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Purification method of Oritavancin intermediate A82846B

A purification method and technology of oritavancin, which are applied in the preparation methods of peptides, chemical instruments and methods, organic chemistry, etc., can solve the problems of inability to provide high-purity oritavancin intermediates, etc., and achieve simple operation and solvent use. Low volume and low energy consumption

Active Publication Date: 2017-12-05
JIANGSU HENGRUI MEDICINE CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Although the above-mentioned literatures all give more or less purification methods or ideas for oritavancin intermediate analogues, but because there are more impurities in the A82846B fermentation broth, especially there are more A82846B structural analogues, for this reason, the above-mentioned The method in the literature does not provide high-purity oritavancin intermediates and is suitable for commercial production. In view of this, it is necessary to develop a new method for preparing oritavancin intermediate A82846B

Method used

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  • Purification method of Oritavancin intermediate A82846B
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  • Purification method of Oritavancin intermediate A82846B

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Embodiment 1: solid-liquid separation and cation exchange resin pretreatment

[0043] 300L of A82846B fermented liquid (according to the technology disclosed in CN87106483A is fermented to obtain the fermented liquid, the bacterial strain used is Kibdelosporangium aridum (Pseudocystis) NRRL 18098, microfiltration is carried out with a ceramic membrane with a membrane pore size of 0.1-0.2 μm, water replenishment cycle , Discard the bacteria residue, collect the filtrate 900 L. The detection unit of A82846B is 0.47g / L, and the total amount is 423.0g.

[0044] Adjust the pH of 900L of the clarified liquid to 7.0 and purify it with a 60L FPC22 resin column, and then use 2BV of purified water, 2BV of 70% ethanol to wash and 3BV of 50mM ammonia solution to obtain 180L of A82846B eluent with a purity of 51.9%.

Embodiment 2

[0045] Embodiment 2: solid-liquid separation and cation exchange resin pretreatment

[0046] Take 320L of A82846B fermentation broth, use a plate frame filter cake and wash it with water, discard the filter cake, and collect 350L of filtrate. The detection unit of A82846B was 1.25g / L, and the total amount was 437.5g.

[0047] Adjust the pH of 350L of the filtrate to 7.0 and purify it with a 60L HD-8 resin column, and then wash it with 2BV of purified water, 3BV of 50% ethanol and 2BV of 150mM ammonia solution to obtain 120L of A82846B eluate with a purity of 41.1%.

Embodiment 3

[0048] Embodiment 3: solid-liquid separation and cation exchange resin pretreatment

[0049] Take 320L of A82846B fermentation broth, use a plate frame filter cake and wash it with water, discard the filter cake, and collect 340L of filtrate. The detection unit of A82846B was 1.36g / L, and the total amount was 462.4g.

[0050] Adjust the pH of 600L of the filtrate to 7.0 and purify it with a 60L HD-8 resin column, and then use 2BV of purified water, 3BV of 80% ethanol to wash impurities and 2BV of 100mM sodium hydroxide aqueous solution to obtain 110L of A82846B elution with a purity of 50.2%. .

[0051] Based on Examples 1 and 2, during the sample elution process, the concentration of the elution phase (ammonia solution) used will affect the purity of related substances in the A82846B eluent at this step. Generally speaking, we will use more than 45% of A82846B The eluate is processed in the next step, and finally A82846B with better purity can be obtained, and at the same t...

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Abstract

The invention provides a purification method of an Oritavancin intermediate A82846B. Specifically, the method comprises the following steps: loading an A82846B fermentation broth to an ion exchange resin chromatography column, and carrying out elution separation to obtain a first eluate; loading the first eluate toa reversed phase chromatography chromatography column with silica gel C18 or polystyrene polymer as a filler, carrying out impurity elution, carrying out sample elution and collecting a second eluate. Purity of the obtained A82846B is greater than 80%. By the method, quality of the product can be guaranteed; and the method is suitable for an expanded commercial market. The invention also provides a method for preparing the Oritavancin intermediate A82846B salt and a method for synthesizing Oritavancin by the use of the A82846B salt.

Description

technical field [0001] The present invention relates to a method for the separation and purification of antibiotics, in particular to a method for the separation and purification of oritavancin intermediate A82846B, which uses silica gel C18 or polystyrene polymer as a filler for the reverse phase chromatography column containing A82846B fermentation broth was purified and separated by column chromatography to obtain high-purity oritavancin intermediate A82846B. Background technique [0002] A82846B is a natural glycopeptide, which is the fermentation product of Kibdelosporangium aridum (Pseudocystis) isolated from soil. The chemical structure of the glycopeptide contains a 4-epi-Vancosamine (4-epi-Vancosamine) Externally similar to vancomycin, the molecular formula is C75H91Cl 2 N 9 o 25 , its antibacterial activity is 4 to 8 times greater than that of vancomycin, and its mechanism of blocking cell wall synthesis is the same as that of other glycopeptides such as vancomy...

Claims

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Application Information

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IPC IPC(8): C07K9/00C07K1/18C07K1/20
CPCC07K9/008
Inventor 陈舟舟王宏伟彭洁李劲张也湛滢任宏杰齐艳艳崔亚顺
Owner JIANGSU HENGRUI MEDICINE CO LTD
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