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Preparation method of Dalbavancin key intermediate A40926 BO component by purification

A technology of A40926B0 and daugtomycin, applied in the direction of peptides, etc., can solve problems such as component purification

Active Publication Date: 2012-10-03
CHENGDU YATU BIOLOGICAL TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The main purpose of the present invention is in order to solve the key intermediate A40926 B of daugtomycin 0 Purification of components and supply of high purity A40926 B for the preparation of daaustatin 0 Components (chromatographic purity greater than 97%)

Method used

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  • Preparation method of Dalbavancin key intermediate A40926 BO component by purification

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] 15g A40926 crude product was dissolved in 200ml sodium carbonate: sodium bicarbonate=0.05M: 0.01M buffer solution, filtered to obtain 200ml filtrate, and the filtrate was subjected to HPLC analysis, A40926 B 0 The content of the component is 8.47g, and the pH value of the filtrate is 9.2. The above-mentioned filtrate is dripped on the column (φ 3mm × 30mm.) filled with 200mlsepharose-6B gel at a flow rate of 0.2BV / hr, and then the carbonic acid of 4BV Sodium: sodium bicarbonate = 0.05M: 0.01M buffer solution, 4BV of the above buffer containing 1% tris was pre-washed at a flow rate of 2BV / hr, and finally washed with 1% tris The above buffer was eluted at a flow rate of 2BV / hr. Obtain A40926 crude product eluent 400ml, through HPLC analysis, A40926 B in the eluent 0 The component peak area accounted for 82.7% of the total area, and 7.51 g of high-purity crude extract was obtained with a recovery rate of 88.7%.

Embodiment 2

[0023] 15g A40926 crude product was dissolved in 200ml sodium carbonate: sodium bicarbonate=0.05M: 0.01M buffer solution, filtered to obtain 200ml filtrate, and the filtrate was subjected to HPLC analysis, A40926 B 0 The content of component is 8.47g, and this filtrate pH value is 9.2, above-mentioned filtrate is dripped on the column that has filled with 200ml Sephadex G-25 with the flow velocity of 0.2BV / hr, then with the sodium carbonate of 4BV respectively: Sodium bicarbonate = 0.05M: 0.01M buffer solution, 4BV of the above-mentioned buffer solution containing 1% tris was pre-washed at a flow rate of 2BV / hr, and finally washed with the above-mentioned buffer solution containing 1% tris The buffer was eluted at a flow rate of 2BV / hr. Obtain A40926 crude product eluent 500ml, through HPLC analysis, A40926 B in the eluent 0 The component peak area accounted for 81.4% of the total area, and 7.58 g of high-purity crude extract was obtained with a recovery rate of 89.5%.

Embodiment 3

[0025] The process solution obtained by gel chromatography in Example 1 was adjusted to pH 7.0, passed through macroporous resin D141 (average pore diameter 80 angstroms), and washed with 4BV of hydrochloric acid solution at pH=3, and the flow rate was 2BV / hr to wash the resin column , then wash with 4BV 10% ethanol solution with a flow rate of 2BV / hr, then elute with a 60% ethanol solution with a flow rate of 1BV / hr to obtain 320ml eluate, and B in the eluate 0 The peak area of ​​the component was 87.7% of the total peak area, and A40926 B was recovered 0 Component 6.85g, recovery rate 91.2%, concentrated under reduced pressure at 55-60°C to obtain A40926B 0 The semi-pure product of the component is 7.8g.

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Abstract

The invention discloses a preparation method of a Dalbavancin key intermediate A40926 BO component by purification, which comprises the following two steps: 1. carrying out gelchromatography and macroporous adsorptive separation on the crude A40926 BO component so as to obtain the semi-pure product of the A40926 BO component; and 2. carrying out reverse-phase column chromatography and vacuum concentration on the A40926 BO semi-pure product so as to obtain the high-purity A40926 BO component, and the chromatographic purity is more than 97%.

Description

technical field [0001] The invention relates to the key intermediate A40926 B of dalbavancin 0 Purification and preparation method of components, that is, A40926 B that can be used for the synthesis of dauromycin and has a chromatographic purity greater than 97%. 0 Method of preparation of components. Background technique [0002] Dalbavancin is a second-generation semi-synthetic glycopeptide antibiotic, similar in structure to vancomycin and teicoplanin, and is used for severe systemic tissue infections caused by Gram-positive pathogens. Daaustatin is produced by actinomycetes secondary metabolite A40926 B 0 The components are structurally modified, and have a wider antibacterial spectrum than vancomycin and teicoplanin in vivo and in vitro, and are resistant to all coagulases including staphylococcus, streptococcus, enterococcus and methicillin-resistant strains Negative staphylococcus (coagulase-negative stapHycoccus, CoNS) is effective, and the activity is significant...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K9/00
Inventor 朱辉邹敬源韩晓彤王元桦莫洪刘巍陶永祥朱宇杨旭臣
Owner CHENGDU YATU BIOLOGICAL TECH