阅读说明：本技术 一种r-3-氨基丁酸生产方法 (Production method of R-3-aminobutyric acid ) 是由 陈艳辉 于 2019-11-13 设计创作，主要内容包括：本发明公开了一种R-3-氨基丁酸生产方法,包括以下步骤：S1,制备R-3-氨基丁酸粗料；S2,将制备的粗料进行超滤处理；S3,再对S2步骤中的产物进行纳滤；S4,再将S3步骤中的产物进行脱色处理；S5,然后将S4步骤中的产物进行浓缩处理；S6,再对S5步骤中处理的产物进行结晶；S7,然后对结晶体进行离心处理；S8,再对S7步骤处理的产物进行干燥处理；S9,最后将干燥后的产物进行包装,在S1步骤中制备R-3-氨基丁酸粗料时,首先挑选合适的种子进行培养。本发明添加磷酸二氢钾、磷酸氢二钾和氨水来调节容易的PH,以及调节溶液的温度,从而得出在一定温度和PH数值的催化条件下,可以得到最大催化效果,得到产品的最大转化率,有利于企业大规模生产需要。(The invention discloses a production method of R-3-aminobutyric acid, which comprises the following steps: s1, preparing a R-3-aminobutyric acid coarse material; s2, performing ultrafiltration treatment on the prepared coarse material; s3, nano-filtering the product obtained in the step S2; s4, decoloring the product obtained in the step S3; s5, concentrating the product obtained in the step S4; s6, crystallizing the product processed in the step S5; s7, centrifuging the crystals; s8, drying the product processed in the step S7; s9, finally packaging the dried product, and when preparing the R-3-aminobutyric acid coarse material in the S1 step, firstly selecting proper seeds for culturing. The invention adds the monopotassium phosphate, the dipotassium phosphate and the ammonia water to adjust the easy PH and adjust the temperature of the solution, thereby obtaining the maximum catalytic effect under the catalytic condition of certain temperature and PH value, obtaining the maximum conversion rate of the product and being beneficial to the large-scale production requirement of enterprises.)

1. A production method of R-3-aminobutyric acid is characterized by comprising the following steps:

s1, preparing a R-3-aminobutyric acid coarse material;

s2, performing ultrafiltration treatment on the prepared coarse material;

s3, nano-filtering the product obtained in the step S2;

s4, decoloring the product obtained in the step S3;

s5, concentrating the product obtained in the step S4;

s6, crystallizing the product processed in the step S5;

s7, centrifuging the crystals;

s8, drying the product processed in the step S7;

and S9, finally packaging the dried product.

2. A method for producing R-3-aminobutyric acid according to claim 1, wherein said raw material of R-3-aminobutyric acid is prepared in step S1, wherein said raw material is prepared by selecting suitable seeds for cultivation, said seeds are first cultivated in a shake flask overnight, then transferred to a seed tank for further cultivation until OD reaches a specified range, thereby obtaining seed liquid.

3. The method for producing R-3-aminobutyric acid according to claim 1, wherein in the fermentation operation, prepared peptone, yeast extract, potassium dihydrogen phosphate and dipotassium hydrogen phosphate are put into a fermentation tank filled with a certain amount of water, the pH of the solution is 5.3-6.6 due to weak acidity of potassium dihydrogen phosphate and dipotassium hydrogen phosphate solution, the pH of the solution is adjusted to a process specified range by ammonia water under stirring, the pH of the solution is adjusted to 8.7-10.2 by ammonia water, after the fermentation tank and pipeline steam sterilization is finished, the cultured seed solution is transferred into the fermentation tank for continuous culture, and when the culture is stopped until OD does not rise or rises slowly, the culture is stopped and enzyme concentrated solution is collected by a tube membrane.

4. The method for producing R-3-aminobutyric acid according to claim 1, wherein during the conversion operation, the substrate is added into a conversion tank filled with a certain amount of water under stirring, the temperature is raised to a specified range, after the substrate is completely dissolved, the pH is adjusted to a specified range by using ammonia water, then other raw materials and the enzyme concentrate are added to start the conversion, the temperature and the pH are controlled during the conversion process, the conversion is stopped when the substrate content is less than the specified range, and the temperature is controlled to be 32-46 ℃ and the pH is controlled to be 8.3-9.7 during the conversion process.

5. The method for producing R-3-aminobutyric acid according to claim 1, wherein said converting solution is filtered through a tube membrane, a hollow membrane, a nanofiltration membrane to remove bacteria, proteins and other impurities, thereby obtaining a membrane filtration clear solution.

6. The method for producing R-3-aminobutyric acid according to claim 1, wherein a decolorizing tank is required in decolorizing operation, membrane filtered clear liquid is transferred into the decolorizing tank in use, a certain amount of activated carbon is added for decolorizing for a certain time, and then decolorized decolorizing liquid is decarbonized.

7. The method for producing R-3-aminobutyric acid according to claim 1, wherein an evaporator is required in the evaporation concentration process, and the decolorized solution is transferred to the evaporator for evaporation to obtain a product concentrated solution.

8. The method for producing R-3-aminobutyric acid according to claim 1, wherein a crystallizing tank is required in the crystallizing operation, the product concentrated solution is added into the crystallizing tank, the temperature is controlled to continue evaporating to a certain concentration range, and the temperature is reduced for crystallization.

9. The method for producing R-3-aminobutyric acid according to claim 1, wherein a centrifuge is required for the centrifugation, drying and packaging operations, the crystallized feed liquid is centrifuged by the centrifuge, the wet product crystals are collected, the wet product crystals pass through a drying device to obtain a dried product, the dried product is sampled and inspected, the qualified dried product is detected, the packaged finished product is mixed, and the unqualified product is reworked.

