Chemical semi-synthesis method of artemisinin

Abstract

The invention provides a chemical semi-synthesis method of artemisinin represented by a formula (VI) shown in the specification. The chemical semi-synthesis method comprises the following specific steps: (1) reacting dihydroartemisinic acid represented by a formula (I) shown in the specification with oxalyl chloride represented by a formula (II) shown in the specification to generate dihydroartemisinyl chloride represented by a formula (III) shown in the specification; (2) carrying out an acylation reaction on the dihydroartemisinyl chloride represented by the formula (III) and dihydroarteannuic acid represented by a formula (I) shown in the specification to generate dihydroarteannuic anhydride represented by a formula (IV) shown in the specification; and (3) carrying out a photooxidationreaction on the dihydroarteannuic anhydride represented by the formula (IV) by using a micro-channel reactor, and carrying out an oxidation rearrangement reaction to prepare the target product artemisinin represented by the formula (VI). Compared with the prior art, the method provided by the invention has the advantages of a high product yield, good purity of the product, a stable process, mild reaction conditions, easiness in industrial production and the like.

Description

technical field [0001] The invention relates to the field of bioengineering pharmaceuticals, in particular to a chemical semi-synthesis method for artemisinin. Background technique [0002] Artemisinin is a sesquiterpene lactone drug with peroxy groups extracted from the stems and leaves of the compound inflorescence plant Artemisia annua. It was discovered by Chinese pharmacist Tu Youyou in 1971. The molecular formula of artemisinin is C 15 h 22 o 5 , its chemical structure is shown in the following formula (VI): [0003] [0004] Artemisinin is the most effective anti-malarial drug after pyrimethamine, chloroquine, and primaquine, especially for cerebral malaria and anti-quinoline malaria. "The World's Only Effective Malaria Treatment". According to statistics, the annual sales of artemisinin and its derivatives worldwide are as high as 1.5 billion US dollars. In recent years, artemisinin has also shown attractive prospects in the treatment of other diseases such ...

AI Technical Summary

Problems solved by technology

M.Jung et al. reported (Tetrahedron Letters, 20, 5973 (1989)) that artemisinic acid was reduced to obtain artenimol, and then artenimol was autoxidized to obtain cyclic alkenyl ether, and then triphenyl phosphite was used to obtain artenimol. - Treatment with ozone compounds to obtain decarburized artemisinin, but the process is complex and the yield is only 4%

Wu Yulin also reported (J.Chem.Soc, Chem.Commun., 727, 1990) the process of synthesizing artemisinin from artemisinic acid. ℃, the reaction conditions are harsh, and the yield is relatively low, which is not suitable for industrial production

[0007] Patent WO2009088404 discloses a method for preparing artemisinin by introducing a peroxy bond by using dihydroartemisinic acid as a starting material, sodium molybdate as a catalyst, and hydrogen peroxide as an oxidizing agent. The selectivity of the product obtained by this method is poor. And there are many by-products, the final total yield of artemisinin is low, and there is still a certain distance from industrial application

[0008] Patent ZL201280042681.7 discloses a method and device for synthesizing artemisinin from dihydroartemisinic acid. Because the tube is illuminated, the mixing effect is uneven, the flux is small, the efficiency of daily artemisinin production is low, and a large amount of energy is required for amplification. Tubes require a lot of space and are not easy to produce industrially

[0009] Patent ZL201310615102.X discloses a large-scale preparation method and equipment for artemisinin. The reactor is a chromatography column with a sand core, a glass tube is embedded in the middle of the chromatography column, and a reaction system is set between the chromatography column and the glass tube , There is a light source in the glass tube, the reactor has no mixing device, the reaction light is uneven, the temperature is uneven, and the reaction temperature is harsh -20 ℃ ~ -50 ℃, the reaction time is slow

[0010] In summary, the existing artemisinin preparation methods have disadvantages such as poor synthesis selectivity, low yield, harsh reaction conditions, and difficult scale-up production.

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