Simple and rapid preparation process of dihydroartemisinin

Abstract

The invention relates to a novel semisynthesis process of an important pharmaceutical intermediate dihydroartemisinin, and a further separation and purification process of the dihydroartemisinin as a raw material. The method is as below: using natural artemisinin as a raw material and mixed low alcohols as a solvent; adding a Lewis catalyst and metal borohydride for reduction at low temperature; then concentrating to recover reaction solvent; adding water for crystallization; and finally washing and purifying by methanol to obtain a qualified dihydroartemisinin product with high content and high purity. The method has green environment-friendly processes and great economic and social benefits.

Description

technical field [0001] The invention relates to a new semi-synthetic preparation process of dihydroartemisinin, an important pharmaceutical and chemical intermediate, and a further separation and purification process as a raw material medicine. Background technique [0002] Dihydroartemisinin (also known as: dihydroartemisinin, English abbreviation: DHA, dihydroartemisinin, artenimol) is obtained from natural antimalarial raw material artemisinin through reduction reaction. Artemisinin is an anti-malarial natural active ingredient jointly researched and developed by the Chinese Academy of Military Medical Sciences and the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences. It has good anti-malarial effect and no drug resistance. The older generation of anti-malarial raw materials such as naphthoquine and quinine are the first-choice anti-malarial drugs identified by the WHO. Since artemisinin is a low-polar compound, its water solubility is very small, res...

AI Technical Summary

Problems solved by technology

[0004] The above dihydroartemisinin preparation method has the following disadvantages: (1) the yield of dihydroartemisinin is generally low, mostly within 93%; 15-25 times the volume, which increases the production cost and also increases the environmental hazards; (3) the amount of reducing agent potassium borohydride and sodium borohydride is also too large, and the molar weight is between 3-5 times, far from Exceeding 0.25 times of theoretical usage, this will also cause economic and environmental cost pressures; (4) the reaction system does not clearly explain how to control the reaction, which makes it difficult to control the danger of using potassium borohydride and sodium borohydride, metal borohydride Hydrides are extremely explosive and ignitable; (5) The post-treatment of dihydroartemisinin, that is, the separation and purification, has not been fully reported, and the content and purity of dihydroartemisinin are rarely reported in detail, which is the most necessary factor for industrial production (6) above reaction system is all in strong base, and this makes artemisinin and dihydrogen degrade extremely easily, causes productive rate to reduce

[0005] The new process of the present invention aims at the relatively large usage of the above chemical reagents, low atom economy, generally low yield, unstable reaction system, high risk, lack of good post-treatment means of separation and purification, etc., which lead to dihydroartemisinin Production costs are too high

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