CN117229146A - Caffeic acid phenethyl ester derivative and preparation method and application thereof - Google Patents

Abstract

The invention discloses a derivative of caffeic acid phenethyl ester or a pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutical composition containing the same. Such compounds have good anti-tumor effects and can effectively inhibit tumor cells. of proliferation. The present invention also discloses the preparation method of such compounds and their use in preparing drugs for preventing and/or treating tumors.

Description

A kind of caffeic acid phenethyl ester derivative and its preparation method and use

Technical field

The invention belongs to the field of medical technology, and specifically relates to a caffeic acid phenethyl ester derivative and its preparation method and use.

Background technique

Diffuse Large B Cell Lymphoma (DLBCL) is a rapidly growing hematologic malignancy and one of the most common types of non-Hodgkin lymphoma. The annual incidence of DLBCL in adults is approximately 7-8 cases per 100,000 people. The disease mainly affects older people, with the average age at diagnosis being around 70 years old, but it can occur at any age.

Epstein-Barr virus is a virus that exists widely in the human population and mainly targets B lymphocytes. Most people have been infected during adolescence, and the infection lasts for life and usually does not cause obvious symptoms. However, in some cases, EBV infection can cause some hematological malignancies, such as non-Hodgkin lymphoma, of which EBV-positive DLBCL (EBV+DLBCL) is one of them. EBV-infected B cells result in latent infection, and most EBV-infected B cells are eliminated by cytotoxic T cells and NK cells, but some EBV-infected B cells escape by downregulating antigen expression. They then pass through the germinal centers and subsequently exist as EBV-infected memory cells. EBV-infected B cells will express viral proteins, such as LMP1, EBNA1, EBNA2, etc. Among them, LMP1 is a transmembrane protein related to cell cycle and apoptosis regulation, which promotes the growth of virus-invasive B cells. EBNA1 is a nuclear antigenic protein that plays a key role in the replication and stability maintenance of viral genomes. EBNA2 participates in the activation of early and late transcription of EBV and plays a role in the expression of other genes. The functions of these proteins are closely related to the processes of EBV infection, replication, and cell transformation.

The frequency of EBV-positive DLBCL in DLCBL is approximately 2.5-14.0%, with a higher incidence in East Asian populations. Most cases occur in patients over 50 years old, predominantly male. Compared with EBV-DLBCL, the clinical characteristics of EBV+DLBCL include older age, more advanced clinical stage, higher rate of extranodal involvement, and worse physical status.

EBV+DLBCL is also usually treated with R-CHOP, which consists of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. The response rate of EBV-positive patients and EBV-negative patients to first-line treatment (complete remission or partial remission) was 72% and 92.3% respectively (P=0.006), that is, the response rate of EBV-positive DLBCL patients to first-line treatment was significantly lower. The 5-year OS and PFS rates of EBV+DLBCL patients were 58.9% and 48.6% respectively. Compared with EBV-negative patients, EBV+DLBCL patients had worse OS and PFS. Therefore, there is an urgent clinical need for new drugs or pharmaceutical compositions that can effectively treat EBV+DLBCL and DLBCL.

Caffeic acid phenethyl ester (CAPE) is a natural product commonly found in plant propolis. Its structural formula is as follows:

Its chemical structure is phenylene glycol caffeic acid. CAPE has a variety of biological activities and is widely used in medicine, food, cosmetics and other fields. Research shows that CAPE has various biological activities such as antioxidant, anti-inflammatory, antibacterial, antiviral, and anti-tumor. It also has the functions of regulating the immune system, lowering cholesterol, inhibiting platelet aggregation, and promoting skin repair. In recent years, the anti-tumor effect of CAPE has received widespread attention and research. Experiments have shown that CAPE can induce tumor cell apoptosis, inhibit tumor cell proliferation, and prevent tumor cell invasion and metastasis. In addition, CAPE can also increase the activity of immune cells, strengthen the body's immunity, and reduce the side effects of radiotherapy and chemotherapy.

Therefore, the development of a class of caffeic acid phenethyl ester derivatives is of great significance for the study of new drugs or pharmaceutical compositions for the treatment of EBV+DLBCL and DLBCL.