Technical Field

The invention relates to the technical field of medicine production, in particular to a production method of R-3-aminobutyric acid.

Background

R-3-aminobutyric acid (R-3-aminobutyricacid), CAS: 3775-73-3, which is mainly used as the precursor of R-3-aminobutanol as the medical intermediate. R-3-aminobutanol (R-3-amino-1-butanol), CAS: 61477-40-5, is a key intermediate of medicine for treating AIDS, Dolutegravir. Dolutegravir is an integrase inhibitor of human immunodeficiency virus type I (HIV-1), a chemical synthesis thereofMore raw materials are needed, and R-3-aminobutyric acid is one of important raw materials. The molecular structural formula of the R-3-aminobutyric acid is shown as the formula (I):

at present, when R-3-aminobutyric acid is prepared, an enzyme catalysis method is mainly adopted, and catalytic preparation is carried out by using enzyme, however, when the enzyme is used for catalytic reaction, reaction conditions need to be strictly controlled, such as temperature and pH of the reaction need to be strictly controlled, because the enzyme is very sensitive to temperature and pH, the catalytic efficiency of the enzyme is affected by slight changes of temperature and pH, the enzyme can be seriously inactivated, in order to meet production requirements of enterprises, a preparation method of R-3-aminobutyric acid with high conversion rate is obtained, a method for knowing the optimal temperature and pH of the enzyme catalysis preparation of R-3-aminobutyric acid is urgently needed, and therefore, a production method of R-3-aminobutyric acid is provided.

Disclosure of Invention

The invention aims to solve the defects in the prior art and provides a production method of R-3-aminobutyric acid.

In order to achieve the purpose, the invention adopts the following technical scheme:

a production method of R-3-aminobutyric acid comprises the following steps:

s1, preparing a R-3-aminobutyric acid coarse material;

s2, performing ultrafiltration treatment on the prepared coarse material;

s3, nano-filtering the product obtained in the step S2;

s4, decoloring the product obtained in the step S3;

s5, concentrating the product obtained in the step S4;

s6, crystallizing the product processed in the step S5;

s7, centrifuging the crystals;

s8, drying the product processed in the step S7;

and S9, finally packaging the dried product.

Preferably, when preparing the R-3-aminobutyric acid coarse material in the step S1, firstly, selecting proper seeds for culturing, firstly, culturing the seeds in a shake flask overnight, then transferring the seeds into a seeding tank for continuous culture until OD reaches a specified range, thereby obtaining a seed solution.

Preferably, in the fermentation operation, prepared raw materials of peptone, yeast extract, potassium dihydrogen phosphate and dipotassium hydrogen phosphate are put into a fermentation tank filled with a certain amount of water, the pH of the solution is 5.3-6.6 due to weak acidity of potassium dihydrogen phosphate and dipotassium hydrogen phosphate solution, the pH of the solution is adjusted to a process specified range by ammonia water under the stirring condition, the pH of the solution is adjusted to 8.7-10.2 by ammonia water, after the fermentation tank and a pipeline are subjected to steam sterilization, the cultured seed solution is transferred into the fermentation tank for continuous culture, and when the culture is not increased any more or is slowly increased, the culture is stopped, and a tube membrane is used for collecting the obtained enzyme concentrated solution.

Preferably, during the conversion operation, adding the substrate into a conversion tank filled with a certain amount of water under the stirring condition, heating to a specified range, adjusting the pH to the specified range by using ammonia water after the substrate is completely dissolved, then adding other raw materials and an enzyme concentrated solution to start conversion, controlling the temperature and the pH during the conversion process, stopping the conversion when the content of the substrate is less than the specified range, and controlling the temperature to be 32-46 ℃ and the pH to be 8.3-9.7 during the conversion process.

Preferably, after the conversion is completed, the conversion solution is filtered through a tube membrane, a hollow membrane or a nanofiltration membrane to remove bacteria, proteins and other impurities, thereby obtaining a membrane filtration clear solution.

Preferably, a decoloring tank is needed in the decoloring operation, membrane filtration clear liquid is transferred into the decoloring tank when in use, a certain amount of activated carbon is added for decoloring for a certain time, and then the decolored liquid is decarburized.

Preferably, an evaporator is needed in the evaporation concentration process, and the decolorized solution is transferred to the evaporator to be evaporated to obtain a product concentrated solution.

Preferably, a crystallizing tank is needed in the crystallization operation, the product concentrated solution is added into the crystallizing tank, the temperature is controlled to be continuously evaporated to a certain concentration range, and the temperature is reduced for crystallization.

Preferably, a centrifugal machine is needed in the centrifuging, drying and packaging operations, the feed liquid after crystallization is centrifuged by the centrifugal machine, the wet product crystals are collected, the wet product crystals pass through drying equipment to obtain dry products, then sampling and inspecting are carried out, qualified dry products are detected, the mixed and packaged finished products are processed, and unqualified products are processed by reworking.

According to the invention, the PH value is easily adjusted by adding the monopotassium phosphate, the dipotassium phosphate and the ammonia water, and the temperature of the solution is adjusted, so that the maximum catalytic effect can be obtained under the catalytic condition of a certain temperature and a certain PH value, the maximum conversion rate of the product is obtained, and the requirement of large-scale production of enterprises is facilitated.

Drawings

FIG. 1 is a schematic view of a process structure of a method for producing R-3-aminobutyric acid according to the present invention;

FIG. 2 is a schematic view of a detailed flow structure of the production method of R-3-aminobutyric acid provided by the present invention.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments.