Preparation method of calcium 2-ketophenylalanine

A technology of ketophenylalanine calcium and phenylalanine, which is applied in the field of drug biosynthesis, can solve the problems of harsh reaction conditions, high energy consumption, and low yield, and achieve tolerant conditions, cost reduction, and high conversion rate Effect

Active Publication Date: 2018-10-19
JING JING PHARMA
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] 2-ketophenylalanine calcium (ketophenylalanine calcium, also known as 2-oxo-3-phenylpropionate calcium) is a calcium salt formed by the reaction of aliphatic amino acid ketoacids and calcium ions, which can improve nutrition It is a very effective drug for the treatment of uremia due to emaciation, loss of appetite and endocrine function caused by adverse reactions. The current synthesis methods include: using ethyl cyanoacetate and benzaldehyde as starting materials, and through Knoevenagel-Cope reaction, 2 - ethyl benzylidene cyanoacetate, then oxidized and hydrolyzed to obtain α-ketophenylalanine calcium, the invention patent application CN101759553 discloses a method of obtaining α-ketophenylalanine calcium by reacting 3-phenyl-2-oxopropionic acid with calcium bicarbonate Calcium α-ketophenylalanine, CN102050725 is a method for preparing 4-benzylidene-2-methyldihydrooxazolone by reacting glycine, benzaldehyde, acetic anhydride and an organic base, and then reacting with calcium hydroxide. All adopt chemical synthesis, the process operation is complicated, the yield is low, the product contains many unknown impurities, and the organic solvent with high COD is used, the energy consumption is large and the reaction conditions are harsh, which is not conducive to clean production
At present, there have been reports on the conversion of phenylalanine to 2-ketophenylalanine calcium by biological enzymatic methods, but the conversion rate of the wild-type enzyme is low, and it is necessary to modify the enzyme through complex genetic engineering to improve the conversion rate.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] 40kg of phenylalanine is dissolved in a certain amount of water to prepare 1000L of 4% aqueous solution, the temperature of the process is controlled between 5-30°C, and 12kg of compound microorganisms are added to the feed solution for reaction. The composition of the composite microorganisms was 3:1:1 Bacillus cereus CGMCC No.7433, Bacillus licheniformis CGMCC No.6102 and Paracoccus denitrificans CGMCC No.3658. The process tracked the remaining substrate and the amount of product generated. After 4.5 hours of reaction, the substrate phenylalanine remained at 0.5 g / L, and the product content did not increase any more. The reaction ended and the conversion rate was greater than 99%. After the reaction is completed, the complex microorganisms are removed by filtration, washed with a small amount of water, and put into the next batch.

[0023] Add 1.5 kg of activated carbon to the obtained feed solution at 5-30°C for decolorization for half an hour, then filter to remove ...

Embodiment 2

[0025] 30kg of phenylalanine is dissolved in a certain amount of water to prepare 100L of 30% aqueous solution, the process temperature control material temperature is between 31-60°C, and 15kg of composite microorganisms are added to the feed liquid for reaction. The composition of the composite microorganisms was 5:2:1 Bacillus cereus CGMCC No.7433, Bacillus licheniformis CGMCC No.6102 and Paracoccus denitrificans CGMCC No.3658. The process tracked the remaining substrate and the amount of product generated. After 5 hours of reaction, the substrate phenylalanine remained 1 g / L, and the product content did not increase any more. The reaction ended and the conversion rate was greater than 99%. After the reaction is completed, the complex microorganisms are removed by filtration, washed with a small amount of water, and put into the next batch.

[0026] Add 0.4 times the mole of calcium chloride to the obtained feed solution at 31-60°C. During the addition, a precipitate forms....

Embodiment 3

[0028] 30kg of phenylalanine is dissolved in a certain amount of water to prepare 200L of 15% aqueous solution, the temperature of the process is controlled between 31-60°C, and 1.2kg of composite microorganisms are added to the feed solution for reaction. The composition of the composite microorganisms was 4:2:1 Bacillus cereus CGMCC No.7433, Bacillus licheniformis CGMCC No.6102 and Paracoccus denitrificans CGMCC No.3658. The process tracked the remaining substrate and the amount of production. After 6 hours of reaction, the remaining substrate was less than 0.4g / L, and the product content no longer increased, and the reaction was considered to be over. After the reaction is completed, the complex microorganisms are removed by filtration, washed with a small amount of water, and put into the next batch.

[0029] Add 0.4 times the mole of calcium chloride to the obtained feed solution at 31-60°C. During the addition, a precipitate forms. After the addition is complete, stir fo...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention relates to the technical field of biosynthesis of medicines, specifically to a preparation method of calcium 2-ketophenylalanine. According to the preparation method, 2-ketophenylalanineis prepared through microbial conversion of phenylalanine, and the 2-ketophenylalanine and calcium ions form salt to obtain the calcium 2-ketophenylalanine. According to the preparation method, a condition is mild, steps are simple, and the conversion rate is high.

Description

technical field [0001] The invention relates to the technical field of biosynthesis of medicines, in particular to a preparation method of 2-ketophenylalanine calcium. Background technique [0002] 2-ketophenylalanine calcium (ketophenylalanine calcium, also known as 2-oxo-3-phenylpropionate calcium) is a calcium salt formed by the reaction of aliphatic amino acid ketoacids with calcium ions, which can improve nutrition It is a very effective drug for the treatment of uremia due to emaciation, loss of appetite and endocrine function caused by adverse reactions. The current synthesis methods include: using ethyl cyanoacetate and benzaldehyde as starting materials, and through Knoevenagel-Cope reaction, 2 - ethyl benzylidene cyanoacetate, then oxidized and hydrolyzed to obtain α-ketophenylalanine calcium, the invention patent application CN101759553 discloses a method to obtain α-ketophenylalanine calcium by reacting 3-phenyl-2-oxopropionic acid with calcium bicarbonate Calci...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C12P13/00C12R1/085C12R1/10C12R1/01
CPCC12P13/00
Inventor 何连顺李霆李斌水米造吉马静
Owner JING JING PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap