Synthesis method for salidroside and intermediate compound obtained in synthesis method

A synthesis method and technology of salidroside, which are applied in the directions of esterification saccharides, chemical instruments and methods, sugar derivatives, etc., can solve the problems of difficult glycosidation reaction, high time and cost consumption, and no protection of phenolic hydroxyl groups. , to achieve the effect of simplifying the operation steps and processing technology, the safety of human medicine, and avoiding by-products

Active Publication Date: 2016-02-03
YICHANG HUMANWELL PHARMA
View PDF3 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Li Guoqing et al. (Li Guoqing, Li Zhan. Improvement of the synthetic method of salidroside [J], Chinese Journal of Medicinal Chemistry, 1996, 6 (2): 136-137) reported a synthetic method of salidroside, using hydroxybenzene Ethyl acetate is used as a raw material to synthesize salidroside through the steps of benzyl protection, lithium aluminum hydride reduction, glycoside formation with bromoacetylglucose, and deprotection. The reaction process requires anhydrous operation, and a large amount of aluminum is produced during post-treatment. Salt, causing environmental pollution, lower yield and higher cost.
[0006] Zhang Sanqi et al. (Zhang Sanqi, Shang Gangwei, Li Zhongjun, etc. A new approach to the synthesis of salidroside [J], Chinese Journal of Medicinal Chemistry, 1997, 7(4): 256-257) reported the synthesis of a salidroside method, using p-bromophenol to synthesize salidroside through the steps of allylation, epoxidation, glycosidation and deprotection. This reaction uses the catalyst silver nitrate, which has high cost and has caused heavy metal pollution
[0007] Zhang Lianji (Zhang Lianji, Li Xuemei, Tian Guanrong. Synthesis of salidroside [J]. Yanbian University Journal, 2002, 28 (2): 97-98) reported a synthetic method of salidroside, using hydroxyphenylacetic acid as The raw material is synthesized into salidroside through seven steps. This reaction has many steps, consumes too much time and cost, and the yield is not high. The flammable palladium carbon and lith

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 for salidroside and intermediate compound obtained in synthesis method
  • Synthesis method for salidroside and intermediate compound obtained in synthesis method
  • Synthesis method for salidroside and intermediate compound obtained in synthesis method

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0060] Example 1

[0061] (1) Intermediate II (R 1 Is pivaloyl, R 2 Is the synthesis of trifluoroacetyl)

[0062] Add 60g (0.1mol) pentapivaloyl glucose, 300ml of acetic acid, 21g of trifluoroacetic anhydride, 40ml of boron trifluoride ether to a 500ml three-necked flask, heat to reflux for 10h, after the reaction is complete, cool, pour into 1L of water for crystallization, and filter , Washed with water to neutral, dried under reduced pressure at 60°C to obtain 53.3g of white solid, yield 87.1%, 1 H-NMR(300MHz, CDCl 3 ): δ=6.42~6.40(d,1H), 5.24~5.79(m,2H,CH), 3.73~3.62(m,1H,CH), 4.27~4.14(m,1H,CH), 3.46~2.94( m, 2H), 2.56~2.48 (m, 4H, CH), 1.12 (s, 36H, CH) 3 ).

[0063] (2) Synthesis of the compound represented by formula IV (the phenolic hydroxyl group of formula III is protected by a benzoyl group, namely compound 9)

[0064] Add 33.4g (0.06mol) of Intermediate II, 10.4g (0.05mol) of Intermediate III, 120ml of acetonitrile to a 500ml three-necked flask, add 10ml of boron trifluo...

