Polyboronic acid-substituted phenylalanine compounds, their preparation methods and applications

Abstract

This invention discloses a polyboronic acid-substituted phenylalanine compound, its preparation method, and its application, belonging to the field of tumor therapeutic drug technology. The structure of the polyboronic acid-substituted phenylalanine compound is shown in formula (I). Under normal conditions, this compound has no obvious cytotoxicity and can be effectively taken up by tumor cells at high concentrations, exhibiting better efficacy than BPA currently approved for clinical use. It can overcome the problems of poor water solubility, poor targeting, and low drug enrichment in tumor tissues of small molecule boron drugs in the current field of boron neutron capture cancer therapy.

Description

Technical Field

[0001] This invention belongs to the field of tumor therapeutic drug technology, specifically relating to polyboronic acid-substituted phenylalanine compounds, their preparation methods, and applications. Background Technology

[0002] Boron neutron capture therapy (BNCT) is a next-generation, cell-level precision binary targeted tumor therapy that combines biological targeting with the effects of heavy ions. It selectively and precisely kills cancer cells at the cellular level. Its principle involves using boron neutrons carrying non-radioactive nuclides... 10 B-targeted drugs are injected into the patient's body. 10 B will specifically accumulate in tumor tissue, and the affected area will be irradiated with hyperthermic neutrons. The neutrons and 10 B occurred 10 B(n,α) 7 Li nuclear reaction, forming its isotopes 11 B, which then splits to produce high energy. 7 Li ions and alpha particles have a radiation range of only about one cell diameter (5 micrometers and 9 micrometers, respectively). Cancer cells are precisely killed because their DNA undergoes irreversible breaks under the influence of heavy ions, while normal cells remain largely undamaged. BNCT has a significant advantage for treating mid-to-late-stage malignant tumors that are untreatable by surgery or traditional radiotherapy and chemotherapy. The therapeutic effect of BNCT depends on... 10 Whether boron atoms can selectively and at high concentrations accumulate in tumor cells. Key performance indicators for boron-containing drugs are the tumor / normal tissue (T / N) and tumor / blood (T / B) ratios. 10 The B concentration ratio is greater than 3:1, and each tumor cell contains at least 10 9 indivual 10 B atoms, thereby reducing the side effects of treatment while ensuring the tumor-killing power of BNCT.

[0003] Currently, only 4-dihydroxyboron-L-phenylalanine (BPA) is approved for clinical use in BNCT (tumor-associated tumor repair). However, BPA has drawbacks such as insufficient tumor specificity, short blood half-life, and short retention time. In particular, BPA has poor water solubility and low boron loading, resulting in low boron atom enrichment in tumor tissue. Furthermore, the extensive use of fructose as an excipient to improve its water solubility significantly increases nephrotoxicity, severely limiting the therapeutic effect of BNCT. Therefore, developing a small-molecule boron drug with high water solubility, high targeting, and high tumor enrichment capacity is crucial to improving the clinical efficacy of BNCT. Summary of the Invention

[0004] In order to overcome the shortcomings of the prior art, the present invention aims to provide polyboronic acid-substituted phenylalanine compounds, their preparation methods and applications, in order to solve the technical problems of poor water solubility, low boron loading, poor targeting and low tumor tissue enrichment of BPA.

[0005] To achieve the above objectives, the present invention employs the following technical solution:

[0006] The first aspect of the invention discloses polyboronic acid-substituted phenylalanine compounds having compounds of formula (I) or pharmaceutically acceptable salts thereof, as well as stereoisomers, derivatives, and isotopic products of said compound (I) or pharmaceutically acceptable salts thereof:

[0007]

[0008] Among them, at least two of the groups R1 to R5 are B(OH)2, and the rest are H.

[0009] Preferably, in B(OH)2, B is... 10 B.

[0010] A second aspect of the present invention discloses a method for preparing the above-mentioned polyboronic acid-substituted phenylalanine compound, comprising the following steps:

[0011] 1) Polyhalotoluene reacts with a silylating agent via a Grignard reaction to yield polysilyl-substituted toluene;

[0012] 2) Polysilyl-substituted toluene undergoes halogenation or sulfonation to yield polysilyl-substituted benzyl halides or polysilyl-substituted benzyl sulfonates;

[0013] 3) The polysilyl-substituted benzyl halide or polysilyl-substituted benzyl sulfonate reacts with glycine-derived benzophenone Schiff base to obtain polysilyl-substituted phenylalanine derivatives.

