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Preparation and application of caffeic acid ethyl benzene phenol hydroxyl protecting derivative taken as neuroprotective agent and antitumor medicine

A hydroxyl protecting group and phenylethyl alcohol ester technology, which is applied in the preparation of antineoplastic drugs, organic compounds, and carboxylic acid halides, can solve the problems of low bioavailability, strong gastric irritation, and insufficient antitumor activity. people's satisfaction

Inactive Publication Date: 2014-09-03
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

First of all, the antitumor activity of caffeic acid phenethyl ester is not very satisfactory; secondly, the existence of its phenolic hydroxyl structure will cause strong gastric irritation, thereby reducing the patient's medication compliance; thirdly, the phenolic hydroxyl and ester The structure is easy to metabolize in vivo, resulting in poor drug stability and low bioavailability

Method used

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  • Preparation and application of caffeic acid ethyl benzene phenol hydroxyl protecting derivative taken as neuroprotective agent and antitumor medicine
  • Preparation and application of caffeic acid ethyl benzene phenol hydroxyl protecting derivative taken as neuroprotective agent and antitumor medicine
  • Preparation and application of caffeic acid ethyl benzene phenol hydroxyl protecting derivative taken as neuroprotective agent and antitumor medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Preparation of phenethyl caffeate (a)

[0034] Caffeic acid (9g, 50mmol) was added in batches to the reaction flask filled with 50ml DMSO, fully stirred, solid base potassium phosphate (12.74g, 60mmol) was added, fully stirred at room temperature, then slowly added dropwise bromoethylbenzene ( 7.48ml, 55mmol) of DMSO (20ml) solution into the reaction bottle, stirred at room temperature overnight, the reaction solution was dropped into 100ml of ice water, acidified with hydrochloric acid to pH 6, extracted with ethyl acetate, combined ester layer with saturated saline Washed, dried over anhydrous sodium sulfate, separated and purified by silica gel column (petroleum ether / ethyl acetate elution) to obtain white solid a, 11.36g, yield 80.0%, needle crystal, m.p., 102-103°C. 1 H-NMR (400MHz, DMSO) δ=9.21 (b, 2H, ArOH), 7.46 (d, J=16.0Hz, 1H, ArCH=CHCOO), 6.24 (d, J=16.0Hz, 1H, ArCH=CHCOO) , 6.75-7.34(m, 8H, ArH), 4.32(t, 2H, COOCH 2 R), 2.95(t, 2H, PhCH 2 R). 13 C-NMR (...

Embodiment 2

[0036] Preparation of (Z)-3-(3'-hydroxy-4'-acetoxyphenyl)-phenylethyl acrylate (b1)

[0037] Dissolve a (0.28g, 1mmol) in a reaction flask filled with 7ml of tetrahydrofuran, measure pyridine (0.08ml, 1mmol) with a pipette and add it dropwise to the reaction flask, then slowly add acetyl chloride (0.08g, 1mmol) of tetrahydrofuran (3ml) solution into the reaction flask, stirred at room temperature for 5h, TLC detection of complete reaction, spin-dried solvent under reduced pressure, added a small amount of water, extracted with ethyl acetate, the combined ester layer was washed with saturated brine, anhydrous sodium sulfate Dry, separate and purify with silica gel column (petroleum ether / ethyl acetate elution), and if necessary, separate and purify with thin-layer plate chromatography to obtain white solid b1, 0.08g, yield 24.5%, block crystal, m.p., 107- 108°C. 1 H-NMR (400MHz, CDCl 3 ) δ = 6.65 (s, 1H, ArOH), 7.55 (d, J = 16.0Hz, 1H, ArCH = CHCOO), 6.23 (d, J = 16.0Hz, 1H, ...

Embodiment 3

[0065] Preparation of (Z)-3-(3',4'-diacetoxyphenyl)-phenylethyl acrylate (c1)

[0066] Dissolve a (0.28g, 1mmol) in a reaction flask filled with 7ml of tetrahydrofuran, measure pyridine (0.32ml, 4mmol) with a pipette and add it dropwise to the reaction flask, then slowly add acetyl chloride (0.32g, 4mmol) of tetrahydrofuran (3ml) solution into the reaction flask, stirred at room temperature for 5h, TLC detection of complete reaction, spin-dried solvent under reduced pressure, added a small amount of water, extracted with ethyl acetate, the combined ester layer was washed with saturated brine, anhydrous sodium sulfate Dry, separate and purify with silica gel column (petroleum ether / ethyl acetate elution), if necessary, separate and purify with thin-layer plate chromatography to obtain white solid c1, 0.33g, yield 90.3%, needle crystal, m.p.82-83 ℃. 1 H-NMR (400MHz, CDCl 3 )δ=7.60(d, J=16.0Hz, 1H, ArCH=CHCOO), 6.36(d, J=16.0Hz, 1H, ArCH=CHCOO), 7.20-7.57(m, 8H, ArH), 4.41(t, ...

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Abstract

The invention relates to applications of a caffeic acid phenethyl ester phenol hydroxyl protecting derivative as shown in a general formula I in preparation of a neuroprotective medicine or a medicine composition for a neurodegenerative disease and in treatment of various types of tumors. In the formula I, the definition of each group is described as the claims in the specification. The invention further relates to a preparation method of the caffeic acid phenethyl ester phenol hydroxyl protecting derivative.

Description

technical field [0001] The invention relates to the preparation method of the single-hydroxyl-protected or di-hydroxyl-protected compound of caffeic acid phenethyl ester, and also relates to the neuroprotective effect of this compound in the treatment of neurodegenerative diseases and the tumor growth inhibitory effect of different types of tumors. Background technique [0002] Neurodegenerative diseases are a class of chronic, progressive neurological diseases. Such diseases mainly include Alzheimer's disease, Parkinson's disease, Huntington's chorea, different types of spinocerebellar ataxia, dentate nucleus rubrum pallidus subthalamic nucleus atrophy and amyotrophic lateral sclerosis, etc. In recent years, the number of neurodegenerative diseases has been increasing. For example, the prevalence of Alzheimer's disease in my country is 2% to 5%, and the annual new incidence is 1%. Studies have found that neurodegenerative diseases are caused by many different reasons, incl...

Claims

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Application Information

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IPC IPC(8): C07C69/732C07C69/73C07C205/57C07C69/92C07C69/78C07C67/14C07C201/12A61K31/216A61K31/24A61K31/235A61P25/00A61P35/00A61P25/28A61P25/16A61P25/14A61P9/10A61P35/02
CPCY02P20/55C07C69/732C07C69/73C07C69/734C07C69/76C07C69/78C07C69/92C07C205/57
Inventor 刘俊义朱仁宗张志丽王孝伟郭莹田超
Owner PEKING UNIV
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