CN101914125A - Extraction process of 5'-guanosine acidized reaction liquid - Google Patents
Extraction process of 5'-guanosine acidized reaction liquid Download PDFInfo
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- CN101914125A CN101914125A CN 201010253938 CN201010253938A CN101914125A CN 101914125 A CN101914125 A CN 101914125A CN 201010253938 CN201010253938 CN 201010253938 CN 201010253938 A CN201010253938 A CN 201010253938A CN 101914125 A CN101914125 A CN 101914125A
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Abstract
The invention provides an extraction process of a 5'-guanosine acidized reaction liquid, comprising the following steps of: A. adding the 5'-guanosine acidized reaction liquid in an NaCl water solution to obtain a hydrolysis liquid of the 5'-guanosine acidized reaction liquid; B. standing the hydrolysis liquid of the 5'-guanosine acidized reaction liquid for demixing, wherein the upper layer is an organic phase layer, the intermediate layer is a water phase layer and the water phase layer is separated; C. adding the organic phase in the NaCl water solution and repeatedly extracting and demixing; and D. mixing all water phase layers to obtain the water solution of the 5'-guanosine. The 5'-guanosine acidized reaction liquid is hydrolyzed with an NaCl solution, and extracted with the NaCl water solution; the organic phase layer and the water phase layer are naturally stood and demixed, so that the extraction process is simple and convenient; and the lower-price NaCl is used without introducing new toxic solvents, so that the extraction process ensures better quality of products, requires lower cost and is more applied to industrial large-batch production.
Description
Technical field
The present invention relates to the preparation method of 5 '-guanylic acid thing, relate in particular to the extraction process of kind of 5 '-5 '-guanosine acidized reaction liquid.
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, now looks back 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 hydrolyzed solution suitable substance P H value 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 frozen water hydrolysis, 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 frozen water hydrolysis, 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 frozen water hydrolysis, 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, but never too big improvement of post-reaction treatment technology: with reaction solution 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, 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.5 '-Sodium guanylate is 5 '-guanylic acid aqueous solution to be regulated with the PH agent just get, in the preparation method of whole 5 '-Sodium guanylate, make 5 '-guanylic acid aqueous solution such as above-mentioned technology by 5 '-guanylic acid aqueous solution, yield is lower, and these extraction agents of residual minim in the finished product influence the quality of product.
Summary of the invention
At above-mentioned shortcoming, the technical problem to be solved in the present invention is to simplify complicated in the past technology and reduce technology pollution, raising 5 '-guanylic acid aqueous products quality.
For solving the problems of the technologies described above, the technical solution adopted in the present invention is: a kind of extraction process of 5 '-5 '-guanosine acidized reaction liquid, step is: A, 5 '-5 '-guanosine acidized reaction liquid is added in the NaCL aqueous solution, obtains guanosine 5 '-phosphorylation reaction liquid hydrolyzed solution; B, with 5 ' of steps A-5 '-guanosine acidized reaction liquid hydrolyzed solution standing demix, the upper strata is an organic layer, lower floor is an aqueous phase layer, tells aqueous phase layer; C, organic phase is added the NaCL aqueous solution, extracting and demixing repeatedly again; D, mix all aqueous phase layers, obtain 5 '-guanosine aqueous acid.
Further: in the extraction process of above-mentioned 5 '-5 '-guanosine acidized reaction liquid, in the described steps A, the temperature of the described NaCL aqueous solution is-20 ℃～+ 20 ℃, and the concentration of the NaCL aqueous solution is 5-26.5%.Among described step B, the C, organic layer and aqueous phase layer are the nature standing demix.
Compared with prior art, the extraction process of above-mentioned 5 '-5 '-guanosine acidized reaction liquid is promptly used the NaCL aqueous hydrolysis, uses the NaCL aqueous solution extraction again, and organic layer and aqueous phase layer are the nature standing demix.The extraction process of this 5 '-5 '-guanosine acidized reaction liquid is simple, convenient, and uses more cheap NaCL and do not introduce new noxious solvent, and quality product is better, and cost is lower, is more suitable for industrialized production.About existing more abroad,, be not repeated here as " background technology " 2,3,4 document of being mentioned and patents with the report and the patent of the aftertreatment crystallization processes of the reaction of 5 '-guanylic acid and 5 '-guanosine aqueous acid.
Figure of description
Fig. 1 is the liquid chromatographic detection figure of embodiment 1;
Fig. 2 is the liquid chromatographic detection figure of embodiment 2;
Embodiment
Below in conjunction with embodiment content of the present invention is described in further detail, mentioned content is not a limitation of the invention among the embodiment, and each raw-material selection can be suited measures to local conditions and the result be there is no substantial effect in the preparation process.
