A photosensitizer for selectively eliminating senescent cells and preparation method thereof

Abstract

The present invention relates to the field of biomedicine, and in particular to a photosensitizer for selectively eliminating senescent cells and a preparation method thereof, including a compound shown in the following chemical structure: A preparation method of the compound is also disclosed. Before the photosensitizer enters the senescent cells, the black hole quenching group of the photosensitizer quenches the fluorescence of the BODIPY molecule and the generation of singlet oxygen through the intramolecular fluorescence resonance energy transfer effect. After entering the senescent cells, it can be activated by the β-galactosidase highly expressed in the senescent cells, thereby exhibiting photodynamic activity and achieving efficient elimination of senescent cells.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and in particular to a photosensitizer for selectively eliminating senescent cells and a preparation method thereof. Background Art

[0002] Cellular senescence refers to the process in which the cell division ability and physiological function gradually decline over time. Senescent cells are unable to repair tissues through cell division, and they also have some common biological characteristics. They will promote the secretion of a series of inflammatory cytokines, chemokines and growth factors, respond to DNA damage persistently, and express β-galactosidase at high levels. Senescent cells will change or inhibit the function of neighboring cells and thus interfere with the physiological function of tissues. Among them, β-galactosidase is easy to be detected in cells and tissues and is the most commonly used biomarker for senescent cells. Studies have shown that cellular senescence can induce age-related tissue dysfunction. Many age-related diseases are closely related to cellular senescence, such as atherosclerosis, hypertension, Alzheimer's disease, etc. Senescent cells have become a potential therapeutic target for geriatric diseases. Eliminating senescent cells or shutting down their secretion mechanisms can prevent or delay age-related degeneration and extend the lifespan of organisms. In recent years, some potential compound molecules have been reported in the literature for anti-aging effects in vivo, such as navitoclax, which is used to selectively remove senescent cells, thus having a therapeutic effect on atherosclerosis models; UBX0101 can remove senescent cells in osteoarthritis mouse models, thereby alleviating osteoarthritis symptoms in mice. Although these drug molecules have certain therapeutic effects, they show potential off-target effects.

[0003] Photodynamic therapy is a technology that uses the photodynamic effect to treat superficial tumors and skin diseases. Its action is based on the photodynamic effect. This is a photosensitization reaction with biological effects involving oxygen molecules. The process is that laser irradiation of a specific wavelength excites the photosensitizer absorbed by the tissue, and the excited photosensitizer transfers energy to the oxygen molecules around the cell tissue to generate highly active singlet oxygen. The singlet oxygen and adjacent biological macromolecules undergo oxidation reactions to produce cytotoxic effects, which in turn lead to tumor cell damage or even death. Compared with traditional tumor treatment methods, photodynamic therapy has the advantages of minimal trauma, few side effects, low toxicity, and tumor cells will not develop resistance to photosensitizers. In the entire photodynamic therapy process, photosensitizers are the core key. And how to use the photodynamic effect to eliminate senescent cells requires the design of a photosensitizer that can eliminate senescent cells by exerting the photodynamic effect. Summary of the invention

[0004] In view of the existing deficiencies, the present invention provides a photosensitizer for selectively eliminating senescent cells and a preparation method thereof.

[0005] The technical solution adopted by the present invention to solve the technical problem is: a photosensitizer that selectively eliminates senescent cells, the photosensitizer is a compound shown in the following chemical formula:

[0006] A method for preparing a photosensitizer for selectively eliminating senescent cells comprises carrying out the following reactions in sequence at room temperature:

[0007] S1, dispersing compound 1 in a mixed solvent of water and tetrahydrofuran, adding triphenylphosphine, stirring, and purifying after the reaction to obtain compound 2, then dispersing compound 2 in dichloromethane, adding N-iodosuccinimide, stirring, and purifying after the reaction to obtain compound 3;

[0008] S2, dispersing compound 4 and compound 5 in N,N-dimethylformamide, adding triethylamine and HBTU, stirring, and purifying after the reaction to obtain compound 6, then dispersing compound 6 in dichloromethane, adding trifluoroacetic acid, stirring, and after the reaction, obtaining compound 7 which can be directly used;

