阅读说明：本技术 一种制备Artemisinin G的方法 (Method for preparing Artemisinin G ) 是由 陈海军 罗伊宁 张宇彤 高瑜 于 2021-09-28 设计创作，主要内容包括：本发明属于医药技术领域,提出了一种制备Artemisinin G的方法。该方法是以青蒿素为起始原料,通过一步反应合成Artemisinin G。本合成所用试剂为实验室常用试剂,且反应在室温条件下即可快速完成。综上,本发明所需材料易得、成本低廉、反应操作简单,反应时间短,反应液易于处理,可以大量获得Artemisinin G,供医药研发使用。(The invention belongs to the technical field of medicines, and provides a method for preparing Artemisinin G. The method takes Artemisinin as a starting material and synthesizes Artemisinin G through one-step reaction. The reagents used in the synthesis are common reagents in laboratories, and the reaction can be rapidly completed at room temperature. In conclusion, the invention has the advantages of easily obtained required materials, low cost, simple reaction operation, short reaction time and easy treatment of reaction liquid, and can obtain large amount of Artemisinin G for medicine research and development.)

1. A method of preparing Artemisinin G, comprising: artemisinin G is obtained by one-step reaction at room temperature and under the condition of illumination by taking Artemisinin as a starting material and TBADT as a catalyst.

2. The process for preparing Artemisinin G according to claim 1, wherein: the method comprises the following specific steps:

acetonitrile and chloroform are used as a mixed solvent, Artemisinin serving as a raw material and TBADT serving as a catalyst are added into the mixed solvent, a reaction is carried out at room temperature and under the illumination condition in the argon atmosphere to obtain a crude product, and the product Artemisinin G is obtained after purification.

3. The process for preparing Artemisinin G according to claim 2, wherein: the volume ratio of acetonitrile to chloroform is 5: 1.

4. the process for preparing Artemisinin G according to claim 2, wherein: the amount of TBADT is 0.5% of the molar amount of artemisinin.

5. The process for preparing Artemisinin G according to claim 2, wherein: the illumination wavelength was 370 nm.

6. The process for preparing Artemisinin G according to claim 2, wherein: the reaction time was 30 min.

Technical Field

The invention belongs to the field of pharmaceutical chemistry, and particularly relates to a method for preparing Artemisinin G.

Background

Artemisinin and its derivatives are often used as anti-malarial drugs, and combined therapy mainly based on artemisinin drugs is also the most effective and important means for treating malaria at present. In recent years, with the progress of research, other effects of artemisinin drugs are increasingly discovered and researched, such as various pharmacological effects of resisting tumor, treating pulmonary hypertension, resisting diabetes, resisting fungi, regulating immunity, resisting virus, resisting pulmonary fibrosis, resisting cardiovascular effect, and the like. Li et al extracted Artemisinin G as another active substance from Artemisia annua leaves in the study of Artemisinin: (Planta Med,1992, 58). Artemisinin G can be obtained by biological metabolism of Artemisinin in vivo. Artemisinin G, which does not contain the characteristic peroxide bridge of Artemisinin and therefore presumably acts in humans in a different mechanism than Artemisinin and has the potential to develop new antimalarial drugs: (J. Agric. Food Chem., 2018, 66,10490-10495). The commonly used method for synthesizing Artemisinin G includes, for example, dissolving Artemisinin in acetonitrile, adding FeCl, etc. Charles W.Jefford₂·4H₂The O reaction can achieve higher yield (78%) (Helv. Chim. Acta1996, 791475-1487), but FeCl₂·4H₂The amount of O used is large (1 equivalent), the subsequent treatment steps are complicated, and the by-product has similar properties to Artemisinin G and is difficult to separate by simple steps, thus being unsuitable for industrial production. According to the invention, Artemisinin is taken as an initial raw material, TBADT (tetrabutylammonium decatungstate) with extremely low catalytic amount of 0.5 mol% is taken as a catalyst, Artemisinin G with yield of more than 90% can be quickly obtained through one-step reaction, obvious byproducts are not generated, the conditions are mild, the post-treatment is simple, and the application value is very high.

Disclosure of Invention

The invention aims to provide a method for preparing Artemisinin G, by which a sample can be quickly and simply obtained for biomedical research.

In order to achieve the above purpose, the invention adopts the following technical scheme:

a method of making Artemisinin G: artemisinin G is obtained by one-step reaction at room temperature and under the condition of illumination by taking Artemisinin as a starting material and TBADT as a catalyst.

