A kind of preparation method of milbexime

Abstract

The invention provides a preparation method of milbemycin oxime. The preparation method of milbemycin oxime comprises the following steps: extracting milbemycins, namely taking milbe mycelia obtained through fermentation as a raw material, extracting, concentrating, extracting, concentrating, extracting again and concentrating again, so as to obtain milbemycin; preparing milbemycin ketone, namely taking the milbemycin as a raw material, establishing an oxidation reaction system, after reaction is finished, filtering, concentrating, extracting and concentrating the reaction system, so as to obtain an intermediate product milbemycin ketone; synthesizing milbemycin oxime, namely dissolving milbemycin ketone with methanol and dioxane, dropwise adding hydroxylamine hydrochloride solution and reacting, concentrating the reaction system, extracting, drying and concentrating, so as to obtain a milbemycin oxime crude product; and purifying milbemycin oxime, namely crystallizing the milbemycin oxime crude product with a mixed solvent of trichloromethane and normal heptane, dissolving a crystalline product with ethanol, dropwise adding into water while stirring for carrying out crystallization, filtering, and drying, so that the milbemycin oxime finished product is obtained. The preparation method of the milbemycin oxime has the advantages that productivity is greatly improved, and cost is obviously reduced, so that the preparation method provided by the invention is obviously better than an existing preparation method.

Description

technical field [0001] The invention belongs to the field of synthesis and purification of chemicals, and in particular relates to a synthesis and purification method of a semi-synthetic macrolide anthelmintic. Background technique [0002] Milbemycin Oxime (Milbemycin Oxime) is a macrolide anti-endoparasite drug, and it is an oxime derivative of Milbemycin A3 and A4. Milbexime has a broad-spectrum anti-parasitic effect, and has a good killing effect on internal and external parasites, especially nematodes and arthropods. Lee et al. studied the neuropharmacological mechanism of milbexime on the viability of Bloodstrongylus cantonensis and Dirofilaria imimaginum in vitro, and showed that the inhibitory and stimulatory effects of milbexime on the two worms were achieved through gabergic and cholinergic mechanisms . The drug binds to the specific high-affinity site on the target worm cells, which affects the permeability of the cell membrane to Cl-, and then causes the inhibi...

AI Technical Summary

Problems solved by technology

The main problem of the above-mentioned preparation method of milbexime is that silica gel chromatography or preparative chromatography not only requires a large investment in equipment, consumes a large amount of solvent, and has high cost, but also is difficult to scale up and realize industrial production.