Contents of the invention

Object of the invention: The object of the present invention is to provide a (E)-3-(5,6-dihydroxy-2-naphthylene)acrylate compound of general formula I or a pharmaceutically acceptable salt or stereoisomer thereof. :

in,

R is selected from -H, -F, -Cl, -Br, -I, -CF ₃ , -CCl ₃ , -NO ₂ , -COCH ₃ , -OCOCH ₃ , -CH ₃ , -OCH ₃ , -OC ₂ H ₅ , -NH ₂ , -NHSO ₂ CH ₃ , -SO ₂ NH ₂ or NHCOCH ₃ ;

n=1, 2, 3, 4 or 5.

In some preferred embodiments, the pharmaceutically acceptable salts include acid addition salts of compounds of formula I and the following acids: hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, benzenesulfonic acid, p- Toluenesulfonic acid, naphthalenesulfonic acid, citric acid, tartaric acid, lactic acid, pyruvic acid, acetic acid, maleic acid or succinic acid, fumaric acid, salicylic acid, phenylacetic acid, mandelic acid; also includes compounds of general formula I and inorganic Acid salts formed from bases.

In some more preferred embodiments, the pharmaceutically acceptable salts include basic metal cation salts, alkaline earth metal cation salts and ammonium cation salts.

The compounds of general formula I of the present invention are preferably the following compounds: (E)-3-(5,6-dihydroxy-2-naphthylene)phenylethyl acrylate, (E)-3-(5,6-dihydroxy-2 -Naphthylene)phenylpropyl acrylate, (E)-3-(5,6-dihydroxy-2-naphthylene)phenylbutyl acrylate, (E)-3-(5,6-dihydroxy-2-naphthylene) Phenylhexyl acrylate, (E)-3-(5,6-dihydroxy-2-naphthylene)phenylhexyl acrylate, (E)-3-(5,6-dihydroxy-2-naphthylene) 2-Fluorophenylethyl acrylate, (E)-3-(5,6-dihydroxy-2-naphthylene)acrylate-2-Fluorophenylpropyl acrylate, (E)-3-(5,6- Dihydroxy-2-naphthylene)acrylic acid-2-fluorophenylbutyl ester, (E)-3-(5,6-Dihydroxy-2-naphthylene)acrylic acid-2-fluorophenylbutyl ester, (E) -2-fluorophenylhexyl 3-(5,6-dihydroxy-2-naphthylene)acrylate.

The compounds of general formula I of the present invention are further preferably the following compounds:

The above-mentioned compounds of formula I involved in the present invention can also exist in the form of their salts, which are converted into compounds of formula I in vivo. For example, it is within the scope of the present invention to convert the compounds of the present invention into the form of a pharmaceutically acceptable salt according to procedures known in the art and to use them in the salt form.

All tautomeric forms of the compounds of formula I of this invention are included within the scope of this invention. The compounds of the present invention may exist in specific geometric or stereoisomeric forms. There may be additional asymmetric carbon atoms in the alkyl and other substituents, and all these isomers, as well as their mixtures, are included within the scope of the present invention.

Another object of the present invention is to provide a preparation method of the compound of general formula I, comprising the following steps:

(1) Evenly disperse 6-bromo-2-naphthol, 1,3-bis(diphenylphosphine)propane and palladium acetate in DMF, then add triethylamine and ethyl acrylate in sequence, under argon protection , heated and reacted at 115°C overnight, and post-processed to obtain a crude product, which was subjected to silica gel column chromatography to obtain a white solid;

(2) Dissolve the above solid in ethanol, add potassium hydroxide and stir thoroughly until the reaction is complete to obtain a white solid;

(3) Dissolve the above white solid in tetrahydrofuran for later use, then dissolve the alcohol fragment and triphenylphosphine in tetrahydrofuran, add diisopropyl azodicarboxylate to phenylethyl alcohol and triphenylphosphine under ice bath conditions into the tetrahydrofuran solution, stir thoroughly, then add the initially prepared tetrahydrofuran solution to the reaction system in the ice bath, move the system to room temperature, stir thoroughly, and post-process to obtain a crude product, which is subjected to silica gel column chromatography to obtain a white solid;

(4) Dissolve the white solid in the previous step in DMSO, then add 2-iodoacylbenzoic acid to the reaction system, and stir thoroughly. The reaction system changes from colorless to yellow, and finally to orange-red, and is post-processed to obtain an orange-red solid;

(5) Dissolve the above orange-red solid in acetonitrile, add sodium dithionite aqueous solution to the above acetonitrile solution, stir thoroughly under argon protection, the reaction system changes from orange-red to light yellow, post-process to obtain a crude product, and column the crude product Chromatographic separation yielded a white solid as the target compound.

