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

Synthesis method of (-)-huperzine A

A synthesis method and technology of huperzine A, applied in the field of drug synthesis, can solve problems such as many types of impurities, and achieve the effects of less types of impurities, high chemical and optical purity, and high yield

Pending Publication Date: 2022-03-22
杭州易合生物医药科技有限公司
View PDF4 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] It can be seen that there are many types of impurities in the final product obtained by the above-mentioned method. Analyzing its reasons, some of these impurities may be brought in by (±)-huperzine A mixture obtained by chemical synthesis, and the implementation of the above-mentioned method must rely on Obtain (±)-huperzine A mixture in compound synthesis

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
  • Synthesis method of (-)-huperzine A
  • Synthesis method of (-)-huperzine A
  • Synthesis method of (-)-huperzine A

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] The present embodiment provides a kind of synthetic method of (-)-huperzine A, and its synthetic route is as follows figure 1 Shown:

[0061] Each reaction step is as follows:

[0062] Synthesis of step 1, compound 2

[0063] The reaction formula is as follows:

[0064]

[0065] The specific preparation process is: in a three-necked flask, first add toluene (1L), then add 1,4-cyclohexanedione monoethylene glycol ketal (compound 1, 1.6mol) and compound 1a (3mol), and heat up to The reaction was stirred at 75°C, and the progress of the reaction was detected by TLC. After 2 hours, the reaction was complete, and the heating was stopped. The reaction solution was directly spin-dried to obtain compound 2 (yield 80%). MS, 'HNMR are consistent with the structure.

[0066] Step 2, the synthesis of compound 3

[0067] The reaction formula is as follows:

[0068]

[0069] The specific preparation process is as follows: in a 2L three-necked flask, respectively add comp...

Embodiment 2

[0121] Each step is with embodiment 1, and difference is:

[0122] In step 1, the molar ratio of compound 1 and compound 1a is 1:1.5, and the reaction temperature is 70°C.

[0123] In step 6, compound 6, MeONa and (MeO) 2 The molar ratio of CO was 1:1:1.5, the reaction temperature was 85°C, and the reaction time was 5 hours.

[0124] In step 7, the molar ratio of compound 7, cinchonidine and methacrolein was 1:1:2, and the reaction was carried out at room temperature for 5 hours.

[0125] In step 8, compound 8, MsCl, Py, Li 2 CO 3 The molar ratio to LiBr is 1:1:0.8:0.5:0.5, the reaction is carried out at a temperature of 100° C. for 3 hours, and the stirring time is 20 minutes.

[0126] In step 9, compound 9 and PPh 3 The molar ratio of EtBr was 1:1.8, and the reaction was carried out at a temperature of 20° C. for 3 hours.

[0127] In step 11, the solvent is an aqueous solution of DSMO, the base is an aqueous KOH solution with a mass fraction of 20%, the volume ratio of...

Embodiment 3

[0135] Each step is with embodiment 1, and difference is:

[0136] In step 1, the molar ratio of compound 1 and compound 1a is 1:3, and the reaction temperature is 80°C.

[0137] In step 6, compound 6, MeONa and (MeO) 2 The molar ratio of CO was 1:1.5:2.5, the reaction temperature was 90°C, and the reaction time was 8 hours.

[0138] In step 7, the molar ratio of compound 7, cinchonidine and methacrolein was 1:1.5:3, and the reaction was carried out at room temperature for 8 hours.

[0139] In step 8, compound 8, MsCl, Py, Li 2 CO 3 The molar ratio to LiBr is 1:1.5:1.2:1.5:1.5, the reaction is carried out at a temperature of 120° C. for 5 hours, and the stirring time is 30 minutes.

[0140] In step 9, compound 9 and PPh 3 The molar ratio of EtBr was 1:2.4, and the reaction was carried out at a temperature of 35° C. for 8 hours.

[0141] In step 11, the solvent is an aqueous solution of DSMO, the base is an aqueous KOH solution with a mass fraction of 30%, the volume rati...

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 belongs to the technical field of medicine synthesis, and particularly relates to a synthesis method of (-)-huperzine A. According to the synthetic method, 1, 4-cyclohexanedione monoethylene ketal is used as a raw material, chemical synthesis of (-)-huperzine A is completed at a high yield, the chemical purity and optical purity of the obtained product are high (greater than 99%), the variety of impurities is few, only one impurity WB0002 in known WB0001, WB0002, WB0003, WB0004, WB0005 and WB0006 is contained, the content of the impurity WB0002 can be controlled to be 0.005% or below, and the yield of (-)-huperzine A is greatly improved. A novel and more effective chemical synthesis method from a raw material medicine to the (-)-huperzine A is provided for synthesis of the (-)-huperzine A.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis, and in particular relates to a synthesis method of (-)-huperzine A. Background technique [0002] Huperzine A is a highly active alkaloid isolated from Huperzia serrata (Thunb) Thev., which has the following structure: [0003] [0004] Its optical isomer (-)-huperzine A is usually used as the active ingredient of the drug. (-)-Huperzine A is a highly efficient and highly selective reversible acetylcholinesterase inhibitor, which has the function of improving learning and memory, and can be used for the treatment of various neuropsychiatric diseases. [0005] (-)-Huperzine A Tablets was launched in China in 1995, and is clinically used for the treatment of Alzheimer's disease (AD) and memory impairment; in foreign countries, Huperzine A is widely used as a food additive and active ingredient in functional drinks. It is mainly used to improve the memory function of the elderly 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
Patent Type & Authority Applications(China)
IPC IPC(8): C07D221/22
CPCC07D221/22C07B2200/07
Inventor 王克猛黄伟素
Owner 杭州易合生物医药科技有限公司
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