[0009] S3, dispersing compound 8 and compound 9 in dichloromethane, adding triethylamine, stirring, and purifying after the reaction to obtain compound 10, then dispersing compound 10 in dichloromethane, adding trifluoroacetic acid, stirring, and after the reaction to obtain compound 11 which can be directly used;

[0010] S4, dispersing compound 11 and compound 12 in dichloromethane, adding triethylamine, stirring, and purifying after the reaction to obtain compound 13, then dispersing compound 13 in tetrahydrofuran, adding tetrabutylammonium fluoride, stirring, and purifying after the reaction to obtain compound 14;

[0011] S5, dispersing compound 14 and compound 15 in dichloromethane, adding triethylamine, stirring, and purifying after the reaction to obtain compound 16;

[0012] S6, dispersing compound 16 in N,N-dimethylformamide, adding triethylamine and stirring to form reaction solution 1; then dispersing compound 3 in N,N-dimethylformamide, and then slowly dropping it into reaction solution 1, and after the reaction is completed, reaction solution 2 is formed, and then dispersing compound 7 in N,N-dimethylformamide, and then slowly dropping it into reaction solution 2, and after the reaction is completed, purifying to obtain compound 17;

[0013] S7, dispersing compound 17 in a mixed solvent of dichloromethane and methanol, adding potassium carbonate, stirring at room temperature, and purifying after the reaction to obtain compound 18;

[0014] The structural formulas of the compounds are shown in the following table:

[0015]

[0016]

[0017]

[0018] Preferably, in step S1, the molar ratio of compound 1 to triphenylphosphine is 1:2.0-1:4.0, and the solvent is a mixture of water and tetrahydrofuran in a volume ratio of 1:4; the molar ratio of compound 2 to N-iodosuccinimide is 1:2.0-1:3.0; the reaction time of the first stage is 10 to 24 hours, and the reaction time of the second stage is 4 to 8 hours.

[0019] Preferably, in step S2, the molar ratio of compound 4, compound 5 and HBTU is 1:2.0:1.0; the volume ratio of trifluoroacetic acid to dichloromethane is 1:2.0-1:3.0; the reaction time of the first stage is 20 to 48 hours, and the reaction time of the second stage is 6 to 12 hours.

[0020] Preferably, in step S3, the molar ratio of compound 8 to compound 9 is 1:1.1-1:1.5; the volume ratio of trifluoroacetic acid to dichloromethane is 1:2.0-1:3.0; the reaction time of the first stage is 10 to 24 hours, and the reaction time of the second stage is 6 to 12 hours.

[0021] Preferably, in step S4, the molar ratio of compound 11 to compound 12 is 1:1.0 to 1:1.5; the molar ratio of compound 13 to tetrabutylammonium fluoride is 1:2.0 to 1:4.0; the reaction time of the first stage is 8 to 16 hours, and the reaction time of the second stage is 8 to 12 hours.

[0022] Preferably, in step S5, the molar ratio of compound 14 to compound 15 is 1:2.0 to 1:3.0; and the reaction time is 8 to 16 hours.

[0023] Preferably, in step S6, the molar ratio of compound 16, compound 3 and compound 7 is 1:1.0:2.0; and the reaction time is 12 to 36 hours.

[0024] Preferably, the molar ratio of the compound 17 to potassium carbonate is 1:3.0 to 1:6.0; the solvent is a mixed solvent of dichloromethane and methanol in a volume ratio of 4:1; and the reaction time is 10 to 20 hours.

