A side-chain tetraphenylethylene mono-arm thiol mannose polymer, its preparation method and application

Abstract

This invention belongs to the field of glycopolymer technology, and particularly relates to a tetraphenylethylene mono-arm thiomannose polymer with a side chain, its preparation method, and its application. The chemical structural formula of the tetraphenylethylene mono-arm thiomannose polymer is shown in formula (I). Wherein, n is an integer ≥2. The glycopolymer of this invention exhibits high biocompatibility and fluorescent recognition properties, and innovatively utilizes efficient and rapid RAFT polymerization and click chemistry to prepare the tetraphenylethylene mono-arm thiomannose polymer.

Description

Technical Field

[0001] This invention belongs to the field of sugar polymer technology, and particularly relates to a side chain containing tetraphenylethylene mono-arm thiol mannose polymer, its preparation method and application. Background Technology

[0002] Sugar-containing polymers possess excellent biocompatibility, superior water solubility, and multivalent interactions with lectins, demonstrating superior performance and broad application potential in biomedical fields such as drug modification for pharmacokinetics, drug delivery as carriers, enzyme inhibitors for treating various diseases, and simulating natural carbohydrates to study sugar-protein binding.

[0003] Reversible addition-fracture-chain transfer (RAFT) polymerization is the most common and convenient type of reversible deactivating radical polymerization (RDRP). Polymers obtained by this type of polymerization have controllable molecular weight, narrow molecular weight distribution (MWDs), high-end group fidelity, and functional group tolerance.

[0004] Click chemistry, proposed by Sharpless, is a highly efficient organic reaction. These click reactions are characterized by modularity, simplicity, efficiency, and no byproducts. In particular, the widely used Thiol-ene click reaction can not only synthesize sugar-containing derivatives (such as glycoamines) that are modified on polymer scaffolds, but also synthesize functional sugar-containing monomers that are directly polymerized. It has been proven to be an effective route for synthesizing sugar-containing polymers.

[0005] Aggregation-induced emission (AIE) materials possess the unique optical property of emitting strong fluorescence in an aggregated state. Compared to aggregation-induced quenching materials, they exhibit better photostability and a higher signal-to-noise ratio, demonstrating significant market potential and scientific research value. Tetraphenylene oxide (TPE), a typical AIE luminogen, is currently widely used in the construction of fluorescent probes and imaging agents. Compared to other AIE active materials, TPE offers advantages such as high emission efficiency, ease of synthesis, ease of structural modification, and good stability. Fluorescent glycopolymers that specifically bind to corresponding proteins or lectins can be prepared through the coupling of TPE with specific carbohydrates. TPE compounds with glycosyl groups effectively improve the poor water solubility of AIE molecules, reducing the background fluorescence and biotoxicity of AIE polymers, greatly expanding the application prospects of glycopolymers in the field of biomaterials. Glycopolymers containing TPE structures possess advantages such as certain water solubility, good biocompatibility, good photostability, and a high signal-to-noise ratio. Combined with fluorescence technology, they can sensitively detect various lectins, toxins, pathogens, and enzymes, with important applications in cell imaging, biosensing, drug tracking, and other scientific fields, making them an important research tool for glycobiology. However, the construction of sugar-containing monomers is relatively complex and direct polymerization still cannot achieve high yields. Some of these polymers lack biocompatibility, making them difficult to apply in medicine. Summary of the Invention

[0006] To address the aforementioned problems, the present invention aims to provide a tetraphenylethylene mono-arm mannose polymer with a side chain, its preparation, and its applications. The sugar polymer described in this invention exhibits high biocompatibility and fluorescent recognition properties. Furthermore, it innovatively utilizes efficient and rapid RAFT polymerization and click chemistry to prepare a tetraphenylethylene mono-arm thiol mannose polymer, providing a practical and feasible route for preparing a series of tetraphenylethylene mono-arm thiol mannose polymers.

[0007] The objective of this invention can be achieved through the following technical solutions:

[0008] The first objective of this invention is to provide a tetraphenylethylene mono-arm thiomannose polymer with a side chain containing tetraphenylethylene mono-arm thiomannose. The chemical structural formula of the tetraphenylethylene mono-arm thiomannose polymer is shown in formula (I):

[0009]

[0010] Where n is an integer ≥ 2.