The compounds of general formula I of the present invention can be prepared by the above-mentioned or similar preparation methods, and the corresponding starting materials can be selected according to the different substituents. Those skilled in the art should realize that the above route is helpful for understanding the present invention, but does not limit the content of the present invention. Unless otherwise specified, the variables are defined as mentioned in general formula I.

Another object of the present invention is to provide a pharmaceutical composition, which includes a compound of formula I or a pharmaceutically acceptable salt thereof, a stereoisomer, and a pharmaceutically acceptable carrier or excipient.

The pharmaceutical compositions of the present invention may be administered in a variety of known ways, such as orally, parenterally, by inhalation spray or via an implanted depot. The pharmaceutical composition of the present invention can be administered alone or in combination with other anti-tumor drugs. Oral compositions can be in any orally acceptable dosage form, including, but not limited to, tablets, capsules, emulsions, and suspensions, dispersions, and solutions. Commonly used pharmaceutically acceptable carriers or excipients include stabilizers, diluents, surfactants, lubricants, antioxidants, adhesives, colorants, fillers, emulsifiers, etc.

Sterile injectable compositions may be formulated according to techniques known in the art using suitable dispersing or wetting agents and suspending agents. Pharmaceutically acceptable carriers and solvents that can be used include water, mannitol, sodium chloride solution, and the like.

The actual dosage levels of the active ingredients in the pharmaceutical compositions of the present invention can be varied to obtain an amount of active ingredient that is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration without being toxic to the patient. The dosage level selected will depend on a variety of factors, including the activity of the particular compound of the invention or salt thereof employed, the route of administration, the time of administration, the rate of excretion of the particular composition employed, the duration of treatment, and the The specific compositions are combined with other drugs, compounds and/or materials, the age, sex, weight, general health and past medical history of the patient being treated, and similar factors well known in the medical field.

Another object of the present invention is to provide the use of a compound of general formula I or a pharmaceutically acceptable salt or stereoisomer thereof in the preparation of a medicament for the prevention and/or treatment of tumors.

The tumors include Epstein-Barr virus-positive diffuse large B-cell lymphoma, diffuse large B-cell lymphoma, hepatocellular carcinoma or glioma.

Beneficial effects:

The invention synthesizes a type of derivative of caffeic acid phenethyl ester, which is called (E)-3-(5,6-dihydroxy-2-naphthylene)acrylate compound. Pharmacological experiments have proven that the caffeic acid phenethyl ester derivative of the present invention has good anti-tumor effects, can effectively inhibit the proliferation of tumor cells, and has good prospects in the development of anti-tumor drugs.

Detailed ways

The preparation methods of the compound of formula I of the present invention are described below with reference to specific examples, but these specific methods do not constitute any limitation to the present invention. The compounds of the present invention can also be optionally prepared by combining various synthetic methods described in the specification or known in the art, and such combinations can be easily performed by those skilled in the art to which the present invention belongs.

The starting materials, reaction reagents, etc. used in the specific embodiments of the present invention are all commercially available. The present invention can adopt salt-forming methods commonly used in this field to prepare the salt form. For example, at room temperature, the compound is dissolved in hydrochloric acid ethanol and reacted to generate the hydrochloride; or benzenesulfonic acid is added thereto to react to generate benzenesulfonic acid. Salt. Example 32 lists the synthesis method of the hydrochloride salt of compound I-27. This method can be referred to for the synthesis of salts of other compounds. Other salts can also be formed using methods commonly used in the art.

Example 1 (E) Synthesis of phenethyl 3-(5,6-dihydroxy-2-naphthylene)acrylate

6-bromo-2-naphthol (300mg, 1.34mmol), 1,3-bis(diphenylphosphine)propane (DPPP, 54mg, 0.13mmol), palladium acetate (Pd(OAc) 2,30mg, 0.13mmol) ) in a schlenk tube, disperse evenly in 3ml DMF (N,N-dimethylformamide), add triethylamine (541mg, 5.36mmol), ethyl acrylate (1.3g, 13.40mmol) in sequence, and infuse under argon Under protection, heat the reaction at 115°C overnight. Monitor the reaction for completeness the next day. Cool the system to room temperature, extract with ethyl acetate and water, combine the organic phases, wash the organic phase with saturated sodium chloride solution, and use Dry over anhydrous sodium sulfate and concentrate under reduced pressure. The crude product was subjected to silica gel column chromatography and eluted with n-hexane:ethyl acetate (volume ratio 8:1) mixed solvent to obtain a white solid.

