CN101993466B - Method for preparing 5'-disodium guanylate - Google Patents
Method for preparing 5'-disodium guanylate Download PDFInfo
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- CN101993466B CN101993466B CN2010105091367A CN201010509136A CN101993466B CN 101993466 B CN101993466 B CN 101993466B CN 2010105091367 A CN2010105091367 A CN 2010105091367A CN 201010509136 A CN201010509136 A CN 201010509136A CN 101993466 B CN101993466 B CN 101993466B
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Abstract
The invention discloses a method for preparing 5'-disodium guanylate. The method comprises the following steps of: A, performing 5'-phosphorylation reaction by taking guanosine sodium salt and triethyl phosphate serving as raw materials; B, hydrolyzing phosphorylation reaction solution obtained in the step A in ice water to obtain hydrolyzate containing 5'-guanylate; C, adjusting the pH value of the hydrolyzate of the step B to be 9.0 to 10.0 with ammonium to obtain aqueous solution of the 5'-guanylate; D, standing aqueous solution of the step C and naturally demixing, and adjusting the pH value of a water phase layer of a lower layer to be 3.0+/-0.5 with hydrochloric acid to obtain mixed solution containing a large amount of 5'-guanylate precipitate; E, separating the mixed solution of the step D to obtain a wet product of the 5'-guanylate; and F, dissolving the wet product of the 5'-guanylate of the step E in water, adjusting the pH value to be 8.0+/-0.5 with sodium hydroxide, flowing 95 percent ethanol and crystallizing to obtain the 5'-disodium guanylate. The preparation method is simple and has light pollution.
Description
Technical field
The present invention relates to the food and medicine technical field, be specifically related to a kind of preparation technology of simple and easy to do 5 '-Sodium guanylate.
Background technology
5 '-Sodium guanylate is a kind of powerful fragrance adding agent, can be widely used in food flavourings such as specially fresh monosodium glutamate, chickens' extract, special delicious sauce; In addition, 5 '-Sodium guanylate also can be used as the baby milk powder additive.For many years, its preparation technology has had continuous development, the existing review as follows:
1, with guanosine and POCL3 in the presence of alkaline mediums such as pyridine, triethylamine, in DMF, DMSO or acetonitrile, carry out 5 '-phosphorylation reaction.1. the hydrolysis of reaction solution water transfers to suitable substance P H value with hydrolyzed solution then, again with activated carbon column absorption, alkali lye wash-out; Or with water-fast organic solvent extraction triethyl phosphates such as ethylene dichloride, water is transferred pH value, carries out separation and purification with anion-exchange column or activated carbon column.(Gulland?et?al.，J.Chem.Soc.，1940；Tsurushma?Massaki?et?al.，JP59167599，1984)。
2, guanosine and POCL3 are directly carried out 5 '-phosphorylation reaction in triethyl phosphate.Reaction solution is used the frozen water hydrolysis, and hydrolyzed solution adsorbs with anion-exchange column after transferring PH, wash-out, crystallization.(Masaharu?Yoshikawa?et?al.，US3347846，1967)。
3, an alkali metal salt and the POCL3 with guanosine directly carries out 5 '-phosphorylation reaction in triethyl phosphate.Reaction solution is used the frozen water hydrolysis, and with water-fast organic solvent extraction triethyl phosphates such as ethylene dichloride, water is transferred pH value, and crystallization obtains 5 '-Sodium guanylate.(Shigemitsu?Abe?et?al.，EP453597，1991)。
4, guanosine and triethyl phosphate elder generation reacting by heating are generated a kind of mixture, drip POCL3 then and carry out 5 '-phosphorylation reaction.Reaction solution is used the frozen water hydrolysis, and with water-fast organic solvent extraction triethyl phosphates such as ethylene dichloride, water is transferred pH value, and crystallization obtains 5 '-Sodium guanylate.(Tomomi?Ikemoto?et?al.，Chem.Pharm.Bull.，1995；Akira?Haze?et?al.，CA2100027，1994)。In the above technology, the selectivity of 1 pair 5 '-position is bad, and yield is lower.Found afterwards, in the triethyl phosphate solvent system, 5 ' of guanosine-phosphorylation selectivity higher (2,3,4), therefore, 5 '-phosphorylation reaction of guanosine all is chosen in the triethyl phosphate and carries out at present.Although 5 '-phosphorylation reaction has had bigger improvement, reaction solution is used the frozen water hydrolysis, again with activated carbon column absorption, purification; Perhaps separate and purify with anion-exchange column; The recovery of triethyl phosphate is difficult, and gac and regeneration of ion-exchange resin are polluted all bigger; And,, influence the quality of product owing to the carcinogenic toxicity of extraction agent, these extraction agents of residual minim in the finished product with the triethyl phosphate in the organic solvent extraction hydrolyzed solutions such as ethylene dichloride.
Summary of the invention
To above-mentioned shortcoming, the technical problem that the present invention will solve is to simplify in the past complicated technology, reduce technology and pollute, improve the quality of products.
