Oleanolic acid triterpene with A ring and C ring both containing multiple oxygen-containing substituents and use thereof

Abstract

The invention provides an oleanolic acid triterpenoid, whose A ring and C ring contain multiple oxygen substituents, represented as formula (1). The inventive compound can inhibit the growth activity of tumor cell, thereby being applied in the preparation of anti-tumor drug and can inhibit mice ear swelling caused by dimethylbenzene, thereby being applied in the preparation of anti-inflammatory agent. The formula (1) is represented as above.

Description

[0001] This application is a divisional application of a Chinese patent application with an application date of December 29, 2004 and an application number of 200410102895.6. technical field

[0002] The invention relates to the fields of organic chemistry and medicinal chemistry, in particular, the invention relates to polyoxidatively substituted pentacyclic triterpene derivatives, a preparation method and application thereof. The present invention treats the series of compounds on six tumor cell lines such as human prostate cancer cell (PC-3), nasopharyngeal carcinoma cell line (CNE), oral epithelial cancer cell line (KB), human lung cancer cell (A549), human liver cancer cell line (BEL-7404), human cervical cancer cells (Hela) were screened for tumor cell growth inhibitory activity. The compounds are found to have a certain activity of inhibiting the growth of tumor cells, and can be expected to be used as antitumor drugs. In addition, these compounds also have a significa...

Examples

preparation example 1

[0036] Preparation Example 1: Preparation of Compound Ii

[0037] The compound 3-methylsulfonyloxy-oleanane-28-acid-12-ene (1.0mmol) was dissolved in 5 ml of DMAC (N,N'-dimethylacetamide), and lithium carbonate ( 2.0 mmol). The reaction mixture was heated to reflux for half an hour. After cooling, excess lithium carbonate was filtered off, the filtrate was added to 10 ml of water, extracted with ether, and the organic phase was washed with water until neutral. Dry over anhydrous sodium sulfate. Silica gel column chromatography (eluent: petroleum ether / ethyl acetate: 8 / 1) gave oleanane-28-acid-2,12-diene as a white solid with a yield of 82%.

[0038] In 20 ml of acetic acid (containing 5% acetic anhydride), the compound oleanane-28-acid-2,12-diene (0.82 mmol) and chromium trioxide (4.92 mmol) were added, and stirred overnight at room temperature. The reaction compound was poured into 20 ml of water, and extracted with chloroform. The organic phase was washed with saturated...

preparation example 2～ preparation example 22

[0040] According to the method of Preparation Example 1, the compounds of Preparation Example 2 to Preparation Example 22 shown below were prepared:

preparation example 2

[0041] Preparation Example 2: Preparation of oleanane-28-acid-2,11,13(18)-triene (Ia), C 30 h 44 o 2 , MS: ESI m / e436 (M + ); Rf (petroleum ether / chloroform / methanol: 4 / 4 / 0.6): 0.63, 1 HNMR (400MHz, CDCl 3 )δ: 2.51(brd, 1H, J=14.2Hz, H-19), 5.31-5.43(m, 3H, H-2, H-3, H-12), 6.35(d, 1H, J=10.4Hz , H-11).

[0001] This application is a divisional application of a Chinese patent application with an application date of December 29, 2004 and an application number of 200410102895.6. technical field

[0002] The invention relates to the fields of organic chemistry and medicinal chemistry, in particular, the invention relates to polyoxidatively substituted pentacyclic triterpene derivatives, a preparation method and application thereof. The present invention treats the series of compounds on six tumor cell lines such as human prostate cancer cell (PC-3), nasopharyngeal carcinoma cell line (CNE), oral epithelial cancer cell line (KB), human lung cancer cell (A549), human liver cancer cell line (BEL-7404), human cervical cancer cells (Hela) were screened for tumor cell growth inhibitory activity. The compounds are found to have a certain activity of inhibiting the growth of tumor cells, and can be expected to be used as antitumor drugs. In addition, these compounds also have a significa...

Examples

preparation example 1

[0036] Preparation Example 1: Preparation of Compound Ii

[0037] The compound 3-methylsulfonyloxy-oleanane-28-acid-12-ene (1.0mmol) was dissolved in 5 ml of DMAC (N,N'-dimethylacetamide), and lithium carbonate ( 2.0 mmol). The reaction mixture was heated to reflux for half an hour. After cooling, excess lithium carbonate was filtered off, the filtrate was added to 10 ml of water, extracted with ether, and the organic phase was washed with water until neutral. Dry over anhydrous sodium sulfate. Silica gel column chromatography (eluent: petroleum ether / ethyl acetate: 8 / 1) gave oleanane-28-acid-2,12-diene as a white solid with a yield of 82%.

[0038] In 20 ml of acetic acid (containing 5% acetic anhydride), the compound oleanane-28-acid-2,12-diene (0.82 mmol) and chromium trioxide (4.92 mmol) were added, and stirred overnight at room temperature. The reaction compound was poured into 20 ml of water, and extracted with chloroform. The organic phase was washed with saturated...

preparation example 2～ preparation example 22

[0040] According to the method of Preparation Example 1, the compounds of Preparation Example 2 to Preparation Example 22 shown below were prepared:

preparation example 2

[0041] Preparation Example 2: Preparation of oleanane-28-acid-2,11,13(18)-triene (Ia), C 30 h 44 o 2 , MS: ESI m / e436 (M + ); Rf (petroleum ether / chloroform / methanol: 4 / 4 / 0.6): 0.63, 1 HNMR (400MHz, CDCl 3 )δ: 2.51(brd, 1H, J=14.2Hz, H-19), 5.31-5.43(m, 3H, H-2, H-3, H-12), 6.35(d, 1H, J=10.4Hz , H-11).

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