Preparation method of draxxin

A technology of tyramectin and a synthesis method, applied in the field of preparation of tyramectin, can solve the problems of harsh reaction conditions, high price of di-tert-butyl dicarbonate, high cost and safety, etc., and achieves rapid reaction and comprehensive The effect of improving yield and shortening operation time

Inactive Publication Date: 2015-08-26
RINGPU TIANJIN BIOLOGICAL PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Disadvantages: the use of Swern reaction requires reaction at ultra-low temperature, and there are safety and cost problems in industrialization
The price of di-tert-butyl dicarbonate is higher
In the process of hydroxyl oxidation and epoxidation, the methods currently used generally use a reaction temperature of -70 to -30°C, the reaction conditions are harsh, or a highly toxic oxidant is used for the reaction, and the product is not easy to separate and purify. Apps have significant cost and security concerns

Method used

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  • Preparation method of draxxin
  • Preparation method of draxxin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] ((2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[[2,6-Dideoxy-3-C-methyl-3-O-methyl--α -L-nucleo-hexapyranosyl]-oxy]-2-ethyl-3,4,10-trihydroxy acid-3,5,8,10,12,14-hexamethyl-11-[[ 3,4,6-Tideoxy-3-(dimethylamino)-2-O-acetyl-β-D-wood-hexapyranosyl]oxy)-1-oxa-6-azacyclodeca Pentaxane (15-membered macrocycle) (attached Figure II Preparation of compound II):

[0032] Add 500 ml of dichloromethane to a 1000 mL three-necked reaction flask, raise the temperature to 40° C., add 50 g of desmethyl azithromycin, start stirring to dissolve. Then add 6.9 g of triethylamine and stir evenly. Then, 6.9 g of acetic anhydride was slowly added, and the reaction was stirred for 3 hours to obtain a reaction liquid. After the reaction is over, add 80ml of water to the above reaction solution, add sodium hydroxide to adjust the pH value to 9, stir for 10 minutes, stand for phase separation, wash the water phase with dichloromethane, combine the organic phases, and add to the organic phase 80mL sat...

Embodiment 2

[0034] ((2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[[2,6-Dideoxy-3-C-methyl-3-O-methyl--α -L-nucleo-hexapyranosyl]-oxy]-2-ethyl-3,4,10-trihydroxy acid-3,5,8,10,12,14-hexamethyl-11-[[ 3,4,6-Tideoxy-3-(dimethylamino)-2-O-acetyl-β-D-wood-hexapyranosyl]oxy)-1-oxa-6-azacyclodeca Preparation of pentane (15-membered macrocycle) (compound II)

[0035] Add 500ml of acetone to a 1000mL three-necked reaction flask, heat to 30°C, add 50g of desmethylazithromycin, start stirring to dissolve. Then add 9.9 g of diethylamine and stir evenly. Then slowly add 20.8 g of acetic anhydride, stir and react for 1 hour to obtain a reaction liquid. After the reaction is over, add 80ml of water to the above reaction solution, add sodium hydroxide to adjust the pH to 9.5, stir for 10 minutes, stand for phase separation, wash the water phase with dichloromethane, combine the organic phases, and add to the organic phase 80mL saturated NaCl solution, washed, phase separation, take the organic phase, add an ap...

Embodiment 3

[0037] ((2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[[2,6-Dideoxy-3-C-methyl-3-O-methyl--α -L-nucleo-hexapyranosyl]-oxy]-2-ethyl-3,4,10-trihydroxy acid-3,5,8,10,12,14-hexamethyl-11-[[ 3,4,6-Tideoxy-3-(dimethylamino)-2-O-acetyl-β-D-wood-hexapyranosyl]oxy)-1-oxa-6-azacyclodeca Preparation of pentane (15-membered macrocycle) (compound II)

[0038] Add 500 ml of trichloromethane to a 1000 mL three-necked reaction flask, raise the temperature to 50° C., add 50 g of desmethyl azithromycin, start stirring and dissolve. Then add 26.8 g of pyridine and stir evenly. Then slowly add 234 g of acetic anhydride, stir and react for 5 hours to obtain a reaction liquid. After the reaction is over, add 80ml of water to the above reaction solution, add sodium hydroxide to adjust the pH to 10, stir for 10 minutes, stand for phase separation, wash the water phase with dichloromethane, combine the organic phases, and add to the organic phase 80mL saturated NaCl solution, washed, phase separation, take...

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PUM

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Abstract

The invention discloses a preparation method of draxxin. The preparation method comprises the following steps: the Grignard reaction is adopted, hydroxyl protection ketone reacts with a Grignard reagent, a chloromethyl is introduced in the position of a carbonyl, the carbonyl is reduced to hydroxyl, and then the hydroxyl reacts with n-propylamine to prepare draxxin, so that the harsh reaction condition during the carbonyl epoxidation process is avoided. According to the preparation method of draxxin, the temperature range during the epoxidation reaction process is controlled to be from the room temperature to 80 DEG C, the reaction is fast, the operating time is shortened by 15% or above, the comprehensive yield is increased by 5% or above, the operation is simple and convenient, and the enlarged production is facilitated.

Description

Technical field [0001] The invention belongs to the field of chemical synthesis of veterinary raw materials, and specifically relates to a preparation method of tyramectin. Background technique [0002] Tyramectin, the English name Tulathromycin, is also known as tyramycin, turamycin, tyramectin. The molecular formula is C 41 H 79 N 3 O 12 , Molecular weight is 806.23, CAS number: 280755-12-6. A new type of animal-specific macrolide antibiotic, Tyramectin was approved by EMEA in July 2002. In July 2005, the US FDA approved Pfizer's product Recoxin (10% Tyramectin injection). . Mainly used for Actinobacillus pleuropneumoniae, Pasteurella, Haemophilus, Bordetella, Mycoplasma, bronchial septicemia caused by swine and bovine respiratory diseases and bovine infectious keratoconjunctivitis caused by Moraxella bovis. [0003] According to the molecular structure of tyramectin (attached Figure one ) It can be seen that it has three more amine groups than other macrolides, so the solutio...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H17/00C07H1/00
CPCC07H17/00C07H1/00
Inventor 井丁丁李旭东刘爱玲夏雪林刘拓孟小宾付春香
Owner RINGPU TIANJIN BIOLOGICAL PHARMA
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