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

Conversion of amorpha-4,11- diene to artemisinin and artemisinin precursors

A kind of technology of amorpha and dihydroartemisinic acid, applied in the direction of organic chemistry and so on

Inactive Publication Date: 2008-06-25
AMYRIS BIOTECHNOLOGIES INC (US)
View PDF6 Cites 20 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the yield of artemisinic acid from A. annua is variable, and despite the rapid growth of A. annua, it is currently estimated that the worldwide supply of the plant will fall short of the worldwide demand for artemisinic acid and artemisinin. 10%
[0013] While the regioselective synthesis of bridged monoepoxides of (+) valencene has been reported (Ali et al., Tetrahedron Lett, 47:8769 (2002)), no selective synthesis of exocyclic monoepoxides has been reported.

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
  • Conversion of amorpha-4,11- diene to artemisinin and artemisinin precursors
  • Conversion of amorpha-4,11- diene to artemisinin and artemisinin precursors
  • Conversion of amorpha-4,11- diene to artemisinin and artemisinin precursors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

1.1.1 to 5 conversion

[0135] To a 250 mL flask equipped with a septum inlet and a magnetic stir bar, add 50 mmol of BH 3 SM 2 and 18 mL of freshly distilled THF. It was cooled to 0° C. and 115 mmol of cyclohexene were added dropwise. After stirring the mixture for 1 hour at 0 °C, (C 6 h 11 ) 2 BH was isolated as a white solid.

[0136] To (C 6 h 11 ) 2 To BH (solid, 50 mmol), 75 mmol of amorphadiene 1 was added. The reaction mixture was stirred for one hour at -25°C, then it was left in the refrigerator for one day. The trialkylborane was treated with 50 mL of 3N sodium hydroxide, 7.5 mL of 30% hydrogen peroxide and the reaction mixture was stirred at 25°C for 5 hours. The product was then extracted with ether and dried over sodium sulfate. Ether was then evaporated. The residue was filtered through silica gel (petroleum ether:ethyl acetate 9:1 as eluent) to remove olefins and cyclohexanol, then eluted with petroleum ether:ethyl acetate (1:1) to give Pure alcoho...

Embodiment 2

Transformation from 2.1.5 to 3

[0137] By adding sulfuric acid (17 mL) dropwise to CrO in water 3 The Jones reagent was prepared by cooling the solution (200 mmol), and the resulting solution was diluted with water until the total volume of the solution was 60 mL.

[0138] Alcohol 5 (65 mmol) was dissolved in acetone (150 mL) and cooled to 0 °C. Jones reagent was added dropwise through the dropping funnel over a period of 2 hours until the orange-brown color of the reagent persisted. The reaction mixture was stirred for another 2 hours. Diethyl ether was then added to precipitate chromeous salts. The reaction mixture was filtered and the residue was washed with ether. The organic layer was dried over anhydrous sodium sulfate, concentrated and purified by adding 5% aqueous sodium hydroxide. The product was washed with ether to remove impurities. The aqueous layer was acidified and extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and conce...

Embodiment 3

3.1. Transformation of 1 into 3 via 9, 6 and 5

[0139] In a 250 mL three-necked flask equipped with a thermometer, condenser and magnetic stirring bar, 50 mmol of calcium hypochlorite and 50 mL of water were added, and while adding amorphadiene 1 dissolved in 200 mL of dichloromethane over 30 minutes, Stir vigorously. Stirring was continued for 3 h while 50 g of dry ice was added in small portions at regular intervals. The cloudy white slurry was filtered to remove inorganic salts. These inorganic salts were washed with two 25 mL portions of dichloromethane. The filtrate and washings were combined, the aqueous layer was decanted and the organic layer was dried over anhydrous sodium sulfate. The organic layer was filtered to remove the drying agent and concentrated under vacuum to give (9, X=Cl). The chlorine on 9 is hydrolyzed by boiling the concentrate with a 50:50 mixture of dioxane and water to give the unsaturated alcohol 6 after concentration. The unsaturated alcohol...

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 relates to a method for converting amorpha-4,11-diene into artemisinin and various artemisinin precursors.

Description

[0001] Cross References to Related Applications [0001] This application claims U.S. Provisional Patent Application No. 60 / 685,713, filed May 27, 2006; U.S. Provisional Patent Application No. 60 / 775,517, filed February 21, 2006; and U.S. Patent Application No. 11, filed May 23, 2006 / 419,975 priority, which are hereby incorporated by reference in their entirety for all purposes. Background of the invention [0002] About 270 million people are infected with malaria, making it one of the world's leading infectious diseases. The development of new anti-malarial drugs, and alternative methods of producing anti-malarial drugs, is therefore an important worldwide health goal. [0003] One of these antimalarial drugs is artemisinin (compound 4 in Table 1). Artemisinin is a component of the traditional Chinese herbal medicine Artemisia annua, which has been used in China for more than 1000 years to control fever symptoms. In the scientific literature, artemisinin is also sometime...

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): C07D493/00C07D493/18C07D321/02
Inventor 基思·金基德·雷林尼尔·斯蒂芬·伦宁格德雷克·詹姆斯·麦克菲卡尔·约瑟夫·费希尔丹尼丝·安·奥凯
Owner AMYRIS BIOTECHNOLOGIES INC (US)
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