Synthetic intermediate of pleuromutilin antibiotics and synthetic method thereof

A technology for pleuromutilin and a synthesis method, which is applied to the synthetic intermediates of pleuromutilin antibiotics and the field of synthesis thereof, can solve the problems of destruction selectivity, the inability of mtriptyline to be used for the synthesis of antibiotics, etc., and achieves cost controllable Effect

Inactive Publication Date: 2016-03-09
宁夏泰瑞制药股份有限公司
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the synthesis of tiamulin is mainly obtained by modifying the two active hydroxyl groups on the inner core of mutriptyline, but since mutriptyline itself has two non-selective hydroxyl groups, if pleuromutilin is directly hydrolyzed to obtain mutriptyline , will destroy its selectivity, making mu

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
  • Synthetic intermediate of pleuromutilin antibiotics and synthetic method thereof
  • Synthetic intermediate of pleuromutilin antibiotics and synthetic method thereof
  • Synthetic intermediate of pleuromutilin antibiotics and synthetic method thereof

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0020] Example 1

[0021] Take 1000kg of pleuromutilin crystals, put them into a 10m3 glass-lined reactor, add 4000kg of pyridine, stir to dissolve, cool to 0°C, put in 300kg of di-tert-butyl dicarbonate and 50kg of tetrahydrofuran, keep the reaction temperature for 3 hours. After the reaction, it was concentrated and distilled under reduced pressure until a dry solid was obtained. Add 4000kg of water to the tank, adjust the pH to 10.5 with 20% sodium hydroxide, raise the temperature to 40℃, hydrolyze for 20 hours, add 2000kg of methyl isobutyl ketone in the ratio of water: methyl isobutyl ketone = 2:1 Base ketones are kept at 40°C for extraction, and the organic phase is retained after extraction. In the state of heat preservation, slowly add 250kg of acetic anhydride to the organic phase and react for 3 hours to obtain a methyl isobutyl ketone solution of double-protected Mtriptyline. The content is 37.68% and the yield is 90.44%, which can be directly used for the synthesis o...

Example Embodiment

[0022] Example 2

[0023] Take 200kg of pleuromutilin crystals and put them into a 6m3 glass-lined reactor, add 900kg of piperidine, stir to dissolve, cool to 5°C, put in 50kg of di-tert-butyl dicarbonate and 12kg of tetrahydrofuran, and keep the reaction for 4 hours. After the reaction is over, the temperature is raised and concentrated and distilled under reduced pressure until a dry solid is obtained. Add 1000kg of water to the tank, adjust the pH to 11.0 with 15% potassium hydroxide, heat up to 42°C, hydrolyze for 22 hours, add 400kg of methyl isobutyl at the ratio of water: methyl isobutyl ketone = 2.5:1 Keep the ketone at 42°C for extraction, and keep the organic phase after extraction. Under the heat preservation state, 40 kg of acetic anhydride was slowly added dropwise to the organic phase, and the reaction was kept for 4 hours to obtain a methyl isobutyl ketone solution of double protection mtriptyline with a content of 38.40% and a yield of 92.15%. It can be directly...

Example Embodiment

[0024] Example 3

[0025] Take 100g of pleuromutilin crystals, put it into a 1000L three-necked flask, add 500g of diethylamine, stir to dissolve, cool to 2°C, put in 25g of di-tert-butyl dicarbonate and 7.5g of tetrahydrofuran, and heat the reaction for 5 hours. After the reaction is over, the temperature is raised and concentrated and distilled under reduced pressure until a dry solid is obtained. Add 450g of water to the tank, adjust the pH to 10.7 with 20% ethanol / sodium ethoxide, increase the temperature to 44°C, hydrolyze for 21 hours, add 150g of methyl isopropyl ketone at the ratio of water: methyl isobutyl ketone = 3:1 Butyl ketone was kept at 44°C for extraction, and the organic phase was retained after extraction. Under the heat preservation state, 30 g of acetic anhydride was slowly added dropwise to the organic phase, and the reaction was kept for 5 hours to obtain a methyl isobutyl ketone solution of double protection mtriptyline with a content of 49.05% and a yiel...

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 a synthetic intermediate of pleuromutilin antibiotics and a synthetic method thereof. The synthetic intermediate and the synthetic method have the beneficial effects that pleuromutilin is used as a synthetic precursor; double protection Mutilin capable of selectively modifying two active hydroxyl respectively is obtained after a molecule-glycolic acid is removed through hydrolysis; such 4,7-OH double protection Mutilin can be used for further synthesizing tiamulin fumarate or other pleuromutilin antibiotics as needed and is a good semi-synthetic antibiotic precursor; double protection Mutilin is synthesized with pleuromutilin; the yield is between 85% and 96% according to changes of selected raw materials and process ratios; the organic amine recovery rate is more than 84%; the cost is controllable.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, in particular to a synthetic intermediate of pleuromutilin antibiotics and a synthetic method thereof. Background technique [0002] Pleuromutilin antibiotics are a group of relatively mature semi-synthetic veterinary antibiotics: among them, tiamulin and warnimulin are effective against a variety of Gram-positive cocci, including most staphylococci and streptococci, as well as a variety of mycoplasma and Certain spirochetes have good antibacterial activity, and tiamulin fumarate is also a widely used pleuromutilin antibiotic. At present, the synthesis of tiamulin is mainly obtained by modifying the two active hydroxyl groups on the inner core of mutriptyline, but since mutriptyline itself has two non-selective hydroxyl groups, if pleuromutilin is directly hydrolyzed to obtain mutriptyline , will destroy its selectivity, so that mutriptyline cannot be used for antibiotic synthesis. For exam...

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): C07C69/28C07C67/08
CPCC07C69/28C07C67/03C07C67/08C07C67/297C07C69/675
Inventor 赵伯龙
Owner 宁夏泰瑞制药股份有限公司
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