[0011] A second objective of this invention is to provide a method for preparing a tetraphenylethylene mono-arm thiol-mannose polymer with a side chain. The preparation method includes the following steps:

[0012] (1) 4-Bromo-4'-methoxybenzophenone reacts with diphenylmethane via a nucleophilic addition-elimination reaction to give the first compound;

[0013] (2) The first compound reacts with boron tribromide via a demethylation reaction to yield the second compound;

[0014] (3) The second compound and N-Boc-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester were coupled via a Suzuki reaction to give the third compound;

[0015] (4) The third compound is reacted with acryloyl chloride and anhydrous triethylamine by esterification to obtain the fourth compound;

[0016] (5) The fourth compound, acetyl-protected thiol mannose, and n-hexylamine undergo a Thiol-ene click chemistry reaction to obtain the fifth compound;

[0017] (6) The fifth compound reacts with trifluoroacetic acid via a substitution reaction to yield the sixth compound;

[0018] (7) Pentafluorophenol reacts with triethylamine and acryloyl chloride via esterification to give compound VII;

[0019] (8) The seventh compound, along with a chain transfer agent and an initiator, undergoes a RAFT polymerization reaction to obtain the eighth compound;

[0020] (9) The eighth compound, the sixth compound, and 4-diaminopyridine undergo an ammonolysis reaction to obtain the ninth compound;

[0021] (10) The ninth compound was reacted with sodium methoxide via a substitution reaction to obtain a thiomannose polymer with a tetraphenylethylene monoarm side chain;

[0022] The chemical structural formulas of the tetraphenylethylene mono-arm thiol mannose polymer, compound 1, compound 2, compound 3, compound 4, compound 5, compound 6, compound 7, compound 8, and compound 9 are shown in formulas (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), and (X), respectively:

[0023]

[0024] In the formula, n is an integer ≥ 2.

[0025] Preferably, in the nucleophilic reaction of step (1), the molar ratio of 4-bromo-4'-methoxybenzophenone to diphenylmethane is 1:(1.1~1.3); the reaction temperature is 0 ℃~100 ℃; and the reaction time is 3 h~24 h.

[0026] Preferably, in the demethylation reaction of step (2), the ratio of the first compound to boron tribromide is 1 g: (2~3) mL; the reaction temperature is 10 ℃~30 ℃; and the reaction time is 18 h~30 h.

[0027] Preferably, in the Suzuki coupling reaction of step (3), the molar ratio of the second compound and N-Boc-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester is 1:(1~3); the reaction temperature is 105 ℃~115 ℃, and the reaction time is 16 h~20 h.

[0028] Preferably, in the esterification reaction of step (4), the molar ratio of the third compound, acryloyl chloride and anhydrous triethylamine is 1:(1~3):(1~3); the reaction temperature is 0 ℃~25 ℃, and the reaction time is 18 h~24 h.

[0029] Preferably, in the Thiol-ene click chemical reaction in step (5), the molar ratio of the fourth compound, acetyl-protected thiol mannose, and n-hexylamine is 1:(1~3):(0.1~0.15); the reaction temperature is 15 ℃~30 ℃, and the reaction time is 18 h~24 h.

[0030] Preferably, in the substitution reaction of step (6), the ratio of the fifth compound to trifluoroacetic acid is 1 mmol: (1~6) ml; the reaction temperature is 15 ℃~25 ℃; and the reaction time is 4 h~6 h.

[0031] Preferably, in the esterification reaction of step (7), the molar ratio of pentafluorophenol, triethylamine and acryloyl chloride is 1:(0.5~2):(0.5~2); the reaction temperature is 0 ℃~25 ℃, and the reaction time is 16 h~36 h.

[0032] Preferably, in step (8) of the RAFT polymerization process, the molar ratio of the seventh compound, the chain transfer agent, and the initiator is (150~220):(7~10):1; the chain transfer agent is trithiocarbonate, and the initiator is azobisisobutyronitrile; the reaction temperature is 70 ℃~90 ℃, and the reaction time is 20 h~30 h.

[0033] Preferably, in the ammonolysis reaction of step (9), the molar ratio of compound 8, compound 6, and 4-diaminopyridine is (1~3):(2~5):1; the reaction temperature is 50℃~70℃; and the reaction time is 18 h~24 h.

[0034] Preferably, in the substitution reaction of step (10), the ratio of compound 9 to sodium methoxide is 0.1 g: (30~60) mg; the reaction temperature is 15 ℃~30 ℃; and the reaction time is 1 h~3 h.