[0025] The beneficial effects of the present invention are as follows: the photosensitizer of the invention has three different functional molecular groups, namely, galactose substrate activated by β-galactosidase, fluoroboron dipyrrole dye (BODIPY) molecule, and black hole quenching group (BHQ-2) as energy acceptor. Since the fluorescence emission band of BODIPY molecule overlaps effectively with the absorption band of BHQ-2, effective resonance energy transfer will occur between the two components, resulting in the photosensitizer molecule being non-fluorescent and non-photodynamically active, and being in a "closed" state; once the photosensitizer molecule enters the senescent cell, the galactose substrate in the photosensitizer is activated by the β-galactosidase expressed at a high level in the senescent cell, and the photosensitizer releases the BODIPY molecule with photodynamic activity, thereby emitting fluorescence, and selectively eliminating the senescent cells through photodynamic action. At the same time, the photosensitizer can be directly added to the cell culture medium, co-cultured with the cells, and efficiently exert a photodynamic effect on the senescent cells, thereby selectively eliminating the senescent cells. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 1 is the fluorescence spectrum of Example Compound 18 of the present invention before and after the solution is activated by β-galactosidase (1 is before activation, 2 is after activation);

[0027] Figure 2 This is a study on the specificity of Example Compound 18 of the present invention for β-galactosidase;

[0028] Figure 3 It is the evaluation of the photodynamic activity of compound 18 of the present invention on senescent cells;

[0029] Figure 4 is the hydrogen nuclear magnetic resonance spectrum of Example Compound 18 of the present invention;

[0030] Figure 5 is the carbon NMR spectrum of Example Compound 18 of the present invention;

[0031] Figure 6 is a mass spectrum characterization diagram of Example Compound 18 of the present invention; DETAILED DESCRIPTION

[0032] In order to more clearly illustrate the purpose, technical solutions and advantages of the embodiments of the present invention, the present invention will be further described below in conjunction with the accompanying drawings and embodiments for a clear and complete description. Obviously, the embodiments described are partial embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work belong to the protection scope of the present invention.

[0033] The "embodiment" mentioned in this article means that the specific features described in conjunction with the embodiment can be included in at least one embodiment of the present invention. The appearance of this phrase in various places in the specification does not necessarily refer to the same embodiment, nor is it an independent or alternative embodiment that is mutually exclusive with other embodiments. It is explicitly and implicitly understood by those skilled in the art that the embodiments described herein can be combined with other embodiments. At the same time, the "dispersion, stirring, purification" and the like mentioned in this article are all operating methods of the prior art.

[0034] A photosensitizer for selectively eliminating senescent cells and a preparation method thereof, wherein the photosensitizer is a compound having the following chemical structural formula:

[0035]

[0036] It is prepared at room temperature, and the reaction route of its preparation method is as follows:

[0037]

[0038] The specific steps are as follows:

[0039] S1, compound 1 is dispersed in a mixed solvent of water and tetrahydrofuran, triphenylphosphine is added, stirred, and purified after the reaction is completed to obtain compound 2. At this time, the molar ratio of compound 1 to triphenylphosphine is 1:2.0-1:4.0, the solvent is a mixture of water and tetrahydrofuran in a volume ratio of 1:4, and the reaction time is 10-24 hours. In this process, compound 1 (0.88 g, 2.08 mmol), 5 ml of water + 20 ml of tetrahydrofuran, triphenylphosphine (1.64 g, 6.24 mmol) are stirred at room temperature for 12 hours. After the reaction is completed, silica gel column chromatography is used for purification. During the purification, a mixed solution of dichloromethane: methanol = 5:1 is used for elution to obtain an orange oily compound 2 ( 0.54 g, 65%); then disperse compound 2 in dichloromethane, add N-iodosuccinimide, stir, and purify after the reaction to obtain compound 3. At this time, the molar ratio of compound 2 to N-iodosuccinimide is 1:2.0-1:3.0; the reaction time is 4 to 8 hours. In the embodiment, compound 2 (0.43 g, 1.06 mmol), dichloromethane (50 mL), N-iodosuccinimide (0.60 g, 2.65 mmol) are stirred at room temperature for 6 hours. After the reaction, silica gel column chromatography is used for purification. During the purification, a mixed solution of dichloromethane: methanol = 4:1 by volume is used for elution to obtain a light red solid compound 3 (0.52 g, 75%).