[0014] 4) Polysilicic substituted phenylalanine derivatives react with boron trihalides to obtain polyboronic acid substituted phenylalanine compounds.

[0015] Preferably, the equivalence ratio of polyhalogenated toluene to silylating agent is 1:(2-50), the equivalence ratio of polysilyl substituted toluene to halogenating agent or sulfonating agent is 1:(1-5), the equivalence ratio of polysilyl substituted benzyl halide or polysilyl substituted benzyl sulfonate to glycine-derived benzophenone Schiff base is 1:(1-5), and the equivalence ratio of polysilyl substituted phenylalanine derivative to boron trihalide is 1:(1-15).

[0016] Preferably, the boron trihalide is 10 Boron trihalides enriched with boron (B).

[0017] A third aspect of the present invention discloses the use of the above-mentioned polyboronic acid-substituted phenylalanine compounds in the preparation of medicaments or preparations for treating tumors, or medicaments or preparations for inhibiting tumor progression.

[0018] In a fourth aspect, the invention discloses the use of the above-mentioned polyboronic acid-substituted phenylalanine compounds in the preparation of medicaments or formulations for the treatment of tumors by boron neutron capture.

[0019] Preferably, the tumor is glioblastoma multiforme, malignant meningioma, intramedullary spinal glioma, advanced or recurrent head and neck cancer, thyroid cancer, malignant melanoma, recurrent breast cancer, metastatic liver cancer, malignant brain tumor, osteosarcoma, lung cancer, squamous cell carcinoma of the skin, or nasopharyngeal carcinoma.

[0020] Preferably, the formulation is an injectable preparation made by mixing a polyboronic acid-substituted phenylalanine compound with physiological saline, phosphate buffer solution, sterile water or glucose solution.

[0021] Compared with the prior art, the present invention has the following beneficial effects:

[0022] The polyboronic acid-substituted phenylalanine compound provided by this invention introduces multiple sterically more sterically hindered boric acid groups into the molecule, thereby breaking the π-π stacking interaction between L-phenylalanine molecules. This results in a compound with better water solubility and higher boron loading. Under normal circumstances, it does not exhibit significant cytotoxicity and can be effectively taken up and retained within tumor cells. It shows better efficacy than currently approved BPA drugs and overcomes the problems of poor water solubility, low boron loading, poor targeting, and low tumor tissue enrichment of current small molecule BPA boron drugs. It has good application prospects in BNCT treatment. Attached Figure Description

[0023] Figure 1 Compound 4 in Example 1 of this invention 1 H NMR spectrum;

[0024] Figure 2 This is the high-resolution mass spectrum of compound 4 in Example 1 of the present invention;

[0025] Figure 3 The figure shows the cytotoxicity test results of compound 4 prepared in this invention;

[0026] Figure 4 The figure shows the experimental results of boron atom uptake of compound 4 prepared in this invention; where DPA represents the cells affected by compound 4. Detailed Implementation

[0027] To enable those skilled in the art to understand the features and effects of the present invention, the following descriptions and definitions are only general descriptions of the terms and expressions mentioned in the specification and claims. Unless otherwise specified, all technical and scientific terms used herein have the ordinary meaning understood by those skilled in the art regarding the present invention, and in the event of any conflict, the definitions in this specification shall prevail.

[0028] The theories or mechanisms described and disclosed herein, whether right or wrong, should not in any way limit the scope of the invention, that is, the contents of the invention can be implemented without being limited by any particular theory or mechanism.

[0029] In this document, all features defined by numerical ranges or percentage ranges, such as numerical values, quantities, contents, and concentrations, are for the sake of brevity and convenience only. Accordingly, descriptions of numerical ranges or percentage ranges should be considered as covering and specifically disclosing all possible sub-ranges and individual numerical values ​​(including integers and fractions) within those ranges.

[0030] For the sake of brevity, not all possible combinations of the technical features in each implementation scheme or embodiment are described herein. Therefore, as long as there is no contradiction in the combination of these technical features, the technical features in each implementation scheme or embodiment can be combined arbitrarily, and all possible combinations should be considered within the scope of this specification.

[0031] In this document, the term "boron neutron capture therapy" (BNCT) refers to a tumor treatment method comprising the steps of administering a boron-containing compound to the subject requiring treatment and irradiating the subject with thermal neutrons. The term "tumor" refers to the uncontrolled and progressive growth of tissue with proliferating cells. Uncontrolled proliferation is a state different from normal cell proliferation, such as a state of significantly increased cell proliferation rate. The term "progressive" refers to strong progression or increase. The term "tumor cell" refers to cells in histology. The term "tumor treatment" refers to the treatment of diseases caused by or related to tumors.

