Preparation method of ursolic acid derivative

Abstract

The invention relates to a preparation method of ursolic acid derivatives. According to the invention, the structure-function relationship is deeply researched, the chemical modification method of ursolic acid is comprehensively considered, the efficient and economical synthesis and preparation method is obtained by taking substituent-free aniline, triethyl orthoformate and methyl carbazate as raw materials, the yield of UA770 obtained by the method is high, the method is simple and easy to implement, and industrial production of ursolic acid derivatives is easy to realize. Meanwhile, the UA770 can obviously down-regulate the expression of NLRP3 / GSDMD signal axis related protein, relieve pyroptosis of liver cells, reduce the MDA content in liver tissues, increase the SOD activity and improve the antioxidant capacity of the liver cells, so that the UA770 plays a role in protecting acute liver injury.

Description

Technical Field

[0001] The invention relates to the technical field of chemical modification methods of natural compound ursolic acid, and more specifically to a preparation method of ursolic acid derivatives. Background Art

[0002] Ursolic acid, also known as ursolic acid and ursolic acid, is a natural pentacyclic triterpenoid compound. Its chemical name is 3β-hydroxy-12-ene-28-ursolic acid, and its molecular formula is C 30 H 48 O3, molecular weight is 456.70. Ursolic acid is widely present in nature and can be found in many plants, such as apple peel, hawthorn, Ligustrum lucidum, Prunella vulgaris, loquat leaves, bearberry and other plants, which contain relatively rich ursolic acid. It can be obtained from these plants through extraction, separation and other processes. Generally speaking, the extraction methods include solvent extraction (such as ethanol, methanol and other organic solvents), ultrasound-assisted extraction, microwave-assisted extraction, etc., and then high-purity ursolic acid is obtained through separation and purification methods such as column chromatography and recrystallization.

[0003] Ursolic acid has the effects of inhibiting proliferation, inducing apoptosis and differentiation on a variety of tumor cells. Its mechanism of action may involve multiple aspects, such as regulating the expression of cell cycle proteins and cell cycle protein-dependent kinases, blocking the cell cycle, causing tumor cells to stagnate at a specific cell cycle stage, thereby inhibiting the growth and division of tumor cells; at the same time, it may also affect the intracellular signal transduction pathway, such as affecting the PI3K / Akt signaling pathway, reducing the phosphorylation level of Akt protein, thereby inhibiting the survival and proliferation of tumor cells; in addition, ursolic acid can also upregulate the expression of pro-apoptotic proteins (such as Bax), downregulate the expression of anti-apoptotic proteins (such as Bcl-2), change the permeability of mitochondrial membranes, promote the release of cytochrome C, activate caspase cascade reactions, and induce tumor cell apoptosis.

[0004] Ursolic acid can inhibit the production and release of inflammatory factors (such as TNF-α, IL-1β, IL-6, etc.), and reduce the synthesis and release of inflammatory mediators by inhibiting the activation of inflammation-related signaling pathways (such as the NF-κB signaling pathway), thereby alleviating the inflammatory response. In animal experiments, when ursolic acid was used on model animals with inflammation, it was observed that symptoms such as redness, swelling, heat and pain at the inflammatory site were significantly alleviated, and the infiltration of inflammatory cells was also reduced.

[0005] With people's attention to the medicinal value of natural products and in-depth research on their pharmacological activities, ursolic acid has shown broad market prospects in the fields of medicine, health care products, cosmetics, etc. In medicine, it is expected to be developed into a drug for the treatment of diseases such as tumors and inflammation; in the field of health care products, it can be added as a functional ingredient to antioxidant and anti-inflammatory health care products; in cosmetics, its antioxidant and anti-inflammatory properties make it a natural skin protection ingredient, which helps to reduce skin inflammation and delay skin aging, and is added to skin care products (such as creams, lotions, etc.) to meet consumers' demand for natural skin care products. However, in the process of industrialization, it is necessary to solve problems such as the source of raw materials, extraction and purification costs, and product quality control to ensure the quality and safety of ursolic acid products and promote their widespread application.

[0006] Ursolic acid derivatives refer to a class of compounds obtained by chemical modification or structural transformation with ursolic acid as the parent structure. Since ursolic acid has multiple biological activities, but it may have limitations in some aspects, such as solubility, bioavailability or activity intensity, etc., it is structurally modified to obtain ursolic acid derivatives in order to improve its performance or give it new properties.