[0040] S2, compound 4 and compound 5 are dispersed in N, N-dimethylformamide, triethylamine and HBTU are added, stirred, and purified after the reaction to obtain compound 6. At this time, the molar ratio of compound 4, compound 5, and HBTU is 1:2.0:1.0; the reaction time is 20 to 48 hours. In the example of this stage, compound 4 (1.63 g, 3.20 mmol) and 5 (1.03 g, 6.40 mmol), N, N-dimethylformamide (20 mL), triethylamine (2.2 mL), HBTU (1.22 g, 3.20 mmol) are stirred at room temperature for 24 hours. After the reaction, silica gel column chromatography is used for purification. The mixture was eluted with a mixture of petroleum ether and ethyl acetate = 6:1 to obtain a black solid compound 6 (1.58 g, 76%). Compound 6 was then dispersed in dichloromethane, trifluoroacetic acid was added, and the mixture was stirred. After the reaction was completed, compound 7 which could be directly used was obtained. At this time, the volume ratio of trifluoroacetic acid to dichloromethane was 1:2.0-1:3.0. The reaction time was 6 to 12 hours. In the example of this stage, compound 6 (1.32 g, 2.03 mmol), dichloromethane (20 mL), and trifluoroacetic acid (10 mL) were stirred at room temperature for 4 hours. After the reaction was completed, no purification was required to obtain a black solid compound 7 (1.01 g, 91%), which was used directly later.

[0041] S3, compound 8 and compound 9 are dispersed in dichloromethane, triethylamine is added, stirred, and purified after the reaction to obtain compound 10. At this time, the molar ratio of compound 8 to compound 9 is 1:1.1-1:1.5, and the reaction time is 10 to 24 hours. In the example of this stage, compound 8 (1.83 g, 2.74 mmol), compound 9 (0.62 g, 3.28 mmol), dichloromethane (50 mL), triethylamine (1.2 mL, 8.22 mmol) are stirred at room temperature for 12 hours. After the reaction, the mixture is purified by silica gel column chromatography. The volume ratio of petroleum ether: ethyl acetate is 3:1 in the purification. The mixed solution was used for elution to obtain white solid compound 10 (1.39 g, 71%), and then compound 10 was dispersed in dichloromethane, trifluoroacetic acid was added and stirred. After the reaction was completed, compound 11 which could be directly used was obtained; at this time, the volume ratio of trifluoroacetic acid to dichloromethane was 1:2.0-1:3.0; the reaction time was 6 to 12 hours. In the example of this stage, compound 10 (1.25 g, 1.75 mmol), dichloromethane (20 mL), trifluoroacetic acid (10 mL), stirred at room temperature for 8 hours, and after the reaction was completed, no purification was required to obtain colorless oily compound 11 (1.02 g, 95%).

[0042] S4, compound 11 and compound 12 are dispersed in dichloromethane, triethylamine is added, stirred, and purified after the reaction to obtain compound 13. At this time, the molar ratio of compound 11 to compound 12 is 1:1.0-1:1.5, and the reaction time is 8-16 hours. In the example of this stage, compound 11 (0.93 g, 1.50 mmol), compound 12 (1.01 g, 1.80 mmol), dichloromethane (50 mL), triethylamine (0.65 mL, 4.50 mmol) are stirred at room temperature for 12 hours. After the reaction, the mixture is purified by silica gel column chromatography. During the purification, a mixed solution of petroleum ether: ethyl acetate = 4:1 by volume is used for elution to obtain white solid compound 13 ( 1.01 g, 65%); then, compound 13 was dispersed in tetrahydrofuran, tetrabutylammonium fluoride was added, stirred, and purified after the reaction to obtain compound 14; at this time, the molar ratio of compound 13 to tetrabutylammonium fluoride was 1:2.0-1:4.0; the reaction time was 8-12 hours. In the embodiment of this stage, compound 13 (0.83 g, 0.85 mmol), tetrahydrofuran (20 mL), tetrabutylammonium fluoride (0.93 g, 2.55 mmol) were stirred at room temperature for 10 hours. After the reaction, silica gel column chromatography was performed for purification, and a mixed solution of petroleum ether: ethyl acetate = 6:1 was used for elution to obtain white solid compound 14 (0.56 g, 82%).