For solving the problems of the technologies described above; The technical scheme that the present invention adopted is: a kind of preparation method of 5 '-Sodium guanylate; Step is: A, be that raw material carries out 5 '-phosphorylation reaction with guanosine sodium salt, triethyl phosphate; The mass ratio of described guanosine sodium salt and triethyl phosphate is 1: 3～20, and the mol ratio of guanosine sodium salt and POCl3 is 1: 1.05～5.0; B, with phosphorylation reaction liquid hydrolysis in frozen water of steps A gained, obtain containing the hydrolyzed solution of 5 '-guanylic acid; The hydrolyzed solution of 5 '-guanylic acid is the hydrolyzed solution that contains triethyl phosphate, phosphoric acid, hydrochloric acid, 5 '-guanylic acid and minor by-products; C, the hydrolyzed solution of step B is regulated pH value to 9.0～10.0 with ammonia, obtain 5 '-guanosine aqueous acid; 5 '-guanosine aqueous acid contains the aqueous solution of triethyl phosphate, diammonium phosphate, ammonium chloride, 5 '-guanylic acid di-ammonium salts and minor by-products; D, the aqueous solution of step C is left standstill natural layering, the aqueous phase layer of lower floor with salt acid for adjusting pH value to 3.0 ± 0.5, is obtained containing the sedimentary mixed solution of a large amount of 5 '-guanylic acids; The upper strata is the triethyl phosphate layer, and lower floor is for containing the aqueous phase layer of diammonium phosphate, ammonium chloride, 5 '-guanylic acid di-ammonium salts and minor by-products; E, the mixed solution of step D is separated, obtain the wet article of 5 '-guanylic acid; The wet article of 5 '-guanylic acid of F, step e are used water dissolution, regulate pH value to 8.0 ± 0.5 with caustic soda, flow to add 95% alcohol crystal and obtain 5 '-Sodium guanylate again.
Further: in the preparation method of above-mentioned 5 '-Sodium guanylate, in the described steps A, when guanosine sodium salt and triethyl phosphate carried out 5 '-phosphorylation reaction, temperature of reaction was-10～+ 20 ℃.Among the described step C, when aqueous phase layer was regulated the pH value with ammonia, used ammonia was a kind of in ammonia or the ammoniacal liquor, and aqueous temperature is controlled at-10～+ 20 ℃, and triethyl phosphate layer and aqueous phase layer do not need with an organic solvent to extract for leaving standstill natural layering.
Report and patent about guanosine sodium salt 5 '-phosphorylation reaction are existing more abroad, like document and the patent that " background technology " 3 mentioned, and no longer tired here stating.
Compared with prior art, the present invention provides a kind of preparation method of simple 5 '-Sodium guanylate, particularly simple aftertreatment technology, thus realize safety in production, minimizing pollution.After the hydrolysis of phosphorylation reaction liquid finishes; The present invention is through study and test repeatedly; Employing is regulated hydrolyzed solution pH value to 9.0～10.0 with ammonia; Utilize the big characteristic of 5 '-guanylic acid, two ammoniums solubleness in this PH scope, mixing solutions can leave standstill natural layering as a result, can directly the triethyl phosphate layer be separated with aqueous phase layer.Purify thereby improved in the past, perhaps separate and purify, perhaps with the method for the triethyl phosphate in the organic solvent extraction hydrolyzed solutions such as ethylene dichloride with anion-exchange column with activated carbon column absorption.The present invention is through a large amount of experiment and analyze and find, 5 '-guanylic acid when the PH=3.0 left and right sides in water slightly soluble, employing will say that layer is with salt acid for adjusting pH value to 3.0 ± 0.5 mutually, 5 '-guanylic acid is separated out deposition, separation obtains 5 '-guanylic acid.Then the wet article of 5 '-guanylic acid are used water dissolution, using caustic soda to regulate pH value is 8.0 ± 0.5, flows to add 95% alcohol crystal and obtain 5 '-Sodium guanylate again.
Figure of description
Fig. 1 is the liquid chromatographic detection figure of embodiment;
Embodiment
Below in conjunction with embodiment content of the present invention is done further to detail, mentioned content is not to qualification of the present invention among the embodiment, and each raw-material selection can be suited measures to local conditions and the result is not had substantial effect in the preparation process.
Embodiment
54g guanosine sodium, 480mL triethyl phosphate stirred be cooled to 0 ℃, Dropwise 35 mL POCl3 slowly again is then 0 ℃ of reaction 4 hours.
The 350mL water-cooled is frozen to 0 ℃, and above-mentioned then guanosine 5 '-phosphorylation reaction flow adds down, and stream added in about 1 hour, continues to stir 0.5 hour.
In hydrolyzed solution, slowly feed ammonia then, the control solution temperature when the pH value is 9.4, stops to feed ammonia at 0～5 ℃, continues to stir 1 hour.Left standstill then 10 minutes, and told lower floor's aqueous phase layer.
