A benzyl chromone compound, a preparation method and application thereof

Abstract

The application provides a benzyl chromone compound and a preparation method and application thereof. The application takes dry fruit bodies of Leucangium alectorium as raw materials, carries out ethanol extraction, ethyl acetate extraction, then carries out rough separation on the ethyl acetate phase obtained by extraction with different proportions of dichloromethane-methanol solution, and then carries out elution separation with different proportions of methanol-water to obtain a novel structure benzyl chromone compound. The benzyl chromone compound provided by the application has significant in-vitro inhibition activity on HepG2 cell proliferation, and when the treatment concentration is below 160 muM, the inhibition activity on liver cancer cells is obviously better than that of cisplatin, and the benzyl chromone compound can be used for preparing drugs for treating and preventing liver cancer. Meanwhile, the raw material of the compound is rich in source, low in price, simple in preparation process and convenient for industrial application, so the discovery of the compound is expected to provide a promising treatment scheme for liver cancer patients, and has great significance for breaking through the bottleneck of liver cancer treatment.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of bioengineering technology, and particularly relates to a benzyl chromone compound and a preparation method and application thereof. BACKGROUND

[0002] Cancer is a global public health problem, which has a great impact on human health and life. Among many cancers, liver cancer is one of the most common cancers in the world, especially in Asia and Africa, and has a high incidence and mortality, which seriously threatens human life and health. In recent years, although the diagnosis and treatment methods of liver cancer have developed a lot, the treatment effect is still not satisfactory. For liver cancer patients found at an early stage, surgical resection is still one of the most effective treatment methods. Early liver cancer has no obvious symptoms and is easily ignored, but as the disease progresses, patients may gradually develop symptoms such as fatigue, loss of appetite, weight loss, and abdominal discomfort, which is usually at the middle and late stages of liver cancer. For liver cancer patients at the middle and late stages, chemotherapy is generally used to relieve symptoms and prolong survival. Due to the strong drug resistance of liver cancer to chemical drugs, the chemotherapy effect of most patients will become worse and worse over time. And long-term use of chemotherapy drugs will have great side effects on the body, and many patients cannot withstand the side effects of continuous chemotherapy, leading to rapid decline in physical function. Therefore, finding a safer and more effective alternative to traditional drugs to prevent and treat liver cancer has become an important problem to be solved. SUMMARY

[0003] To solve the above technical problems, the present application provides a benzyl chromone compound and a preparation method and application thereof.

[0004] To solve the above technical problems, the present application provides a benzyl chromone compound and a preparation method and application thereof.

[0005] A benzyl chromone compound, the structural formula of which is shown as formula I:

[0006]

[0007] The chemical name of the above benzyl chromone compound provided by the present application is 2-(3,4-dihydroxybenzyl)-3,6-dihydroxy-4H-chromen-4-one, the molecular weight is 300.0634, the molecular formula is C 16 H 12 O6, yellow oil, soluble in organic solvents such as methanol, ethanol, ethyl acetate, etc.

[0008] The present application provides a benzyl chromone compound with a completely new structure, enriches the database of benzyl chromone compounds, and provides a material basis for the activity research and single component new drug development of benzyl chromone compounds.

[0009] The benzyl chromone compound provided by the application is composed of two structural units of chromone and aromatic ring, and the compound only has biological activities of antioxidation, anti-inflammation, and sugar reduction reported in the literature at present, and the application first finds that the benzyl chromone compound has significant anti-hepatoma activity, can be used for preparing a medicine for treating and preventing hepatoma, and has wide potential application value.

[0010] The application further provides a preparation method of the benzyl chromone compound.

[0011] Step one, alcohol-extracted concentrated extract of Leucellinum carthusianum is added into water and mixed uniformly to obtain an alcohol-extracted concentrated extract aqueous solution; ethyl acetate is added into the alcohol-extracted concentrated extract aqueous solution for extraction, the extract is concentrated under reduced pressure, and dried to obtain an ethyl acetate-extracted concentrated extract of Leucellinum carthusianum;

[0012] Step two, the ethyl acetate-extracted concentrated extract of Leucellinum carthusianum is mixed and ground with silica gel particles, then added into a silica gel chromatographic column, eluted with dichloromethane-methanol solution with a volume ratio of 100:0-50:1, the eluate is discarded, then eluted with dichloromethane-methanol solution with a volume ratio of 30:1-15:1, the eluate is collected to obtain sample a;

[0013] Step three, the sample a is added into a reversed-phase silica gel chromatographic column, eluted with methanol-water solution with a volume ratio of 1:9-2:3, the eluate is discarded, then eluted with methanol-water with a volume ratio of 1:1.5-1.5:1, the eluate is collected, concentrated under reduced pressure to obtain the benzyl chromone compound.

[0014] Compared with the prior art, the application has the following beneficial effects:

[0015] The preparation method of the benzyl chromone compound provided by the application can effectively remove a large amount of impurities in Leucellinum carthusianum and effectively separate the benzyl chromone compound by selecting specific elution solvents and elution sequences and controlling appropriate parameters, so that the benzyl chromone compound with a new structure shown in formula I with high purity (more than 99%) is obtained. The separation and purification method of the benzyl chromone compound provided by the application can obtain the benzyl chromone compound with new drug activity, provides high-purity raw materials for industrial development of safe and efficient new anti-hepatoma drugs, and has high popularization value due to simple separation method and high separation efficiency.

[0016] Suillus granulatus, also known as pine mushroom, sticky group, and chestnut shell boletus, is a common ectomycorrhizal edible fungus that grows with Pinus. It contains polysaccharides, ergosterol, essential amino acids, trace elements, and other bioactive substances, and has various medicinal activities such as antioxidant, antibacterial, and antiviral activities. The present application first isolates a benzyl chromone compound with significant anti-liver cancer activity from the fruiting bodies of Suillus granulatus, providing a new idea for the development and utilization of Suillus granulatus and new anti-liver cancer drugs.

[0017] Further, in step one, the alcohol-extracted concentrated extract of Suillus granulatus is prepared by the following method: crushing the dried fruiting bodies of Suillus granulatus, adding 3-5 times the volume of ethanol based on the mass of the fruiting bodies, extracting 2-4 times, and concentrating under reduced pressure to obtain the alcohol-extracted concentrated extract of Suillus granulatus.

[0018] As a specific embodiment of the present application, the fruiting bodies of Suillus granulatus are removed from impurities, dried in an oven at 40-45°C for 24 hours, and crushed to obtain the fruiting body powder of Suillus granulatus.

[0019] Specifically, anhydrous ethanol is used to extract the fruiting bodies of Suillus granulatus.

[0020] Further, in step one, each extraction time is 8-12 hours, and the extraction temperature is 20-40°C. The volume of anhydrous ethanol added during each extraction is 3-5 times the mass of the fruiting body powder of Suillus granulatus.

[0021] Preferably, in step one, the temperature for concentration under reduced pressure is 55-55°C, and the concentration is performed under reduced pressure until no ethanol flows out.

[0022] The above extraction method can remove a large amount of impurities from Suillus granulatus, which is beneficial to improve the efficiency of subsequent separation and purification.

[0023] Preferably, in step one, the volume ratio of the alcohol-extracted concentrated extract of Suillus granulatus to water is 1:2-1:10.

[0024] Preferably, in step one, the volume ratio of the alcohol-extracted concentrated extract of Suillus granulatus to water is 1:2-1:10.

[0025] Preferably, in step one, the volume ratio of the alcohol-extracted concentrated extract of Suillus granulatus to water is 1:2-1:10.

[0026] Further preferably, in step one, the volume of ethyl acetate added during each extraction is 1-2 times the volume of the alcohol-extracted concentrated extract of Suillus granulatus.

[0027] The preferred extraction method can further remove impurities from the alcohol-extracted concentrated extract of Suillus granulatus, which is beneficial to improve the subsequent elution and separation effect.

[0028] Preferably, in step two, the mass ratio of the Boletus lactarius ethyl acetate extract to silica gel is 1:1.5-1:2.

[0029] Preferably, in step two, the particle size of the silica gel particles is 100-200 mesh.

[0030] As a specific embodiment of the present application, in step two, the Boletus lactarius ethyl acetate extract is mixed with silica gel particles, the extract sample is fully adsorbed on the silica gel particles, and then the sample is placed on the top of a silica gel chromatographic column for elution. This method can effectively improve the separation degree of the target compound and impurities and improve the separation efficiency.

[0031] Preferably, in step two, the particle size of the silica gel packed in the silica gel chromatographic column is 200-300 mesh.

[0032] Preferably, in step three, the reverse phase silica gel chromatographic column is an octadecylsilane bonded silica gel chromatographic column.