Dissolve the above solid (300 mg, 1.24 mmol) in 4 ml of ethanol, add potassium hydroxide (208 mg, 3.72 mmol) and stir thoroughly for 3 hours. After monitoring the reaction is complete, add 20 ml of water to dilute, wash the water layer three times with dichloromethane, and The pH of the aqueous layer was adjusted to acidic with 1N hydrochloric acid, the aqueous layer was extracted with ethyl acetate, the organic phases were combined, the organic phase was washed with saturated sodium chloride solution, the resulting organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting white solid was obtained.

Dissolve the above white solid (500mg, 2.33mmol) in 2ml tetrahydrofuran (THF) and set aside. Then dissolve phenylethyl alcohol (2.33mmol) and triphenylphosphine (TPP, 612mg, 2.33mmol) in 4ml tetrahydrofuran (THF). Add diisopropyl azodicarboxylate (DIAD, 463 mg, 2.33 mmol) dropwise to 4 ml of the tetrahydrofuran solution of phenyl alcohol and triphenylphosphine under ice bath conditions, stir thoroughly for 15 minutes, and then add the initially prepared tetrahydrofuran solution. Add the reaction system in the ice bath dropwise, and move the system to room temperature and stir thoroughly. After TLC monitors the complete reaction of the raw materials, add water to quench. Extract with ethyl acetate, combine the organic phases, wash the organic phase with saturated sodium chloride solution, dry the obtained organic phase with anhydrous sodium sulfate and concentrate under reduced pressure. The crude product was subjected to silica gel column chromatography and eluted with n-hexane:ethyl acetate (volume ratio 8:1) mixed solvent to obtain a white solid.

Dissolve the white solid (0.87mmol) in the previous step in 2ml DMSO, then add 2-iodobenzoic acid (IBX, 269mg, 0.96mmol) to the reaction system, stir thoroughly, the reaction system changes from colorless to yellow, and finally to orange. Red, TLC monitors that after the raw material reaction is complete, add water to quench the reaction. Extract with ethyl acetate, combine the organic phases, wash the organic phase with saturated sodium chloride solution, dry the obtained organic phase with anhydrous sodium sulfate and concentrate under reduced pressure to obtain an orange-red solid.

Dissolve the above orange-red solid in 2 ml of acetonitrile (MeCN), dissolve sodium dithionite (Na ₂ S ₂ O ₄ , 166 mg, 0.96 mmol) in 2 ml of water, and slowly add the aqueous sodium dithionite solution to the acetonitrile solution of the above-mentioned orange-red solid. , stir thoroughly under the protection of argon, and the reaction system gradually changes from orange-red to light yellow. After TLC monitors that the reaction is complete, acetonitrile is removed by rotary evaporation under reduced pressure, and then extracted three times with ethyl acetate. The organic phases are combined, dried over anhydrous sodium sulfate, and spin-dried to remove ethyl acetate before making sand. The obtained sand sample was separated by column chromatography and eluted with a mixed solvent of n-hexane:ethyl acetate (volume ratio 8:1) to obtain a white solid as the compound.

1H NMR (300MHz, Methanol-d4) δ (ppm) 7.86-7.55 (m, 5H), 7.36-7.06 (m, 7H), 6.48 (d, J = 15.9Hz, 1H), 4.39 (t, J = 7.0 Hz, 2H), 3.00 (t, J = 7.0Hz, 2H); 13C NMR (75MHz, Methanol-d4) δ 167.55, 145.46, 138.00, 136.25, 130.10, 130.01, 128.91, 128.64, 128.17, 128.07, 126.71, 126. 19, 123.47,118.70,115.78,108.81,64.89,34.79.; MS(ESI)m/z,335.12[M+H] ⁺ .

Example 2 (E)-3-(5,6-dihydroxy-2-naphthylene)phenylpropyl acrylate

Refer to the synthesis method of Example 1.