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

[0036] (1) This invention generates tetraphenylmethane and 4-bromo-4'-methoxybenzophenone to produce a tetraphenyl alcohol derivative, which is then dehydrated by p-toluenesulfonic acid to produce a tetraphenyl compound. This is then used to modify and synthesize a thiol sugar compound with acetyl protection of a single-arm tetraphenyl, providing a practical and feasible route for preparing sugar polymers with functionalized tetraphenyl cores. The synthesis method is stable and efficient.

[0037] (2) The present invention combines tetraphenylethylene and sugar units into a compound, which can be linked to the polymer chain through post-polymerization modification to form a sugar-containing polymer.

[0038] (3) Sugar-containing polymers can achieve molecular recognition with specific types of proteins through multivalent interactions, which provides a good foundation for drug carrier materials. The AIE effect of the tetraphenylethylene structure has important scientific applications in imaging and tracing in vivo. It has high responsivity and large fluorescence changes, and can be used as a fluorescent probe. Therefore, the sugar-containing compound polymerization precursor with a tetraphenylethylene structure designed and synthesized in this invention can combine the characteristics of two separate components, and has the potential to examine the recognition performance of proteins and drug release after polymerization. Attached Figure Description

[0039] Figure 1 The first compound in Example 1 of this invention has a hydrogen NMR spectrum.

[0040] Figure 2 The carbon NMR spectrum of the first compound in Example 1 of this invention;

[0041] Figure 3 The first example is the hydrogen NMR spectrum of the second compound in Example 1 of this invention;

[0042] Figure 4 The carbon NMR spectrum of the second compound in Example 1 of this invention;

[0043] Figure 5 The above is the 1H NMR spectrum of the third compound in Example 1 of this invention;

[0044] Figure 6 The carbon NMR spectrum of the third compound in Example 1 of this invention;

[0045] Figure 7 The above is the 1H NMR spectrum of the fourth compound in Example 1 of this invention;

[0046] Figure 8 The carbon NMR spectrum of the fourth compound in Example 1 of this invention;

[0047] Figure 9 The hydrogen NMR spectrum of the fifth compound in Example 1 of this invention;

[0048] Figure 10 The carbon NMR spectrum of the fifth compound in Example 1 of this invention;

[0049] Figure 11 The 1H NMR spectrum of the sixth compound in Example 1 of this invention;

[0050] Figure 12 The 1H NMR spectrum of the sixth compound in Example 1 of this invention;

[0051] Figure 13 The 1H NMR spectrum of the seventh compound in Example 1 of this invention;

[0052] Figure 14 The 1H NMR spectrum of the eighth compound in Example 1 of this invention;

[0053] Figure 15 The 1H NMR spectrum of the ninth compound in Example 1 of this invention;

[0054] Figure 16 The above is the 1H NMR spectrum of the tetraphenylethylene monoarm thiol mannose polymer with a side chain in Example 1 of this invention;

[0055] Figure 17 This is a flowchart illustrating an exemplary preparation method of the present invention;

[0056] Figure 18 This is a fluorescence binding assay of the polymer containing tetraphenylethylene mono-arm thiol mannose in the side chain of Example 1 of the present invention, with the concentration of Con A gradually increased in HEPES buffer at pH=7.4;

[0057] Figure 19 This is a flowchart illustrating an exemplary preparation method for Comparative Example 1;

[0058] Figure 20 This is a diagram illustrating the recognition effect between the tetraphenylethylene mono-arm thiomannose polymer with side chains in Embodiment 1 of the present invention and Con A. Detailed Implementation

[0059] The present invention is further illustrated by the following embodiments. It should be understood that the following embodiments are for illustrative purposes only and are not intended to limit the present invention.

[0060] The chemical structural formula of the polymer containing tetraphenylethylene monoarm thiomannose in the side chain is shown in formula (I):

[0061]

[0062] Where n is an integer ≥ 2. Preferably, 2 ≤ n ≤ 40.

[0063] This invention also provides a method for preparing the aforementioned tetraphenylethylene mono-arm thiomannose polymer with a side chain containing tetraphenylethylene. First, tetraphenylethylene alcohol derivatives are generated from diphenylmethane and 4-bromo-4'-methoxybenzophenone using n-butyllithium. Then, the derivatives are dehydrated with p-toluenesulfonic acid to produce a tetraphenylethylene compound. Boron tribromide treatment yields a phenolic hydroxyl compound, which is then obtained via a Suzuki coupling reaction to form an amino-protected iso-hydroxyl group and a bromotetraphenylethylene compound. This compound undergoes esterification with acryloyl chloride, and the resulting propylene ester compound is subsequently reacted with α-D-pyranomannose thiolate via a Thiol-ene reaction between an olefin and a thiol. After detert-butoxycarbonylation, a tetraphenylethylene mono-arm thiomannose derivative is obtained. Finally, a polymer containing tetraphenylethylene and thiomannose with a side chain is prepared via RAFT polymerization and post-polymerization modification.

