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

Method for preparing 9-nitro-20(s)-camptothecine

A technology of nitrocamptothecin and hydroxycamptothecin, applied in the direction of organic chemistry, which can solve the problems of low yield, difficult separation and purification, complicated separation and purification process, etc.

Inactive Publication Date: 2006-06-07
CHENGDU ORGANIC CHEM CO LTD CHINESE ACAD OF SCI
View PDF2 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The presence of a large amount of 12-nitro-20(S)-camptothecin not only brings considerable difficulties to separation and purification, but also wastes a large amount of expensive camptothecin to obtain another inactive isomer compound 12 -Nitro-20(S)-camptothecin
This complex separation and purification process and lower yield cannot meet the requirements of obtaining a considerable amount of 9-nitro-20(S)-camptothecin in industry

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
  • Method for preparing 9-nitro-20(s)-camptothecine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] 10-Hydroxy-20(S)-camptothecin

[0028] 2 g of 20(S)-camptothecin, 20 ml of glacial acetic acid, 0.2 g of PtO 2 And 2 drops of dimethyl sulfoxide were added to a 100 ml autoclave. 6 kg of hydrogen pressure, 60 ° C reaction for 12 hours. After filtration, 20 ml of deionized water was added to the filtrate, and 4.8 g of iodobenzene diacetate was added in one go, and reacted at room temperature overnight. Filter and dry the solid to obtain 1.43 g of 10-hydroxy-20(S)-camptothecin with a yield of 70%.

[0029] h 1 NMR (DMSO-d 6 ), δppm: 0.86(3H, t); 1.84(2H, q); 5.21(2H, s); 5.40(2H, s); 6.54(1H, s); 7.25(1H, s); d); 7.41(1H, q); 8.00(1H, d); 8.43(1H, s); 10.42(1H, s).

Embodiment 2

[0031] 10-Hydroxy-9-nitro-20(S)-camptothecin

[0032] (Method A)

[0033] Suspend 0.365 g of 10-hydroxy-20(S)-camptothecin in 10 ml of glacial acetic acid, add dropwise 80 ul of fuming nitric acid, and react overnight at room temperature. After adding 100ml of water, a large amount of solids were precipitated, filtered and dried to obtain 0.342 g of 10-hydroxy-9-nitro-20(S)-camptothecin, yield 83.4%, HPLC, 93%.

[0034] (Method B)

[0035] Dissolve 0.365 g of 10-hydroxyl-20(S)-camptothecin in 30% dilute sulfuric acid, add 0.5 g of potassium nitrate, react at room temperature overnight, and extract with chloroform to obtain 10-hydroxyl-9-nitro-20(S) -Camptothecin 0.3 g, yield 73%.

[0036] h 1 NMR (CDCl 3 ), δppm: 1.05 (3H, t); 1.89 (2H, q); 3.74 (1H, s); 5.36 (2H, s); 5.50 (2H, dd); 7.61 (1H, s); s); 8.40(1H, d); 9.54(1H, s); 12.20(1H, s).

Embodiment 3

[0038] 9-nitro-10-(p-toluenesulfonyloxy)-20(S)-camptothecin

[0039] Suspend 0.409 g of 9-nitro-10-hydroxy-20(S)-camptothecin in 50 ml of dichloromethane, add 0.21 g of triethylamine to dissolve the solid, and add 0.2 g of p-toluenesulfonyl chloride at room temperature. React at room temperature for 24 hours, extract with dichloromethane, wash with 0.5 N hydrochloric acid and saturated sodium chloride solution, dry over anhydrous sodium sulfate, and distill off the solvent to obtain 9-nitro-10-(p-toluenesulfonyloxy)- 0.48 g of 20(S)-camptothecin, yield 83%.

[0040] h 1 NMR (CDCl 3), δppm: 1.05(3H, t); 1.90(2H, q); 2.48(3H, s); 3.87(3H, s); 5.30(2H, s); d); 7.68(1H, s); 7.81(2H, d); 7.95(1H, d); 8.31(1H, s); 8.41(1H, d).

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 present invention provides a practical method of preparing 9-nitro camtothecine and the method has high selectivity and no need of chromatographic separation. The new anticancer medicine 9-nitro camtothecine is obtained in high selectivity by means of controlling the amount of the reductant, the reaction time, the reaction temperature and material feeding mode. The present invention also provides the intermediate and the destination product purifying method.

Description

[0001] Field [0002] The invention relates to a method for preparing 9-nitro-20(S)-camptothecin, which belongs to the field of organic synthesis. Background technique [0003] Camptothecin is a trace anticancer alkaloid obtained from Camptotheca involucrata, a plant endemic to my country. Due to its high toxicity, its clinical application is limited. Subsequently, a series of semi-synthesized camptothecin derivatives have become new anti-cancer drugs that have been marketed or are in different stages of research and development due to their unique biological activity mechanism and excellent drug properties. Camptothecin derivatives have formed a large class of very active chemical drugs. [0004] The new camptothecin derivatives include the water-insoluble derivatives 9-amino-20(S)-camptothecin and 9-nitro-20(S)-camptothecin. Unfortunately, although 9-amino-20(S)-camptothecin has shown antitumor activity in preclinical trials, the results of clinical trials have been disap...

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 Applications(China)
IPC IPC(8): C07D491/22C07D209/00C07D221/00C07D311/00
Inventor 胡文浩陈志勇付清泉
Owner CHENGDU ORGANIC CHEM CO LTD 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