Preparation method of high-purity selamectin

Abstract

The invention provides an improved selamectin preparation process. The process comprises the following steps: (1) performing hydrogen reduction on doramectin DL in the presence of a Wilson catalyst to obtain an intermediate SL1; (2) recrystallizing and purifying the intermediate SL1 obtained in the step (1) by use of methyl alcohol; (3) desugarizing the intermediate SL1 obtained in the step (2) by use of sulfuric acid to obtain an intermediate SL2; (4) oxidizing the intermediate SL2 obtained in the step (3) by use of manganese dioxide to obtain an intermediate SL3; (5) performing oximation on the intermediate SL3 obtained in the step (4) by use of hydroxylamine hydrochloride to obtain selamectin SL; (6) recrystallizing the crude product SL obtained in the step (5) for three times by use of methylbenzene, acetone and methyl alcohol to obtain purified SL.

Description

technical field [0001] The invention belongs to the field of pharmaceutical production, and relates to a preparation method of selamectin, in particular to a preparation method of high-purity selamectin. Background technique [0002] Abamectins are a group of macrolides fermented by Streptomyces, which can effectively control agricultural pests and a variety of harmful mites, especially those resistant to commonly used pesticides. Control effect. It is relatively safe for crops and will not kill natural enemies, which is conducive to ecological balance. At the same time, abamectins have a strong killing effect on human and animal parasitic nematodes and arthropod parasites, and have the advantages of broad spectrum, high efficiency and low toxicity. very broad. In the past two decades, good progress has been made in structural modification and transformation using natural avermectin components as parent compounds, such as ivermectin, doramectin, and moxidectin, Eprinomec...

AI Technical Summary

Problems solved by technology

This process is the basic patented process route of selamectin. Many domestic manufacturers use this route, but the total yield of this process is not high, and each intermediate needs to be separated by silica gel chromatography. The crude selamectin obtained at last is also It needs to be purified by silica gel column chromatography and high pressure liquid chromatography, and the whole process is very unfavorable for industrial production

[0006] Chinese patent 98808106.7 is an improved selamectin preparation method patent applied by Pfizer Co., Ltd. of the United States. The whole route has undergone hydrogenation, oxidation, desugaring, and oximation, and desugaring and oximation are completed in one step. Although the route Relatively short, but toluene or methanol is used for the purification of the final product selamectin. These two solvents have no effect on the removal of some impurities, and the purity of the resulting refined selamectin is still not high enough.

[0011] However, the purity of the crude product of selamectin obtained by this process is relatively low, ranging from 65.2% to 81.2%, and the last step still needs reversed-phase C18 silica gel to prepare selamectin with higher purity, which does not utilize industrial production

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