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

Preparation method and application of (20s, 24r/s)-epoxy-12β, 25-hydroxyl-dammarane-3β-amine derivative

A technology of epoxydammarane and drugs, which is applied in the application field of preparing drugs for reversing multi-drug resistance of tumors, and can solve problems such as threats to human health, drug resistance, and sensitivity reduction

Inactive Publication Date: 2018-08-24
CHINA PHARM UNIV
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] The emergence of antibiotics and chemotherapeutic drugs has made great contributions to human health, but with the application of these drugs, pathogens and tumor cells are less sensitive to chemotherapeutic drugs, resulting in drug resistance, and the emergence of drug resistance has become serious threat to human health

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
  • Preparation method and application of (20s, 24r/s)-epoxy-12β, 25-hydroxyl-dammarane-3β-amine derivative
  • Preparation method and application of (20s, 24r/s)-epoxy-12β, 25-hydroxyl-dammarane-3β-amine derivative
  • Preparation method and application of (20s, 24r/s)-epoxy-12β, 25-hydroxyl-dammarane-3β-amine derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] (20S, 24S)-epoxydammarane-12β, 25-diol-3β-amine (OSA)

[0052] Dissolve 20(S)-protopanaxadiol (500mg, 1.08mmol) in anhydrous pyridine (3mL), add DMAP (20mg, 0.16mmol), stir well and slowly add acetic anhydride (0.42mL, 4.43mmol) dropwise , stirred at room temperature for 12h. Dilute with ethyl acetate (20 mL), wash with 10% hydrochloric acid until acidic, wash with water, wash with saturated brine, dry over anhydrous sodium sulfate, filter, concentrate, and column chromatography (petroleum ether: ethyl acetate = 10:1) to give white Solid 1 (508 mg, 85%).

[0053]The above-obtained 1 (208 mg, 0.38 mmol) was dissolved in anhydrous dichloromethane (6 mL), and the dichloromethane of m-chloroperoxybenzoic acid (185 mg, 75%, 0.16 mmol) was slowly added dropwise under ice-salt bath precooling. Methane (5 mL) solution, half an hour after the dropwise addition was completed, the mixture was raised to room temperature and stirred for 2 h. Add isopropanol (0.1mL), continue to s...

Embodiment 2

[0061] (20S, 24R)-epoxydammarane-12β, 25-diol-3β-amine (ORA)

[0062] Referring to the synthesis method of (20S, 24S)-epoxydammarane-12β, 25-diol-3-amine (OSA), a white solid ORA (120 mg, 73%) was obtained from compound 4 through compounds 6 and 8. 1 H NMR (CDCl 3 , 300MHz) δ3.84(dd, J=13.7Hz, 7.0Hz, 1H), 3.50(td, J=10.4Hz, 4.6Hz, 1H), 2.35(dd, J=11.5Hz, 4.4Hz, 1H), 2.18(td, J=10.9Hz, 3.5Hz, 1H), 1.28(s, 3H), 1.26(s, 3H), 1.09(s, 3H), 0.98(s, 3H), 0.94(s, 3H), 0.90(s, 3H), 0.83(s, 6H), 0.74(s, 3H). 13 C NMR (CDCl 3 , 75MHz) δ86.5, 85.4, 80.0, 70.1, 59.7, 56.6, 52.0, 50.6, 49.4, 47.9, 39.6, 39.5, 38.1, 37.3, 34.8, 32.6, 31.2, 28.6, 28.3, 27.9, 27.6, 26.1, 25.0 , 18.6, 18.1, 16.2, 15.5, 15.4; ESI-MS m / z 476.4 [M+H] + ; HR-MS (ESI) m / z: calculated for C 30 h 54 NO 3 [M+H] + : 476.4098, found: 476.4091.

Embodiment 3

[0064] (20S, 24S)-epoxy-3β-methylaminodammarane-12β, 25-diol

[0065] (20S,24S)-epoxydammarane-12β,25-diol-3-amine (OSA, 200 mg, 0.42 mmol) and anhydrous potassium carbonate (60 mg, 0.42 mmol) were added to anhydrous THF (8 mL) , then iodomethane (60 mg, 0.42 mmol) was added. N 2 React at room temperature for 5 hours under protection. Diluted with ethyl acetate, washed with water, washed with saturated brine, dried over anhydrous sodium sulfate, and column chromatographed to give a pale yellow product (155 mg, 75%). 1 H NMR (CDCl 3 , 300MHz) δ3.86(dd, J=10.2Hz, 5.0Hz, 1H), 3.51(td, J=9.8Hz, 4.0Hz, 1H), 3.16(s, 3H), 2.54(m, 1H), 2.22 (td, J=9.8Hz, 5.8Hz, 1H), 1.26(s, 3H), 1.21(s, 3H), 1.10(s, 3H), 1.02(s, 3H), 1.00(s, 3H), 0.89 (s,6H), 0.88(s,3H), 0.85(s,3H); ESI-MS m / z 490.4[M+H] + .

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 the field of organic synthesis and pharmaceutical chemistry and concretely relates to dammarane derivatives with novel structures shown in the formulas (I) and (II). The invention also discloses a preparation method of the (20S, 24R / S)-epoxy-12 beta, 25-hydroxy-dammarane-3 beta-amine derivatives, a pharmaceutical composition containing the (20S, 24R / S)-epoxy-12 beta, 25-hydroxy-dammarane-3 beta-amine derivatives and a use of the (20S, 24R / S)-epoxy-12 beta, 25-hydroxy-dammarane-3 beta-amine derivatives in preparation of drugs for reversion of tumor resistance to multiple drugs.

Description

technical field [0001] The present invention relates to the fields of organic synthesis and medicinal chemistry, in particular to (20S, 24R / S)-epoxy-12β, 25-hydroxyl-dammarane-3β-amine derivatives, and the present invention also discloses these dammarane derivatives The preparation method of the compound, the pharmaceutical composition containing the compound and the application of the compound in the preparation of drugs for reversing tumor multidrug resistance. technical background [0002] The emergence of antibiotics and chemotherapeutic drugs has made great contributions to human health, but with the application of these drugs, pathogens and tumor cells are less sensitive to chemotherapeutic drugs, resulting in drug resistance, and the emergence of drug resistance has become serious threaten human health. It has been found that although the mechanisms of drug resistance are diverse, the common main reason is that some active transporters pump a series of molecules with...

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
Patent Type & Authority Patents(China)
IPC IPC(8): C07J41/00A61K31/58A61P35/00
Inventor 徐进宜陈哲生张恒源张运闿周志文魏国湘
Owner CHINA PHARM UNIV
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