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A kind of synthetic method of telamectin

A synthesis method and technology of tyramectin, applied in the fields of medicinal chemistry and organic chemistry, can solve the problems of difficult industrial scale-up, failure to achieve effective synthesis, inconvenient operation, etc., and achieve the effects of low raw material cost, simple method and convenient operation.

Active Publication Date: 2011-12-28
武汉回盛生物科技股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] The literature (US 6329345B1) reported a method of synthesizing telamectin using azithromycin A as a raw material through six steps of protection, oxidation, ring formation, deprotection, ring opening, and purification. Ultralow temperature (-70°C) was used in the synthesis route. , inconvenient to operate, difficult to implement industrial amplification; and the method reported in the literature (Boorg.Med.Chem.Lett.12 (2002), 2771-2774), we failed to achieve effective synthesis during research

Method used

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  • A kind of synthetic method of telamectin

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Embodiment 1

[0060] A kind of synthetic method of telamectin, its step is as follows:

[0061] 1) Preparation of Protected Azithromycin A (II)

[0062] Add 5g of azithromycin A and 75ml of dichloroethane to a 250ml one-mouth bottle, slowly add 2.4ml of benzyl chloroformate dropwise at 0°C, keep the temperature of the reaction solution at 0-5°C during the whole dropping process, and keep it warm for 3h after the drop is complete , the solution was concentrated to 25ml, HPLC analysis contained 5.25 grams of product (yield 94.4%), and the solution was directly used in the next step reaction.

[0063] 2) Preparation of protected ketone (III)

[0064] Add 1.4ml dimethyl sulfoxide (DMSO) to the concentrated solution obtained in the previous step, cool the mixed solution to -10°C with an ice-salt bath, add 2.2 grams of phenyl dichlorophosphate, keep the reaction for half an hour, add 3.44 grams of trichlorophosphate Ethylamine, continue to stir and react for half an hour, add 35ml of water to the...

Embodiment 2

[0083] A kind of synthetic method of telamectin, its step is as follows:

[0084] 1) Preparation of Protected Azithromycin A (II)

[0085] Add 5g (0.033mol) of azithromycin A and 75ml of dichloromethane to a 250ml single-necked bottle, slowly add 2.4ml (0.3mol) of benzyl chloroformate dropwise at 0°C, and maintain the temperature of the reaction solution at 0-5°C throughout the dropping process. After dropping, the reaction was incubated for 3 hours, and the solution was concentrated to 25 ml. HPLC analysis contained 5.15 grams of product (yield 92.6%), and the solution was directly used in the next reaction.

[0086] 2) Preparation of protected ketone (III)

[0087]Add 1.4ml dimethyl sulfoxide (DMSO) to the concentrated solution obtained in the previous step, cool the mixed solution to -10°C with an ice-salt bath, add 2.2 grams of phenyl dichlorophosphate, keep the reaction for half an hour, add 3.44 grams of trichlorophosphate Ethylamine, continue to stir and react for hal...

Embodiment 3

[0100] A kind of synthetic method of telamectin, its step is as follows:

[0101] 1) Preparation of Protected Azithromycin A (II)

[0102] Add 5g of azithromycin A and 75ml of chloroform to a 250ml single-necked bottle, slowly add 2.4ml of benzyl chloroformate dropwise at 0°C, keep the temperature of the reaction solution at 0-5°C during the whole dropping process, keep the temperature for 3h after dropping, and dissolve the solution Concentrated to 25ml, HPLC analysis contained 5.3 grams of product (yield 90.6%), and the solution was directly used in the next reaction.

[0103] 2) Preparation of protected ketone (III)

[0104] Add 1.4ml dimethyl sulfoxide (DMSO) to the concentrated solution obtained in the previous step, cool the mixed solution to -10°C with an ice-salt bath, add 4.2 grams of bis(2-oxo-3-oxazolidinyl) once Phosphorus oxychloride (BOP-Cl), heat preservation reaction for half an hour, add 4.8ml triethylamine, continue to stir and react for half an hour, add 3...

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Abstract

The present invention relates to the technical fields of organic chemistry and pharmaceutical chemistry, concretely discloses a synthetic method for a known compound tylosin. The synthetic method comprises the following steps: taking Azithromycin A as a raw material, the protected Azithromycin A can be obtained by Cbz-Cl and then oxidized through a modified Pfitznor-Moffat method, the protected ketone by Cbz can be obtained, ketone is reacted through Wittig-Horner, keto is conversed into alkenyl to obtain the protected alkene, the protected alkene is oxidized to obtain an epoxy compound protected by Cbz, the epoxy compound protected by Cbz is deprotected to obtain a deprotected epoxy compound under the catalysis of Pd / C, the deprotected epoxy compound is reacted with n-propylamine and is performed a ring-opening to obtain a tylosin crude product, the tylosin crude product and acid are carried out a salt forming and purifying, then tylosin can be obtained by resolving. The synthetic route is changed by the method of the invention, the super low-temperature is not employed in the route, and the tylosin enables the effective industrialization production.

Description

technical field [0001] The invention relates to the technical fields of organic chemistry and medicinal chemistry, in particular to a method for synthesizing a known compound telamectin. Background technique [0002] Tyramectin is a new type of antibiotic synthesized and developed by Pfizer Animal Health, which can selectively penetrate Gram-negative bacterial pathogens. Tyramectin can be rapidly released from the injection site and reach inhibitory concentrations in the lungs, and has excellent efficacy against common pathogens that cause respiratory diseases in pigs. also. Its unique pharmacokinetic profile provides an ultra-long therapeutic effect. Therefore, a single dose can act on the entire course of treatment, which is a unique and epoch-making revolutionary product in the world. Since its listing, it has attracted the attention of domestic and foreign pharmaceutical industries. [0003] The literature (US 6329345B1) reported a method of synthesizing telamectin u...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H17/08C07H1/00
Inventor 张卫元申永存杨乐武夏定刘国庆
Owner 武汉回盛生物科技股份有限公司
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