[0032] This invention provides polyboronic acid-substituted phenylalanine compounds having compounds of formula (I) or pharmaceutically acceptable salts thereof, as well as stereoisomers, derivatives, and isotopic products of said compound (I) or pharmaceutically acceptable salts thereof:

[0033]

[0034] Wherein: at least two of the groups R1 to R5 are B(OH)2, and the rest are H; preferably, B is... 10 B.

[0035] The structural formulas of representative compounds of the above-mentioned polyboronic acid-substituted phenylalanine compounds are as follows:

[0036]

[0037] The present invention also provides a method for preparing the above-mentioned polyboronic acid-substituted phenylalanine compound, comprising the following steps:

[0038] (1) The reactants polyhalotoluene (1 equivalent) reacted with magnesium powder (5-50 equivalents) and chlorosilane (2-50 equivalents) through Grignard reaction and silylation reaction to obtain polysilyl-substituted toluene;

[0039] The polyhalogenated toluene includes, but is not limited to, polychlorinated toluene or polybrominated toluene.

[0040] (2) Polysilyl-substituted toluene (1 equivalent) reacts with a halogenating agent or a sulfonating agent (1 to 5 equivalents) to obtain polysilyl-substituted benzyl halides or polysilyl-substituted benzyl sulfonates;

[0041] (3) A polysilyl-substituted benzyl halide or a polysilyl-substituted benzyl sulfonate (1 equivalent) and a glycine-derived benzophenone Schiff base (1-5 equivalents) are reacted under alkaline conditions to obtain a polysilyl-substituted phenylalanine derivative.

[0042] When a chiral phase transfer catalyst is added as a catalyst, chiral polysilyl substituted phenylalanine derivatives can be obtained stereoselectively. The chiral phase transfer catalyst includes, but is not limited to, chiral onium salts, chiral phosphate anions, or chiral diurea hydrogen bond donors.

[0043] (4) The polysilicic substituted phenylalanine derivative (1 equivalent) obtained in step 3 is reacted with boron trihalide (1 to 15 equivalents) to obtain polyboronic acid substituted phenylalanine compound;

[0044] Boron trihalides include, but are not limited to, boron trifluoride, boron trichloride, or boron tribromide; preferably, boron trihalides are... 10 Boron trihalides enriched with boron (B).

[0045] This invention also provides the application of the above-mentioned polyboronic acid-substituted phenylalanine compounds in the preparation of boron neutron capture therapeutic drugs;

[0046] Wherein, the boron neutron capture therapy drug is a drug for treating tumors or a drug for inhibiting the development of tumors; the tumor includes, but is not limited to, malignant tumors; the malignant tumors include, but are not limited to, glioblastoma multiforme, malignant meningioma, intramedullary spinal cord glioma, advanced or recurrent head and neck cancer, thyroid cancer, malignant melanoma, recurrent breast cancer, metastatic liver cancer, malignant brain tumor, osteosarcoma, lung cancer, squamous cell carcinoma of the skin or nasopharyngeal carcinoma.

[0047] The polyboronic acid-substituted phenylalanine compound can be directly dissolved in physiological saline, phosphate buffer, sterile water or glucose solution to prepare boron drug preparations for infusion.

[0048] The polyboronic acid-substituted phenylalanine compound requires no excipients and has a water solubility more than 40 times that of commercially available BPA boron drugs. The boron loading of the polyboronic acid-substituted phenylalanine compound is more than twice that of commercially available BPA boron drugs.

[0049] The present invention will now be described in further detail with reference to embodiments and accompanying drawings, but the implementation of the present invention is not limited thereto. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

[0050] Unless otherwise specified, the experimental conditions in the following embodiments are generally in accordance with conventional experimental conditions and equipment in the art. Unless otherwise specified, all materials and reagents used are commercially available. Experimental methods in the following examples that do not specify specific conditions are generally performed under conventional conditions or as recommended by the manufacturer. All raw materials used in the following examples are conventional commercially available products with specifications in the art, unless otherwise stated.

