | 2008-10-23 | 2008-10-23 | Method for synthesizing glycylglycine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810121715A CN101759767A (en) | 2008-10-23 | 2008-10-23 | Method for synthesizing glycylglycine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101759767A true CN101759767A (en) | 2010-06-30 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200810121715A Pending CN101759767A (en) | 2008-10-23 | 2008-10-23 | Method for synthesizing glycylglycine |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103204905A (en) * | 2013-03-15 | 2013-07-17 | 四川同晟生物科技有限公司 | Method for synthesizing tetra-glycylglycine |
| CN105254576A (en) * | 2014-02-26 | 2016-01-20 | 中国科学院长春应用化学研究所 | Method for preparing glutamic piperazinedione |
| WO2019028340A1 (en) | 2017-08-03 | 2019-02-07 | Jazz Pharmaceuticals Ireland Limited | Formulations comprising a nucleic acid in a high concentration |
| WO2019200251A1 (en) | 2018-04-12 | 2019-10-17 | Jazz Pharmaceuticals, Inc. | Defibrotide for the prevention and treatment of cytokine release syndrome and neurotoxicity associated with immunodepletion |
| WO2020118165A1 (en) | 2018-12-07 | 2020-06-11 | Jazz Pharmaceuticals Ireland Limited | Subcutaneous delivery of high concentration formulations |
| WO2021174039A1 (en) | 2020-02-28 | 2021-09-02 | Jazz Pharmaceuticals Ireland Limited | Delivery of low viscosity formulations |
-
2008
- 2008-10-23 CN CN200810121715A patent/CN101759767A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103204905A (en) * | 2013-03-15 | 2013-07-17 | 四川同晟生物科技有限公司 | Method for synthesizing tetra-glycylglycine |
| CN105254576A (en) * | 2014-02-26 | 2016-01-20 | 中国科学院长春应用化学研究所 | Method for preparing glutamic piperazinedione |
| WO2019028340A1 (en) | 2017-08-03 | 2019-02-07 | Jazz Pharmaceuticals Ireland Limited | Formulations comprising a nucleic acid in a high concentration |
| WO2019200251A1 (en) | 2018-04-12 | 2019-10-17 | Jazz Pharmaceuticals, Inc. | Defibrotide for the prevention and treatment of cytokine release syndrome and neurotoxicity associated with immunodepletion |
| WO2020118165A1 (en) | 2018-12-07 | 2020-06-11 | Jazz Pharmaceuticals Ireland Limited | Subcutaneous delivery of high concentration formulations |
| WO2021174039A1 (en) | 2020-02-28 | 2021-09-02 | Jazz Pharmaceuticals Ireland Limited | Delivery of low viscosity formulations |
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| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| DD01 | Delivery of document by public notice |
Addressee: Huzhou Laise Biological Gene Engineering Co., Ltd. Document name: Notification that Application Deemed to be Withdrawn |
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| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20100630 |