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Oridonin derivative and preparation method thereof

A technology of Rubescensin A and Rubescensin A, applied in drug combination, organic chemistry, anti-tumor drugs, etc., can solve the problems of poor water solubility, limited use, and insufficient anti-tumor activity of compounds

Inactive Publication Date: 2010-06-09
YANTAI TARGET DRUG RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

When summarizing the basis of previous work, we found that the antitumor activity of all compounds was not high enough, and its use was limited due to poor water solubility

Method used

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  • Oridonin derivative and preparation method thereof
  • Oridonin derivative and preparation method thereof
  • Oridonin derivative and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1 when R 1 =R 2 = 3', 4'-dimethoxybenzylidene, the oridonin derivative (7,14-(3',4'-dimethoxy)benzylidene shown in general formula 1 Forbescensine A, the preparation of compound II):

[0027]

[0028] In a 250ml round bottom flask, add 5g oridonin and 100ml toluene, add 8g 3,4-dimethoxybenzaldehyde and 0.2g p-toluenesulfonic acid under stirring, and react at 80°C for 4 hours. Stop the reaction, extract with water and ethyl acetate, wash the organic phase with saturated sodium bicarbonate solution and saturated ammonium chloride solution, add anhydrous sodium sulfate to dry overnight, filter, and the filtrate is concentrated under reduced pressure to obtain a white solid, which is subjected to silica gel column chromatography , and eluted with petroleum ether-acetone (6:1) to obtain 6.5 g of colorless needle-like crystals with a yield of 92%. M.p.252~254°C.

[0029] Compound Molecular Formula: C 29 h 36 o 8

[0030] The spectrogram data is as follows: ...

Embodiment 2

[0035] Example 2 when R 1 = p-toluenesulfonyl, R 2 When =H, the preparation of Rubescensine A derivative (14-tosyl oridonine A, compound III) shown in general formula 1:

[0036]

[0037] In a 250ml round bottom flask, add 5g oridonin, 150ml dichloromethane and 2ml triethylamine, add 5g p-toluenesulfonyl chloride under stirring, after reacting at 0°C for 4 hours, add a small amount of water to quench the reaction, water and Extract with ethyl acetate, wash the organic phase with saturated sodium bicarbonate solution and saturated ammonium chloride solution, add anhydrous sodium sulfate to dry overnight, filter, and concentrate the filtrate under reduced pressure to obtain a white solid, which is recrystallized from petroleum ether-acetone to obtain a colorless 6.8 g of needle-like crystals, yield 95%. M.p.260~262℃.

[0038] Compound Molecular Formula: C 27 h 34 o 8 S

[0039] The spectrogram data is as follows: IR v max KBr (cm -1 ): 3557, 3377, 2951, 2868, 1713, ...

Embodiment 3

[0043] Example 3 When R 1 =R 2 =3',4'-dimethoxybenzylidene, the Rubescensin A derivative represented by the general formula 2 (1-carbonyl 7,14-(3',4'-dimethoxy) ) Preparation of Rubescensine A, Compound IV):

[0044] The first step (preparation of 1-carbonyl Rubescensin A): in a 100ml round bottom flask, add 0.5g Rubescensin A, 40ml acetone, slowly drop 6ml Jone's reagent under stirring at 0°C, and react at room temperature for 2 hours Then, add 0.4 ml of isopropanol, react for 0.5 hour, add 0.5 g of sodium bicarbonate, react for 0.5 hour, add 50 ml of ethyl acetate to dilute, filter, and concentrate the filtrate under reduced pressure to obtain a white solid, which is recrystallized with petroleum ether-acetone to obtain Colorless needle crystals 0.423 g, yield 85%. M.p.220~222℃. ESI-MS(m / z): 385.4([M+Na] + ); 1 H-NMR (400MHz, Acetone) δ: 6.53 (1H, s, 14-OH), 6.10 (1H, s, 17-H), 5.62 (1H, s, 17-H), 5.40 (1H, d, J = 11.3 Hz, 6-OH), 5.24 (1H, s, 7-OH), 4.90 (1H, s, 14-H)...

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Abstract

The invention provides an oridonin derivative as expressed in the general formula by changing substituent groups in a first position, a fourth position and a seventeenth position on the premise of not destroying the active center of oridonin. The oridonin derivative has higher anti-tumor cell activity. Meanwhile, the invention also provides a preparation method of the compound.

Description

technical field [0001] The present invention relates to novel oridonin derivatives and a preparation method thereof. Background technique [0002] Among the more than 100 diterpenoid components that have been isolated from the plant of the genus Camellia, more than 30 have certain antitumor activity. Among them, there are about 17 types of oridonin (kaurene type), and among them, oridonin has the highest content in plants, and its activity research is also on oridonin. Oridonin A is a diterpene compound with α-methylene cyclopentanone. Its anticancer activity has been extensively studied by scholars at home and abroad. Tumor activity, its anti-tumor spectrum is wide, such as human nasopharyngeal cancer cells, human liver cancer cells, human cervical cancer cells, human esophageal cancer cells, etc. all have obvious killing effects (a Zhang Junfeng, Chen Guihua, Lu Minqiang, etc. Journal of Prevention and Treatment, 2006, 13(15): 1131-1133.b Li Ruifang, Wang Qingduan. Acta ...

Claims

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Application Information

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IPC IPC(8): C07D493/08A61P35/00
Inventor 刘珂赵烽伍旭刘军锋
Owner YANTAI TARGET DRUG RES
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