Ursolic acid derivative, preparation method thereof, and application thereof in preparation of drug for treating MRSA infection

A technology of ursolic acid and derivatives, applied in antibacterial drugs, steroids, organic chemistry, etc., can solve the problems of enhanced druggability, insoluble in water, and the activity needs to be further improved, and achieves rapid reaction and selectivity. Strong, water-soluble improvement effect

Active Publication Date: 2018-11-16
JIANGXI AGRICULTURAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In view of the urgency of research and development of anti-MRSA drugs, through systematic research on ursolic acid against Gram-positive bacteria (including anti-multi-drug-resistant bacteria), negative bacteria and fungi, we found for the first time that ursolic acid has certain

Method used

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  • Ursolic acid derivative, preparation method thereof, and application thereof in preparation of drug for treating MRSA infection
  • Ursolic acid derivative, preparation method thereof, and application thereof in preparation of drug for treating MRSA infection
  • Ursolic acid derivative, preparation method thereof, and application thereof in preparation of drug for treating MRSA infection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] Weigh 0.91g (2.0mmol) of ursolic acid (98.6%) and add it to a 100mL round bottom flask, add 50mL of dichloromethane, stir well until it is completely dissolved, add 0.11g (5.0mmol) of Sarrite reagent, and stir at 10°C for reaction 8h, add pure water to quench the reaction, separate the liquid in a separatory funnel, extract the aqueous layer once more with dichloromethane, combine the dichloromethane extracts, and pass through a silica gel chromatography column (dichloromethane:ethyl acetate, 5:1) Separation and purification to obtain ursolic acid C 3 Oxidation product of hydroxyl group (UA-O) 0.74g, purity 98.2%.

[0017] Take 0.14g UA-O (0.30mmol) into a 50mL three-necked flask, add ammonia-saturated absolute ethanol solution to fully dissolve, add 0.50mL isopropyl titanate solution under the protection of argon, and stir at 25°C for 6 hours. Then add 0.063g (0.3mmol) sodium triacetoxyborohydride and react for 2h, then quench the reaction with pure water, extract wit...

Embodiment 2

[0022]Weigh 1.37g (3mmol) of purchased ursolic acid (99%) and add it to a 100mL round-bottomed flask, add 50mL of dichloromethane, stir well until completely dissolved, add 1.61g (about 7.5mmol) of Sarrite reagent, and heat at 40°C Stir the reaction for 1 h, add pure water to quench the reaction, separate the layers in a separatory funnel, extract the aqueous layer once more with dichloromethane, combine the dichloromethane extracts, and pass through a silica gel chromatography column (dichloromethane:ethyl acetate, 5: 1) separation and purification to obtain ursolic acid C 3 Oxidation product of hydroxyl group (UA-O) 1.02g, purity 98.6%.

[0023] Take 0.28g UA-O (0.60mmol) into a 100mL three-necked flask, add ammonia-saturated absolute ethanol solution to fully dissolve, add 1.0mL isopropyl titanate solution under the protection of argon, stir and react at 35°C for 5h, then drop to to room temperature, then add 0.13g (0.6mmol) sodium triacetoxyborohydride to react for 2h, th...

Embodiment 3

[0028] Weigh 1.37g (3mmol) of ursolic acid (98.6%) into a 100mL round-bottomed flask, add 50mL of dichloromethane, stir well until completely dissolved, add 1.61g (about 7.5mmol) of Sarrite reagent, and stir at 15°C for reaction 6h, add pure water to quench the reaction, separate the liquid in a separatory funnel, extract the aqueous layer once more with dichloromethane, combine the dichloromethane extracts, and pass through a silica gel chromatography column (dichloromethane:ethyl acetate, 5:1) Separation and purification to obtain ursolic acid C 3 Oxidation product of hydroxyl group (UA-O) 1.19g, purity 98.7%.

[0029] Take 0.28g UA-O (0.60mmol) into a 100mL three-necked flask, add ammonia-saturated absolute ethanol solution to dissolve, add 1.0mL isopropyl titanate solution under the protection of argon, stir and react at 35°C for 5h, then drop to At room temperature, add 0.13g (0.6mmol) sodium triacetoxyborohydride and react for 3h, then quench the reaction with pure wate...

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Abstract

The invention discloses an ursolic acid derivative, a preparation method thereof, and an application thereof in the preparation of a drug for treating methicillin-resistant Staphylococcus aureus (MRSA) infection. The preparation method comprises the following steps: oxidizing ursolic acid by a Sarrett reagent to obtain a 3-hydroxy oxidation product of ursolic acid, and carrying out reductive amination on the 3-hydroxy oxidation product of ursolic acid by isopropyl titanate and sodium triacetoxyborohydride in order to prepare the ursolic acid derivative. Anti-MRSA activity test proves that theMIC of the obtained ursolic acid derivative on MRSA test strains is 16-32 [mu]g/mL, the anti-MRSA activity of the ursolic acid derivative is 4-8 times higher than that of the ursolic acid, and the derivative can form a salt together with equimolar hydrochloric acid in order to significantly improve the water solubility. The ursolic acid derivative has a significant anti-MRSA activity and a good development prospect, and can be used to prepare the drug for treating the MRSA infection.

Description

technical field [0001] The present invention relates to ursolic acid derivative and its preparation method and the application in the preparation treatment MRSA infection medicine. Background technique [0002] In recent years, Methicillin-resistant Staphylococcusaureus (MRSA) infection has spread all over the world, and the infection rate has continued to rise, and resistance to various structural types of clinical antibiotics has emerged one after another, and its speed has exceeded the current rate. The speed of research and development of new antibiotics has become a super broad-spectrum drug-resistant bacteria, which seriously threatens human life and health. The drug resistance of pathogenic bacteria is inherent in nature. During the use of antibiotics, people have enriched these drug-resistant bacteria and made them become dominant pathogens for widespread transmission and infection. Long-term clinical and scientific research practices have shown that many antibacter...

Claims

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Application Information

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IPC IPC(8): C07J63/00A61P31/04
CPCA61P31/04C07J63/008
Inventor 袁干军李菌芳王一旻宋晓媛许雪杰
Owner JIANGXI AGRICULTURAL UNIVERSITY
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