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

Method for synthesizing R-3-(2-chloro-1-hydroxyethyl) phenol, phenylephrine and eye drops

A hydroxyethyl, R-3- technology, applied in chemical instruments and methods, botanical equipment and methods, preparation of organic compounds, etc., can solve problems such as complex steps

Pending Publication Date: 2020-07-07
ENZYMASTER NINGBO BIO ENG CO LTD
View PDF2 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the embodiments of the present invention is to provide a method for synthesizing R-3-(2-chloro-1-hydroxyethyl)phenol, phenylephrine, eye drops, to solve the existing R -3-(2-Chloro-1-hydroxyethyl)phenol synthesis method has the problem of complicated steps

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 synthesizing R-3-(2-chloro-1-hydroxyethyl) phenol, phenylephrine and eye drops

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0071] An Escherichia coli expressing ketoreductase, said ketoreductase is a reductase encoded by a ketoreductase gene, the amino acid sequence of said ketoreductase is shown in SEQ ID No.2, said ketoreductase gene The nucleotide sequence is shown in SEQ ID No.1.

[0072] Specifically, the construction and culture method of the Escherichia coli expressing ketoreductase are as follows:

[0073] 1) Digest the artificially synthesized DNA fragment of the ketoreductase gene with restriction endonuclease NdeI and restriction endonuclease EcoRI at 37°C for 8 h, purify by agarose gel electrophoresis, and use agarose gel DNA The recovery kit recovers the target fragment;

[0074] 2) Under the action of T4 DNA ligase, the target fragment is ligated with the plasmid pET24a that has also been digested with restriction endonuclease NdeI and restriction endonuclease EcoRI at 25°C, and the ligated product is transformed overnight Obtain recombinant Escherichia coli;

[0075] 3) Inoculate...

Embodiment 2

[0077] The thalline prepared in Example 1 was lysed back with 0.1 mol / L PBS buffer solution (pH=7.0), homogeneously crushed, centrifuged to collect the supernatant of the enzyme solution and freeze-dried to obtain ketoreductase (enzyme powder) , wherein, the added amount of the PBS buffer is added according to the weight ratio of bacteria: PBS buffer = 1:5.

Embodiment 3

[0079] The ketoreductase prepared in Example 2 is used as a catalyst to catalyze the synthesis of R-3-(2-chloro-1-hydroxyethyl)phenol, specifically, the catalytic synthesis of R-3-(2-chloro-1- The method of hydroxyethyl) phenol comprises the following steps: with 2-chloro-1-(3-hydroxyphenyl) ethanone as substrate, with the ketoreductase prepared in embodiment 2 as catalyst, adding hydrogen donor, buffer Liquid and coenzyme NAD form a reaction system to carry out catalytic reaction in a reaction bottle. Specifically, add magnets to the reaction bottle and place it on a reactor preheated to 30°C, and adjust the reactor speed to 400rpm for stirring reaction. 24 After 1 hour, 5 mL of acetonitrile was added to terminate the reaction to obtain a reaction solution.

[0080] In the embodiment of the present invention, the phenylephrine intermediate is R-3-(2-chloro-1-hydroxyethyl)phenol.

[0081] In the embodiment of the present invention, the total volume of the catalytic system is ...

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 the field of bioengineering and particularly discloses a method for synthesizing R-3-(2-chloro-1-hydroxyethyl) phenol, phenylephrine and eye drops. The method for synthesizingthe R-3-(2-chloro-1-hydroxyethyl) phenol comprises the steps of taking 2-chloro-1-(3-hydroxyphenyl) ethanone as a substrate and ketoreductase as a catalyst, adding a hydrogen donor, a buffer solutionand a coenzyme to form a reaction system for catalytic reaction and obtaining a phenylephrine intermediate. The ketoreductase provided by the embodiment of the invention has high activity and stereoselectivity. The synthesis method provided by the embodiment of the invention is enzymatic synthesis of the phenylephrine intermediate by adopting the ketoreductase, just one-step reaction is needed and the amount of a used reagent is small, so that the synthesis step is greatly simplified, the problem of complicated steps in an existing method for synthesizing the R-3-(2-chloro-1-hydroxyethyl) phenol is solved, and the method provided by the invention is mild in reaction condition, high in optical purity, green and environment-friendly.

Description

technical field [0001] The invention relates to the field of bioengineering, in particular to a method for synthesizing R-3-(2-chloro-1-hydroxyethyl)phenol, phenylephrine and eye drops. Background technique [0002] Phenylephrine is a potent vasoconstrictor widely used in hypotension first aid or as a pupil dilator in eye examinations, because the agonistic effect of its R-isomer is much higher than that of the S-isomer , so chiral selectivity needs to be considered when preparing phenylephrine, wherein R-3-(2-chloro-1-hydroxyethyl)phenol is a common intermediate of phenylephrine, which belongs to the R-type isomer. [0003] At present, the synthetic method of R-3-(2-chloro-1-hydroxyethyl)phenol is usually synthesized by resolution method, that is, the synthesis of phenylephrine intermediate by splitting and flipping two steps, which cannot be directly Solving the chirality problem in the synthesis process of phenylephrine involves many reagents, complicated operation, and...

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): C12P7/22C12N9/04C12N15/53C07C39/24A61K31/137C07C215/60C07C213/02
CPCC12P7/22C12N9/0006C07C39/24A61K31/137C07C215/60C07C213/02Y02P20/52
Inventor 胡虎马克·博科拉格雷戈日·库比克陈海滨金炉萍
Owner ENZYMASTER NINGBO BIO ENG CO LTD
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