[0043] S5, compound 14 and compound 15 are dispersed in dichloromethane, triethylamine is added, stirred, and purified after the reaction is completed to obtain compound 16; at this time, the molar ratio of compound 14 to compound 15 is 1:2.0 to 1:3.0; the reaction time is 8 to 16 hours. In the embodiment, compound 14 (0.41g, 0.50mmol), compound 15 (0.24g, 1.20mmol), dichloromethane (20mL), triethylamine (0.43mL, 3.0mmol), stirred at room temperature for 12 hours, and purified by silica gel column chromatography after the reaction is completed. During the purification, a mixed solution of petroleum ether: ethyl acetate = 3:1 was used for elution to obtain compound 16 (0.44g, 78%) as a white solid.

[0044] S6, compound 16 is dispersed in N, N-dimethylformamide, triethylamine is added and stirred to form reaction solution 1; compound 3 is then dispersed in N, N-dimethylformamide, and then slowly added dropwise to reaction solution 1, reaction is completed to form reaction solution 2, compound 7 is then dispersed in N, N-dimethylformamide, and then slowly added dropwise to reaction solution 2, after the reaction is completed, compound 17 is purified to obtain compound 17, at this time, the molar ratio of compound 16, compound 3, and compound 7 is 1:1.0:2.0; the reaction time is 12 to 48 hours. In the embodiment, first, compound 16 (149 mg, 0.13 mmol) is dispersed in N, N-dimethylformamide (10 mL), and Triethylamine (55 μL, 0.39 mmol) was added and stirred at room temperature for 10 minutes to form reaction solution 1; compound 3 (85 mg, 0.13 mmol) was then dispersed in N, N-dimethylformamide (5 ml) and slowly added dropwise to reaction solution 1 using a separatory funnel. After reacting for 24 hours, reaction solution 2 was formed. Compound 7 (144 mg, 0.26 mmol) was dispersed in N, N-dimethylformamide (5 ml) and slowly added dropwise to reaction solution 2 using a separatory funnel. After reacting for another 24 hours, the mixture was purified by silica gel column chromatography. During the purification, a mixture of petroleum ether: ethyl acetate in a volume ratio of 4:1 was used for elution to obtain purple solid compound 17 (56 mg, 21%).

[0045] S7, compound 17 is dispersed in a mixed solvent of dichloromethane and methanol, potassium carbonate is added, and the mixture is stirred at room temperature. After the reaction is completed, compound 18 is purified by purifying. At this time, the molar ratio of compound 17 to potassium carbonate is 1:3.0-1:6.0; the solvent is a mixed solvent of dichloromethane and methanol in a volume ratio of 4:1; the reaction time is 10-20 hours. In the embodiment, compound 17 (29 mg, 0.014 mmol), 8 ml of dichloromethane, 2 mL of methanol, potassium carbonate (10 mg, 0.07 mmol), are stirred at room temperature for 12 hours. After the reaction is completed, the mixture is purified by silica gel column chromatography. During the purification, a mixed solution of dichloromethane: methanol in a volume ratio of 6:1 is used for elution to obtain the final product, purple solid compound 18 (21 mg, 81%).

[0046] Such photosensitizers are based on the β-galactosidase expressed at high levels in senescent cells as a target, and connect the galactose group to the BODIPY molecule and the black hole quencher group through a rearrangeable linker to construct a photosensitizer molecule with high selectivity to eliminate senescent cells; before being activated by β-galactosidase, due to the effective resonance energy transfer (FRET) between the BODIPY molecule and the quencher group (BHQ-2), this photosensitizer has no fluorescence and no photodynamic activity, and is in a "closed" state; once the photosensitizer molecule enters the senescent cell, it can be activated by the β-galactosidase expressed at high levels in the senescent cell, and the BODIPY molecule with photodynamic activity is released through the rearrangement reaction within the molecule, thereby emitting fluorescence, and eliminating the senescent cell through photodynamic action, while because normal cells lack or low-express β-galactosidase, the photosensitizer molecule cannot be effectively activated by β-galactosidase after entering the normal cell, and cannot show photodynamic activity, so the normal cell will not be eliminated by photodynamic action. The reaction principle is as follows:

[0047]

