Synthesis method of antibacterial agent cefoxitin acid

A technology for cefoxitin and antibacterial drugs, which is applied in the field of synthesis of antibacterial cefoxitin, can solve the problems of high cost, complicated production process, and low product yield of cefoxitin, and achieve easy implementation and shortened production The steps and synthesis process are simple and the effect

Inactive Publication Date: 2016-01-06
四川清山绿水医药化工股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The use of dangerous materials such as sodium methoxide, tert-butyl hypochlorite, and liquid nitrogen in the existing technology not only results in high cost of cefoxitin acid, complicated production process, low yield of final product, but also serious environmental pollution

Method used

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  • Synthesis method of antibacterial agent cefoxitin acid
  • Synthesis method of antibacterial agent cefoxitin acid
  • Synthesis method of antibacterial agent cefoxitin acid

Examples

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Embodiment 1

[0019] see figure 1 , in the embodiment of the present invention, a kind of synthetic method of antibacterial drug cefoxitin acid, use 7-amino cephalosporanic acid as raw material, use sodium bicarbonate solution to dissolve it, add etherification enzyme in the weak alkaline solution, and then Add methanol, introduce a methoxy group at the 7-position, and carry out an etherification reaction, wherein the molar ratio of methanol to 7-aminocephalosporanic acid is 1:1, the etherification reaction temperature is 30°C, and the etherification reaction time is 1h. After the conversion reaction, filter out the etherification enzyme; then add the deacetylase into the feed solution for hydrolysis, the hydrolysis temperature is 30°C, and the hydrolysis time is 0.5h. After the hydrolysis, add ethyl acetate to the solution and start Drop into 2-thiophene acetyl chloride reaction, the molar ratio of 2-thiophene acetyl chloride and 7-amino cephalosporanic acid is 1.2:1; After the reaction is...

Embodiment 2

[0023] In the embodiment of the present invention, a method for synthesizing the antibacterial drug cefoxitin acid uses 7-aminocephalosporanic acid as a raw material, dissolves it in a sodium bicarbonate solution, adds etherifying enzyme into the weakly alkaline solution, and then adds Methanol, introduce a methoxy group at the 7-position, carry out etherification reaction, wherein the molar ratio of methanol to 7-aminocephalosporanic acid is 2:1, the etherification reaction temperature is 25°C, the etherification reaction time is 2h, etherification After the reaction, filter out the etherification enzyme; then add the deacetylase to the feed solution for hydrolysis, the hydrolysis temperature is 25°C, and the hydrolysis time is 0.8h. After the hydrolysis, add ethyl acetate to the solution and start to drop Add 2-thiopheneacetyl chloride to react, the molar ratio of 2-thiopheneacetyl chloride to 7-aminocephalosporanic acid is 1.6:1; after the reaction is completed, drop benzath...

Embodiment 3

[0025] In the embodiment of the present invention, a method for synthesizing the antibacterial drug cefoxitin acid uses 7-aminocephalosporanic acid as a raw material, dissolves it in a sodium bicarbonate solution, adds etherifying enzyme into the weakly alkaline solution, and then adds Methanol, introduce a methoxyl group at the 7-position, and carry out an etherification reaction, wherein the molar ratio of methanol to 7-aminocephalosporanic acid is 1.5:1, the etherification reaction temperature is 20°C, and the etherification reaction time is 1.5h. After the conversion reaction, filter out the etherification enzyme; then add the deacetylase to the feed solution for hydrolysis, the hydrolysis temperature is 20°C, and the hydrolysis time is 0.7h. After the hydrolysis, add ethyl acetate to the solution and start Drop into 2-thiophene acetyl chloride reaction, the molar ratio of 2-thiophene acetyl chloride and 7-aminocephalosporanic acid is 1.4:1; Reaction finishes, drips benzath...

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Abstract

The invention discloses a synthesis method of an antibacterial agent cefoxitin acid. The method comprises the following steps: with 7-aminocephalosporanic acid as a raw material, dissolving the aminocephalosporanic acid with a weak alkaline solution; adding an etherified enzyme to the weak alkaline solution, adding a methoxide reagent, carrying out etherification reaction, and filtering out the etherified enzyme after etherification reaction is ended; adding solidified enzyme to a feed liquid for carrying out hydrolysis; after hydrolysis is ended, adding ethyl acetate to the solution, and beginning to drop a 2-thiophene acetyl reagent; after reaction is ended, dropping a benzthine cellulose acetate water solution to a reaction liquid, and separating out crystal to obtain a compound I; and reacting the compound I with an ammonia methoxyl acylation reagent, and introducing carbamyl methoxyl group to the third site of the compound I to obtain the cefoxitin acid. The synthesis method is mild in reaction condition, simple in synthesis process and easy to implement; the yield is effectively improved; the production steps are shortened; the production cost is reduced; the product purity is improved; the energy consumption is reduced; the wastewater output is reduced; the synthesis method is suitable for carrying out large-scale production.

Description

technical field [0001] The invention relates to the technical field of drug synthesis, in particular to a method for synthesizing antibacterial drug cefoxitin. Background technique [0002] Cefoxitin acid, the chemical name is (6R,7S)-3-carbamoyloxymethyl-7-methoxy-8-oxo-7-(2-(2-thiazolyl)acetamide base)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid. Cefoxitin acid is a semi-synthetic cefoxitin antibiotic developed by MercK in the United States. Its sodium salt, cefoxitin sodium, has a balanced antibacterial spectrum and is stable to β-lactamase. At present, there is a relatively serious abuse of antibiotics, which has gradually increased the resistance of antibiotics, and the resistance of bacteria has constituted a serious threat to β-lactam antibiotics. The hydrolytic ring opening under the action of β-lactamase is the main reason for the inactivation of these antibiotics. Cefoxitin, as a second-generation cephalosporin, has once again attracted people's attent...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/57C07D501/04
CPCC07D501/57C07D501/04
Inventor 梁建中朱昌凡卢祖强
Owner 四川清山绿水医药化工股份有限公司
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