[0033] Further preferably, the specifications of the packing in the reverse phase silica gel chromatographic column are a particle size of 5 μm and a pore size of 12 nm.

[0034] The present application also provides the use of the above-mentioned benzyl chromone compound in the preparation of an anti-liver cancer drug.

[0035] The benzyl chromone compound provided by the present application has significant in-vitro inhibitory activity on the proliferation of HepG2 cells. When the treatment concentration is below 160 μM, the inhibitory activity on liver cancer cells is significantly better than that of cisplatin, which proves that the compound has significant anti-liver cancer activity and can be used for the preparation of drugs for treating and preventing liver cancer. Meanwhile, the raw material of the compound is abundant, the price is low, the preparation process is simple, and the compound is convenient for industrial application. Therefore, the discovery of the compound is expected to provide a promising treatment scheme for liver cancer patients and has great significance for breaking through the bottleneck of liver cancer treatment. BRIEF DESCRIPTION OF DRAWINGS

[0036] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings needed in the embodiments will be briefly introduced below. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative labor.

[0037] Figure 1 is the high-resolution mass spectrum of the benzyl chromone compound prepared in Example 1 of the present application;

[0038] Figure 2 is the ultraviolet spectrum of the benzyl chromone compound prepared in Example 1 of the present application;

[0039] Figure 3 is the H NMR spectrum of the benzyl chromone compound prepared in Example 1 of the present application 1 H NMR spectrum;

[0040] Figure 4 is the C NMR spectrum of the benzyl chromone compound prepared in Example 1 of the present application 13 C NMR spectrum;

[0041] Figure 5 is the HMBC spectrum of the benzyl chromone compound prepared in Example 1 of the present application

[0042] Figure 6 is the HSQC spectrum of the benzyl chromone compound prepared in Example 1 of the present application

[0043] Figure 7 is the H-H COSY spectrum of the benzyl chromone compound prepared in Example 1 of the present application

[0044] Figure 8 is the effect diagram of the benzyl chromone compound prepared in Example 1 of the present application on the proliferation of HepG2 cells. DETAILED DESCRIPTION

[0045] In order to make the purpose, technical scheme and advantages of the present application clearer, the present application will be further described in detail below in combination with examples. It should be understood that the specific examples described herein are only used to explain the present application and do not limit the present application.

[0046] Example 1

[0047] A method for separating and purifying a benzyl chromone compound:

[0048] Step one, take Suillus granulatus fruiting bodies, remove impurities, dry in a 40℃ oven for 24h, crush, add anhydrous ethanol to the dry powder of Suillus granulatus, wherein the mass-volume ratio of the dry powder of Suillus granulatus to anhydrous ethanol is 1:4 (g / mL), stir and soak for 10h at room temperature, filter, repeat, soak for 3 times, combine the extract, distill at 50℃ under reduced pressure, obtain the ethanol extract of Suillus granulatus;

[0049] Step two, mix the ethanol extract of Suillus granulatus with ultrapure water according to a volume ratio of 1:2, stir uniformly, add ethyl acetate, extract 3 times, the volume of ethyl acetate added each time is 1 times the volume of the ethanol extract aqueous solution, after extraction, combine the ethyl acetate phase, perform reduced pressure distillation on a rotary evaporator, control the temperature to be no more than 55℃, collect the extract, dry the extract in a vacuum drying oven, the drying temperature is no more than 40℃, obtain the ethyl acetate extract of Suillus granulatus;

[0050] Step three, the ethyl acetate extract of Suillus granulatus was fully stirred with silica gel particles (100-200 mesh), the mass ratio of the extract to the silica gel particles was 1:1.5, and then dried and ground. The ground material was added to a silica gel (200-300 mesh) chromatographic column, and gradient elution was performed with dichloromethane-methanol solution at normal pressure. The gradient elution process was as follows: 100:0 and 50:1 (volume ratio) dichloromethane-methanol solution was used for elution, respectively, 4 column volumes for each gradient elution, the eluate was discarded, and then 30:1, 20:1 and 15:1 dichloromethane-methanol solution was used for elution, respectively, 4 column volumes for each gradient elution, the eluate of the three gradients was combined, and sample a was obtained by distillation at 45℃ under reduced pressure;

[0051] Step four, sample a was added to a reverse silica gel (ODS, 5 μm, 12 nm) chromatographic column, and elution was performed with methanol-water solution in the order of 1:9, 1:4, 3:7 and 2:3, respectively, 3 column volumes for each gradient elution, the eluate was discarded, and then elution was performed with 1:1 methanol-water solution, 3 column volumes. The collected eluate was concentrated and dried to obtain the benzyl chromone compound shown in formula I.