Embodiment 1:
100g guanosine, the stirring of 960mL triethyl phosphate are cooled to 0 ℃, slowly drip the 70mL phosphorus oxychloride again, then 2 ℃ of reactions 6 hours.The 700mL 15%NaCL aqueous solution is freezing to below 0 ℃, and above-mentioned then guanosine 5 '-phosphorylation reaction liquid stream adds down, and stream added in about 1 hour, continues to stir 0.5 hour.Left standstill 10 minutes, and told lower floor's aqueous phase layer.Add the 350mL15%NaCL aqueous solution in the organic phase, in advance that the NaCL aqueous solution is freezing to below 0 ℃, extracting and demixing is 2 times again.Mix 3 times aqueous phase layer, get 5 '-guanosine aqueous acid.
This aqueous solution is detected with high performance liquid chromatograph, and purity is very high, as the liquid chromatographic detection figure that shows of Fig. 1.Relevant testing conditions is: liquid chromatographic detection instrument: 29 degrees centigrade of peak pressure 200bar of AgilentTechnologies model 1200 flow velocity 1.2ml/ 5min second column temperatures moving phase: 0.5% potassium dihydrogen phosphate.
Embodiment 2
54g guanosine sodium, 480mL triethyl phosphate stirred be cooled to 0 ℃, Dropwise 35 mL phosphorus oxychloride slowly again is then 0 ℃ of reaction 4 hours.The 350mL15%NaCL aqueous solution is freezing to below 2 ℃, and above-mentioned then guanosine 5 '-phosphorylation reaction liquid stream adds down, and stream added in about 1 hour, continues to stir 0.5 hour.Left standstill 10 minutes, and told lower floor's aqueous phase layer.Add the 170mL15%NaCL aqueous solution in the organic phase, in advance that the NaCL aqueous solution is freezing to below 2 ℃, extracting and demixing is 3 times again.Mix 4 times aqueous phase layer, get 5 '-guanosine aqueous acid.
This aqueous solution is detected with high performance liquid chromatograph, and purity is very high, as the liquid chromatographic detection figure that shows of Fig. 2.Relevant testing conditions is: liquid chromatographic detection instrument: 29 degrees centigrade of peak pressure 200bar of Agilent Technologies model 1200 flow velocity 1.2ml/ 5min second column temperatures moving phase: 0.5% potassium dihydrogen phosphate.
Claims (3)
1. the extraction process of 5 '-5 '-guanosine acidized reaction liquid, step is:
A, 5 '-5 '-guanosine acidized reaction liquid is added in the NaCL aqueous solution, obtains guanosine 5 '-phosphorylation reaction liquid hydrolyzed solution;
B, with 5 ' of steps A-5 '-guanosine acidized reaction liquid hydrolyzed solution standing demix, the upper strata is an organic layer, lower floor is an aqueous phase layer, tells aqueous phase layer;
C, organic phase is added the NaCL aqueous solution, extracting and demixing repeatedly again;
D, mix all aqueous phase layers, obtain 5 '-guanosine aqueous acid.
2. the extraction process of 5 '-5 '-guanosine acidized reaction liquid according to claim 1, it is characterized in that: in the described steps A, the temperature of the described NaCL aqueous solution is-20 ℃～+ 20 ℃, and the concentration of the NaCL aqueous solution is 5-26.5%.
3. the extraction process of 5 '-5 '-guanosine acidized reaction liquid according to claim 1, it is characterized in that: among described step B, the C, organic layer and aqueous phase layer are the nature standing demix.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3413282A (en) * | 1965-03-17 | 1968-11-26 | Ajinomoto Kk | Method of preparing 5'-nucleotides |
| CN1086219A (en) * | 1992-07-08 | 1994-05-04 | 武田药品工业株式会社 | 5 '-production method of Nucleotide |
| CN1539846A (en) * | 2003-10-29 | 2004-10-27 | 徐昌洪 | Technique for preparing 5'nucleotide bi-sodium |
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2010
- 2010-08-12 CN CN 201010253938 patent/CN101914125A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3413282A (en) * | 1965-03-17 | 1968-11-26 | Ajinomoto Kk | Method of preparing 5'-nucleotides |
| CN1086219A (en) * | 1992-07-08 | 1994-05-04 | 武田药品工业株式会社 | 5 '-production method of Nucleotide |
| CN1539846A (en) * | 2003-10-29 | 2004-10-27 | 徐昌洪 | Technique for preparing 5'nucleotide bi-sodium |
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Application publication date: 20101215 |