Applications of alcohol dehydrogenase in asymmetric reduction

An alcohol dehydrogenase, asymmetric technology, applied in atomoxetine, the field of preparation of single-configuration oxetine drugs, can solve the problems of unfriendly environment, low reaction yield, unsuitable for large-scale industrial production and the like, To achieve the effects of environmental friendliness, high product concentration, and good industrial application prospects

Active Publication Date: 2015-07-29
ABIOCHEM BIOTECH CO LTD
View PDF5 Cites 10 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For chiral hydroxyl compounds, in the prior art, ruthenium or rhodium metal catalysts are mainly used for asymmetric reduction preparation, but this type of method has

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
  • Applications of alcohol dehydrogenase in asymmetric reduction
  • Applications of alcohol dehydrogenase in asymmetric reduction
  • Applications of alcohol dehydrogenase in asymmetric reduction

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0041] Example 1

[0042] Dissolve 163g of 3-(methylamino)-1-phenylpropan-1-one in 150mL of isopropanol, add 400mL of sodium phosphate buffer and adjust the pH to 7.0 with 20% (w / v) NaOH solution, add 450mL of the whole bacterial lysate, stirred at 30°C for reaction, and TLC was used to detect the reaction progress. After the reaction is over, add dilute hydrochloric acid to adjust the pH to 2 to precipitate the protein, and then filter with diatomaceous earth. The filtrate is adjusted to pH 12 with 20% (w / v) sodium hydroxide solution, and the same volume of ethyl acetate is extracted 3 times. The organic phases are combined, dried and spin-dried to obtain the product. The weight of the product is 150.1 g, and the molar yield is 91.0%.

[0043] Confirm the product structure by proton nuclear magnetic resonance spectrum and ee value determination:

[0044]

[0045] 1 H NMR(300MHz, CDCl 3 ): δ7.19 (5H, s, Ar-H), 4.50 (1H, t, -CHOH), 2.55 (2H, t, -CH 2 NHCH 3 ),2.47(3H,s,-CH 3 ),2.0(...

Example Embodiment

[0047] Example 2-5

[0048] With reference to the method of Example 1, combined with the parameters in Table 1, the preparation of the compounds of Examples 2-5 was carried out. Wherein, when NADP+ is used in the reaction system, NADP+ and the whole bacteria lysate are simultaneously added to the reaction system.

[0049] Table 1

[0050]

[0051]

[0052] The results of product detection and structural characterization are as follows.

Example Embodiment

[0053] Example 2:

[0054]

[0055] The weight of the product is 92.0 g, and the molar yield is 91.0%.

[0056] 1 H NMR (300MHz, CDCl3): δ7.19 (5H, s, Ar-H), 4.50 (1H, t, -CH (OH)), 2.36 (2H, t, -CH 2 NMe 2 ), 2.27(6H,s,-N(CH 3 ) 2 ),2.0(1H,s,-OH).1.87(2H,m,-C(OH)CH 2 -),

[0057] ee value> 99%.

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 discloses an enzyme-chemical synthetic method used for preparing chiral alcohol via asymmetric reduction with alcohol dehydrogenase, and further discloses a method used for preparing medicines, especially tomoxetine, of single configuration, with the chiral alcohol, wherein the medicines possesses a 3-aryloxy-3-aryl propylamine structure. Reaction conditions are mild; raw material cost is low; the method is friendly to the environment; reaction yield is high; product optical purity is high; and the method possesses obvious advantages compared with conventional asymmetric reduction preparation methods.

Description

technical field [0001] The invention belongs to the field of biochemical engineering, and in particular relates to an enzymatic-chemical synthesis method for preparing chiral alcohols through asymmetric reduction reaction catalyzed by alcohol dehydrogenase, and further using the chiral alcohols to prepare single-configuration cetines Drugs especially atomoxetine approach. Background technique [0002] Selective serotonin reuptake inhibitors and norepinephrine reuptake inhibitors are mostly cetines containing 3-aryloxy-3-arylpropylamine structure, such as fluoxetine, The structures of Nisoxetine and Tomoxetine are as follows: [0003] [0004] Atomoxetine is the first non-central nervous system stimulant drug approved by the US Food and Drug Administration, mainly for the treatment of ADHD in children and adolescents. It is not a central nervous system stimulant, is not addictive, and is not a controlled drug. The main pharmacological effect is to increase the chemical s...

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): C12P13/00C12P7/22
Inventor 罗煜丁时澄瞿旭东王海涛
Owner ABIOCHEM BIOTECH CO LTD
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