The method comprises the following specific steps: acetonitrile and chloroform are used as a mixed solvent, Artemisinin serving as a raw material and TBADT serving as a catalyst are added into the mixed solvent, a reaction is carried out at room temperature and under the illumination condition in the argon atmosphere to obtain a crude product, and the product Artemisinin G is obtained after purification.

Further, the volume ratio of acetonitrile to chloroform is 5: 1.

further, TBADT is used in an amount of 0.5% based on the molar amount of artemisinin.

Further, the illumination wavelength was 370 nm.

Further, the reaction time was 30 min.

The invention has the advantages that: compared with the prior art, the method has the advantages of simple synthetic route, easily obtained raw materials, low cost, simple reaction operation, easy treatment and higher yield, and can obtain a large amount of Artemisinin G for medicine research and development.

In the prior art, ferrous salt is used as a catalyst, oxygen free radicals and iron oxide are formed mainly through the steps that ferrous ions destroy peroxide bridge bonds, the oxygen free radicals promote C-C bonds to break to form carbon free radicals, unstable carbon free radicals are combined with oxygen in the iron oxide to form stable five-membered rings, the ferrous ions leave to generate Artemisinin G, and the like. When the very low catalytic amount of TBADT (catalytic ratio 200: 1) is used, the decatungstate is excited under the illumination, hydrogen atoms are abstracted, free radicals are released, the decatungstate returns to the ground state to wait for the next excitation, and the free radicals continue to react, so that the catalytic efficiency is far higher than that of ferrous ions, obvious byproducts are not generated, the purification process is simple, and the method is suitable for large-scale production.

Detailed Description

In order to make the present invention more comprehensible, the technical solutions of the present invention are further described below with reference to specific embodiments, but the present invention is not limited thereto.

Solvent: CHCl₃(chloroform), CH₃CN (acetonitrile), PE (petroleum ether), EtOAc (ethyl acetate).

Reagent: artemisinin, TBADT (tetrabutylammonium decatungstate, CAS number: 68109-03-5).

Example 1:

3 mL of acetonitrile was mixed with 0.6 mL of chloroform, and artemisinin (0.282 g, 1 mmol) and TBADT (13.6 mg, 0.005 mmol) were added at room temperature. The reaction system is in an argon atmosphere and is placed at room temperature under the illumination of 370 nm for half an hour. The solvent was then removed to give the crude product, which was purified by silica gel column chromatography (PE/EtOAc = 4:1, volume ratio) to give a white solid (0.259 g, 92% reaction yield).

Physical state: a white powdery solid;

Melting point: 91-93℃；

¹H NMR (400 MHz, CDCl₃) δ 6.65 (1H, s), 4.21 (1H, t, J = 7.6 Hz), 3.94 (1H, dd, J = 7.4, 15.8 Hz), 3.16 (1H, dq, J = 2.7, 7.2 Hz), 2.16 (3H, s), 1.8-2.1 (4H, m),1.73 (1H, m), 1.60 (1H, m), 1,47 (1H, m), 1.21 (3H, d, J = 7.3 Hz), 1.08 (1H, m), 0.99 (3H, d, J = 6.3 Hz).

¹³C NMR (90 MHz, CDCl₃) δ 12.4, 20.3, 21.1, 24.2, 27.6, 30.8, 34.6, 34.9, 46.6, 54.8, 69.1, 79.3, 92.9, 168.3, 171.5.

HRMS (ESI): calcd for C₁₅H₂₃O₅ ⁺m/z: 283.1540 (M+1), found 283.1551.

example 2:

15 mL of acetonitrile was mixed with 3 mL of chloroform and artemisinin (1.41 g, 5 mmol) and TBADT (68 mg, 0.025 mmol) were added at room temperature. The reaction system was filled with argon and left to react at room temperature under 370 nm light for half an hour. The solvent was then removed to give the crude product, which was purified by silica gel column chromatography (PE/EtOAc = 4:1, volume ratio) to give a white solid (1.33 g, 94%).

Example 3:

150 mL acetonitrile was mixed with 30 mL chloroform and artemisinin (14.1 g, 50 mmol) and TBADT (680 mg, 0.25 mmol) were added at room temperature. The reaction system was filled with argon and left to react at room temperature under 370 nm light for half an hour. The solvent was then removed to give the crude product, which was purified by silica gel column chromatography (PE/EtOAc = 4:1, volume ratio) to give a white solid (12.8 g, 91%).

The above description is only a preferred embodiment of the present invention, and all equivalent changes and modifications made in accordance with the claims of the present invention should be covered by the present invention.