[0064] The following combination Figure 17 An exemplary method for preparing a tetraphenylethylene monoarm thiol mannose polymer with a side chain is provided.

[0065] Step (1): 4-Bromo-4'-methoxybenzophenone reacts with diphenylmethane via a nucleophilic addition-elimination reaction, followed by post-treatment to obtain the first compound. In one embodiment of the present invention, in step (1), the molar ratio of 4-bromo-4'-methoxybenzophenone, diphenylmethane, n-butyllithium, and p-toluenesulfonic acid is 1:(1.1~1.3):(1.3~1.5):(0.05~0.1). During the nucleophilic reaction, the reaction temperature is 0 ℃~100 ℃, and the reaction time is 3 h~24 h. In one embodiment of the present invention, in step (1), the post-treatment includes neutralization, washing, drying, and purification.

[0066] Step (2): The first compound obtained in step (1) undergoes a demethylation reaction with boron tribromide, followed by post-treatment to obtain the second compound. In one embodiment of the present invention, the ratio of the first compound to boron tribromide is 1 g: (2~3) mL; during the demethylation reaction, the reaction temperature is 10 ℃~30 ℃, and the reaction time is 18 h~30 h. In one embodiment of the present invention, in step (2), the post-treatment includes extraction, drying, and purification.

[0067] Step (3): The second compound obtained in step (2) undergoes a Suzuki coupling reaction with N-Boc-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester, followed by post-treatment to obtain the third compound. In one embodiment of the present invention, in step (3), the molar ratio of the first compound, N-Boc-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester, anhydrous potassium phosphate, and X-Phos-Pd-G3 is 1:(1~3):(1~3):(0.05~0.1); during the Suzuki coupling reaction, the reaction temperature is 105 ℃~115 ℃, and the reaction time is 16 h~20 h. In one embodiment of the present invention, in step (3), the post-treatment is washing, drying, and purification.

[0068] Step (4): The third compound obtained in step (3) undergoes an esterification reaction with acryloyl chloride and anhydrous triethylamine, followed by post-treatment to obtain the fourth compound. In one embodiment of the present invention, in step (4), the molar ratio of the third compound, acryloyl chloride, and anhydrous triethylamine is 1:(1~3):(1~3); during the esterification reaction, the reaction temperature is 0 ℃~25 ℃, and the reaction time is 18 h~24 h. In one embodiment of the present invention, in step (4), the post-treatment includes washing, drying, and purification.

[0069] Step (5): The fourth compound obtained in step (4) undergoes a Thiol-ene click chemistry reaction with acetyl-protected thiomannose (α-D-pyranomannothiolate) and n-hexylamine, followed by post-treatment to obtain the fifth compound. In one embodiment of the present invention, in step (5), the molar ratio of the fourth compound, α-D-pyranomannothiolate, and n-hexylamine is 1:(1~3):(0.1~0.15); during the Thiol-ene click chemistry reaction, the reaction temperature is 15 ℃~30 ℃, and the reaction time is 18 h~24 h. In one embodiment of the present invention, in step (5), the post-treatment includes washing, drying, and purification.

[0070] Step (6): The fifth compound obtained in step (5) undergoes a substitution reaction with trifluoroacetic acid, followed by post-treatment to obtain the sixth compound. In one embodiment of the present invention, in step (6), the concentration ratio of the fourth compound to trifluoroacetic acid is 1 mmol: (1~6) ml; during the substitution reaction, the reaction temperature is 15 ℃~25 ℃, and the reaction time is 4 h~6 h. In one embodiment of the present invention, in step (6), the post-treatment is concentration.

[0071] Step (7): Pentafluorophenol undergoes an esterification reaction with triethylamine and acryloyl chloride, followed by post-treatment to obtain the seventh compound. In one embodiment of the present invention, in step (7), the molar ratio of pentafluorophenol, triethylamine, and acryloyl chloride is 1:(0.5~2):(0.5~2); during the esterification reaction, the reaction temperature is 0 ℃~25 ℃, and the reaction time is 16 h~36 h. In one embodiment of the present invention, in step (7), the post-treatment includes washing, drying, and purification.