[0007] Common modification methods of ursolic acid derivatives are as follows:

[0008] 1. Esterification modification:

[0009] By utilizing the carboxyl group in the molecular structure of ursolic acid and reacting it with different alcohol compounds for esterification, ursolic acid ester derivatives are obtained. This modification can change the lipophilicity or hydrophilicity of ursolic acid, affecting its absorption, distribution, metabolism and excretion in the body. The introduction of long-chain esters can increase its fat solubility and help improve its ability to penetrate cell membranes, thereby potentially improving its bioavailability.

[0010] 2. Modification of hydroxyl groups:

[0011] Ursolic acid contains multiple hydroxyl groups in its molecular structure, which can be modified by etherification, acylation, etc. These modifications can adjust the chemical stability and metabolic properties of ursolic acid derivatives. By changing the properties of hydroxyl groups, the interaction between ursolic acid derivatives and targets in the body may be affected, thereby changing their pharmacological activity.

[0012] 3. Modification of double bonds:

[0013] The double bonds in the ursolic acid molecule can undergo hydrogenation reactions, converting them into single bonds, which changes the spatial structure and electron cloud distribution of the molecule. The hydrogenated ursolic acid derivatives may have different physical and chemical properties and biological activities. For example, their chemical stability may be improved, while their biological activities may also be affected, such as reducing their antioxidant activity, but they may enhance their cytotoxicity or other pharmacological activities in some aspects, depending on their specific targets and mechanisms of action.

[0014] Modified ursolic acid derivatives can show stronger anti-tumor activity than ursolic acid. For example, ursolic acid derivatives with specific structural modifications may be more effective in inhibiting the growth and metastasis of tumor cells, which may be because the modified structure can better bind to receptors on the surface of tumor cells, or more effectively enter the interior of tumor cells and interfere with key signaling pathways in the cells.

[0015] In terms of anti-inflammatory, some ursolic acid derivatives can more strongly inhibit inflammation-related signaling pathways, such as by more persistent or stronger inhibition of the NF-κB signaling pathway, thereby reducing the production and release of inflammatory factors (such as IL-1β, TNF-α, etc.) and alleviating the degree of inflammatory response.

[0016] In addition, the metabolic rate of ursolic acid derivatives may change. By adjusting their structure, their half-life in the body can be prolonged, allowing them to maintain effective blood drug concentrations in the body for a longer time, thereby improving the efficacy and duration of the drug's action.

[0017] Therefore, the relationship between the structure and activity of ursolic acid derivatives needs to be studied in depth. Although it is known that certain modifications will affect the activity, more in-depth structure-activity relationship research is needed to accurately design ursolic acid derivatives with ideal activity and properties. In particular, the cost and operability of the preparation process are also aspects that need to be considered. Some complex chemical modifications may lead to high preparation costs. It is necessary to develop more efficient and economical synthesis and preparation methods to realize the industrial production of ursolic acid derivatives.

[0018] In conclusion, ursolic acid derivatives are a class of compounds with potential application value. By structurally modifying ursolic acid, new compounds with better performance and broader application prospects can be developed. However, in the process of their development and application, it is necessary to comprehensively consider their synthesis, activity, safety, industrialization and other aspects to promote their development and application in different fields. Summary of the invention

[0019] In order to solve the problems in the prior art, the present invention provides a method for preparing an ursolic acid derivative UA770.

[0020] The ursolic acid derivative is UA770 having the following structure:

[0021]

[0022] The preparation method specifically comprises the following steps:

[0023] S1. Synthesis of the compound 2-(2-bromoethyl)-4-phenyl-2,4-dihydro-[1,2,4]triazol-3-one

[0024] According to the molar ratio of 1:(1-2):(1-2), unsubstituted aniline, triethyl orthoformate and methyl hydrazinecarboxylate were weighed and dissolved in anhydrous ethanol, and then refluxed for reaction at a temperature of 75-80°C for 23-25 ​​hours. Then, sodium methoxide was added and refluxed with stirring for 23-25 ​​hours. After the reaction was completed, benzotriazolone was obtained by suction filtration, washing and drying. Benzotriazolone was added with an excess of dibromoethane reagent and an appropriate amount of catalyst, dissolved in acetone solution, and refluxed with stirring for reaction for 5-7 hours. After the reaction was completed, it was distilled under reduced pressure, extracted and dried to obtain a white solid compound 2-(2-bromoethyl)-4-phenyl-2,4-dihydro-[1,2,4]triazol-3-one.