1H NMR (300MHz, Methanol-d4) δ (ppm) 7.86-7.55 (m, 5H), 7.36-7.06 (m, 7H), 6.48 (d, J = 15.9Hz, 1H), 4.39 (t, J = 7.0 Hz,2H),3.00(t,J＝7.0Hz,2H),2.08(m,2H);13CNMR(75MHz,Methanol-d4)δ167.55,145.46,138.00,136.25,130.10,130.01,128.91,128.64,128.17, 128.07,126.71,126.19,123.47,118.70,115.78,108.81,64.89,34.79,21.06; MS(ESI)m/z,349.12[M+H] ⁺ .

Example 3 (E)-Phenylbutyl 3-(5,6-dihydroxy-2-naphthylene)acrylate

Refer to the synthesis method of Example 1.

1H NMR (300MHz, Methanol-d4) δ (ppm) 7.86-7.55 (m, 5H), 7.36-7.06 (m, 7H), 6.48 (d, J = 15.9Hz, 1H), 4.39 (t, J = 7.0 Hz, 2H), 3.00 (t, J = 7.0Hz, 2H), 1.78 (m, 4H); 13CNMR (75MHz, Methanol-d4) δ 167.55, 145.46, 138.00, 136.25, 130.10, 130.01, 128.91, 128.64, 128.17, 128.07,126.71,126.19,123.47,118.70,115.78,108.81,64.89,34.79,21.06,20.56; MS(ESI)m/z,363.12[M+H] ⁺ .

Example 4: Biological activity

Test method: Prepare a specific small molecule compound into a 100mM stock solution.

For the suspension cells Farage and MC116, place them into a 96-well plate at a density of 6000 cells/well and 60 μL per well, and prepare the corresponding small molecule stock solution to 600 μM, and 3-fold gradient dilution of the drug-containing culture medium. The working solution was added into the wells of the culture plate where the cells were seeded at a volume of 30 μL per well. After culturing for 48 hours, the absorbance was measured using the CCK8 method, and the IC ₅₀ value was calculated using Graphpad Prism.

For adherent cells Hep3B and U87, place them into a 96-well plate at a density of 3000 cells/well and 100 μL per well, prepare the corresponding small molecule stock solution to 200 μM, and dilute the drug-containing culture medium 3 times in a gradient. Discard the original culture medium after walling, and add the serially diluted working solution at a volume of 100 μL per well into the wells of the culture plate where the cells were seeded. After culturing for 48 hours, measure the absorbance using the CCK8 method, and use Graphpad Prism to calculate its IC. ₅₀ value. The experimental results are shown in Table 1. CAPE was used as a positive control drug.

Table 1 IC ₅₀ values (μM) of the anti-proliferative activity of the examples on four human cancer cell lines

compound Farage MC116 Hep3B U87 Example 1 0.873 2.546 48.338 61.584 Example 2 0.998 2.235 49.524 58.452 Example 3 0.924 1.687 50.127 53.696 CAPE 1.525 2.762 58.667 69.935

Farage cells were originally derived from an EBV-positive B-cell lymphoma patient, therefore, Farage cells are EBV-positive; MC116 cells are a type of B lymphocyte used for experimental research on B lymphocyte-related diseases, including the study of DLBCL; Hep3B The cells are a liver cancer cell line widely used in liver cancer research; the U87 cells are a human glioblastoma cell line widely used in glioma and cancer research.

As can be seen from Table 1, the IC ₅₀ values of the compounds of Example 1, Example 2 and Example 3 for various cell lines are all lower than CAPE, and they can effectively inhibit EBV+DLBCL, EBV-DLBCL, hepatocellular carcinoma and In vitro growth of glioblastoma cell lines.

The above experimental results show that the compounds provided by the invention can effectively inhibit the in vitro growth of EBV+DLBCL, EBV-DLBCL, HCC and glioblastoma cell lines.

The above compounds of the present invention and their medically acceptable salts can effectively inhibit the in vitro growth of EBV+DLBCL, EBV-DLBCL, HCC and glioblastoma cell lines, and can be used as active ingredients in pharmaceuticals. Therefore, drugs containing the above compounds as active ingredients can be used to prepare drugs for preventing and/or treating tumors.

As stated above, although the present invention has been shown and described with reference to specific preferred embodiments, this is not to be construed as limiting the invention itself. Various changes may be made in form and details without departing from the spirit and scope of the invention as defined by the appended claims.

