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

Process of synthesizing taxol and docetaxel

A technology of docetaxel and synthesis method, which is applied in the field of synthesis of paclitaxel and docetaxel, can solve the problem of expensive baccatin III, and achieve the effect of high optical purity and simple process

Active Publication Date: 2007-12-19
重庆赛诺生物药业股份有限公司
View PDF12 Cites 17 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0044] Compared with the two methods, 10-DAB is used as the starting material, and the operation is simple and the yield is high. The disadvantage is that baccatin III is more expensive than 10-DAB

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
  • Process of synthesizing taxol and docetaxel
  • Process of synthesizing taxol and docetaxel
  • Process of synthesizing taxol and docetaxel

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0091] Preparation of compound 47i

[0092]

[0093] Sodium ethoxide (0.70g, 10.36mmol) was added to 10mL of ethanol, stirred slowly, and an ethanol solution of benzaldehyde (0.96mL, 9.42mmol) was added dropwise under ice-cooling. After the addition was completed, it was raised to room temperature to continue the reaction. After cooling in a bath, ethyl chloroacetate (1.1 mL, 10.36 mmol) was added dropwise. After the dropwise addition, it was warmed to room temperature and tracked by TLC. After 12 hours, the reaction was complete. Added 100 mL of deionized water and extracted with ethyl acetate (50 mL×3). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was distilled under reduced pressure to obtain a colorless oil 47i (1.63 g, 90.1% yield).

[0094] Colorless oil; IR υ max : 3015, 2978, 2950, ​​2919, 2880, 1730, 1455, 1360, 1046cm -1 ; MSm / z (%): 192, 176, 146, 135, 118.

[0095] 1 H NMR (300MHz, CDCl 3 )δ7.24 (5H, m, P...

Embodiment 2

[0097] Preparation of compound 48i

[0098]

[0099]Dissolve compound 47i (0.72g, 3.75mmol) in 10mL of benzonitrile, add boron trifluoride ether solution (2equiv.), stir at room temperature, and detect by TLC. After 3h, the reaction is complete. The solvent is evaporated under reduced pressure, and the residue is dissolved in In methanol, add 0.05g containing 10% Pd / C, pass hydrogen, stir at normal temperature and pressure, TLC tracking, after 11h, the reaction is complete, filter, evaporate the solvent under reduced pressure, the crude product is subjected to column chromatography to obtain colorless Oil 48i (0.92 g, 82.9% yield).

Embodiment 3

[0101] Preparation of compound 49i

[0102]

[0103] Dissolve the racemic compound 48i (0.60g, 2.02mmol) in 10mL of toluene, add 0.03g of Novozymes lipase, and octanol (1equiv.), stir slowly, and control the temperature of the liquid in the device at about 30°C. After 26 hours, the reaction was completed, Novozymes lipase was filtered off, the filtrate was spin-dried, and the residue was distilled under reduced pressure to obtain compound 49i (0.25 g, 41.7% yield). Yellow oil; [α] D 20 =+18.0°(C1.0, CHCl 3 ).

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 discloses semi-synthesis process of taxol and decetaxel. The side chain of taxol and decetaxel is synthesized through the first Darzens condensation reaction of benzaldehyde and chloroacetate under the catalysis of alkali to produce racemized alpha, beta-epoxy carboxylate; the subsequent Ritter type reaction, reduction reaction and enzyme splitting to obtain optically pure oxazolinyl intermediate; and final protection of active hydrogen on nitrogen with benzoyl radical or tert-butyl oxycarbonyl radial and ester group hydrolysis. The side chain is then synthesized with the other part to obtain taxol and decetaxel product. The key reaction is simple and low in cost, and has low probability of condensation between the side chain and the mother cycle.

Description

technical field [0001] The present invention relates to a method for synthesizing paclitaxel and docetaxel, in particular to the synthesis of paclitaxel and docetaxel side chains and the modification of the parent ring 10-deacetylbaccatin III (10-DAB) , and then the parent ring and the side chain undergo a condensation reaction to obtain paclitaxel and docetaxel. Background technique [0002] Taxol (paclitaxel) is a natural organic compound extracted from taxus species. In 1967, American chemists Wall and Wani first extracted it from the bark of Pacific yew (Taxus brevifolia, Taxus.brevifolia) with a unique Antitumor activity of diterpenoids. In 1971, Wani (J.Amer.Chem.Soc., 1971, 93, 2325) reported for the first time that paclitaxel was isolated from Indian yew (Taxus.brevifolia). The cells have a wide range of strong killing effects, and the side effects are very small. [0003] In 1972, Schiff et al. (Nature, 1979, 277, 665) confirmed the pharmacological mechanism of p...

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): C07D305/14
CPCY02P20/55
Inventor 康立涛王刚王涛吕伟陈艳
Owner 重庆赛诺生物药业股份有限公司
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