[0025] S2. Synthesis of the compound 4-phenyl-2-(2-(1-piperazinyl)ethyl)-2,4-dihydro-[1,2,4]triazol-3-one

[0026] 2-(2-bromoethyl)-4-phenyl-2,4-dihydro-[1,2,4]triazol-3-one is reacted with excess anhydrous piperazine, acetone is used as solvent, an appropriate amount of catalyst is added, and the reaction is refluxed for 8 to 12 hours. After the reaction, the solvent is evaporated under reduced pressure, dissolved, extracted, and dried to obtain a white solid compound. Impurities are separated by column chromatography to obtain an intermediate compound 4-phenyl-2-(2-(1-piperazinyl)ethyl)-2,4-dihydro-[1,2,4]triazol-3-one.

[0027] S3. Synthesis of target compound UA770

[0028] The intermediate compound 4-phenyl-2-(2-(1-piperazinyl)ethyl)-2,4-dihydro-[1,2,4]triazol-3-one is reacted with excess 1,3-dibromopropane and ursolic acid, and an appropriate amount of catalyst is added and dissolved in acetone solution, and the reaction is refluxed with stirring for 9 to 11 hours and monitored. After the reaction is completed, it is subjected to reduced pressure distillation, extraction, drying and other operations, and then the impurities are separated by column chromatography to finally obtain the target compound UA770.

[0029] Preferably, the molar ratio of aniline, triethyl orthoformate and methyl carbazate is 1:1.5:1.5.

[0030] Preferably, the temperature in step S1 is preferably 78°C.

[0031] The appropriate amount of catalyst in steps S1 and S2 is an equimolar amount of potassium carbonate and 0.1 to 0.3 molar amount of potassium iodide.

[0032] More preferably, in the steps S1, S2 and S3, the catalysts are potassium iodide and potassium carbonate, the amount of potassium carbonate is in an equimolar ratio to the reactants, and the molar ratio of potassium iodide to potassium carbonate is 1:5.

[0033] The present invention also seeks to protect the use of the ursolic acid derivative UA770 prepared by the above preparation method in drugs for treating acute liver injury.

[0034] Application of ursolic acid derivative UA770 in the treatment of acute liver injury, with an application concentration of 20-40 mg kg -1 .

[0035] Compared with the prior art, the present invention has the following beneficial effects:

[0036] The present invention deeply studies the structure-activity relationship, comprehensively considers the chemical modification method of ursolic acid, and obtains an efficient and economical synthesis and preparation method. The UA770 obtained by the method has a high yield, and the method is simple and easy to implement, and it is easy to realize the industrial production of ursolic acid derivatives. At the same time, UA770 can significantly downregulate the expression of proteins related to the NLRP3 / GSDMD signaling axis, alleviate hepatocyte pyroptosis, reduce the MDA content in liver tissue and increase SOD activity, improve the antioxidant capacity of hepatocytes and play a protective role against acute liver damage. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 Reaction mechanism diagram of the present invention;

[0038] Figure 2 UA770 mass spectrum;

[0039] Figure 3 UA770 carbon spectrum;

[0040] Figure 4 UA770 hydrogen spectrum;

[0041] Figure 5 Effect of UA770 on the expression of NLRP3, Caspase1, IL-1β, IL-18, and GSDMD proteins in the liver of ALI mice. DETAILED DESCRIPTION

[0042] In order to more clearly explain the purpose, technical solutions and advantages of the present invention, the present invention will be described in detail in conjunction with the embodiments below. It should be understood that the following description of the embodiments is intended to explain and illustrate the overall concept of the present invention, and should not be understood as a limitation of the present disclosure. Unless otherwise defined, the technical terms or scientific terms used in the present disclosure should be the common meanings understood by people with ordinary skills in the field to which the present disclosure belongs.