Again aqueous phase layer being used the salt acid for adjusting pH value is 3.0, stirs 1 hour at 0 ℃, filters and obtains 5 '-guanylic acid.
The article that should wet are with 360mL water dispersed with stirring, and to use caustic soda to regulate pH value be 8.0, and reaction solution are warming up to 80 ℃, adding 1g activated carbon decolorizing 30 minutes, suction filtration.In filtrating, slowly drip 95% alcohol crystal, 0 ℃, filter.Wet article oven dry obtains 77g 5 '-Sodium guanylate.Products obtained therefrom is detected with high performance liquid chromatograph, and purity is very high, liquid chromatographic detection figure as shown in Figure 1.Relevant testing conditions is: liquid chromatographic detection appearance: 29 degrees centigrade of peak pressure 200bar of Agi lent Technologies model 1200 flow velocity 1.2ml/ 5min second column temperatures moving phase: 0.5% potassium dihydrogen phosphate.
Claims (3)
1. the preparation method of 5 '-Sodium guanylate, step is:
A, be raw material with guanosine sodium salt, triethyl phosphate, feed POCl3 and carry out 5 '-phosphorylation reaction that the mass ratio of described guanosine sodium salt and triethyl phosphate is 1: 3～20, the mol ratio of guanosine sodium salt and POCl3 is 1: 1.05～5.0;
B, with phosphorylation reaction liquid hydrolysis in frozen water of steps A gained, obtain containing the hydrolyzed solution of 5 '-guanylic acid;
C, the hydrolyzed solution of step B is regulated pH value to 9.0～10.0 with ammonia, obtain 5 '-guanosine aqueous acid;
D, the aqueous solution of step C is left standstill natural layering, the aqueous phase layer of lower floor with salt acid for adjusting pH value to 3.0 ± 0.5, is obtained containing the sedimentary mixed solution of a large amount of 5 '-guanylic acids;
E, the mixed solution of step D is separated, obtain the wet article of 5 '-guanylic acid;
The wet article of 5 '-guanylic acid of F, step e are used water dissolution, regulate pH value to 8.0 ± 0.5 with caustic soda, drip 95% alcohol crystal again and obtain 5 '-Sodium guanylate.
2. the preparation method of 5 '-Sodium guanylate according to claim 1, it is characterized in that: in the described steps A, when guanosine sodium salt and triethyl phosphate carried out 5 '-phosphorylation reaction, temperature of reaction was-10～+ 20 ℃.
3. the preparation method of 5 '-Sodium guanylate according to claim 1 is characterized in that: among the described step C, when aqueous phase layer was regulated the pH value with ammonia, used ammonia was a kind of in ammonia or the ammoniacal liquor, and aqueous temperature is controlled at-10～+ 20 ℃.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105348347A (en) * | 2015-12-14 | 2016-02-24 | 山东凯盛新材料有限公司 | Refining method of guanosine-5-monophosphate disodium |
| CN108991523A (en) * | 2018-06-22 | 2018-12-14 | 金少举 | A kind of preparation method of environment-friendly type Sodium guanylate oral liquid of Chinese wolfberry |
| CN108991113A (en) * | 2018-06-22 | 2018-12-14 | 金少举 | A kind of preparation method of soybean peptide Sodium guanylate beverage |
Citations (4)
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|---|---|---|---|---|
| CN1539846A (en) * | 2003-10-29 | 2004-10-27 | 徐昌洪 | Technique for preparing 5'nucleotide bi-sodium |
| EP1411059A4 (en) * | 2001-07-26 | 2008-01-23 | Ajinomoto Kk | Method for producing mixed crystal of disodium 5'-guanylate and disodium 5'-inosinate |
| CN101654469A (en) * | 2009-09-04 | 2010-02-24 | 华南理工大学 | 5'-guanosine-disodium phosphate crystallizing method |
| CN101665525A (en) * | 2009-09-10 | 2010-03-10 | 广东肇庆星湖生物科技股份有限公司 | Synthetic method of nucleotide |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS55139400A (en) * | 1979-04-13 | 1980-10-31 | Ajinomoto Co Inc | Separation of sodium guanylate |
| JP2671446B2 (en) * | 1988-10-25 | 1997-10-29 | 味の素株式会社 | Method for mixed phosphorylation of inosine and guanosine |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1411059A4 (en) * | 2001-07-26 | 2008-01-23 | Ajinomoto Kk | Method for producing mixed crystal of disodium 5'-guanylate and disodium 5'-inosinate |
| CN1539846A (en) * | 2003-10-29 | 2004-10-27 | 徐昌洪 | Technique for preparing 5'nucleotide bi-sodium |
| CN101654469A (en) * | 2009-09-04 | 2010-02-24 | 华南理工大学 | 5'-guanosine-disodium phosphate crystallizing method |
| CN101665525A (en) * | 2009-09-10 | 2010-03-10 | 广东肇庆星湖生物科技股份有限公司 | Synthetic method of nucleotide |
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