Example Embodiment

[0069] Example 2

[0070] (1) Intermediate II (R 1 Is pivaloyl, R 2 Is the synthesis of trifluoromethanesulfonyl)

[0071] Add 60g (0.1mol) pivaloyl glucose, 300ml acetic acid, 28.2g trifluoromethanesulfonic anhydride, 40ml boron trifluoride ether to a 500ml three-necked flask, heat and reflux for 10h, after the reaction is complete, cool, pour into 1L of water for crystallization, Filter, wash with water to neutral, and dry under reduced pressure at 60°C to obtain 59.4 g of white solid with a yield of 94%. 1 H-NMR(300MHz, CDCl 3 ): δ=6.82(d,1H), 5.14~5.57(m,2H,CH), 3.23~3.16(m,1H,CH), 4.17~4.08(m,1H,CH), 3.41~2.84(m, 2H), 1.22(s,36H, CH 3 ).

[0072] (2) Synthesis of compound represented by formula IV (the phenolic hydroxyl group of formula III is protected by isobutyryl group, namely compound 8)

[0073] Add 38g (0.06mol) of Intermediate II, 10.4g (0.05mol) of Intermediate III, 120ml of dichloromethane, 2.8g of zinc chloride to a 500ml three-necked flask, and react for 8h at 25~30℃...

Example Embodiment

[0076] Example 3

[0077] (1) Synthesis of Intermediate II (R1 is isobutyryl, R2 is trifluoromethylsulfonyl)

[0078] Add 53g (0.1mol) pentaisobutyryl glucose, 300ml of acetic acid, 28.2g of trifluoromethanesulfonic anhydride, 35ml of boron trifluoride ether to a 500ml three-necked flask, heat and reflux for 10h, after the reaction is complete, cool, pour into 1L of water to crystallize , Filtered, washed with water until neutral, dried under reduced pressure at 60°C to obtain 53.5g of white solid with a yield of 93%. 1 H-NMR(300MHz, CDCl 3 ): δ=6.64~6.59(d,1H,CH),5.34~5.29(m,2H,CH), 3.71~3.61(m,1H,CH), 4.23~4.16(m,1H,CH), 3.45~ 2.94 (m, 2H), 2.56~2.48 (m, 4H, CH), 1.32 (d, 24H, CH) 3 ).

[0079] (2) Synthesis of the compound represented by formula IV (the phenolic hydroxyl group of formula III is protected by an isobutyryl group, namely compound 2)

[0080] Add 34.6g (0.06mol) of Intermediate II, 11.8g (0.05mol) of Intermediate III, 120ml of nitromethane, 3.5g of zinc bromide to a 5...

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 synthesis method for salidroside and an intermediate compound obtained in the synthesis method. The synthesis method comprises the following steps: (1) under the catalytic action of Lewis acid, carrying out a reaction between hydroxyl-protected benzyl carbinol and acyl-protected glucose ester to obtain the intermediate compound shown in formula (IV); (2) putting the intermediate compound shown in formula (IV) in C1-C4 alkanol, removing acyl protecting groups in the presence of alkali, and carrying out drying to obtain salidroside shown in the formula (I). The detailed definitions of substituent groups in formula (III) and formula (IV) are shown in the description. The synthesis method has the advantages of being simple to operate, mild in condition, high in yield and easy for industrialization.

Description

technical field [0001] The invention belongs to the field of pharmaceutical chemical synthesis, and relates to a synthesis method of natural products, more specifically, to a synthesis method of salidroside and an intermediate compound thereof. Background technique [0002] Salidroside is the active ingredient of Rhodiola rosea, which has the functions of protecting the cardiovascular system, protecting the central nervous system, anti-virus, anti-tumor, anti-aging, anti-radiation, anti-hypoxia, anti-injury, promoting blood circulation and removing blood stasis and improving Immunological function and many other significant effects. Rhodiola is a perennial herb or subshrub of Crassulaceae. The whole herb can be used as medicine. Its stems, roots, and flower extracts are all red in color. The content of salidroside in the medium is low (1.0%), so that the cost of extracting salidroside from Rhodiola rosea is high, the yield is low and the purity is poor. [0003] [0004...

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): C07H15/18C07H13/06C07H13/08C07H1/00
CPCY02P20/55
Inventor 郭建锋王孟华吕金良符义刚郑华章田峦鸢李莉娥郑炜杜文涛
Owner YICHANG HUMANWELL PHARMA
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