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Astragaloside derivative and preparation method and application thereof

A technology for a drug and methylamine, applied in the field of medicine, can solve the problems of many side reactions in the synthesis route, no prodrug properties, and two sugar chains are easy to fall off, so as to achieve improved druggability, less side reactions, and increased water solubility. Effect

Active Publication Date: 2017-05-10
CHENGDU INST OF BIOLOGY CHINESE ACAD OF S
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the many active reaction sites of astragaloside IV: it involves the protection and deprotection of nine hydroxyl groups of three different types: primary, secondary and tertiary; the two sugar chains are easily detached during the reaction; Both the propane structure and the THF ring structure are very easy to open the ring, therefore, so far there is no practical method to prepare water-soluble derivatives of astragaloside IV
For example, Ren Rong tried to synthesize water-soluble astragaloside IV-C6"-O-phosphate derivatives, but the synthetic route has many side reactions, low yield, complicated separation and purification, and the pharmacokinetic pre-test shows that the derivatives are not Has prodrug properties (Ren Rong. Extraction of Astragaloside IV and Synthesis of Phosphate Water-Soluble Prodrug[D]. Master's Thesis of Tianjin University, 2009)

Method used

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  • Astragaloside derivative and preparation method and application thereof
  • Astragaloside derivative and preparation method and application thereof
  • Astragaloside derivative and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] This embodiment provides the preparation method and structural identification of the compound having the structure of formula 1 described in claim 1:

[0028] (1) Compound preparation: Take 100 mg of astragaloside IV, add it to 500 mL of 10% pyridine, add 25 mg of sodium bromide, 5 mg of 2,2,6,6-tetramethylpiperidine-1-oxyl free radical, 1mL of sodium hypochlorite, reacted at 0°C for 120min, filtered, adjusted the pH of the filtrate to 3 with concentrated hydrochloric acid, concentrated to 20mL after the solid precipitated, separated the solid from the liquid, dissolved the solid with methanol and concentrated to dryness to obtain 89.7mg of white powder. A compound having the structure of formula 1 (HPLC purity 98.8%).

[0029] (2) Structural identification:

[0030] White amorphous powder; after TLC development, spray 5% concentrated sulfuric acid / ethanol to show purple; (c, 1.0, MeOH); IR(KBr): Vmax: 3417, 2968, 1732, 1621, 1378, 1156, 1066, 1045cm -1 . HR-ESI-MS...

Embodiment 2

[0039] This embodiment provides the preparation method of the compound having the structure of formula 1 described in claim 1. Compared with Example 1, the difference is that the ratio of solvent and reagent is adjusted:

[0040] Take 100mg of astragaloside IV, add it to 50mL of water, add 25mg of sodium bromide, 10mg of 2,2,6,6-tetramethylpiperidine-1-oxyl free radical, 0.25mL of sodium hypochlorite, and react at 20°C 120min, filter, the filtrate is adjusted to pH2 with concentrated hydrochloric acid, after the solid is precipitated, concentrate to 10mL, separate the solid and liquid, dissolve the solid with ethanol and transfer, concentrate to dryness, and obtain 91.3mg of white powder which is the compound having the structure of formula 1 (HPLC purity 99.1%).

Embodiment 3

[0042] This embodiment provides the preparation method of the compound having the structure of formula 1 described in claim 1. Compared with Example 1, the difference is that the ratio of solvent and reagent is adjusted:

[0043] Take 100mg of astragaloside IV, add it into 10mL of 10% DMF, add 20mg of sodium bromide, 8mg of 2,2,6,6-tetramethylpiperidine-1-oxyl free radical, 0.20mL of sodium hypochlorite in turn, React at ℃ for 120min, filter, adjust the pH of the filtrate to 3 with concentrated hydrochloric acid, concentrate to 10mL after the solid precipitates, separate the solid from the liquid, dissolve the solid with ethanol and transfer, concentrate to dryness, and obtain 82.7mg of white powder which is the compound with the structure of formula 1 Compound (HPLC purity 97.9%).

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Abstract

The invention discloses an astragaloside water-soluble derivative, namely astragaloside acid or medicinal salt, ester and amide of the astragaloside acid, with the structure shown in the formula 1. According to the defects that water solubility of astragaloside is poor, so that bioavailability of astragaloside is affected, and astragaloside cannot be developed into a single-component medicine, special alcoholic hydroxyl groups in astragaloside molecules are directionally oxidized into carboxyl groups ingeniously, and the astragaloside water-soluble derivative, namely astragaloside acid is prepared. A preparation method is simple in step, mild in reaction condition, small in side reaction, high in yield, easy to implement and suitable for large-scale production. The astragaloside water-soluble derivative, namely astragaloside acid or medicinal salt, ester and amide of the astragaloside acid, with the structure shown in the formula 1 has a protective function on hypoxia injuries of cardiac muscle cells cultured in vitro, and can be used for preventing and / or treating relevant cardiovascular diseases. The formula 1 is defined in the description.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a preparation method and application of an astragaloside IV derivative, astragalinic acid, or a pharmaceutically acceptable salt, ester and amide thereof, which has the activity of preventing and treating cardiovascular diseases. Background technique [0002] Astragaloside IV is one of the main active components of the traditional Chinese medicine Astragalus membranaceus, and it is also the qualitative and quantitative index component of various traditional Chinese medicine compound preparations in the "Chinese Pharmacopoeia". Pharmacological studies have shown that astragaloside IV has various effects such as improving cardiopulmonary function, enhancing body immunity, anti-virus, and anti-stress (Ren S, et al.Pharmacological effects of Astragaloside IV: a literature review.Journal of Traditional Chinese Medicine , 2013, 33(3):413-416). Although astragaloside IV ha...

Claims

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Application Information

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IPC IPC(8): C07J53/00A61K31/704A61P9/00A61P9/10
CPCC07J53/004
Inventor 青琳森丁立生彭树林李帮经梁健
Owner CHENGDU INST OF BIOLOGY CHINESE ACAD OF S
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