Derivatives of 3-O-caffeoyloleanane type pentacyclic triterpene, preparation method thereof and application thereof

Abstract

The invention discloses derivatives of 3-O-caffeoyloleanane type pentacyclic triterpene represented by general formula (I) in the specification (R1 and R2 in the general formula (I) are selected from -CH3, COOH, COOQ, CONQ2, or COSQ, wherein Q is hydrogen, alkyl, substituted alkyl, aryl, or substituted aryl; X is -C=O or CH2; and Y-Z is -CH2-CH2-, cis-CH=CH-, or trans-CH=CH-), a preparation method thereof, and pharmaceutically acceptable esters or salts thereof. The invention also discloses a medicinal composition. The composition comprises an effective dose of the derivatives of 3-O-caffeoyloleanane type pentacyclic triterpene or the pharmaceutically acceptable esters or salts thereof, and pharmaceutically acceptable carriers thereof. The invention also discloses an application of the derivatives of 3-O-caffeoyloleanane type pentacyclic triterpene or the pharmaceutically acceptable esters or salts thereof in the preparation of anti-inflammatory medicines, antiallergic medicines, liver protection medicines, antivirus medicines and the like.

Description

technical field

[0001] The invention relates to a pentacyclic triterpene ester derivative, in particular to a 3-O-caffeoyl oleanane type pentacyclic triterpene ester derivative, its preparation method and application. Background technique

[0002] Glycyrrhetinic acid (Glycyrrhetinic Acid, abbreviated as GA, its chemical structural formula is shown in (A)), also known as glycyrrhetinic acid, is an oleanane-type pentacyclic triterpenoid compound extracted from the rhizome of licorice. 30 h 46 o 4 , Molecular weight 470.64) mainly. Pharmacological effects of glycyrrhetinic acid and its derivatives: it has anti-inflammatory, anti-ulcer, anti-virus, anti-tumor, anti-allergic and other effects. Clinically, glycyrrhetinic acid is a classic anti-inflammatory drug, which can be made into anti-inflammatory and anti-allergic Preparations are used to treat arthritis, dermatitis, ophthalmology, ear, nose and throat inflammation and ulcers, etc.; when applied in cosmetics, it can regul...

Examples

Embodiment 1 2

[0066] The preparation of embodiment 1 diacetyl caffeic acid (2)

[0067]

[0068] Dissolve caffeic acid 1 (18.0g, 0.10mol) in 200mL of acetic anhydride, add anhydrous sodium acetate (1.6g, 0.02mol), heat to reflux for 1 hour, cool to room temperature, pour the reaction solution into 2L with vigorous stirring In ice water, stir well for 3 hours. The mixture was suction filtered, the solid was washed three times with water, and dried to obtain diacetylcaffeic acid 2 (23.5 g, yield 89%) as a light yellow solid.

Embodiment 2 2

[0069] The preparation of embodiment 2 dihydrodiacetyl caffeic acid (3)

[0070]

[0071] Diacetylcaffeic acid 2 (2.6g, 10mmol) was dissolved in 50mL of methanol, 5% palladium carbon (Pd-C) catalyst (0.1g) was added, stirred at normal temperature and pressure for 2 hours in a hydrogen atmosphere, and thin-layer chromatography (TLC) detected no starting material. After filtering off Pd-C, the filtrate was desolventized to obtain dihydrodiacetylcaffeic acid 3 (2.5 g, yield 94%) as a white solid.

[0072] Compound 3 1 HNMR (300MHz, CDCl 3 )d: 2.28(s, 3H, O=C-CH 3 ), 2.29 (s, 3H, O=C-CH 3 ), 2.68(t, J=7.8Hz, 2H, C-H 2 ), 2.96(t, J=7.8Hz, 2H, C-H 2 ), 7.04 (s, 1H, Ar-H), 7.10 (s, 2H, Ar-H).

