Preparation process of 3-deacetylated-7-amino-cephalosporanic acid

A technology for aminocephalosporanic acid and deacetylation, which is applied in the field of medicine, can solve the problems of low yield, long process route, and many product losses, and achieves the effects of high product yield and short process route.

Active Publication Date: 2012-06-20
石药集团内蒙古中诺药业有限公司
View PDF4 Cites 9 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Among the above-mentioned preparation methods, the chemical method and the chemical-biological enzymatic method have a long process route, and all have to undergo three crystallization processes of cephalosporin C sodium salt (or zinc salt), 7-ACA, and D-7-ACA. Due to the crystallization process, product loss Many, resulting in low yield of the method
In addition, the cracking used in the chemical method requires high temperature, high pressure and low cooling, and the organic solvents used in the reaction materials, such as dichloromethane, aniline, and chlorosilane, are poisonous and harmful pollutants, and a large amount of strong acid and alkali are used. The production of D-7-ACA has to bear heavy energy consumption costs ...

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

[0033] a. Weigh 4.1KU cephalosporin acylase and 2.2KU cephalosporin esterase respectively, wash them with anhydrous brine, and put them into a 2.0L enzyme reactor;

[0034] b. Take the cephalosporin C nanofiltration concentrated solution analyzed by sodium bicarbonate with a concentration of 45.6g / L and prepare 1.2L of cephalosporin C solution with a concentration of 30.2g / L and put it into a 2.0L enzyme reactor , the stirring speed is 400rpm, the pH is controlled by 3mol / L ammonia water to be 8.05, the temperature is 18°C, and after 80 minutes of reaction, the reaction solution is transferred to a 2L beaker (cephalosporin acylase and cephalosporin esterase are absorbed by the bottom of the enzyme reactor. sieve retention);

[0035] c. Cool the reaction solution to 5°C, add 10% hydrochloric acid dropwise to adjust the pH to 5.85, let it grow for 30 minutes, then continue to add hydrochloric acid to pH 4.01, grow the crystal for 4 hours, filter with suction, wash twice with 1...

Embodiment 2

[0037] a. Weigh 7.5KU cephalosporin acylase and 3.1KU cephalosporin esterase respectively, wash them with anhydrous brine, and put them into a 2.0L enzyme reactor;

[0038] b. Take the cephalosporin C nanofiltration concentrate that is analyzed by sodium acetate with a concentration of 56.7g / L and prepare 1.2L of cephalosporin C solution with a concentration of 36.8g / L with no salt water, and put it into a 2.0L enzyme reactor. The stirring speed is 400rpm, the pH is controlled to be 8.10 with 3mol / L ammonia water, and the temperature is 20°C. After reacting for 90min, the reaction solution is transferred to a 2L beaker (cephalosporin acylase and cephalosporin esterase are sieved by the bottom of the enzyme reactor. net intercept);

[0039] c. Cool the reaction solution to 5°C, add 10% hydrochloric acid dropwise to adjust the pH to 5.80, let it grow for 30 minutes, then continue to add hydrochloric acid dropwise to pH 4.08, grow the crystal for 4 hours, filter with suction, was...

Embodiment 3

[0041] a. Weigh 10KU cephalosporin acylase and 4.0KU cephalosporin esterase respectively, wash them with anhydrous brine, and put them into a 2.0L enzyme reactor;

[0042]b. Take the cephalosporin C nanofiltration concentrate that is analyzed by sodium acetate with a concentration of 56.7g / L and prepare 1.2L of cephalosporin C solution with a concentration of 44.6g / L with no salt water, and put it into a 2.0L enzyme reactor. The stirring speed is 400rpm, the pH is controlled to be 8.30 with 3mol / L ammonia water, and the temperature is 20°C. After reacting for 90min, the reaction solution is transferred to a 2L beaker (cephalosporin acylase and cephalosporin esterase are sieved by the bottom of the enzyme reactor. net interception);

[0043] c. Cool the reaction solution to 5°C, add 10% hydrochloric acid dropwise to adjust the pH to 6.10, let stand to grow the crystal for 30 minutes, then continue to drop hydrochloric acid to pH 4.04, grow the crystal for 4 hours, filter with ...

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 discloses a preparation process of 3-deacetylated-7-amino-cephalosporanic acid and belongs to the technical field of medicine. A method of the preparation process comprises the steps that: cephalosporin acylase and cephalosporin esterase are mixed, then, cephalosporin C extracting solution is added, next, acid is added for crystallization, washing and drying, and the solid 3-deacetylated-7-amino-cephalosporanic acid is obtained. The method only needs the one-step normal-temperature cracking reaction and one-step crystallization process, the process route is short, the pollution is little, the product mol yield is higher than 85 percent, and the preparation process is suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation process of a pharmaceutical intermediate, in particular to a preparation process of 3-deacetyl-7-aminocephalosporanic acid, which belongs to the technical field of medicine. Background technique [0002] 3-deacetyl-7-aminocephalosporanic acid is called D-7-ACA for short. Because the amino group at the 7th position and the hydroxyl group at the 3rd position are relatively active, different side chains can be introduced to synthesize a series of cephalosporin antibiotics, such as cephalosporin Cefuroxime, Cefuroxime, Cefpirome, Cefcapene Proxetil, Cefdinir, Ceftazidime, etc. With the increase in the amount of cephalosporin antibiotics and the development of new cephalosporin antibiotics, the demand for D-7-ACA in pharmaceutical production is also increasing. [0003] Currently, there are three main methods for preparing D-7-ACA: chemical method, chemical-biological enzymatic method and biological enzymatic method. ...

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): C12P35/00
Inventor 卢华袁国强朱科王艳艳丁海平薛瀚孟德程延国东王进贤刘萌
Owner 石药集团内蒙古中诺药业有限公司
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