Ursolic acid diethanol amine derivative with anti-tumor activity and preparation method thereof

A technology of ursolic acid diethanol and amine derivatives, applied in the field of ursolic acid derivatives and their preparation, to achieve a strong tumor inhibitory effect

Inactive Publication Date: 2010-11-24
FUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The foothold of the present invention is to develop novel N-[3β-acetoxy-arbutane-12-en-28-yl]-aminodiethanol and N-[3β-hydroxyl-arbutane with anticancer activity -12-ene-28-acyl]-aminodiethanol and its preparation method, no reports at home and abroad

Method used

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  • Ursolic acid diethanol amine derivative with anti-tumor activity and preparation method thereof
  • Ursolic acid diethanol amine derivative with anti-tumor activity and preparation method thereof
  • Ursolic acid diethanol amine derivative with anti-tumor activity and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Preparation of 3-O-acetyl ursolic acid (compound II):

[0039] Weigh 0.7062 g of ursolic acid, add 30 ml of pyridine, stir to dissolve, add 1.8 ml of acetic anhydride dropwise, add a small amount of DMAP, stir at room temperature for 16 h, after the reaction, adjust the pH to 3-4 with 2 N HCl, evaporate Solvent, suction filtration, washing filter cake with water until neutral, drying at normal pressure 100°C, dry loading of the dried product, column chromatography purification (petroleum ether (60-90°C): ethyl acetate = 3:1), Dissolve in absolute ethanol, cool and recrystallize to obtain 3-Oacetyl ursolic acid.

[0040] Properties: white powder; yield: 86.17%; mp: 286-288°C.

[0041] IR Data (KBr, cm -1 ) and its attribution: υ: 3293 (O-H stretching vibration), 2927 (C-H stretching vibration), 1736 (s, C=O stretching vibration), 1370 (UA A region characteristic absorption), 1245 (s, C-O-C asymmetric stretching vibration ) cm -1 .

[0042] ESI-MS : m / z 497.5 [M-H]...

Embodiment 2

[0045] Preparation of N-[3β-acetoxy-arbutan-12-en-28-yl]-aminodiethanol (compound I):

[0046] Weigh 0.1954 g 3-O-acetyl ursolic acid and dissolve in 20 ml CH 2 Cl 2 0.19 ml of oxalyl chloride was added dropwise in batches, stirred at room temperature for 36 h, and the solvent and gas generated by the reaction were evaporated to obtain the crude product of 3-O-acetyl UA acid chloride intermediate, which was directly used for the next reaction. Add 20 mL of CH to the above intermediate 2 Cl 2 , triethylamine to adjust the pH of the solution to 8-9, add 0.19 ml of diethanolamine, stir and react at room temperature for 3 h, after the reaction, add 10 ml of distilled water to the reaction solution, adjust the pH to 3-4 with 2N HCl, filter, and wash the filter cake with water to The filtrate was pH neutral and dried. Purified by column chromatography (petroleum ether (60-90°C): ethyl acetate = 1:3), dissolved in absolute ethanol, cooled and recrystallized to obtain N-[3β-acetox...

Embodiment 3

[0052] Preparation of N-[3β-hydroxy-arbutane-12-en-28-yl]-aminodiethanol (compound III):

[0053] Weigh 0.5859g of N-[3β-acetoxy-arbutane-12-en-28-yl]-aminodiethanol, dissolve it in 20ml CH 3 OH-THF (1:1.5 v:v), add 2.0ml 4N NaOH, stir at room temperature for 3.5 h, the reaction is complete, add an appropriate amount of water to the mixture, adjust the pH to 3-4 with 2 N HCl, evaporate under reduced pressure Solvent, washed with water and precipitated to neutral, purified by column chromatography (petroleum ether (60-90°C): ethyl acetate = 1:3), dissolved in absolute ethanol, cooled and recrystallized to obtain N-[3β-hydroxy-benzyl Fran-12-en-28-yl]-aminodiethanol.

[0054] Properties: white powder; yield: 89.37%; mp: 270-272°C.

[0055] IR data (KBr, cm -1 ) and its attribution: υ: 3399 (-OH stretching vibration), 2926 (C-H stretching vibration), 1606 (s, C=O stretching vibration, amide I peak), 1408 (UA A region characteristic absorption) cm -1 .

[0056] ESI-MS : m / z...

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Abstract

The invention provides an ursolic acid diethanol amine derivative with anti-tumor activity and a preparation method thereof. The ursolic acid diethanol amine derivative is N-[3beta-acetoxy-ursa-12-alkene-28-acyl]-diethanolamine (I) or N-[3beta-hydroxy-ursa-12-alkene-28-acyl]-diethanolamine (III). The preparation method comprises the following steps: allowing ursolic acid to react with acetic oxide to generate 3-O-acetyl ursolic acid; allowing the 3-O-acetyl ursolic acid to react with oxalyl chloride and then react with diethanol amine to obtain a compound (I); and carrying out hydrolysis reaction between the compound (I) and NaOH to obtain a compound (III). The obtained ursolic acid diethanol amine derivative is used for preparing anti-tumor drugs, the proliferation inhibition effect thereof on tumor cells is superior to that of the ursolic acid, and the toxic effect thereof on human embryonic lung fibroblasts (HELF) is lower than that of the ursolic acid.

Description

technical field [0001] The invention relates to an ursolic acid derivative and a preparation method thereof, in particular to an ursolic acid diethanolamine derivative with antitumor activity and a preparation method thereof. Background technique [0002] Ursolic acid (Ursolic acid, UA), also known as ursolic acid, ursolic acid, belongs to pentacyclic triterpenoids, chemical name (3β)-3-Hydroxyurs-12-en-28-oic acid, its relative molecular weight is 456.68, and the molecular formula is C 30 h 48 o 3 , which is widely distributed in nature in the form of free or glycosides. Pharmacological studies have found that ursolic acid has a wide range of biological effects, and ursolic acid has a variety of biological activities, such as anti-cancer, anti-HIV, anti-liver damage, anti-malarial, anti-inflammatory and antibacterial, etc., especially anti-cancer The activity is the most significant, and its anti-cancer spectrum is broad. It not only has resistance to various carcinogen...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J63/00A61K31/56A61P35/00
Inventor 邵敬伟林凤屏
Owner FUZHOU UNIV
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