[0052]

[0053]

[0054] Example 2

[0055] A method for separating and purifying a benzyl chromone compound:

[0056] Step one, the fruiting bodies of Suillus granulatus were removed from impurities, dried in an oven at 45℃ for 24 h, and then crushed. Anhydrous ethanol was added to the dried Suillus granulatus powder, and the mass-volume ratio of the dried Suillus granulatus powder to anhydrous ethanol was 1:3 (g / mL). The mixture was stirred at room temperature for 12 h, and then filtered. The above steps were repeated four times. The filtrate was combined and distilled at 55℃ under reduced pressure to obtain an ethanol extract of Suillus granulatus;

[0057] Step two, the ethanol extract of Suillus granulatus was mixed with ultrapure water at a volume ratio of 1:5, and then stirred uniformly. Ethyl acetate was added twice, and the volume of ethyl acetate added each time was twice the volume of the ethanol extract aqueous solution. After extraction, the ethyl acetate phases were combined and distilled under reduced pressure on a rotary evaporator, with the temperature controlled at no more than 55℃. The extract was dried in a vacuum drying oven at a temperature of no more than 40℃ to obtain an ethyl acetate extract of Suillus granulatus;

[0058] Step three, the ethyl acetate extract of Suillus granulatus was fully stirred with silica gel particles (100-200 mesh), the mass ratio of the extract to the silica gel particles was 1:1.8, and then the mixture was dried and ground. The ground mixture was added to a silica gel (200-300 mesh) column, and gradient elution was performed under normal pressure using dichloromethane-methanol solution. The gradient elution process was as follows: 100:0 and 50:1 (volume ratio) dichloromethane-methanol solution was used for elution, respectively, and each gradient elution was performed for 3 column volumes. The eluate was discarded, and then 30:1, 20:1 and 15:1 dichloromethane-methanol solution was used for elution, respectively, and each gradient elution was performed for 3 column volumes. The eluate of the three gradients was combined, and sample a was obtained by distillation under reduced pressure at 45°C.

[0059] Step four, sample a was added to a reversed-phase silica gel (ODS, 5 μm, 12 nm) column, and elution was performed using methanol-water solution with a gradient of 1:9, 1:4, 3:7 and 2:3, respectively, and each gradient elution was performed for 4 column volumes. The eluate was discarded, and then elution was performed using 1:1.5 methanol-water solution, and the elution was performed for 4 column volumes. The collected eluate was concentrated and dried to obtain the benzyl chromone compound shown in formula I.

[0060] Example 3

[0061] A method for separating and purifying a benzyl chromone compound

[0062] Step one, the fruiting bodies of Suillus granulatus were removed from impurities, dried in an oven at 43°C for 24 h, and then crushed. Anhydrous ethanol was added to the dried Suillus granulatus powder, and the mass-volume ratio of the dried Suillus granulatus powder to anhydrous ethanol was 1:5 (g / mL). The mixture was stirred at room temperature for 8 h, and then filtered. The above steps were repeated twice, and the filtrates were combined. The combined filtrate was distilled under reduced pressure at 53°C to obtain an ethanol extract of Suillus granulatus;

[0063] Step two, the ethanol extract of Suillus granulatus was mixed with ultrapure water at a volume ratio of 1:10, and then stirred uniformly. Ethyl acetate was added, and the extraction was performed four times. The volume of ethyl acetate added each time was 1 times the volume of the ethanol extract aqueous solution. After the extraction, the ethyl acetate phases were combined, and then distilled under reduced pressure on a rotary evaporator. The temperature was controlled to be not higher than 55°C. The extract was collected, and then dried in a vacuum drying oven. The drying temperature was controlled to be not higher than 40°C to obtain an ethyl acetate extract of Suillus granulatus;