Claims (9)

1. A (E)-3-(5,6-dihydroxy-2-naphthylene)acrylate compound of general formula I or a pharmaceutically acceptable salt or stereoisomer thereof: in, R is selected from -H, -F, -Cl, -Br, -I, -CF ₃ , -CCl ₃ , -NO ₂ , -COCH ₃ , -OCOCH ₃ , -CH ₃ , -OCH ₃ , -OC ₂ H ₅ , -NH ₂ , -NHSO ₂ CH ₃ , -SO ₂ NH ₂ or NHCOCH ₃ ; n=1, 2, 3, 4 or 5. 2. The compound according to claim 1, characterized in that: the pharmaceutically acceptable salts include acid addition salts formed by the compound of formula I and the following acids: hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonate Acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, citric acid, tartaric acid, lactic acid, pyruvic acid, acetic acid, maleic or succinic acid, fumaric acid, salicylic acid, phenylacetic acid, mandelic acid; also Including acid salts formed by compounds of general formula I and inorganic bases. 3. The compound according to claim 2, wherein the pharmaceutically acceptable salts include basic metal cation salts, alkaline earth metal cation salts and ammonium cation salts. 4. The compound according to claim 1, characterized in that it is selected from: (E)-3-(5,6-dihydroxy-2-naphthylene) phenethyl acrylate, (E)-3-(5, 6-Dihydroxy-2-naphthylene)phenylpropyl acrylate, (E)-3-(5,6-dihydroxy-2-naphthylene)phenylbutyl acrylate, (E)-3-(5,6- Dihydroxy-2-naphthylene)phenyl acrylate, (E)-3-(5,6-dihydroxy-2-naphthylene)phenylhexyl acrylate, (E)-3-(5,6-dihydroxy -2-Fluorophenylethyl 2-naphthylene)acrylate, (E)-3-2-Fluorophenylpropyl 3-(5,6-dihydroxy-2-naphthylene)acrylate, (E)-3 -(5,6-dihydroxy-2-naphthylene)acrylic acid-2-fluorophenylbutyl ester, (E)-3-(5,6-dihydroxy-2-naphthylene)acrylic acid-2-fluorophenyl Pentyl ester, (E)-3-(5,6-dihydroxy-2-naphthylene)acrylate-2-fluorophenylhexyl ester. 5. The compound according to claim 4, characterized in that it is selected from: 6. A preparation method of the compound of general formula I according to claim 1, characterized in that: comprising the following steps: (1) Evenly disperse 6-bromo-2-naphthol, 1,3-bis(diphenylphosphine)propane and palladium acetate in DMF, then add triethylamine and ethyl acrylate in sequence, under argon protection , heated and reacted at 115°C overnight, and post-processed to obtain a crude product, which was subjected to silica gel column chromatography to obtain a white solid; (2) Dissolve the above solid in ethanol, add potassium hydroxide and stir thoroughly until the reaction is complete to obtain a white solid; (3) Dissolve the above white solid in tetrahydrofuran for later use, then dissolve the alcohol fragment and triphenylphosphine in tetrahydrofuran, add diisopropyl azodicarboxylate to phenylethyl alcohol and triphenylphosphine under ice bath conditions into the tetrahydrofuran solution, stir thoroughly, then add the initially prepared tetrahydrofuran solution to the reaction system in the ice bath, move the system to room temperature, stir thoroughly, and post-process to obtain a crude product, which is subjected to silica gel column chromatography to obtain a white solid; (4) Dissolve the white solid in the previous step in DMSO, then add 2-iodoacylbenzoic acid to the reaction system, and stir thoroughly. The reaction system changes from colorless to yellow, and finally to orange-red, and is post-processed to obtain an orange-red solid; (5) Dissolve the above orange-red solid in acetonitrile, add the sodium dithionite aqueous solution to the above acetonitrile solution, stir thoroughly under argon protection, the reaction system changes from orange-red to light yellow, post-process to obtain a crude product, and column the crude product Chromatographic separation yielded a white solid as the target compound. 7. A pharmaceutical composition, characterized by comprising the compound of any one of claims 1 to 5 or a pharmaceutically acceptable salt, stereoisomer thereof, and a pharmaceutically acceptable carrier or excipient. 8. Use of the compound according to any one of claims 1 to 5 in the preparation of medicaments for the prevention and/or treatment of tumors. 9. The use according to claim 8, wherein the tumor includes Epstein-Barr virus-positive diffuse large B-cell lymphoma, diffuse large B-cell lymphoma, hepatocellular carcinoma or glioma.