Catalpol derivative and application thereof

A derivative, catalpol technology, applied in the field of medicine, can solve unrealistic problems

Active Publication Date: 2019-05-10
SHANGHAI UNIV OF T C M
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since catalpol belongs to the polyhydroxy iridoid glycosides, it is unrealistic to selectively introduce the corresponding group on the 6-position hydroxyl group by conventional glycoside or esterification.

Method used

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  • Catalpol derivative and application thereof
  • Catalpol derivative and application thereof
  • Catalpol derivative and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] Embodiment 1: the preparation of formula I natural catalpol derivative

[0060] Extract 4.1 kg of Scrophularia serrata medicinal material with 95% ethanol aqueous solution by reflux for 3 times, each time for 2 hours, each time with 40 L of ethanol aqueous solution, combine the extracts, concentrate under reduced pressure to obtain extract (about 570 g); Add about 3 times the amount (1500mL) of water to the extract to suspend, then extract with petroleum ether (1500mL×3) and ethyl acetate (1500mL×3) in sequence, collect the ethyl acetate extract; recover ethyl acetate under reduced pressure Carry out silica gel column chromatography after esterification, carry out gradient elution with petroleum ether and ethyl acetate successively (10:1~0:1); Use silica gel column chromatography of the obtained fraction: first carry out gradient with petroleum ether-ethanol mixed solvent Elution (volume ratio from 10:1 to 3:1), then reverse column chromatography: gradient elution with ...

Embodiment 2

[0086] Embodiment 2: the preparation of formula II natural catalpol derivative

[0087] Rhizome of Coptis chinensis 1kg, crushed into coarse powder, heated and refluxed with 10 times the amount of methanol to extract 3 times, concentrated and then added 200-300 mesh silica gel to mix the sample, 300-400 mesh silica gel column chromatography, chloroform-methanol (1:20 -1:5) gradient elution to obtain 2 fractions. Wherein Fraction 2 is chromatographed on a reversed-phase ODS column, eluted with a gradient of methanol-water (10%-30%), and the fraction of the resulting Pibroside II fraction is purified by a sephadex LH-20 column (50% methanol), and the II -1~II-6, all are white powder.

[0088] 10 kg of catalpa, crushed into coarse powder, heated and refluxed with 10 times the amount of 75% ethanol for 3 times, each time for 2 hours, the extract was decompressed to recover the ethanol until it had no alcohol smell, and extracted 3 times with the same amount of dichloromethane to ...

Embodiment 3

[0120] Embodiment 3 Catalbin is structurally modified to obtain the preparation of catalpol derivatives

[0121] Add catalpaside 24mg (0.05mmol) and 3mL N,N-dimethylformamide (DMF) into the reaction flask, add R under stirring at room temperature 1 X (0.10mmol) (Table 1) and anhydrous K 2 CO 3 (21mg, 0.15mmol), reacted at 30°C to the end point (TLC tracking). An appropriate amount of 100-200 mesh silica gel was added to mix the sample, and the solvent was recovered under reduced pressure until it was in the shape of quicksand, and the corresponding compound of formula III was obtained by silica gel and MCI column chromatography, with a yield between 50% and 98%.

[0122] Table 1 prepares the substrate reagent of necatapol derivative

[0123]

[0124]

[0125] III-1: 1 H NMR (600 MHz, C 5 D. 5 N): δ H 5.53(1H,d,J=9.1 Hz,H-1),6.43(1H,dd,J=1.4 / 5.9 Hz,H-3),5.06(1H,dd,J=5.9 / 4.1 Hz,H-4 ),2.91(1H,m,H-5),5.28(1H,brd,J=7.6 Hz,H-6),3.97(1H,brs,H-7),2.88(1H,m,H-9) ,4.50(1...

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Abstract

The invention belongs to the technical field of the medicine and chemical industry, discloses a natural catalpol derivative and a novel modified catalpol derivative derived from catalposide and picroside II, and provides a preparation method of the derivative and application of the derivative in the preparation of anti-inflammatory drugs. The structure of the natural catalpol derivative is shown in a formula (I) or a formula (II), and the structure of the novel modified catalpol derivative derived from the catalposide and the picroside II is shown in a formula (III) or a formula (IV). Experimental results show that compounds of which the structures are shown in formula (I), formula (II), formula (III) and formula (IV) or hydrates of the compounds, pharmaceutically acceptable salt, tautomers, stereisomers and precursor compounds have a significant inhibiting effect on 8-hydroxytridine DNA glycosylase 1 (8-hydroxytridine DNA glycosylase 1, OGG1), and has wide application space in the preparation of the anti-inflammatory drugs and antitumor drugs.

Description

technical field [0001] The invention belongs to the field of medicine, and relates to a class of compounds with inhibitory activity on 8-hydroxyguanine DNA glycosylase 1 (8-hydroxytridine DNA glycosylase 1, OGG1), specifically a natural or Modified catalpol derivatives and their applications. Background technique [0002] Oxidative stress (ROS) can lead to the oxidation of various intracellular biomacromolecules, including proteins, lipids and nucleic acids. The main type of oxidative base caused by ROS on DNA is 8-hydroxyguanine (8-oxoG). 8-Hydroxyguanine DNA glycosylase 1 (OGG1) is a repair protein that specifically repairs 8-oxoG. It recognizes and corrects 8-oxoG through the base excision repair pathway initiated by OGG1 (OGG1-BER). bases. Unexpectedly, an abnormal excess of 8-oxoG on the genome did not affect embryonic development, precancerous lesions, or lifespan in mice [Arai et al., Toxicology 2006, 221:179–186; Leopoldo et al., Free Radical Bio.Med. 2015,8:1107...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H17/04A61P29/00A61P37/02A61P31/12A61P35/00A23L33/10A23L33/105
Inventor 张刘强薛海兵马钢华李医明陈凯先贾琦
Owner SHANGHAI UNIV OF T C M
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