[0064] Step three, the ethyl acetate extract of Leucopaxillus gregarius is fully stirred with silica gel particles (100-200 mesh), the mass ratio of the extract and silica gel particles is 1:2, dried, ground, and the ground material is added to a silica gel (200-300 mesh) chromatographic column, and gradient elution is carried out under normal pressure with dichloromethane-methanol solution, the gradient elution process is as follows: 100:0 and 50:1 of dichloromethane-methanol solution by volume ratio is used for elution, respectively, 5 column volumes for each gradient elution, the eluent is discarded, then 30:1, 20:1 and 15:1 of dichloromethane-methanol solution is used for elution, respectively, 5 column volumes for each gradient elution, the eluents of the three gradients are combined, and sample a is obtained by distillation under reduced pressure at 45℃;

[0065] Step four, sample a is added to a reversed phase silica gel (ODS, 5 μm, 12 nm) chromatographic column, and elution is carried out with methanol-water solution with a volume ratio of 1:9, 1:4, 3:7 and 2:3, respectively, in sequence, 5 column volumes for each gradient elution, the eluent is discarded, then elution is carried out with methanol-water solution with a volume ratio of 1.5:1, 5 column volumes, the collected eluent is concentrated and dried, and the benzyl chromone compound shown in formula I is obtained.

[0066] Example 4

[0067] Structure determination of the benzyl chromone compound shown in formula I:

[0068] The structural formula of the benzyl chromone compound in the application is determined based on high resolution mass spectrometry, nuclear magnetic resonance and ultraviolet spectroscopy, etc., see Figures 1 to 7 .

[0069] Ultraviolet data: UV (MeOH) λmax (logε) 285 (4.72), 347 (3.21) nm.

[0070] High resolution mass spectrometry data: HRESI-MS m / z 299.0555 [M-H] - , Calcd for 300.0634.

[0071] The relevant nuclear magnetic data are shown in the following table:

[0072] Table 1 Nuclear magnetic resonance spectroscopy data of the compound of the application

[0073] No. 1 H NMR ​ 13 C NMR ​ 2 ― 154.2(s) 3 ― 138.9(s) 4 ― 174.4(s) 5 7.38 (1H, d, 2.8) 108.1(d) 6 ― 155.7(s) 7 7.16 (1H, dd, 9.1, 2.8) 124.1(d) 8 7.37 (1H, d, 9.1) 120.5(d) 9 ― 151.1(s) 10 ― 124.1(s) 1’ ― 129.5(s) 2’ 6.77 (1H, d, 1.6) 116.9(d) 3’ ― 146.4(s) 4’ ― 145.3(s) 5’ 6.68 (1H, d, 8.1) 116.5(d) 6’ 6.65 (1H, dd, 8.1, 1.6) 121.3(d) 7’ 3.97 (2H, s) 35.1(t)

[0074] Through the above data, it is finally determined that the structures of the benzyl chromone compounds obtained by separation and purification in Example 1-Example 3 are as follows:

[0075]

[0076] The chemical name of the compound is 2-(3,4-dihydroxybenzyl)-3,6-dihydroxy-4H-chromen-4-one, the molecular weight is 300.0634, the molecular formula is C 16 H 12 O6, yellow oil, soluble in organic solvents such as methanol, ethanol, ethyl acetate, etc.

[0077] Example 5

[0078] Effect on the proliferation of liver cancer cells HepG2

[0079] CCK-8 experiment is a commonly used method for cell proliferation and toxicity detection, which is based on the reaction of WST-8 reagent with dehydrogenase in cells to generate formazan dye. The proliferation of cells and the toxicity of drugs to cells can be quantitatively analyzed by measuring the absorbance value of formazan dye in the culture medium.

[0080] HepG2 cells were prepared into a 5×10 4 cell / mL cell suspension with complete culture medium (serum-free DMEM medium + fetal bovine serum), inoculated into a 96-well plate at 100 μL per well, cultured for 24 h, and centrifuged to allow the cells to adhere. The benzyl chromone compound obtained by separation in the example was dissolved into a 10 mM stock solution with anhydrous ethanol, and then diluted with complete culture medium to different concentrations (5 μM, 10 μM, 20 μM, 40 μM, 80 μM, 160 μM, 320 μM) to obtain sample solutions of different concentrations. The culture medium was discarded, and sample solutions of different concentrations were added to each group of 6 repeated wells, and cultured for 24 h. The culture medium was discarded, 100 μL of serum-free DMEM medium was added to each well, and 10 μL of CCK-8 reagent was added to each well. The 96-well plate was again placed in the incubator for 1 h, and the absorbance of the solution at 450 nm was detected in the enzyme marker instrument. The cell survival rate was calculated. At the same time, cisplatin was used as a positive control, and the preparation method of the cisplatin solution was the same as that of the benzyl chromone compound. Cisplatin solutions of different concentrations (5 μM, 10 μM, 20 μM, 40 μM, 80 μM, 160 μM, 320 μM) were prepared, and the above operation was repeated. At the same time, a control group without sample solution and a blank group containing only DMEM culture medium and CCK-8 solution were set.

