- Synthesis and antibacterial activity of new 4″-O-carbamates of 11,12-cyclic carbonate erythromycin A 6,9-imino ether
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A series of new 4″-O-carbamates of 11,12-cyclic carbonate erythromycin A 6,9-imino ether were synthesized and evaluated for their in vitro antibacterial activity. All the desired compounds demonstrated favorable activity (0.03 μg ml-1) against erythromycin-susceptible Streptococcus pneumoniae comparable to the references, exhibiting 133-fold higher activity than precursor 2 or 3. Similarly, all of the analogs exhibited improved activity against the erythromycin-resistant S. pneumoniae encoded by the erm gene and the erm and mef genes, showing 4-32-fold more effectiveness than erythromycin A.
- Zhang, Ling,Jiao, Bo,Yang, Xiangrui,Liu, Lin,Ma, Shutao
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- Macrolide derivative and application thereof
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The invention provides a macrolide derivative of a novel structure. Experiments show that the macrolide derivative has a good promoting effect on alimentary motility and is capable of enhancing intestine peristalsis, increasing defecation quantity and accelerating passing of intestinal content; on such basis, it is further discovered that the macrolide derivative is low in antibiotic activity and small in side effect and can be taken as a gastrointestinal motility promoting drug. Particularly, a compound III-3 screened with the optimal efficacy is subjected to further efficacy evaluation as well as acute toxicity and cardiotoxicity evaluation by domestic rabbits, beagles and marmosets. Experiments show that the compound III-3 is safe and capable of effectively promoting gastrointestinal motility, thereby being excellent in druggability.
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- Synthesis method of azithromycin
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The invention relates to a synthesis method of azithromycin. The synthesis method is characterized by comprising the process steps of firstly adding sodium bicarbonate and a rearrangement reaction reagent to erythromycin oxime in a reaction system employing water as a reaction solvent for rearrangement reaction, carrying out heat preservation for 2-3 hours, dropwise adding a reduction reaction regent for reduction reaction and stirring for 1-2 hours during heat preservation; adding a competitive inhibitor for removing boron through reduction hydrolysis for reduction and boron removal reaction; and finally separating out crystal, and cooling and filtering to obtain the azithromycin. Rearrangement and reduction are simultaneously carried out in the same reaction system. Compared with a sodium borohydride reduction method in the prior art, the synthesis method has the advantages that the process is simplified, use of an organic solvent and the like is omitted, the environmental pollution and the product cost are reduced, the influence of a complicated process on the quality of a product is reduced, the quality and the yield of the product are finally improved and the synthesis method is suitable for technological production.
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Paragraph 0003; 0025-0026
(2017/08/29)
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- Preparation method of erythromycin 6,9-imino ether compound
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The invention relates to a preparation method of an erythromycin 6,9-imino ether compound. According to the method, a reaction of acid-catalyzed erythromycin thiocyanate and N-hydroxyamide is adopted, an oximation reaction of erythromycin and a rearrangement reaction of erythromycin oxime are conducted in a one-step mode, and erythromycin 6,9-imino ether is generated. The preparation method of the compound comprises the preparation steps that erythromycin thiocyanate, N-hydroxyamide and acid are taken and added into an organic solvent, heating is conducted, extracting, drying by distillation and water adding are conducted after the reaction is completed, the pH value of the solution is adjusted to range from 10 to 12, precipitating, filtering and drying are conducted, and the erythromycin 6,9-imino ether product is obtained. According to the preparation method, the erythromycin 6,9-imino ether compound is synthesized in a one-step mode, operation is easy, the method is economical and efficient, a venomous sulfonyl chloride reagent is not used, environmental pollution is less, the yield is high, and the application prospect is wide.
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Paragraph 0021
(2017/04/25)
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- Method for synthesizing azithromycin
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The invention relates to a method for synthesizing azithromycin. According to the invention, erythromycin thiocyanate is adopted as an initial raw material of an oximation reaction, such that erythromycin oxime thiocyanate is obtained; the next step of reaction is directly carried out; and through rearrangement, reduction and methylation reactions, azithromycin is obtained. The rearrangement and reduction reactions are carried out with a one-pot method. A reduction reaction product is not separated in a solid form, and is directly used in the methylation reaction. With the synthesizing method provided by the invention, a conversion process from erythromycin oxime thiocyanate to eythromycin oxime is eliminated, and steps that rearrangement and reduction products are separated in solid forms in an original process are also eliminated. The process is environment-friendly and simple, and has the advantages of high yield, low cost, low pollution and high product purity. The method is suitable for industrialized productions.
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- A COST EFFECTIVE PROCESS FOR PREPARING 6,9-IMINO ETHER
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The present invention relates to an improved process for the preparation of 6,9-imino ether of formula (I) an intermediate used in preparation of Azithromycin. The present invention further provides a process for preparation of Azithromycin.
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Page/Page column 7-8
(2010/01/30)
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- Using chemical probes to investigate the sub-inhibitory effects of azithromycin
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The antibacterial drug azithromycin has clinically beneficial effects at sub-inhibitory concentrations for the treatment of conditions characterized by chronic Pseudomonas aeruginosa infection, such as cystic fibrosis. These effects are, in part, the result of inhibition of bacterial biofilm formation. Herein, the efficient synthesis of azithromycin in 4 steps from erythromycin and validation of the drug's ability to inhibit biofilm formation at sub-MIC (minimum inhibitory concentration) values are reported. Furthermore, the synthesis of immobilized and biotin-tagged azithromycin analogues is described. These chemical probes were used in pull-down assays in an effort to identify azithromycin's binding partners in vivo. Results from these assays revealed, as expected, mainly ribosomal-related protein binding partners, suggesting that this is the primary target of the drug. This was further confirmed by studies using a P. aeruginosa strain containing plasmid-encoded ermC, which expresses a protein that modifies 23S rRNA and so blocks macrolide entry to the ribosome. In this strain, no biofilm inhibition was observed. This work supports the hypothesis that the sub-inhibitory effects of azithromycin are mediated through the ribosome. Moreover, the synthesis of these chemical probes, and proof of their utility, is of value in global target identification in P. aeruginosa and other species.
- Glansdorp, Freija G.,Spandl, Richard J.,Swatton, Jane E.,Loiseleur, Olivier,Welch, Martin,Spring, David R.
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supporting information; experimental part
p. 4120 - 4124
(2009/02/07)
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