[0051] I. Preparation of Polyboronic Acid-Substituted Phenylalanine Compounds

[0052] Example 1

[0053] S1. Weigh 122.0 mg of magnesium powder and 1.09 g of trimethylchlorosilane and dissolve them in 10 mL of acetonitrile. Then add 161.0 mg of 3,4-dichlorotoluene and react at room temperature for 5 hours. After the reaction is complete, separate by silica gel column chromatography to obtain compound 1:

[0054]

[0055] S2. Weigh 236.5 mg of compound 1 and 178.0 mg of bromine and dissolve them in 5 mL of 1,2-dichloroethane. React at 70 °C for 6 h. After the reaction is complete, separate by silica gel column chromatography to obtain compound 2.

[0056]

[0057] S3. Weigh 315.4 mg of compound 2, 56.1 mg of sodium hydroxide, and 295.4 mg of N-(diphenylmethylene)glycine tert-butyl ester and dissolve them in 10 mL of benzene. React at room temperature for 24 h. After the reaction is complete, separate by silica gel column chromatography to obtain compound 3:

[0058]

[0059] S4. Weigh 530.0 mg of compound 3 and dissolve it in 2 mL of tetrahydrofuran. Add 3 mL of 1 M boron trifluoride diethyl ether solution and react at room temperature for 10 h. After the reaction is complete, add 1 mL of saturated sodium bicarbonate to quench the reaction. Separate by preparative high-performance liquid chromatography to obtain compound 4.

[0060]

[0061] Among them, the ortho-diboronic acid structure of compound 4 will undergo dehydration to form the corresponding boric anhydride compound 5.

[0062]

[0063] S5. Detection was performed using nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. Compound 4: 1 H NMR (400MHz, D2O) δ7.82 (s, 1H), 7.54 (d, J = 7.6Hz, 1H), 7.17 (d, J = 7.7Hz, 1H), 3.88-3.81 (m, 1H), 3.29 (dd, J = 3.8Hz, 1H), 3.08 (dd, J = 17.0, 12.1Hz, 1H). 13 C NMR (101MHz, D2O) δ171.0,149.2,148.8,138.9,137.8,137.7,130.0,53.8,35.9. 11 B NMR (128 MHz, D₂O) δ 27.9, 22.4. See results below. Figure 1 and Figure 2 Compound 5: 1 H NMR (400MHz, D2O) δ7.75 (s, 1H), 7.30–7.19 (m, 2H), 4.25–4.13 (m, 3H), 3.26 (dd, J = 13.6, 5.2Hz, 1H), 3.12 (dd, J = 14.0, 7.2Hz, 1H). 13 C NMR (101MHz, D2O) δ174.3,147.7,135.9,129.6,129.4,128.9,127.4,58.2,38.3. 11 B NMR(128MHz,D2O)δ27.8,22.4.

[0064] Example 2

[0065] S1. Weigh 183.0 mg of magnesium powder and 2.18 g of trimethylchlorosilane and dissolve them in 10 mL of N,N-dimethylformamide. Then add 328.8 mg of 3,4,5-tribromotoluene and react at room temperature for 4 h. After the reaction is complete, separate by silica gel column chromatography to obtain compound 6:

[0066]

[0067] S2. Weigh 308.7 mg of compound 6, 178.0 mg of N-bromosuccinimide, and 1.7 mg of benzoyl peroxide into 2 mL of tetrahydrofuran and react at 80 °C for 5 h. After the reaction is complete, separate by silica gel column chromatography to obtain compound 7.

[0068]

[0069] S3. Weigh 387.6 mg of compound 7, 56.1 mg of potassium hydroxide, and 295.4 mg of N-(diphenylmethylene)glycine benzyl ester and dissolve them in toluene. Add 42.1 mg of (2S,4S,5R)-1-benzyl-2-((R)-hydroxy(quinoline-4-yl)methyl)-5-vinylquinine-1-onium chloride as a chiral phase transfer catalyst and react at room temperature for 36 h. After the reaction is complete, separate by silica gel column chromatography to obtain compound 8.

[0070]

[0071] S4. Weigh 602.0 mg of compound 8 and dissolve it in 2 mL of toluene. Add 3 mL of 1 M boron trichloride tetrahydrofuran solution and react at room temperature for 12 h. After the reaction is complete, add 1 mL of saturated sodium bicarbonate to quench the reaction. Separate by preparative high-performance liquid chromatography to obtain compound 9.

[0072]

[0073] Among them, the ortho-diboronic acid structure of compound 9 will undergo dehydration to form the corresponding boric anhydride compound 10.