[0043] Drugs and reagents used in the examples: UA (batch number U118635) was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.; UA770 ( Figure 1 ) is the target compound obtained by modifying and transforming the C28 carboxyl position of UA; silymarin (batch number S0292), D-(+)-galactosamine (D-GalN, batch number G1639), and lipopolysaccharide (LPS, batch number L2880) were purchased from Shanghai Merck Co., Ltd.; ALT (batch number C009-2-1), AST (batch number C010-2-1), SOD (batch number A001-3-2), and MDA (batch number A003-1-2) were purchased from Nanjing Jiancheng Bioengineering Institute; NLRP3 and GSDMD antibodies were purchased from Abcam; Caspase1 antibody was purchased from SC; IL-18, IL-1β, and GAPDH antibodies were purchased from CST.

[0044] Experimental animals: This example uses SPF male C57BL / 6 mice as experimental subjects, 8-10 weeks old, weighing 22-24 g, purchased from Liaoning Changsheng Biotechnology Co., Ltd., license number: SCXK (Liao) 2020-0001. The animal experiment was approved by the Ethics Committee of Zhongshan Hospital Affiliated to Dalian University (approval number: DWLL2019060).

[0045] Example 1

[0046] 1. Compound 2-(2-bromoethyl)-4-phenyl-2,4-dihydro-[1,2,4]triazol-3-one

[0047] Synthesis of 2-(2-Bromo-ethyl)-4-phenyl-2,4-dihydro-[1,2,4]triazol-3-one(3)

[0048] In a 100mL round-bottom flask, unsubstituted aniline 1 (0.93g, 10mmol), triethyl orthoformate (2.22g, 15mmol) and methyl hydrazinecarboxylate (1.35g, 15mmol) were weighed and dissolved in 50mL of anhydrous ethanol. The reaction was refluxed at 78°C and the reaction progress was monitored by TLC at a wavelength of 254nm. After 24h of reaction, sodium methoxide (0.81g, 15mmol) was added to the original reaction solution. The reaction solution quickly generated a rose-red precipitate and continued to reflux and stir for 24h. After the reaction was completed, the filter was filtered under reduced pressure and the filter cake was washed with distilled water in small amounts for multiple times. When the filter cake became a white powder, it was placed under a drying lamp to dry and weighed to obtain a white powder compound benzotriazolone 2. Then, compound benzotriazole 2 (5 mmol) was added to a 50 mL round-bottom flask, and an excess of dibromoethane reagent was added. Under the catalysis of potassium iodide (1 mmol) and potassium carbonate (5 mmol), it was dissolved with 20 mL of acetone solution. The reaction was stirred and refluxed at 57 ° C for 6 h. The reaction progress was monitored by thin layer chromatography at a wavelength of 254 nm. After the reaction was completed, the excess solvent was distilled off under reduced pressure, and dichloromethane and water were extracted several times in small amounts. The organic layers were combined, dried with anhydrous magnesium sulfate, and the organic solvent was filtered and dried to obtain a white solid compound 3.

[0049] 2. Synthesis of the compound 4-Phenyl-2-(2-(1-piperazinyl)ethyl)-2,4-dihydro-[1,2,4]triazol-3-one (5)

[0050] Compound 3 (10 mmol) was reacted with excess anhydrous piperazine, acetone was used as solvent, potassium carbonate (10 mmol) and potassium iodide (2 mmol) were added as catalysts, and the reaction was refluxed for 8-12 hours, and the reaction was monitored by TLC until completion; after stopping the reaction, the solvent was evaporated under reduced pressure, and an appropriate amount of water was added to the residue to dissolve it, and then extracted with dichloromethane, washed with water, dried over anhydrous magnesium sulfate, and the solvent was spin-dried to obtain a white solid compound, and the impurities were separated by column chromatography to obtain the intermediate compound 5.

[0051] 3. Synthesis of target compound UA770

[0052] The intermediate compound 5 (10 mmol) was reacted with excess 1,3-dibromopropane and ursolic acid, and dissolved in 20 mL of acetone solution under the catalysis of potassium iodide (2 mmol) and potassium carbonate (10 mmol). The reaction was stirred under reflux at 57 ° C for 10 h. The reaction progress was monitored by thin layer chromatography at a wavelength of 254 nm. After the reaction was completed, the excess solvent was distilled off under reduced pressure, and dichloromethane and water were extracted several times in small amounts. The organic layers were combined, dried with anhydrous magnesium sulfate, and then the organic solvent was filtered and dried to obtain a white solid. Column chromatography (dichloromethane: methanol = 150: 1) was used to separate impurities to obtain the target compound UA770 with a yield of 74%.

