Bearberry type pentacyclic triterpenes amino acid derivates, method for preparing same and pharmaceutical use thereof

A technology of amino acid and amino acid ester, which is applied in the field of natural medicine and medicinal chemistry, and can solve the problems of low bioavailability of preparations, poor water solubility of corosolic acid and asiatic acid, and limited application

Inactive Publication Date: 2009-01-07
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] However, corosolic acid and asiatic acid are extremely poor in water solubility, and th

Method used

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  • Bearberry type pentacyclic triterpenes amino acid derivates, method for preparing same and pharmaceutical use thereof
  • Bearberry type pentacyclic triterpenes amino acid derivates, method for preparing same and pharmaceutical use thereof
  • Bearberry type pentacyclic triterpenes amino acid derivates, method for preparing same and pharmaceutical use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0103] Synthesis of 2a, 3β, 23-triacetoxy asiatic acid

[0104] Add asiatic acid (0.20g, 0.40mmol) and acetic anhydride (76mg, 0.74mmol) into pyridine (10ml), and stir overnight at room temperature. After the reaction solution was diluted with ethyl acetate, it was washed successively with water, 1N dilute hydrochloric acid, saturated sodium bicarbonate solution and saturated brine, the organic phase was dried, filtered, concentrated, and subjected to flash column chromatography (petroleum ether / ethyl acetate: 10 / 1V / V) to give 2a, 3β, 23-O-triacetyl asiatic acid (170mg, 78%). M.p.93-95°C.

[0105] ESI-MSm / z: 637[M+Na] + .

[0106] 1 H-NMR (CDCl 3 , 300MHz): 0.78, 0.85, 0.88, 0.94, 1.07, 1.11(each 3H, s), 1.98, 2.02, 2.08(each 3H, s), 2.19(1H, d, J=11.3Hz), 3.58(1H, d,J=11.8Hz), 3.85(1H,d,J=11.8Hz), 5.07(1H,d,J=10.3Hz), 5.12-5.17(1H,m), 5.25(1H,t).

Embodiment 2

[0108] Synthesis of N-(2a,3β,23-triacetoxyarbutan-12-en-28-amide)-glycine methyl ester

[0109] Dissolve 2a, 3β, 23-triacetoxy asiatic acid (0.25g, 0.40mmol) in refined and dry dichloromethane (20ml), add oxalyl chloride (0.8ml) dropwise under ice-cooling, and stir at room temperature for 24 hours. Dichloromethane was distilled off under reduced pressure, then refined and dry dichloromethane (20×3) was added, dissolved, and distilled off to obtain 2a, 3β, 23-triacetoxy asiaticoyl chloride. Glycine methyl ester hydrochloride (0.15g, 1.20mmol) and DMAP (0.03g, 0.22mmol) were dissolved in dry dichloromethane, and the dichloromethane solution of the above-mentioned freshly prepared triacetylated asiaticoyl chloride was added dropwise, after dropping, stirred at room temperature for 12 hours, the reaction solution was washed successively with 1N aqueous hydrochloric acid solution and saturated brine, the organic layer was dried, filtered, concentrated, and subjected to flash column...

Embodiment 3

[0113] Synthesis of N-(2a,3β,23-triacetoxyarbutan-12-en-28-amide)-L-alanine methyl ester

[0114] Referring to the method of Example 2, N-(2a, 3β, 23-triacetoxyurbutane was prepared with 2a, 3β, 23-triacetoxy asiatic acid and L-alanine methyl ester hydrochloride -12-ene-28-amide)-L-alanine methyl ester. M.p. 220-222°C.

[0115] ESI-MS m / z: 700.5[M+H] + .

[0116] 1 H-NMR (CDCl 3 , 300MHz): 0.70(3H, s), 0.88(6H, s), 0.96(3H, s), 1.09(9H, s), 1.98, 2.02, 2.08(each 3H, s), 3.57(1H, d, J=11.8Hz), 3.75(3H, s), 3.84(1H, d, J=11.8Hz), 4.45-4.49(1H, m), 5.07(1H, d, J=10.3Hz), 5.12-5.17( 1H, m), 5.40(1H, t), 6.57(1H, d, J=5.9Hz).

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Abstract

The invention relates to the field of natural drug and medicinal chemistry, in particular to ursane-type pentacyclic triterpenoid amino acid derivatives (I), and the preparation method and the medicinal application thereof. The compounds have effect on inhibiting glycogen phosphorylase, and can be used for preparing drugs for resisting diabetes, cerebral ischemia, cardiovascular diseases, hyperlipemia, obesity, atherosclerosis and tumor. The invention also relates to the preparation method of the compounds and drug preparations containing the compounds.

Description

technical field [0001] The invention relates to the fields of natural medicine and medicinal chemistry, in particular to a class of novel arbutane-type pentacyclic triterpene derivatives. The compound can be used to prepare anti-diabetes and its complication drugs, anti-cerebral ischemia drugs, anti-cardiovascular disease drugs, blood-lipid-lowering drugs, weight-loss drugs, anti-atherosclerotic drugs, drugs for treating metabolic syndrome or anti-tumor drugs. The present invention also relates to synthesis methods of these compounds and pharmaceutical combinations containing them. Background technique [0002] Ursutane-type pentacyclic triterpenoids are widely distributed in the plant kingdom, and corosolic acid (1) and asiatic acid (2) are representative compounds, which have anti-hepatitis, anti-tumor, anti-virus, hypoglycemic and It has a variety of pharmacological activities such as reducing blood fat, and has low toxicity and small side effects, so it has important de...

Claims

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Application Information

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IPC IPC(8): C07J63/00A61K31/56A61P9/10A61P3/06A61P3/10A61P3/04
Inventor 孙宏斌张丽颖柳军
Owner CHINA PHARM UNIV
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