Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Jatrophane type diterpene derivative as well as preparation method and application thereof

A technology of elemane and its derivatives, applied in the field of pseudolelemane-type diterpene derivatives and their preparation, can solve the problems of increased drug efflux and formation of drug resistance, and achieve simple operation, mild reaction conditions, and high production efficiency. high rate effect

Active Publication Date: 2021-09-17
XINJIANG TECHN INST OF PHYSICS & CHEM CHINESE ACAD OF SCI
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

One of its main mechanisms of action is the overexpression of ABC family transporters (currently the most widely and deeply studied P-gp protein encoded by the ABCB1 gene), which leads to increased drug efflux and drug resistance

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Jatrophane type diterpene derivative as well as preparation method and application thereof
  • Jatrophane type diterpene derivative as well as preparation method and application thereof
  • Jatrophane type diterpene derivative as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] The name of the prepared compound 1 is: (2R, 3R, 4S, 5R, 7S, 8S, 9S, 11S, 12S, 13S, 14S, 15R)-14-benzoyloxy-15-hydroxyl-11,12-epoxy -5,7-Diisobutyryloxy-2,3,8,9-tetraacetoxy-pseudolevan-6(17)-ene:

[0053] Convert ES3 to 14β-benzoyloxy-15β-hydroxy-5α,7β-diisobutyryloxy-2α,3β,8α,9α-tetraacetoxy-pseudolemane-6(17),11E -diene 81mg, 0.10mmol was dissolved in dichloromethane 2mL, m-chloroperoxybenzoic acid 41mg, 0.20mmol, 85%, was added, stirred at room temperature for 6 days, quenched with saturated sodium thiosulfate, extracted with ethyl acetate, followed by Wash with saturated sodium bicarbonate, water, and saturated sodium chloride, dry over anhydrous sodium sulfate, concentrate the organic phase with ethyl acetate, and then pass through a silica gel column for 200-300 mesh gradient elution, and the eluent is petroleum at a volume ratio of 3:1 Ether and ethyl acetate, the white solid compound 1 name is: (2R, 3R, 4S, 5R, 7S, 8S, 9S, 11S, 12S, 13S, 14S, 15R)-14-benzoylox...

Embodiment 2

[0056] The name of the prepared compound 2 is: (2R,3R,5S,7S,8S,9S,13S,14S)-14-benzoyloxy-5,7-diisobutyryloxy-2,3,8,9 -Tetraacetoxy-pseudolemane-6(17),4E,11E-triene:

[0057] Convert ES3 to 14β-benzoyloxy-15β-hydroxy-5α,7β-diisobutyryloxy-2α,3β,8α,9α-tetraacetoxy-pseudolemane-6(17),11E -diene 46mg, 0.056mmol dissolved in toluene 3mL, add thionyl chloride 0.1mL, nitrogen protection, heat to 70°C, react with stirring for 1 hour, add saturated sodium bicarbonate to quench, ethyl acetate extract, water, saturated Wash with sodium chloride, dry over anhydrous sodium sulfate, concentrate the organic phase with ethyl acetate, and then pass through a silica gel column for 200-300 mesh gradient elution, and the eluent is petroleum ether and ethyl acetate at a volume ratio of 5:1, to obtain The name of colorless crystal 2 is: (2R,3R,5S,7S,8S,9S,13S,14S)-14-benzoyloxy-5,7-diisobutyryloxy-2,3,8, 9-tetraacetoxy-pseudolevane-6(17), 4E,11E-triene 40mg, yield 89%;

[0058] Mass spectrum and...

Embodiment 3

[0060] The name of the prepared compound 3 is: 14β-benzoyloxy-2α, 7β, 8α, 9α, 15β-pentahydroxy-5α-isobutyryloxy-3β-acetoxy-pseudolemane-6(17) ,11E-diene

[0061]Convert ES3 to 14β-benzoyloxy-15β-hydroxy-5α,7β-diisobutyryloxy-2α,3β,8α,9α-tetraacetoxy-pseudolemane-6(17),11E -diene 842mg, 1.03mmol was dissolved in methanol 10mL, 1,8-diazabicycloundec-7-ene 318mg, 2.09mmol was added, stirred at room temperature for 3.5 hours, hydrochloric acid 1mmol / L was added, 3mL was quenched, acetic acid Extracted three times with ethyl ester, washed with water, saturated sodium bicarbonate, and saturated sodium chloride successively, dried over anhydrous sodium sulfate, concentrated the organic phase with ethyl acetate, and then eluted through a silica gel column with a gradient of 200-300 mesh. The eluent was Petroleum ether and ethyl acetate at a volume ratio of 1:2, the white solid compound 3 is named 14β-benzoyloxy-2α,7β,8α,9α,15β-pentahydroxy-5α-isobutyryloxy- 3β-Acetoxy-Pseudoolemane-...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to a jatrophane type diterpene derivative as well as a preparation method and application thereof. According to the derivative, a characteristic active component ES3 contained in euphorbia sororia fruits is used as a raw material, and several derivatization methods are adopted to obtain compounds 1-17; the reaction conditions are mild, the experimental steps are simple, and the synthesized compounds 1-17 are subjected to a preliminary multidrug resistance reversal activity test; and experimental results show that the compounds 1-17 show different degrees of multidrug resistance reversal activity, the drug resistance of drug-resistant cells to antitumor drugs can be reversed to different degrees when the compounds 1-17 are combined with the antitumor drugs, the compounds 1, 2, 6, 7, 8, 9, 10, 11, 12, 14, 15, 16 or 17 have high multidrug resistance reversal activity, and the reversal multiple thereof is higher than that of a positive control drug verapamil, wherein the reversal multiple of the compound 12 is the highest. The kind of compounds can be used as a tumor multidrug resistance reversal drug.

Description

technical field [0001] The invention relates to a pseudolevane-type diterpene derivative, a preparation method and application thereof, and the application in the preparation of a multidrug resistance reversal drug or in combination with an antitumor drug. Background technique [0002] The structural feature of the pseudolevane-type diterpene compound is that its skeleton is fused by a five-membered ring and a twelve-membered ring, that is, a 5 / 12 ring system. This type of compound has a complex structure, most of which are highly esterified, and has the characteristics of many types of substituents and large molecular weight. Due to the different positions, numbers, and configurations of these substituents on the skeleton, the steric hindrance of the compounds has changed, making these compounds completely different in structure, so they have a greater impact on the reversing activity of tumor multidrug resistance. Pseudolevane-type diterpenoids are characteristic active c...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07D303/16C07D301/14C07D213/79C07D213/803C07C69/33C07C69/28C07C69/76C07C67/28C07C67/14C07C67/08A61P35/00
CPCC07D303/16C07D301/14C07D213/79C07D213/803C07C69/33C07C69/28C07C69/76A61P35/00C07C2602/32Y02P20/55
Inventor 阿吉艾克拜尔·艾萨杨贺群王边琳汤丹阿依提拉·麦麦提江
Owner XINJIANG TECHN INST OF PHYSICS & CHEM CHINESE ACAD OF SCI
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com