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Jatrophane type diterpenoid and preparation method and application

A technology of elemane and diterpene, applied in the field of medicine, can solve problems such as increased drug efflux, formation of drug resistance, and inability to speculate on the biological activity of new compounds

Active Publication Date: 2018-03-16
XINJIANG TECHN INST OF PHYSICS & CHEM CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In 2013, the research group applied for the patent "Macrocyclic diterpenoids in the fruit of Euphorbia euphorbia and its preparation method and application". The three new compounds in this study are lactone compounds with a pseudolemane-type skeleton discovered for the first time in Euphorbia japonica, which have a six-membered or eight-membered ring lactone structure at the C-5 and 6 positions. The lactone ring has a great influence on its biological activity, which is fundamentally different from the former. Therefore, the biological activity of the new compound cannot be inferred from the existing activity research results
There are many mechanisms for the formation of MDR, one of the most important mechanisms is the overexpression of ABC family transporters (currently the most widely and deeply studied P-glycoprotein encoded by the ABCB1 gene, P-gp), leading to drug efflux increase in drug resistance

Method used

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  • Jatrophane type diterpenoid and preparation method and application
  • Jatrophane type diterpenoid and preparation method and application
  • Jatrophane type diterpenoid and preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] a. Take 10 kg of the fruit of Euphorbia euphorbia, crush it, and use 50 L of 50% ethanol-water solution to extract it by cold soaking at room temperature, and evaporate the solvent to dryness under reduced pressure to obtain the crude extract of Euphorbia ipsifolia;

[0037] b. Disperse the crude extract obtained in step a with ethanol, add petroleum ether for extraction, combine the ethanol layers and evaporate to dryness under reduced pressure to obtain the ethanol extract extract;

[0038] c, the ethanol extract extract obtained in step b is separated with a normal phase silica gel column, and gradient elution is carried out with petroleum ether-ethyl acetate with a volume ratio of 10:1-0:1, and the fraction is subjected to silica gel thin layer chromatography ( TLC) analysis, the same fractions were combined to obtain 6 fractions (F1-F6); fraction F4 was subjected to normal-phase silica gel column separation, and gradient elution was carried out with chloroform-aceto...

Embodiment 2

[0041] a. Take 10 kg of the fruit of Euphorbia euphorbia, crush it, and use 60 L of ethanol-water solution with a concentration of 99% to reflux and extract at a temperature of 80° C., evaporate the solvent under reduced pressure to obtain the crude extract of Euphorbia ipsifolia;

[0042] b. Disperse the crude extract obtained in step a with ethanol, add n-hexane for extraction, combine the ethanol layers and evaporate to dryness under reduced pressure to obtain the ethanol extract extract;

[0043] c, the ethanol extract extract obtained in step b is separated with a normal phase silica gel column, and gradient elution is carried out with n-hexane-ethyl acetate with a volume ratio of 10:1-0:1, and the fraction is subjected to silica gel thin layer chromatography ( TLC) analysis, the same fractions were combined to obtain 6 fractions (F1-F6); fraction F4 was subjected to normal phase silica gel column separation, and gradient elution was carried out with chloroform-methanol wi...

Embodiment 3

[0045]a. Get 10kg of the fruit of Euphorbia euphorbia, pulverize it and extract it by percolation at room temperature with 80L of dehydrated ethanol, and evaporate the solvent to dryness under reduced pressure to obtain the crude extract of Euphorbia ipsifolia;

[0046] b. Disperse the crude extract obtained in step a with ethanol, add cyclohexane for extraction, combine the ethanol layers and evaporate to dryness under reduced pressure to obtain the ethanol extract extract;

[0047] c. Separate the ethanol extract extract obtained in step b with a normal-phase silica gel column, carry out gradient elution with cyclohexane-ethyl acetate with a volume ratio of 10:1-0:1, and fractionate through silica gel thin-layer chromatography (TLC) analysis, the same fractions were combined to obtain 6 components (F1-F6); the component F4 was subjected to normal phase silica gel column separation, and the volume ratio was 100:0-0:100 with dichloromethane-acetone Gradient elution to obtain c...

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Abstract

The invention relates to a jatrophane type diterpenoid compound and a preparation method and application thereof. According to jatrophane type diterpenoid, fruits of euphorbia sororia are used as rawmaterials, are extracted with an organic solvent, are separated by three to four methods in a solvent extraction method, a normal-phase silica gel column chromatography, reverse-phase silica gel column chromatography and a Sephadex LH-20 gel column chromatography, and is detected and analyzed by thin-layer chromatography to obtain three new jatrophane type diterpenoid compounds, and the three compounds are subjected to multidrug resistance reversal activity measurement, results show that the three new jatrophane type diterpenoid compounds have different degrees of multidrug resistance reversalactivity, if the three new jatrophane type diterpenoid compounds are combined and used with anti-tumor drug, drug resistance of drug-resistant cells to anti-tumor drugs can be reversed at different degrees, and the jatrophane type diterpenoid compound can be used for preparing multidrug resistance reversal drugs.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to three pseudolemane-type diterpene lactone compounds and their preparation methods and uses. Background technique [0002] Macrocyclic diterpenoids, that is, diterpenoids containing a six-membered ring structure in the molecule, have rich and varied skeleton structures and various biological activities, including cytotoxicity, reversal of multidrug resistance, antibacterial, and anti-HIV virus Wait. The number of pseudo-elephane (Jatrophane) diterpenes that have been discovered so far is the largest. The structure of the pseudo-elephane diterpene is that the skeleton is fused by a five-membered ring and a twelve-membered ring, that is, the 5 / 12 ring system . Preliminary studies have found that pseudolevane diterpenes are usually in a high oxidation state and generally have a relatively large molecular structure with a molecular weight of more than 700. , propionyloxy, benzoylo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D311/94C07D313/20A61K31/366A61K31/365A61P35/00
CPCC07D311/94C07D313/20
Inventor 阿吉艾克拜尔·艾萨胡蕊高洁信学雷
Owner XINJIANG TECHN INST OF PHYSICS & CHEM CHINESE ACAD OF SCI