Novel method for resolving 1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline through enzyme catalysis

A kind of technology of methoxybenzyl and octahydroisoquinoline, which is applied in the field of preparation of key intermediates of antitussives

Inactive Publication Date: 2016-04-27
TIANJIN INST OF IND BIOTECH CHINESE ACADEMY OF SCI
View PDF5 Cites 10 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] We have found that no enzymatic dynamic kinetic resolution of 1-(4-methoxybenzy

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
  • Novel method for resolving 1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline through enzyme catalysis
  • Novel method for resolving 1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline through enzyme catalysis
  • Novel method for resolving 1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline through enzyme catalysis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Example 1: Dynamic kinetic resolution of 1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline

[0023] 1-(4-Methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline (100mg), supernatant of mutant Y321I strain 50mL (take 8g after centrifugation) The wet cells were dissolved in 100mM, pH 6.5 phosphate buffer, high-pressure crushed, centrifuged at 12000×g for 30min to get the supernatant) and ammonium borate (80mg), and the reaction was carried out at 25°C and 200rpm in a shaker. The reaction progress was monitored by liquid chromatography, and the reaction was completed after 32 hours. The pH was adjusted to 10 with 5M sodium hydroxide and extracted three times with dichloromethane (50 mL×3). The extract was concentrated to 25 mL and then mixed with 25 mL of 1M hydrochloric acid solution. The separated aqueous phase was adjusted to pH 10 with 5M sodium hydroxide and extracted three times with dichloromethane (25 mL×3). The organic extract was dried over anhydrous sodiu...

Embodiment 2

[0024] Example 2: Dynamic kinetic resolution of 1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline

[0025] 1-(4-Methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline (129 mg) was dissolved in 1 mL dimethyl sulfoxide, and added to mutant Y321I to destroy bacteria Supernatant 50mL (dissolve 10g of wet bacteria in 100mM, pH6.5 phosphate buffer after expression and centrifugation, and then centrifuge at 12000×g for 30min to get the supernatant) and ammonium boron (124mg), react at 25°C, 200rpm in a shaker. The reaction process was monitored by liquid chromatography. After 20 hours, the reaction was completed, and 6M hydrochloric acid was added to terminate the reaction. The pH was adjusted to 10 with 5M sodium hydroxide, and then extracted three times by high-speed centrifugation with ethyl acetate (50mL×3). After the organic extract was dried over anhydrous sodium sulfate, 100 mg of the product was obtained by separation and purification by column chromatography, and the ...

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 method for resolving 1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline through enzyme catalysis dynamic kinetics. Specifically, the invention provides a method for resolving 1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline racemate into a single configuration product (S)-1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline through dynamic kinetics and by utilizing cyclohexane oxidase and a mutant thereof, wherein (S)-1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline is a key intermediate for synthesizing the central antitussive drug dextromethorphan. The method has the outstanding characteristics of high yield, good stereoselectivity, mild reaction conditions and the like.

Description

technical field [0001] The present invention relates to a new method for the preparation of key intermediates of antitussives, in particular to enzyme-catalyzed dynamic kinetic resolution for the preparation of key intermediates of dextromethorphan hydrobromide (S)-1-(4-methoxybenzyl) - A new method for 1,2,3,4,5,6,7,8-octahydroisoquinolines. Background technique [0002] Dextromethorphan hydrobromide is also called dextromethorphan hydrobromide, the chemical name is (+)-3-methoxy-17-methyl-(9α,13α,14α)-morphinan hydrobromide monohydrate , suitable for colds, acute or chronic bronchitis, bronchial asthma, pharyngitis, tuberculosis and dry cough caused by other upper respiratory tract infections. [0003] [0004] There are many synthetic methods of dextromethorphan hydrobromide, such as Chinese patents CN201310041846, CN201310051880, CN201210405684, CN201310004262, CN201410169133 and literature [Today’s Pharmacy, 2008, 18 (4), 63-64], [Helv.Chim.Acta1956,39 1376?1386], ...

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): C12P41/00C12P17/12
Inventor 姚培圆李广悦冯进辉吴洽庆朱敦明马延和
Owner TIANJIN INST OF IND BIOTECH CHINESE ACADEMY OF SCI
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap