A kind of membrane separation preparation method of high-purity moxictine

Abstract

The invention discloses a method for separating and preparing a high-purity Moxidectin membrane, and belongs to the technical field of pharmaceutical chemistry. The method comprises the following steps: performing membrane filtration on a pre-purified Nemadectin solution; after extraction with dichloromethane, removing solvents by using conventional concentration; successively performing a protection feeding reaction, an oxidation reaction, an oximation reaction and a protection removing reaction on concentrate to obtain a Moxidectin crude solution; filtering to remove impurities through a membrane separation technique; obtaining a high-purity Moxidectin concentrated solution through a membrane concentration technique. The method disclosed by the invention uses the membrane separation technique to replace column chromatography and a macroporous resin adsorption and separation method, the technique is stable, controllable, simple and practical, the industrialization is easy, the dosage of the solvents is reduced, and a high-temperature solvent removing process of a material solution is omitted, so that the degradation risk of products is reduced, the product purity, the product quality and the product yield are improved, at the same time, the energy resources are saved, and the production cost is reduced.

Description

Technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to a membrane separation preparation method of high-purity moxectine. Background technique [0002] Moxidectin (INN: Moxidectin) is a macrolide agricultural antibiotic. It is mainly used to treat parasitic diseases in animals such as cattle and sheep. It can be fermented by Streptomyces to produce Nimectin (INN: Nemadectin) , And then obtained by chemical reaction, the structural formulas of nemoctine and moxectine are as formula (1). [0003] [0004] US Patent US4916154A discloses a method for preparing moxictine, that is, the fermentation broth produced by the fermentation of Streptomyces is subjected to solid-liquid separation, and the nemoxictine solution obtained after leaching is extracted, silica gel column chromatography, and gel layer Nimoxetine with a purity of more than 90% (HPLC) was obtained by analysis. The purified Nimoktine was subjected to protection, oxidati...

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Problems solved by technology

[0004] U.S. Patent No. 4916154A discloses a method for preparing moxictin, which involves solid-liquid separation of the fermented liquid produced by Streptomyces fermentation, extraction of the nimoctine solution obtained after leaching, silica gel column chromatography, gel layer Nemoctine obtained by analysis with a purity of more than 90% (HPLC), the purified nemoctine is obtained through up-protection, oxidation, deprotection and oximation reactions, which is obtained through silica gel column chromatography, but the The method is complex and requires silica gel chromatography, which is cumbersome to operate and control. The amount of solvent used in this chromatography is large, and the requirements for anhydrous of the upper column entering the silica gel column are high, and the reusability is low, resulting in a decrease in the yield of this chromatography. ,higher cost

The Chinese patent with the application number 200810126358.3 discloses a method of separation using a macroporous adsorption resin column instead of silica gel gel chromatography, but the method of resin adsorption separation still requires the use of a large amount of organic solvents, and at the same time, a large amount of organic solvents need to be reprocessed. Processing, complex procedures, high investment costs and production costs

In the above two methods, the purified feed liquid needs to remove the organic solvent in a vacuum, which leads to high energy consumption and low product yield

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