[0053] 4. The structural formula, yield, melting point and spectral data of the target compound UA770 are as follows:

[0054]

[0055] Yield: 74%; mp124-126℃. 1 H NMR (CDCl3, 300MHz, ppm): δ7.71 (s, 1H), 7.57 (d, J = 7.8Hz, 2H), 7.50 (t, J = 7.8Hz, 2H),7.38(t,J=7.3Hz,1H),5.25(s,1H),4.09-3.97(m,4H),3.23(dd,J=10.6,5.0H z,1H),2.81(t,J=6.8Hz,2H),2.53(dd,J=40.9,22.9Hz,11H),2.23(d,J=11.3Hz,1 H),2.07-1.76(m,7H),1.74-1.43(m,12H),1.40-1.23(m,6H),1.12-0.82(m,20H). 13C NMR (CDCl3, 75MHz, ppm): δ177.52,151.97,138.28,133.96,133.72,129.63,129.63,127.57,1 25.52,121.94,121.94,79.00,62.51,55.97,55.97,55.23,55.23,53.07,52.82,52.71,48.08 ,47.55,42.90,42.05,39.56,39.08,38.87,38.75,38.62,36.98,36.73,33.03,30.67,28.15, 27.97,27.24,25.84,24.22,23.57,23.30,21.18,18.31,18.31,17.12,17.02,15.65,15.46.MS m / z 770.09[M+1].

[0056] Example 2

[0057] C57BL / 6 mice were randomly divided into 9 groups, with 8 mice in each group, namely normal group (Control), UA alone group (UA40 mg·kg -1 ), UA770 alone group (UA77040 mg·kg -1 ), model group (LPS+D-GalN), UA high and low dose groups (40, 20 mg·kg -1 ), UA770 high and low dose groups (40 and 20 mg kg -1 ), positive drug group (Silymarin 100 mg·kg -1 ). Except for the normal group and the model group, the mice in the other groups were gavaged with UA and high and low doses of UA770 and the positive control drug once a day for 5 consecutive days. 2 hours after the last administration, except for the normal group and the single drug group, the mice in the other groups were intraperitoneally injected with LPS (10 μg kg -1 ) and D-GalN (700 mg kg -1 ) was used to induce the ALI model. The mice were killed 5 h later, and blood was collected from the eyeballs and liver samples were collected for subsequent analysis.

[0058] The kit was used to detect the serum ALT and AST levels and the SOD and MDA contents in the liver tissue. The results are shown in Table 1-2. The results of serological indicators showed that the serum ALT and AST levels of mice in the LPS / D-GalN model group were significantly increased, while after pretreatment with UA and UA770, the ALT and AST levels were significantly decreased (P<0.01). This indicates that UA and UA770 have a protective effect on LPS / D-GalN-induced ALI.

[0059] Table 1 Comparison of serum ALT and AST levels in mice of each group ( n=8)

[0060]

[0061] ## P<0.01vs Control; ** P<0.01vs LPS+D-GalN

[0062] Table 2 Comparison of MDA and SOD levels in mouse tissues of each group

[0063]

[0064] ## P<0.01vsControl; ** P<0.01vsLPS+D-GalN

[0065] The MDA content in the liver of mice in the LPS / D-GalN model group was significantly increased, and the SOD activity was significantly decreased, while UA and UA770 could significantly reduce the MDA content and increase the SOD activity (P<0.01).

[0066] The liver tissue of mice was fixed with paraformaldehyde, embedded in paraffin and sectioned, and conventional H&E staining was used to observe the pathological changes of the liver. The liver lobule structure of the mice in the LPS / D-GalN model group was unclear, the hepatocytes were abnormally arranged, and there was hemorrhage in the hepatic sinusoids, and inflammatory cell infiltration was obvious. The liver lesions of mice in the low- and high-dose groups of UA and UA770 were significantly alleviated, and the positive control group also showed significant improvement compared with the model group.

[0067] Proteins were extracted from tissue samples and the expression of NLRP3, Caspase1, GSDMD, IL-1β and IL-18 proteins was detected. Figure 5 shown.

[0068] Compared with the model group, the low-dose and high-dose groups of UA and UA770 and the positive drug group significantly downregulated the expression of NLRP3, Caspase1, IL-1β, IL-18, and GSDMD proteins (P<0.01). The results showed that UA770 can exert anti-inflammatory effects by downregulating the expression of NLRP3 / GSDMD signaling axis proteins.