Embodiment 3

[0073] The preparation of embodiment 3 methyl glycyrrhetinate (6a)

[0074]

[0075] Dissolve glycyrrhetinic acid (4.7 g, 10 mmol) in 50 mL of methanol, add 2 mL of concentrated sulfuric acid, and heat to reflux for 3 hours. After cooling to room temperature, pour the reaction solution into 150 mL of water, stir well, extract with dichloromethane (50 mL×3), combine the organic phases, wash with water, dry over anhydrous sodium sulfate, and remove the solvent under reduced pressure to obtain white solid glycyrrhetinic acid Methyl ester 6a (4.2 g, 87% yield).

technical field

[0001] The invention relates to a pentacyclic triterpene ester derivative, in particular to a 3-O-caffeoyl oleanane type pentacyclic triterpene ester derivative, its preparation method and application. Background technique

[0002] Glycyrrhetinic acid (Glycyrrhetinic Acid, abbreviated as GA, its chemical structural formula is shown in (A)), also known as glycyrrhetinic acid, is an oleanane-type pentacyclic triterpenoid compound extracted from the rhizome of licorice. 30 h 46 o 4 , Molecular weight 470.64) mainly. Pharmacological effects of glycyrrhetinic acid and its derivatives: it has anti-inflammatory, anti-ulcer, anti-virus, anti-tumor, anti-allergic and other effects. Clinically, glycyrrhetinic acid is a classic anti-inflammatory drug, which can be made into anti-inflammatory and anti-allergic Preparations are used to treat arthritis, dermatitis, ophthalmology, ear, nose and throat inflammation and ulcers, etc.; when applied in cosmetics, it can regul...

Examples

Embodiment 1 2

[0066] The preparation of embodiment 1 diacetyl caffeic acid (2)

[0067]

[0068] Dissolve caffeic acid 1 (18.0g, 0.10mol) in 200mL of acetic anhydride, add anhydrous sodium acetate (1.6g, 0.02mol), heat to reflux for 1 hour, cool to room temperature, pour the reaction solution into 2L with vigorous stirring In ice water, stir well for 3 hours. The mixture was suction filtered, the solid was washed three times with water, and dried to obtain diacetylcaffeic acid 2 (23.5 g, yield 89%) as a light yellow solid.

Embodiment 2 2

[0069] The preparation of embodiment 2 dihydrodiacetyl caffeic acid (3)

[0070]

[0071] Diacetylcaffeic acid 2 (2.6g, 10mmol) was dissolved in 50mL of methanol, 5% palladium carbon (Pd-C) catalyst (0.1g) was added, stirred at normal temperature and pressure for 2 hours in a hydrogen atmosphere, and thin-layer chromatography (TLC) detected no starting material. After filtering off Pd-C, the filtrate was desolventized to obtain dihydrodiacetylcaffeic acid 3 (2.5 g, yield 94%) as a white solid.

[0072] Compound 3 1 HNMR (300MHz, CDCl 3 )d: 2.28(s, 3H, O=C-CH 3 ), 2.29 (s, 3H, O=C-CH 3 ), 2.68(t, J=7.8Hz, 2H, C-H 2 ), 2.96(t, J=7.8Hz, 2H, C-H 2 ), 7.04 (s, 1H, Ar-H), 7.10 (s, 2H, Ar-H).

Embodiment 3

[0073] The preparation of embodiment 3 methyl glycyrrhetinate (6a)

[0074]

[0075] Dissolve glycyrrhetinic acid (4.7 g, 10 mmol) in 50 mL of methanol, add 2 mL of concentrated sulfuric acid, and heat to reflux for 3 hours. After cooling to room temperature, pour the reaction solution into 150 mL of water, stir well, extract with dichloromethane (50 mL×3), combine the organic phases, wash with water, dry over anhydrous sodium sulfate, and remove the solvent under reduced pressure to obtain white solid glycyrrhetinic acid Methyl ester 6a (4.2 g, 87% yield).

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