[0048] like Figure 1 The figure shows the fluorescence spectra of compound 18 before and after activation by β-galactosidase. It can be seen that after activation, BODIPY molecules with photodynamic activity can be released, thereby emitting fluorescence and eliminating senescent cells through photodynamic action;

[0049] Figure 2 It is used to prove that compound 18 in the example can only respond to β-galactosidase and emit fluorescence;

[0050] Figure 3 The photodynamic activity of compound 18 on senescent cells was evaluated. It can be seen that compound 18 can eliminate senescent HT29 cells through photodynamic effect under light conditions;

[0051] Figure 4 Attribution of hydrogen spectrum in: 11H NMR (500 MHz, CDCl3): δ 8.37 (d, J = 8.5 Hz, 2H, Ar-H), 8.04 (d, J = 8.50 Hz, 2H, Ar-H), 7.92 (d, J = 8.50 Hz, 2H, Ar-H), 7.87 - 7.83 (m, 1H, Ar-H), 7.79 - 7.76 (m, 1H, Ar-H), 7.49 (s, 1H, Ar-H), 7.45 (s, 1H, Ar-H), 7.33 (s, 1H, Ar-H), 7.20 (s, 1H, Ar-H), 7.15 - 7.11 (m, 3H, Ar-H), 6.96 (s, 2H, Ar-H), 6.75 - 6.73 (m, 2H, Ar-H), 6.37 (br s, 2H, NH), 6.02 (s, 2H, PhCH2), 5.30 (s, 4H, PhCH2), 5.10 - 5.07 (m, 3H), 4.97 - 4.81 (m, 5H), 4.08 (s, 3H, OCH3), 4.03 (s, 3H, OCH3), 3.99 - 3.95 (m, 3H), 3.84 (br s, 2H), 3.64 (br s, 2H), 3.54 (br s, 2H), 3.48 (d, J = 4.35 Hz, 2H), 3.40 - 3.39 (m, 3H), 3.34 (brs, 1H), 3.23 - 3.16 (m, 3H), 3.04 (s, 3H, NCH3), 3.02 - 2.98 (m, 2H), 2.95 - 2.90 (m, 2H), 2.61 (s, 3H, CH3), 2.55 (s, 3H, CH3), 2.29 (s, 3H, PhCH3), 2.17 - 2.01 (m, 5H), 1.90 - 1.86 (m, 3H), 1.40 (s, 6H, CH3);

[0052] Figure 5 Carbon spectrum assignment: 13 C{ 1H}NMR (125.7MHz, CDCl3): δ159.7,159.5,156.7,156.5,154.5,153.7,152.3,151.0,149.1,148.5,146. 8,145.4,144.5,142.2,133.5,133.3,131.2,129.3,129.2,126.4,124.9,124.6,123.6,122.3,119.8,1 15.4,115.3,111.5,101.1,100.8,100.1,71.5,70.6,68.1,68.0,66.8,66.0,65.4,63.6,63.4,61.4,56.9,56.8,51.7,41.3,40.0,38.7,38.6,33.1,30.4,29.4,25.7,22.9,17.3,17.0,16.1,15.9,15.0,14.9;

[0053] Figure 6 HRMS(ESI):m / z calcd for C 79 H 89 BF2I2N 14 O 22 [M+H] + :1889.4511,found1889.4507.

[0054] It should be understood that those skilled in the art can make improvements or changes based on the above description, and all these improvements and changes should fall within the scope of protection of the appended claims of the present invention.

Claims

1. A photosensitizer for selectively eliminating senescent cells, characterized in that: Photosensitizer is a compound shown in the following chemical formula:

