A kind of preparation method of gamitomycin intermediate

Abstract

The present invention relates to a preparation method of a gamithromycin intermediate, which uses 9-deoxy-6-deoxy-6,9-imino ether-(8a-aza-8a)-erythromycin A as a raw material, Dissolve in an organic solvent, adjust the pH to 3~6 with an acid, and use potassium borohydride or sodium borohydride as a reducing agent to perform a reduction reaction; then add an organic sugar acid to perform a hydrolysis reaction to obtain 9‑deoxy‑8a‑aza ‑8a‑homotype erythromycin A, because the organic sugar acid contains hydroxyl group, which is beneficial to the hydrolysis of gamimycin borate intermediate, the acid degradation products are reduced, and it can effectively reduce 9‑deoxy‑6‑deoxy‑6,9‑sub Amino ether-(8a-aza-8a)-erythromycin A was hydrolyzed, which increased the yield of the target product and significantly reduced the 9-deoxy-8a-aza-8a-homoerythromycin A The preparation cost is convenient for industrialized production.

Description

technical field [0001] The invention relates to a preparation method of 9-deoxy-8a-aza-8a-homoerythromycin A, which belongs to the field of drug synthesis. Background technique [0002] Gamithromycin is a new type of second-generation macrolide veterinary antibiotic drug. Like azithromycin, gamimycin is also a ring-expanded derivative obtained after ring-expansion of erythromycin A oxime, and the synthetic intermediate (9Z)-9-deoxy-9-hydroxyiminoerythromycin Erythromycin A and (9E)-9-deoxy-9-hydroxyiminoerythromycin A are isomers. At present, the injection ZACTRAN produced by MERIAL.CO of France, with gamimycin as the main active ingredient, has been approved by the Veterinary Drug Administration of the European Medicines Agency and has realized market production and sales. The structure and efficacy of Gamithromycin have been certified by the Veterinary Medicines Agency of the European Food and Drug Administration. It can be used for food animals. It has the advantages of...

AI Technical Summary

Problems solved by technology

[0006] U.S. Patent US005985844A discloses a method for preparing gamimycin. The disadvantage of this method is that the pressure used for the hydrogen reduction of the intermediate 9-deoxy-8a-aza-8a-homoerythromycin A is too large and requires 50 Atmospheric hydrogen pressure has extremely high requirements on the reactor and operation

The key to the preparation of Gamithromycin is the reduction of imino ether, but the above method either has a low yield, or needs to use precious metals as a catalyst, or needs to use sodium borohydride or potassium borohydride as a reducing agent

Using precious metals as catalysts requires high catalyst recycling requirements, high production equipment requirements, and high production costs

Use sodium borohydride or potassium borohydride as a reducing agent to generate a boric acid ester intermediate. Under acidic conditions, hydrolysis of the boric acid ester results in the breakage of the 3-position glycosidic bond, which affects the yield and quality of the product.

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