[0072] Step (8): The seventh compound obtained in step (7) undergoes RAFT polymerization with a chain transfer agent and an initiator, followed by post-treatment to obtain the eighth compound. In one embodiment of the present invention, in step (8), the molar ratio of the seventh compound, the chain transfer agent, and the initiator is (150~220):(7~10):1; the chain transfer agent is trithiocarbonate, and the initiator is azobisisobutyronitrile; during the RAFT polymerization reaction, the reaction temperature is 70 ℃~90 ℃, and the reaction time is 20 h~30 h. In one embodiment of the present invention, in step (8), the post-treatment includes washing, drying, and purification.

[0073] Step (9): The eighth compound obtained in step (8), the sixth compound obtained in step (6), and 4-diaminopyridine undergo an ammonolysis reaction, followed by post-treatment to obtain the ninth compound. In one embodiment of the present invention, in step (9), the molar ratio of the eighth compound, the sixth compound, and 4-diaminopyridine is (1~3):(2~5):1; during the ammonolysis reaction, the reaction temperature is 50℃~70℃, and the reaction time is 18 h~24 h. In one embodiment of the present invention, in step (9), the post-treatment includes washing, drying, and purification.

[0074] Step (10): The ninth compound (sugar-containing polymer) obtained in step (9) undergoes a substitution reaction with sodium methoxide, followed by post-treatment to obtain a thiomannose polymer with a tetraphenylethylene monoarm side chain. In one embodiment of the present invention, in step (10), the ratio of the ninth compound to sodium methoxide is 0.1 g:(30~60) mg; during the substitution reaction, the reaction temperature is 15 ℃~30 ℃, and the reaction time is 1 h~3 h. In one embodiment of the present invention, in step (10), the post-treatment is purification.

[0075] The chemical structural formulas of the tetraphenylethylene mono-arm thiol mannose polymer, compound 1, compound 2, compound 3, compound 4, compound 5, compound 6, compound 7, compound 8, and compound 9 are shown in formulas (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), and (X), respectively:

[0076]

[0077] Where n is an integer ≥ 2.

[0078] In the above preparation process, firstly, diphenylmethane and 4-bromo-4'-methoxybenzophenone are reacted with n-butyllithium to generate a tetraphenylethylene alcohol derivative. Then, the tetraphenylethylene compound is dehydrated with p-toluenesulfonic acid. After treatment with boron tribromide, a phenolic hydroxyl compound is obtained. Then, an amino-protected ipsilateral hydroxyl group and a bromotetraphenylethylene compound are obtained through a Suzuki coupling reaction. This compound undergoes an esterification reaction with acryloyl chloride. The resulting propylene ester compound then undergoes a Thiol-ene reaction between an olefin and a thiol with α-D-pyranomannose thiolate. After detert-butoxycarbonylation, a ipsilateral mono-arm thiol mannose derivative containing tetraphenylethylene is obtained. A pentafluorophenol active ester polymer is prepared by polymerization with RAFT. A substitution reaction is then carried out to obtain a polymer derivative containing a tetraphenylethylene mono-arm thiol mannose with a side chain. Finally, the acetyl group protection is removed under sodium methoxide conditions to obtain a thiol mannose polymer containing a tetraphenylethylene side chain.

[0079] Therefore, this invention innovatively utilizes efficient and rapid RAFT polymerization and click chemistry to prepare tetraphenylethylene mono-arm thiol mannose polymers with high biocompatibility and fluorescence recognition properties, providing a practical and feasible route for preparing functionalized tetraphenylethylene mono-arm thiol mannose polymers.

[0080] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments. It should also be understood that the following embodiments are only for further illustration of the present invention and should not be construed as limiting the scope of protection of the present invention. Any non-essential improvements and adjustments made by those skilled in the art based on the above description of the present invention are within the scope of protection of the present invention. The specific process parameters, etc., in the following examples are merely examples within a suitable range; that is, those skilled in the art can make appropriate selections within the appropriate range based on the description herein, and are not intended to be limited to the specific values ​​in the examples below.