2. A method for preparing a photosensitizer for selectively eliminating senescent cells, characterized in that : At room temperature, the following steps are carried out in sequence: S1, dispersing compound 1 in a mixed solvent of water and tetrahydrofuran, adding triphenylphosphine, stirring, and purifying after the reaction to obtain compound 2, then dispersing compound 2 in dichloromethane, adding N-iodosuccinimide, stirring, and purifying after the reaction to obtain compound 3; S2, dispersing compound 4 and compound 5 in N,N-dimethylformamide, adding triethylamine and HBTU, stirring, and purifying after the reaction to obtain compound 6, then dispersing compound 6 in dichloromethane, adding trifluoroacetic acid, stirring, and after the reaction, obtaining compound 7 which can be directly used; S3, dispersing compound 8 and compound 9 in dichloromethane, adding triethylamine, stirring, and purifying after the reaction to obtain compound 10, then dispersing compound 10 in dichloromethane, adding trifluoroacetic acid, stirring, and after the reaction to obtain compound 11 which can be directly used; S4, dispersing compound 11 and compound 12 in dichloromethane, adding triethylamine, stirring, and purifying after the reaction to obtain compound 13, then dispersing compound 13 in tetrahydrofuran, adding tetrabutylammonium fluoride, stirring, and purifying after the reaction to obtain compound 14; S5, dispersing compound 14 and compound 15 in dichloromethane, adding triethylamine, stirring, and purifying after the reaction to obtain compound 16; S6, dispersing compound 16 in N,N-dimethylformamide, adding triethylamine and stirring to form reaction solution 1; then dispersing compound 3 in N,N-dimethylformamide, and then slowly dropping it into reaction solution 1, and after the reaction is completed, reaction solution 2 is formed, and then dispersing compound 7 in N,N-dimethylformamide, and then slowly dropping it into reaction solution 2, and after the reaction is completed, purifying to obtain compound 17; S7, dispersing compound 17 in a mixed solvent of dichloromethane and methanol, adding potassium carbonate, stirring at room temperature, and purifying after the reaction to obtain compound 18; The structural formulas of the compounds are shown in the following table:

3. The method for preparing a photosensitizer for selectively eliminating senescent cells according to claim 2, characterized in that: In step S1, the molar ratio of compound 1 to triphenylphosphine is 1:2.0-1:4.0, and the solvent is a mixture of water and tetrahydrofuran in a volume ratio of 1:4; the molar ratio of compound 2 to N-iodosuccinimide is 1:2.0-1:3.0; the reaction time of the first stage is 10 to 24 hours, and the reaction time of the second stage is 4 to 8 hours.

4. The method for preparing a photosensitizer for selectively eliminating senescent cells according to claim 2, characterized in that : In step S2, the molar ratio of compound 4, compound 5 and HBTU is 1:2.0:1.0; the volume ratio of trifluoroacetic acid to dichloromethane is 1:2.0-1:3.0; the reaction time of the first stage is 20 to 48 hours, and the reaction time of the second stage is 6 to 12 hours.

5. The method for preparing a photosensitizer for selectively eliminating senescent cells according to claim 2, characterized in that : In step S3, the molar ratio of compound 8 to compound 9 is 1:1.1-1:1.5; the volume ratio of trifluoroacetic acid to dichloromethane is 1:2.0-1:3.0; the reaction time of the first stage is 10 to 24 hours, and the reaction time of the second stage is 6 to 12 hours.

6. The method for preparing a photosensitizer for selectively eliminating senescent cells according to claim 2, characterized in that : In step S4, the molar ratio of compound 11 to compound 12 is 1:1.0 to 1:1.5; the molar ratio of compound 13 to tetrabutylammonium fluoride is 1:2.0 to 1:4.0; the reaction time of the first stage is 8 to 16 hours, and the reaction time of the second stage is 8 to 12 hours.

7. The method for preparing a photosensitizer for selectively eliminating senescent cells according to claim 2, characterized in that : In step S5, the molar ratio of compound 14 to compound 15 is 1:2.0 to 1:3.0; and the reaction time is 8 to 16 hours.

8. The method for preparing a photosensitizer for selectively eliminating senescent cells according to claim 2, characterized in that : In step S6, the molar ratio of compound 16, compound 3, and compound 7 is 1:1.0:2.0; The reaction time is 12 to 36 hours.

9. The method for preparing a photosensitizer for selectively eliminating senescent cells according to claim 2, characterized in that : The molar ratio of the compound 17 to potassium carbonate is 1:3.0 to 1:6.0; the solvent is a mixed solvent of dichloromethane and methanol in a volume ratio of 4:1; and the reaction time is 10 to 20 hours.

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