Check patentability & draft patents in minutes with Patsnap Eureka AI!

Preparation method of levocarnitine

A technology of coenzyme and reductase, applied in the field of drug synthesis, can solve problems such as poor stereoselectivity, and achieve the effects of improved yield, low environmental pollution and simple operation

Pending Publication Date: 2021-10-22
海南卓科制药有限公司
View PDF17 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The invention provides a preparation method of levocarnitine, which solves the problem of poor stereoselectivity of the existing biocatalytic synthesis of levocarnitine

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

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method of levocarnitine
  • Preparation method of levocarnitine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] The present embodiment provides a kind of preparation method of levocarnitine, comprises the following steps:

[0027] (1) Ethyl 4-chloroacetoacetate in methanol, ketoreductase KRED-101, coenzyme NAD + , glucose dehydrogenase, glucose and glucose solution, adjust the pH value to 7.0, stir at 25°C, and a reduction reaction occurs to generate (R)-4-chloro-3-hydroxybutyric acid ethyl ester; glucose solution The mass percent concentration of 4-chloroacetoacetate is 6.5%; the mass volume ratio of 4-chloroacetoacetate and first form is 1:8g / ml, and the mass volume ratio of 4-chloroacetoacetate and glucose solution is 1:40g / ml . The mass ratios of the carbonyl reductase, coenzyme, glucose dehydrogenase and ethyl 4-chloroacetoacetate are 0.65:1, 0.25:1 and 0.5:1 respectively;

[0028] (2) Ethyl (R)-4-chloro-3-hydroxybutyrate reacts with trimethylamine to generate levocarnitine, specifically: in the presence of sodium hydroxide, slowly add trimethylamine aqueous solution to (R...

Embodiment 2

[0030] The present embodiment provides a kind of preparation method of levocarnitine, comprises the following steps:

[0031] (1) Ethyl 4-chloroacetoacetate in ethanol, ketoreductase KRED-101, coenzyme NAD + , glucose dehydrogenase, glucose and glucose solution, adjust the pH value to 6.5, stir at 30°C, and a reduction reaction occurs to generate (R)-4-chloro-3-hydroxybutyrate ethyl ester; the quality of the glucose solution The percentage concentration is 5%; the mass volume ratio of ethyl 4-chloroacetoacetate to ethanol is 1:10g / ml, and the mass volume ratio of ethyl 4-chloroacetoacetate to glucose solution is 1:30g / ml. The mass ratios of the carbonyl reductase, coenzyme, glucose dehydrogenase and ethyl 4-chloroacetoacetate are 0.8:1, 0.2:1 and 0.6:1 respectively;

[0032] (2) Ethyl (R)-4-chloro-3-hydroxybutyrate reacts with trimethylamine to generate levocarnitine, specifically: in the presence of sodium hydroxide, slowly add trimethylamine aqueous solution to (R) -In the...

Embodiment 3

[0034] The present embodiment provides a kind of preparation method of levocarnitine, comprises the following steps:

[0035] (1) Ethyl 4-chloroacetoacetate in isopropanol, ketoreductase KRED-101, coenzyme NAD + , glucose dehydrogenase, glucose and glucose solution, adjust the pH value to 7.5, stir at 20°C, a reduction reaction occurs to generate (R)-4-chloro-3-hydroxybutyrate ethyl ester; the quality of glucose solution The percentage concentration is 8%; the mass volume ratio of ethyl 4-chloroacetoacetate to isopropanol is 1:5g / ml, and the mass volume ratio of ethyl 4-chloroacetoacetate to glucose solution is 1:50g / ml . The mass ratios of the carbonyl reductase, coenzyme, glucose dehydrogenase and ethyl 4-chloroacetoacetate are 0.5:1, 0.3:1 and 0.4:1 respectively;

[0036](2) Ethyl (R)-4-chloro-3-hydroxybutyrate reacts with trimethylamine to generate levocarnitine, specifically: in the presence of sodium hydroxide, slowly add trimethylamine aqueous solution to (R) -In the...

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 method of levocarnitine, and belongs to the technical field of drug synthesis. The preparation method comprises the following steps: adjusting the pH value of ethyl 4-chloroacetoacetate to 6.5-7.5 under the action of a cosolvent, carbonyl reductase, coenzyme, glucose dehydrogenase, glucose and a glucose solution, conducting stirring at 20-30 DEG C for carrying out reduction reaction to generate ethyl (R)-4-chloro-3-hydroxybutyrate; and subjecting the ethyl (R)-4-chloro-3-hydroxybutyrate and trimethylamine to a reaction to generate levocarnitine. The carbonyl reductase is used for carrying out asymmetric addition reaction on C=O double bonds in ethyl 4-chloroacetoacetate molecules, and the method is very high in reaction selectivity, simple in post-treatment and low in production cost. The process has the advantages of few by-products, few wastes and low environmental pollution. Compared with an existing synthesis route, the method has the advantages of significantly improved yield, few synthesis steps, easily available raw materials, simple operation, greenness and environmental protection.

Description

technical field [0001] The invention relates to the technical field of drug synthesis, in particular to a preparation method of levocarnitine. Background technique [0002] Levocarnitine, also known as L-carnitine, chemical name: (R)-3-hydroxy-4-(trimethylamino)butyrate, structural formula: [0003] [0004] It can be used to treat chronic renal failure, cardiomyopathy, coronary heart disease and organic acidemia, etc. It can also be used as an auxiliary treatment drug for chronic liver disease, and has a certain protective effect on endotoxemia and liver damage. It can also be used as a nutritional and feed additive. [0005] The preparation methods of L-carnitine reported in the literature are generally divided into extraction method, biological fermentation method, enzymatic method, chemical resolution method and asymmetric synthesis method. The main preparation method of optically pure (R)-3-hydroxy-4-(trimethylamino)butyrate is the asymmetric synthesis of acetoacet...

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): C12P7/62C07C227/12C07C229/22C07C227/40
CPCC12P7/62C07C227/12C07C227/40C07C229/22
Inventor 李强
Owner 海南卓科制药有限公司
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

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

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com