Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

A kind of preparation method of tiamulin

A technology of tiamulin and pleuromutilin, which is applied in thioether preparation, organic chemistry and other directions, can solve the problems of toxicity, restricting the market size of tiamulin fumarate, strong irritating odor, etc., and achieves mild conditions and environmental protection. Friendly, low-cost effects

Active Publication Date: 2019-09-10
山东德信生物科技有限公司
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method needs to use 2-diethylaminoethanethiol as an important raw material, and this compound has greater toxicity and a strong pungent smell, especially the main raw material for the synthesis of chemical weapon nitrogen mustard, so it is restricted in use and procurement. The strict control of many departments or organizations in the country has seriously restricted the market size of tiamulin fumarate

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
  • A kind of preparation method of tiamulin
  • A kind of preparation method of tiamulin
  • A kind of preparation method of tiamulin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] A preparation method of tiamulin, the steps are as follows:

[0024] (1) Synthesis of 14-O-[(1-hydroxypropan-2-yl)mercaptoyl]mpirin (intermediate of formula 2)

[0025] Add 8.90g (20mmol) of pleuromutilin with a purity of 85%, 4.28g (22mmol) of 98% p-toluenesulfonyl chloride and 80mL of methyl isobutyl ketone into a 250mL three-necked flask, and heat up , stirred to dissolve pleuromutilin and p-toluenesulfonyl chloride, and when the temperature rose to 60°C, 4.0 mL of NaOH aqueous solution with a concentration of 10 mol / L was added dropwise and reacted for 30 min; then 1.72 g (22 mmol) of mercaptoethanol and 20 mL of Methanol, the reaction was continued at 60°C for 3h. After the reaction, it was extracted three times with 25 mL of distilled water, and the organic phase was washed with anhydrous Na 2 SO 4 After drying and evaporating methyl isobutyl ketone to dryness, 7.55 g (yield 89%) of viscous 14-O-[(1-hydroxypropan-2-yl)mercaptoyl]mylline was obtained.

[0026] ...

Embodiment 2

[0030] A preparation method of tiamulin, the steps are as follows:

[0031] (1) Synthesis of 14-O-[(1-hydroxypropan-2-yl)mercaptoyl]mpirin (intermediate of formula 2)

[0032] Add 8.90g (20mmol) of pleuromutilin with a purity of 85%, 4.62g (24mmol) of p-toluenesulfonyl chloride and 80mL of methyl isobutyl ketone into a 250mL three-necked flask, heat and stir to make pleuromutilin Pleuromutilin and p-toluenesulfonyl chloride were dissolved, and when the temperature rose to 60°C, 4.0 mL of NaOH aqueous solution with a concentration of 10 mol / L was added dropwise and reacted for 30 min; then a mixed solution (1.57 g The mercaptoethanol was dissolved in 20 mL of methanol, and 2 mL of NaOH with a concentration of 10 mol / L was added to react for 30 min), and the reaction was continued at 60° C. for 2.5 h. After the reaction, it was extracted three times with 25 mL of distilled water, and the organic phase was washed with anhydrous Na 2 SO 4 After drying and evaporating methyl iso...

Embodiment 3

[0036] A preparation method of tiamulin, the steps are as follows:

[0037] (1) The synthesis of 14-O-[(1-hydroxypropan-2-yl)mercaptoyl]mpirin (intermediate of Formula 2) is the same as in Example 2.

[0038] (2) Synthesis of Tiamulin (Formula 4 Compound)

[0039] The intermediate 14-O-[(1-hydroxypropan-2-yl) mercaptoyl] Mutilin (compound of formula 2) synthesized by 4.24g (10mmol) is added in the methyl tert-butyl ether of 20mL, drops to After 0°C, 20 mL of a methyl tert-butyl ether solution containing 0.90 g (3.33 mmol) of PBr3 was added dropwise, and after the addition was completed, the temperature was raised to room temperature, and the reaction was stirred for 12 h. After the reaction, add 5-7mL of 1mol / L Na 2 CO 3 The pH of the solution was adjusted to about 8, and the two phases were separated. The organic phase was washed twice with 10 mL of distilled water and evaporated to dryness. Add 30 mL of dimethylformamide, 0.73 g (10 mmol) of diethylamine and 1.66 g (12 ...

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 tiamulin. The synthesis route is as follows: the compound of formula 1-pleuromutilin is used as a raw material, and the intermediate p-toluenesulfonate is synthesized through p-toluenesulfonylation, and no Separation, direct preparation of formula 2 intermediate—14-O-[(1-hydroxypropane-2-yl) mercaptoyl] macrometrin through nucleophilic substitution reaction with β-mercaptoethanol, said formula 2 intermediate After the activation of the halogenating reagent or the sulfonylating reagent, the intermediate of formula 3 is formed, which can be directly reacted with diethylamine to synthesize the compound of formula 4—tiamulin, without separation. The method avoids the use of regulated 2-diethylaminoethanethiol, solves the main unfavorable factors restricting the production of tiamulin, and uses a synthetic route with low cost, mild conditions, environmental friendliness, and suitable for process production Preparation of tiamulin.

Description

technical field [0001] The invention belongs to the technical field of chemical medicines, and in particular relates to a preparation method of tiamulin. Background technique [0002] Tiamulin fumarate (Formula 1) is the first generation of pleuromutilin antibiotics for animals, which was first developed by Sandoz in 1974. The drug is modified by modifying the C22 position of pleuromutilin into a (diethylaminoethyl) sulfhydryl group. After the modification, the water solubility and antibacterial effect are better improved compared with pleuromutilin. In addition to the antibacterial activity of pleuromutilin, it also shows strong activity against Shigella, Klebsiella and Colon bacillus. In addition, the most important biological activity of tiamulin is that it has good antibacterial activity against various Mycoplasma, Brachyspira hyodysenteriae and Brachyspira pilosicoli. MIC of tiamulin against Mycoplasma hyopneumoniae 50 0.039μg / m1, MIC against Mycoplasma gallisepticum...

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
Patent Type & Authority Patents(China)
IPC IPC(8): C07C323/52C07C319/14C07C319/20
Inventor 尚若锋刘宇衣云鹏郝宝成杨珍梁剑平
Owner 山东德信生物科技有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com