Method for chemically synthesising gastrodin

A technology for chemical synthesis and gastrodin, applied in chemical instruments and methods, organic chemistry, bulk chemical production, etc., can solve the problems of high cost, pollution and low total yield, avoid hazards and pollution, and simplify purification operations , the effect of short reaction period

Inactive Publication Date: 2013-03-20
QINGDAO AGRI UNIV
View PDF3 Cites 17 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In 1980, Zhou Jun and others completed the chemical synthesis of gastrodin for the first time [Zhou Jun, Yang Yanbin, Yang Chongren, Chemical Research on Gastrodin II, Acta Chemie Sinica, 1980, 32(2), 162-166]. Large red phosphorus and bromine have serious three waste treatment problems, which are not conducive to production safety and environmental safety, and the total yield is low (24%), and the production cost is high, but this synthetic route is still used by my country to synthesize gastrodin Adopted by major manufacturers of APIs
In 1984, Pang Qijie and others reported an improved method for the synthesis of gastrodin [Pang Qijie, Zhong Yuguo, Improvement of the synthesis method of gastrodin, Pharmaceutical Industry, 1984, (3), 3-4], the synthesis method still uses red phosphorus and bromine , just change the potassium borohydride reduction step to Raney nickel catalytic hydrogenation, although the improvement of this synthesis method has increased the total yield (31%), but the practical application is of little significance, and it also faces the problem of introducing heavy metals
In 2004, Dai Xiaochang et al. reported the chemical synthesis process of gastrodin and its similar phenolic glycosides [Dai Xiaochang, Peng Xiao, Wu Songfu, Yang Wansong, Mao Yu, The chemic

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 chemically synthesising gastrodin
  • Method for chemically synthesising gastrodin
  • Method for chemically synthesising gastrodin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029]

[0030]Pentaacetyl-β-D-glucose (50 mmol, 19.5 g ) and p-cresol (60 mmol, 12.9 g ) were dissolved in 150 mL of dichloromethane, 30 g of 4 A molecular sieves were added, and stirred for 1 hour under nitrogen protection. Then boron trifluoride ether solution (30 mmol, 3.58ml) was added dropwise, stirred at room temperature for 4 hours, molecular sieves were removed by filtration with diatomaceous earth, the filter cake was washed with 50mL of dichloromethane, and the filtrate was washed with 300mL of water and 300mL of saturated sodium bicarbonate in sequence solution, washed with 300mL water, the dichloromethane layer was separated, dried with anhydrous sodium sulfate, filtered, the filtrate was concentrated under reduced pressure to obtain a light yellow solid, recrystallized from absolute ethanol to obtain white crystal 4-methylphenyl-2,3,4 , 6-O-tetraacetyl-β-D-glucopyranoside 11.4g, yield 52%, melting point 117-118°C.

[0031] 1 HNMR (500MHz, CDCl 3 ) δ 7.09 ( ...

Embodiment 2

[0042] Pentaacetyl-β-D-glucose (50mmol, 19.5g ) and p-cresol (60 mmol, 12.9g ) were dissolved in 150mL of dichloromethane, 30g of 4 A molecular sieves were added, stirred for 1 hour under nitrogen protection, and then Add tin tetrachloride solution (30 mmol, 3.5 ml) dropwise, stir at room temperature for 4 hours, filter with diatomaceous earth to remove molecular sieves, wash the filter cake with 50 mL of dichloromethane, and dissolve the filtrate with 300 mL of water, 300 mL of saturated sodium bicarbonate, Wash with 300mL of water, separate the dichloromethane layer, dry it with anhydrous sodium sulfate, filter, concentrate the filtrate under reduced pressure to obtain a light yellow solid, recrystallize from absolute ethanol to obtain a white crystal 4-methylphenyl-2,3,4,6 -O-tetraacetyl-β-D-glucopyranoside 9.42g, yield 43%.

[0043] Dissolve the above 4-methylphenyl-2,3,4,6-O-tetraacetyl-β-D-glucopyranoside (20mmol, 8.73g) in 60mL carbon tetrachloride, add N-bromo Subsuc...

Embodiment 3

[0047] Pentaacetyl-β-D-glucose (25 mmol, 9.75g ) and p-cresol (37.5 mmol, 8.05g ) were dissolved in 75 mL of dichloromethane, 15 g of 4 A molecular sieves were added, and stirred for 1 hour under nitrogen protection. Then boron trifluoride ether solution (30 mmol, 3.58ml) was added dropwise, stirred at room temperature for 4 hours, the molecular sieve was removed by diatom filter, the filter cake was washed with 30mL of dichloromethane, and the filtrate was washed with 150mL of water and 150mL of saturated sodium bicarbonate solution , washed with 150 mL of water, the dichloromethane layer was separated and dried with anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain a light yellow solid, which was recrystallized from absolute ethanol to obtain a white crystal 4-methylphenyl-2,3,4, 6-O-tetraacetyl-β-D-glucopyranoside 6.89g, yield 63%.

[0048] Dissolve the above 4-methylphenyl-2,3,4,6-O-tetraacetyl-β-D-glucopyranoside (10mmo...

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 a method for chemically synthesising gastrodin, comprising the following steps of: in the presence of a molecular sieve, under the catalysis of Lewis acid, and performing glycosylation reaction on pent-acetyl-b-D-glucose and p-cresol in an organic solvent with to generate 4-methylphenyl-2,3,4,6-O-tetra-acetyl-b-D-glucopyranoside; then preparing 4-halomethylphenyl-2,3,4,6-O-tetra-acetyl-b-D-glucopyranoside from 4-methylphenyl-2,3,4,6-O-tetra-acetyl-b-D-glucopyranoside and N-halosuccinimide in the presence of an initiator, and then reacting 4-halomethylphenyl-2,3,4,6-O-tetra-acetyl-b-D-glucopyranoside with the mixed solution of glacial acetic acid and tertiary amine to obtain 4-acetoxylmethylphenyl-2,3,4,6-O-tetra-acetyl-b-D-glucopyranoside; and finally removing the acetyl protecting group from the 4-acetoxylmethylphenyl-2,3,4,6-O-tetra-acetyl-b-D-glucopyranoside in an alkaline condition to obtain gastrodin. Compared with the traditional method, the method disclosed by the invention has easily available raw materials, and is short in reaction time, capable of preparing the reaction product in each step via recrystallization, simple, and more suitable for industrialized production for gastrodin.

Description

technical field [0001] The invention belongs to the field of pharmaceutical chemical industry, in particular to a method for chemically synthesizing gastrodin. Background technique [0002] Gastrodin, namely 4-hydroxymethylphenyl-β-D-glucopyranoside, is the main active ingredient of Gastrodia elata Blume, which has sedative, anticonvulsant, anti-inflammatory and immune-enhancing effects. It is widely used in the auxiliary treatment of vertigo, headache (neurasthenia and neurasthenia syndrome, vascular headache, tension headache, brain trauma syndrome, migraine, etc.) and epilepsy. [0003] At present, gastrodin raw materials for clinical application mainly come from plant extraction and chemical synthesis. Because the content of gastrodin in Gastrodia elata is very low (about 0.1%), there are problems such as high extraction cost, heavy workload, difficult preparation of high-purity samples and unfavorable resource protection by using plant extraction method to obtain gastr...

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): C07H15/203C07H1/00
CPCY02P20/55
Inventor 李玉文马翠丽
Owner QINGDAO AGRI UNIV
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