[0074]

[0075] S5. The compound was detected using nuclear magnetic resonance spectroscopy. Compound 9: 1 H NMR(400MHz,D2O)δ7.65(s,2H),3.85–3.78(m,1H),3.09–2.97(m,2H). 13 C NMR (101MHz, D2O) δ172.7,142.1,139.6,138.2,135.7,63.8,36.9. 11B NMR (128 MHz, D₂O) δ 28.2, 22.9. Compound 10: 1 H NMR(400MHz,D2O)δ7.64(s,2H),3.91–3.80(m,1H),3.13–2.97(m,2H). 13 C NMR (101MHz, D2O) δ173.2, 142.4, 134.1, 136.4, 135.9, 129.4, 128.9, 63.7, 37.1. 11 B NMR (128MHz, D2O) δ28.1, 23.0, 22.4.

[0076] Example 3

[0077] S1. Weigh 122.0 mg of magnesium powder and 1.09 g of trimethylchlorosilane and dissolve them in 10 mL of tetrahydrofuran. Then add 161.0 mg of 3,5-dichlorotoluene and react at room temperature for 10 h. After the reaction is complete, separate by silica gel column chromatography to obtain compound 11:

[0078]

[0079] S2. Weigh 236.5 mg of compound 11, 178.0 mg of N-bromosuccinimide, and 3.3 mg of azobisisobutyronitrile and dissolve them in 2 mL of 1,1,2,2-tetrachloroethane. React at 60 °C for 10 h. After the reaction is complete, separate by silica gel column chromatography to obtain compound 12.

[0080]

[0081] S3. Weigh 315.4 mg of compound 12, 56.1 mg of potassium hydroxide, and 295.4 mg of N-(diphenylmethylene)glycine isopropyl ester and dissolve them in 10 mL of benzene. Add 42.1 mg of (1S,2R,4S,5R)-1-benzyl-2-(hydroxy(quinoline-4-yl)methyl)-5-vinylquinine-1-onium chloride, a chiral phase transfer catalyst, and react at room temperature for 15 h. After the reaction is complete, separate by silica gel column chromatography to obtain compound 13.

[0082]

[0083] S4. Weigh 529.9 mg of compound 13 and dissolve it in 2 mL of chloroform. Add 3 mL of 1 M boron trichloride tetrahydrofuran solution and react at room temperature for 8 h. After the reaction is complete, add 1 mL of saturated sodium bicarbonate to quench the reaction. Separate by preparative high-performance liquid chromatography to obtain compound 14.

[0084]

[0085] S5. Compound 14 was detected using nuclear magnetic resonance spectroscopy. 1 H NMR (400MHz, D2O) δ7.62 (s, 2H), 7.45 (s, 1H), 3.87 (dd, J = 5.5, 7.6Hz, 1H), 3.17 (dd, J = 5.5, 14.6Hz, 1H), 3.01 (dd, J = 7.6, 14.6Hz, 1H). 13 C NMR (101MHz, D2O) δ172.5,140.6,139.0,135.8,133.6,63.8,36.9. 11 B NMR (128MHz, D2O) δ28.5.

[0086] II. Verification of the water solubility, safety, and efficacy of polyboronic acid-substituted phenylalanine compounds

[0087] 1. Experiment to determine the water solubility of compound 4

[0088] Add 200.0 μL of distilled water to 30.0 mg of compound 4 prepared in Example 1 and mix well to obtain a suspension. Sonicate the suspension for 2 h, then centrifuge at 5000 rpm for 10 min. Take 100 μL of the supernatant and dilute it to 5 mL. Measure the boron content in the supernatant by inductively coupled plasma mass spectrometry (ICP-MS). Repeat 6 times and take the average value.

[0089] Meanwhile, the commercially available drug BPA was used as a control.

[0090] The test results showed that compound 4 had a water solubility of 58.12 g / L, while BPA had a water solubility of 1.46 g / L. This result indicates that compound 4 is 40 times more water-soluble than the commercially available drug BPA.

[0091] 2. Cytotoxicity test results of compound 4

[0092] This experiment used L929 cells (mouse fibroblasts) as the research object to study the cytotoxicity of compound 4.

[0093] Compound 4 was dissolved in sterile fetal bovine serum buffer at a concentration of 10 mM, filtered through a microporous membrane for sterilization, and then further sterilized by incubation at 60°C for 24 h, followed by aseptic storage. The 10 mM of compound 4 in sterile fetal bovine serum buffer was diluted to 0.5 mM, 1 mM, 2.5 mM, and 5 mM using DMEM culture medium.

