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

Reversible acetylcholinesterase inhibitor huperzine-A synthesis method

A technology for the synthesis of huperzine A, which is applied in the field of compound preparation, and can solve problems such as danger, the price of methyl propiolate is relatively expensive, and the inability to carry out large-scale production

Inactive Publication Date: 2016-03-16
SHANGHAI HONGJING BIOTECH CO LTD
View PDF5 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0021] Route 5 is to obtain the intermediate 2-hydroxy-6-ethylene glycol ketal-5 by condensing 1,4-cyclohexanedione monoketal with methyl propiolate and ammonia in methanol solution under high pressure and high temperature. 6,7,8-tetrahydroquinoline, and then through alkylation, deprotection, esterification, chiral ring closure and other reactions to obtain optically pure chiral huperzine A, the price of methyl propiolate used in this route is relatively high Expensive, there are few domestic manufacturers, and this step requires the use of ammonia gas, which brings some inconvenience to the feeding. At the same time, it needs to use high temperature and high pressure reaction, which requires high equipment and has certain risks. In addition, the chiral catalyst SL-T002 -01 Only a foreign reagent company sells it, which is expensive and difficult to provide on a large scale
Therefore, mass production is not possible

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
  • Reversible acetylcholinesterase inhibitor huperzine-A synthesis method
  • Reversible acetylcholinesterase inhibitor huperzine-A synthesis method
  • Reversible acetylcholinesterase inhibitor huperzine-A synthesis method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0160] (1) Preparation of compound 2 (2-cyanoethyl-1,4-cyclohexanedione-4-monoethylene glycol ketal)

[0161]

[0162] Add 650g of 1,4-cyclohexanedione monoethylene glycol ketal and 300g of tetrahydropyrrole into a 5L three-neck flask, add 2000mL of glacial acetic acid, and reflux for 4 hours. After the TLC reaction is complete, add 250g of acrylonitrile dropwise, and reflux for 12 hours. , TLC (thin layer chromatography) detects that the reaction is complete, and the glacial acetic acid is recovered under reduced pressure, and the oily matter obtained is dissolved with 3000mL methyl tert-butyl ether, washed with water, washed with saturated saline, dried in a dry bath, suction filtered, and concentrated to obtain 2-cyanoethyl -1,4-cyclohexanedione-4-monoethylene glycol ketal 850g, yield 98%, HPLC≥95.4%.

[0163] MS(ESI)m / z210.23[M+H] of Compound 2 + ;

[0164] Compound 2 1 H-MNR (300MHz, DMSO) δppm: δ2.08 (2H, t, J=6.5Hz, CH 2 ),δ2.15(2H,s,CH 2 ),δ2.27(2H,t,J=6.5Hz,CH...

Embodiment 2

[0222] (1) Preparation of compound 2 (2-cyanoethyl-1,4-cyclohexanedione-4-monoethylene glycol ketal)

[0223]

[0224] Add 400g of 1,4-cyclohexanedione monoethylene glycol ketal and 185g of tetrahydropyrrole into a 5L three-neck flask, add 2000mL of glacial acetic acid, and reflux for 5 hours. After the TLC reaction is complete, add 155g of acrylonitrile dropwise, and reflux for 20 hours. , TLC detected that the reaction was complete, recovered glacial acetic acid under reduced pressure, dissolved the obtained oil in 2000 mL of methyl tert-butyl ether, washed with water, washed with saturated saline, dried in a dry bath, filtered with suction, and concentrated to obtain 2-cyanoethyl-1,4-cyclo 520 g of hexanedione-4-monoethylene glycol ketal, yield 96%.

[0225] (2) Preparation of compound 3 (2-hydroxy-6-ethylene ketal-5,6,7,8-tetrahydroquinoline)

[0226]

[0227] Stir 200g of the above-mentioned 2-cyanoethyl-1,4-cyclohexanedione-4-monoethylene glycol ketal and 15g of s...

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 a reversible acetylcholinesterase inhibitor huperzine-A synthesis method, wherein the route is defined in the specification. The method of the present invention has advantages of easily-available raw materials, simple operation, high yield, low cost, high purity of the final product, easy quality control and the like, and is suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of a compound, in particular to a synthesis method of a reversible acetylcholinesterase inhibitor Huperzine A ((-)-HuperzineA). Background technique [0002] Alzheimer's disease, also known as Alzheimer's disease (Alzheimerdisease, AD), is a degenerative disease of the central nervous system with an insidious onset and a chronic progressive course. The main manifestations are neuropsychiatric symptoms such as progressive memory impairment, cognitive dysfunction, personality changes, and language barriers, which seriously affect social, work, and life functions. The etiology and pathogenesis of AD have not yet been elucidated, but according to relevant research reports, cholinergic system dysfunction is closely related to senile dementia. [0003] At present, with the aging trend of our society, according to statistics, the elderly population over 60 years old in our country has reached about 144 million. I...

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): C07D221/22C07D491/113
Inventor 周伟锋刘桂连施翔戴荣华鞠涛李玉灵王鹏鹏
Owner SHANGHAI HONGJING BIOTECH 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