[0081] Cell survival rate = [(OD1-OD0) / (OD2-OD0)]×100%

[0082] Wherein, OD1 refers to the OD value of the sample solution containing cells, DMEM culture medium, CCK-8 solution and sample solution; OD2 refers to the OD value of the control group containing cells, DMEM culture medium and CCK-8 solution; OD0 refers to the OD value of the blank well containing only DMEM culture medium and CCK-8 solution.

[0083] The test results are shown in Table 1 and Figure 1. Figure 8 As shown in Table 1 and Figure 1, the results show that the benzyl chromone compounds provided by the present application and the positive control cisplatin have dose-dependent inhibitory effects on the proliferation of HepG2 cells, and the benzyl chromone compounds provided by the present application have greater inhibitory effects on the proliferation of HepG2 cells than cisplatin except for the concentrations of 160 μM and 320 μM.

[0084] Table 1 HepG2 cell survival rate (%)

[0085] Concentration (μM) 5 10 20 40 80 160 320 General Formula (I) 76.4±5.6 60.0±5.7 17.1±1.1 10.5±0.6 6.6±0.1 8.5±0.3 4.4±0.4 Cisplatin 97.6±4.8 73.8±3.0 42.2±5.0 19.1±1.6 8.4±0.3 7.1±1.6 3.9±0.5

[0086] In summary, the separation and purification method of the benzyl chromone compounds provided by the present application, by selecting a specific separation method combined with the optimal combination of process parameters, through a one-time separation process, the benzyl chromone compounds having obvious inhibitory activity on liver cancer cells are obtained, which provides a new idea for the prevention and treatment of liver cancer, and the separation and purification process does not require special equipment, the process operation is simple, the extraction efficiency is high, and has a broad application prospect.

[0087] The above only describes the preferred embodiments of the present application and is not intended to limit the present application, and any modification, equivalent replacement or improvement made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A benzylchromone compound, characterized by, The structure is shown as formula I:

2. A method of preparing the benzyl chromone compound according to claim 1, characterized by, The method comprises the following steps: Step one, the alcohol extraction concentrated extract of Suillus granulatus is prepared by the following method: the dried fruiting bodies of Suillus granulatus are crushed, 3-5 times of ethanol by volume of the dried fruiting bodies is added, and the extraction is performed for 2-4 times, and the alcohol extraction concentrated extract of Suillus granulatus is obtained by vacuum concentration. In step one, the volume ratio of the alcohol extraction concentrated extract of Suillus granulatus to water is 1:2-1:

10. In step one, the volume ratio of the alcohol extract aqueous solution to ethyl acetate is 1:1-1:

2.

3. The method of claim 2, wherein the benzhydrol is prepared by the reaction of benzaldehyde with a reducing agent in the presence of a base. In step one, the extraction is performed for 2-4 times.

4. The method of claim 2, wherein the benzhydrol is prepared by the reaction of benzaldehyde with a reducing agent in the presence of a base. In step two, the mass ratio of the ethyl acetate extract of Suillus granulatus to silica gel is 1:1.5-1:2; and / or 5. The method of claim 2, wherein the benzhydrol is prepared by the reaction of benzaldehyde with a reducing agent in the presence of a base. In step two, the particle size of the silica gel particles is 100-200 meshes; and / or 6. The method for preparing benzylchromone compounds as described in claim 2, characterized in that, In step two, the particle size of the silica gel filled in the silica gel chromatographic column is 200-300 meshes.

7. The method for preparing benzylchromone compounds as described in claim 2, characterized in that: In step three, the reverse-phase silica gel chromatographic column is an octadecylsilane bonded silica gel chromatographic column. In step three, the specifications of the filler in the reverse-phase silica gel chromatographic column are that the particle size is 5 μm and the pore size is 12 nm.

10. The benzyl chromone compound of claim 1 in the preparation of an anti-liver cancer drug.

8. The method for preparing benzylchromone compounds as described in claim 2, characterized in that, ​ 9. The method of producing the benzylchromone compound according to claim 2 or 8, characterized by, ​ ​

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