[0094] L929 cells were seeded at a density of 1500 cells / well in 96-well plates in DMEM medium containing 10% (v / v) fetal bovine serum, 1% (v / v) penicillin, and streptomycin. After culturing at 37°C and 5% CO2 for 24 h, the DMEM medium was washed off, and DMEM medium containing different concentrations (0.5 mM, 1 mM, 2.5 mM, and 5 mM) of compound 4 was added. DMEM medium without compound 4 was used as a blank control. Cells were co-cultured for 24 h. Cell viability was assessed using the Almar Blue assay kit after 24 h of co-culture, and the fluorescence intensity of the culture medium at an excitation wavelength of 530 nm and an emission wavelength of 600 nm was measured using a microplate reader to evaluate cell viability. Generally, a cell viability >75% is considered to indicate that the compound is not cytotoxic.

[0095] Experimental results are as follows Figure 3 As shown, at 2.5 mM, 1 mM and 0.5 mM, cell viability was >75%, and compound 4 was essentially non-cytotoxic.

[0096] 3. Results of cellular uptake experiments of compound 4

[0097] This experiment used 4T1 cells (mouse breast cancer cells) as the research object to study the cellular uptake capacity of compound 4.

[0098] The 4T1 tumor cell line, which is in the logarithmic growth phase and has a cell content of 80%–85%, was seeded into 6-well plates (1 × 10⁶ cells per well). 6 Cells were cultured in DMEM medium (without added compounds) until adherence was achieved. Compound 4 and commercially available BPA were added to a final concentration of 1 mM. Cells cultured in DMEM medium without these compounds served as a blank control. Incubation was performed at 37°C for 24 h. After incubation, the culture medium was discarded, cells were washed three times with PBS, and digested for 3 min at 37°C with 0.25% trypsin. Digestion was stopped by adding standard culture medium. The cell suspension was transferred to centrifuge tubes, repeatedly pipetting to form a single-cell suspension. After counting, the cells were centrifuged at 1500 rpm for 5 min, and the supernatant was discarded. The cells were then centrifuged with concentrated nitric acid (per 10 mM). 6 Cells were digested with 0.5 mL of solution for 2 hours, then diluted to 10 mL with ultrapure water and filtered through a microporous membrane. The zero point was adjusted using a sample that had not been incubated with boron-containing culture medium, and the boron concentration in the solution was determined by ICP-MS to calculate the intracellular boron concentration. Three samples were taken, and the average value was calculated.

[0099] Experimental results are as follows Figure 4 As shown, the cellular uptake of BPA was 12.3 μg / 102 6 The cellular uptake of compound 4 was 73.8 μg / 10 cells. 6Cells. Under the same conditions, compound 4 showed 6 times the cellular boron uptake of BPA, significantly superior to BPA, and has promising application prospects.

[0100] The above embodiments are for illustrating the technical concept and preferred implementation of the present invention. However, the implementation of the present invention is not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the claims of the present invention.

Claims

1. A method for preparing polyboronic acid-substituted phenylalanine compounds, characterized in that, Includes the following steps: 1) Polyhalotoluene reacts with a silylating agent via a Grignard reaction to yield polysilyl-substituted toluene; 2) Polysilicone-substituted toluene undergoes halogenation or sulfonation to yield polysilicone-substituted benzyl halides or polysilicone-substituted benzyl sulfonates; 3) The polysilyl-substituted benzyl halide or polysilyl-substituted benzyl sulfonate reacts with glycine-derived benzophenone Schiff base to obtain polysilyl-substituted phenylalanine derivatives. 4) The polysilicon-substituted phenylalanine derivative reacts with boron trihalide to obtain a polyboronic acid-substituted phenylalanine compound, wherein the polyboronic acid-substituted phenylalanine compound is the compound shown in formula (I); Among them, at least two of the groups R1 to R5 are B(OH)2, and the rest are H.

2. The method for preparing the polyboronic acid-substituted phenylalanine compound according to claim 1, characterized in that, The equivalence ratio of polyhalogenated toluene to silylating agent is 1:(2~50), the equivalence ratio of polysilyl-substituted toluene to halogenating agent or sulfonating agent is 1:(1~5), the equivalence ratio of polysilyl-substituted benzyl halide or polysilyl-substituted benzyl sulfonate to glycine-derived benzophenone Schiff base is 1:(1~5), and the equivalence ratio of polysilyl-substituted phenylalanine derivative to boron trihalide is 1:(1~15).

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