Method for directly preparing erythromycin oxime by utilizing erythromycin fermentation liquid

A technology for erythromycin oxime and erythromycin, which is applied in the field of drug synthesis, can solve the problems of affecting the quality and yield of erythromycin oxime products, unstable chemical properties of erythromycin A, adding more organic solvents, etc. By-product formation, high product yield, and the effect of reducing the pressure of environmental protection

Inactive Publication Date: 2018-05-04
NINGXIA QIYUAN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, erythromycin A is chemically unstable, and usually needs to be crystallized into relatively stable erythromycin thiocyanate or erythromycin base before being used as a raw material for erythromycin oxime
In this way, the yield of erythromycin A extracted by crystallization directly affects the product quality and yield of erythromycin oxime after the oximation reaction. , environmental pollution is large, production waste water is much, and finally causes the production cost to increase

Method used

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  • Method for directly preparing erythromycin oxime by utilizing erythromycin fermentation liquid

Examples

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Effect test

Embodiment 1

[0030] Take 50L of erythromycin fermentation broth, under the conditions of pH 8.0 and pressure 0.2MPa, use an organic plate membrane with a pore size of 5-50nm to filter, during the process of peristaltic pump flow plus pure water dialysis; the obtained filtrate 110L is subjected to roll-type nanofiltration Membrane concentration, the membrane with a molecular weight cut-off of 700 or more, the pH of the filtrate during the concentration process is controlled at 6.5-7.5, the pressure is controlled at 4.0MPa, and the concentration of the obtained concentrated solution is 2.23g / 100ml; the concentrated solution is added with 50L butyl acetate and 10% hydrogen Sodium oxide solution for extraction, the pH of the extraction process is controlled at 10.0 to 10.5, stand still and separate phases, separate to obtain the upper layer of butyl acetate solution, add 1% activated carbon to filter, distill and concentrate the butyl acetate solution under reduced pressure, and cool down to bel...

Embodiment 2

[0034] Take 50L of erythromycin fermentation broth, under the conditions of pH 8.2 and pressure 0.22MPa, use an organic plate membrane with a pore size of 5-50nm to filter. During the process, a peristaltic pump flow is added to pure water for dialysis, and 110L of the obtained filtrate is concentrated by nanofiltration. For membranes with a molecular weight cut-off of 700 or more, the pH of the filtrate during the concentration process is controlled at 6.5 to 7.5, the pressure is controlled at 3.9MPa, and the concentration of the resulting concentrated solution is 2.12g / 100ml; Extraction, the pH of the extraction process is controlled at 9.0 to 9.5, stand still and separate the phases, separate to obtain the lower layer of dichloromethane solution, add 1.5% diatomaceous earth to filter, distill and concentrate the dichloromethane solution under reduced pressure, cool to below -15°C to crystallize, Insulated and stirred for 3 hours, centrifuged to obtain erythromycin crude base...

Embodiment 3

[0038] Take 50L of erythromycin fermentation broth, under the conditions of pH 7.8 and pressure 0.16MPa, filter it with an organic plate membrane with a pore size of 5-50nm. The nanofiltration membrane is a membrane with a molecular weight cut-off of more than 700. The pH of the filtrate during the concentration process is controlled at 6.5 to 7.5, and the pressure is controlled at 3.8MPa. The concentration of the concentrated solution is 2.22g / 100ml; Add 15% sodium carbonate solution for extraction, the pH of the extraction process is controlled at 9.5-10.0, stand still and separate the phases, separate to obtain the upper layer of methyl tert-butyl ether solution, add 0.5% polymer filter aid to filter, vacuum distillation and concentration The methyl tert-butyl ether solution was cooled to below -10°C for crystallization, kept stirring for 2 hours, and centrifuged to obtain crude erythromycin base. The obtained erythromycin crude base after drying has a content of 91.6% eryt...

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Abstract

The invention relates to a method for directly preparing erythromycin oxime by utilizing erythromycin fermentation liquid. The method comprises the following steps: filtering the erythromycin fermentation liquid by a membrane filtering method, extracting by an organic solvent, performing dehydration and decoloring treatment, freezing and crystallizing to prepare erythromycin crude alkali, performing oximation reaction to prepare oximate, extracting the oximate by using an organic solvent, performing dehydration and decoloring treatment, freezing for crystallization, and filtering and drying toobtain the erythromycin oxime. By the method, the advantage of the enterprise for producing the erythromycin raw material is completely exerted, the technological process of thiocyanic acid and erythromycin salifying crystallization is eliminated, and the intermediate erythromycin crude alkali for preparing the erythromycin thiocyanate directly serves as a starting raw material for synthesizing erythromycin A9-oxime, so that the process is simplified, the process flow is shortened, the production cost is reduced, environmental pollution is little, the product yield is high and the product quality is high.

Description

technical field [0001] The invention relates to the technical field of drug synthesis, in particular to a method for directly preparing erythromycin oxime by using erythromycin fermentation broth. Background technique [0002] Erythromycin oxime (erythromycin A9-oxime) is a key intermediate of downstream second and third generation macrolide antibiotics such as azithromycin, clarithromycin, roxithromycin, telithromycin and telamycin, Its quality and yield directly affect the quality and cost of antibiotics such as azithromycin, clarithromycin, roxithromycin, telithromycin and telamycin. [0003] In the prior art, the synthesis of erythromycin oxime mostly takes erythromycin thiocyanate or erythromycin base as the starting raw material (the main components are all erythromycin A components), and polar solvents (methanol, ethanol etc.) dissolve erythromycin thiocyanate or erythromycin base, inorganic acid salt and organic base of hydroxylamine, and complete the oximation of e...

Claims

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Application Information

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IPC IPC(8): C07H17/08C07H1/00
CPCC07H1/00C07H17/08
Inventor 鲍晶孙瑞君王东东张志
Owner NINGXIA QIYUAN PHARMA
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