[0069] In summary, UA770 can significantly reduce the levels of ALT and AST in the serum of experimental mice and effectively alleviate liver damage. The activation of NLRP3 inflammasome is a key link in the classical cell pyroptosis pathway, and excessive accumulation of ROS exceeds its own detoxification capacity, causing signal transduction and redox imbalance. UA770 can significantly downregulate the expression of proteins related to the NLRP3 / GSDMD signaling axis, alleviate hepatocyte pyroptosis, reduce the MDA content in liver tissue and increase SOD activity, improve the antioxidant capacity of mouse hepatocytes and play a protective role against ALI.

[0070] The above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical solutions and inventive concepts of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.

Claims

1. A method for preparing an ursolic acid derivative, characterized in that: The steps include: S1. Synthesis of the compound 2-(2-bromoethyl)-4-phenyl-2,4-dihydro-[1,2,4]triazol-3-one According to the molar ratio of 1:(1-2):(1-2), unsubstituted aniline, triethyl orthoformate and methyl hydrazinecarboxylate were weighed, dissolved in anhydrous ethanol, and refluxed for reaction at a temperature range of 75-80°C for 23-25h, and then sodium methoxide was added and refluxed and stirred for 23-25h. After the reaction was completed, benzotriazolone was obtained by suction filtration, washing and drying. Benzotriazolone was added with an excess of dibromoethane reagent and an appropriate amount of catalyst, dissolved in acetone solution, and refluxed and stirred for reaction for 5-7h. After the reaction was completed, it was distilled under reduced pressure, extracted and dried to obtain a white solid compound 2-(2-bromoethyl)-4-phenyl-2,4-dihydro-[1,2,4]triazol-3-one; S2. Synthesis of the compound 4-phenyl-2-(2-(1-piperazinyl)ethyl)-2,4-dihydro-[1,2,4]triazol-3-one 2-(2-bromoethyl)-4-phenyl-2,4-dihydro-[1,2,4]triazol-3-one is reacted with excess anhydrous piperazine, acetone is used as solvent, an appropriate amount of catalyst is added, and the reaction is refluxed for 8 to 12 hours. After the reaction, the solvent is evaporated under reduced pressure, dissolved, extracted, and dried to obtain a white solid compound. Impurities are separated by column chromatography to obtain an intermediate compound 4-phenyl-2-(2-(1-piperazinyl)ethyl)-2,4-dihydro-[1,2,4]triazol-3-one; S3. Synthesis of target compound UA770 The intermediate compound 4-phenyl-2-(2-(1-piperazinyl)ethyl)-2,4-dihydro-[1,2,4]triazol-3-one is reacted with excess 1,3-dibromopropane and ursolic acid, and an appropriate amount of catalyst is added and dissolved in acetone solution, and the reaction is refluxed with stirring for 9 to 11 hours and monitored. After the reaction is completed, it is subjected to reduced pressure distillation, extraction, drying and other operations, and then the impurities are separated by column chromatography to finally obtain the target compound UA770.

2. The preparation method according to claim 1, characterized in that: The ursolic acid derivative is UA770 having the following structure:

3. The preparation method according to claim 1, characterized in that: The molar ratio of aniline, triethyl orthoformate and methyl carbazate is 1:1.5:1.

5.

4. The preparation method according to claim 1, characterized in that: The appropriate amount of catalyst in steps S1, S2 and S3 is an equimolar amount of potassium carbonate and 0.1 to 0.3 molar amount of potassium iodide.

5. The preparation method according to claim 4, characterized in that: In the steps S1, S2 and S3, the catalysts are potassium iodide and potassium carbonate, the amount of potassium carbonate is in an equal molar ratio to the reactants, and the molar ratio of potassium iodide to potassium carbonate is 1:

5.

6. The preparation method according to claim 1, characterized in that: The temperature in step S1 is 78°C.

7. An ursolic acid derivative UA770, characterized in that: Prepared by any method of claims 1 to 5.

8. Use of the ursolic acid derivative UA770 according to claim 1 in drugs for treating acute liver injury.

9. The use according to claim 8, characterized in that: Its application concentration is 20-40mg·kg -1 .

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