[0081] In the following examples, the reagents used were sourced as follows: acetylthiol mannosose (α-Man-OAc-SH) was synthesized according to the method described in the literature (Herzberger J, Leibig D, Langhanki J, Moers C, Opatz T, Frey h. “Clickable PEG” via anionic copolymerization of et hylene oxide and glycidylpropargyl et her. Polymer Chemistry 2017, 8 (12): 1882-1887.); diphenylmethane, 4-bromo-4'-methoxybenzophenone, N-Boc-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester, and X-Phos-Pd-G3 were purchased from Shanghai Shaoyuan Reagent Co., Ltd.; anhydrous potassium phosphate (≥98%) was purchased from Shanghai Haohong Biomedical Technology Co., Ltd.; anhydrous titanium tetrachloride, trifluoroacetic acid, and n-butyllithium (2.5 M The solution in hexane (safely sealed) was purchased from Anaiji Chemical; boron tribromide, pentafluorophenol, acryloyl chloride, triethylamine, azobisisobutyronitrile, and third-generation carbonates were purchased from Bid Pharmaceutical; anhydrous potassium carbonate (>99%), sodium bicarbonate (>99.5%), and other unmentioned reagents were purchased from Shanghai Runjie Technology Development Co., Ltd.

[0082] In addition, in the following embodiments, unless otherwise specified, the other raw materials, reagents or processing techniques are all conventional commercially available raw materials or conventional processing techniques in the art.

[0083] In the following embodiments, the characterization instruments are as follows: nuclear magnetic resonance spectrometer, model AS400 400 MHz, manufactured by Wuhan Zhongke Co., Ltd.; high-resolution mass spectrometer, model Bruker SolariX 7.0, manufactured by Bruker Corporation; fluorescence spectrophotometer, model FS5, manufactured by Edinburgh Instruments; gel permeation chromatograph, model Agilent 1260, manufactured by Agilent.

[0084] Unless otherwise specified in this invention, room temperature or normal temperature refers to 10~30℃.

[0085] Unless otherwise specified in this invention, the eluent ratio refers to the volume ratio.

[0086] Example 1

[0087] This embodiment provides a polymer with a side chain containing tetraphenylethylene mono-arm thiol mannose and its preparation method.

[0088] (1) Preparation of the first compound

[0089] Diphenylmethane (1.75 g, 10.4 mmol) was added to a reaction flask, followed by 50 mL of anhydrous tetrahydrofuran. The mixture was stirred in an ice bath under a nitrogen atmosphere. Then, 5 mL of n-butyllithium (2.5 M solution in n-hexane, sealed tightly) was slowly added, resulting in an orange-red reaction solution. Stirring in the ice bath continued for 1 h. 4-Bromo-4'-methoxybenzophenone (2.5 g, 8.63 mmol) was dissolved in 40 mL of anhydrous tetrahydrofuran and slowly added to the mixture using a syringe. The reaction was continued at room temperature for 24 h. After the reaction was complete, the reaction was quenched with saturated ammonium chloride solution, followed by washing with saturated brine. The organic layer was extracted with dichloromethane, dried over anhydrous magnesium sulfate, and concentrated to obtain the crude product. The crude product was dissolved in 50 mL of toluene, and p-toluenesulfonic acid (0.104 mmol) was added. After complete dissolution, the mixture was reacted at 100 °C for 3 h. After the reaction was completed, the mixture was cooled to room temperature, extracted with dichloromethane and saturated brine, dried with anhydrous magnesium sulfate, and purified by silica gel column chromatography with petroleum ether / ethyl acetate (30:1) to give 1.92 g of a pale yellow oil, with a yield of 50%.

[0090] The 1H and 1C NMR spectra of the first compound are shown in [reference 1]. Figure 1 and Figure 2 As shown.

[0091] The chemical structural formula of the first compound is shown below:

[0092]

[0093] The NMR data for the first compound are shown below:

[0094] 1 H NMR (401 MHz, CDCl3) δ 7.27 (d, J = 8.5 Hz, 2H), 7.22 – 7.12 (m,6H), 7.11 – 7.03 (m, 4H), 7.01 – 6.92 (m, 4H), 6.70 (d, J = 8.8 Hz, 2H), 3.79 (s, 3H).

[0095] 13 C NMR (101 MHz, CDCl3) δ 158.27, 143.70, 143.03, 140.74, 139.27, 135.63, 133.11, 132.58, 131.32, 130.86, 127.86, 126.53, 120.41, 113.21, 55.16.

[0096] (2) Preparation of the second compound

[0097] The first compound (1.2 g, 2.71 mmol) was dissolved in 20 mL of anhydrous dichloromethane, purged three times with nitrogen, and allowed to dissolve completely in an ice bath. Then, BBr3 (3.6 mL) was slowly injected into the mixture using a syringe, and the reaction was continued at room temperature for 24 h. After the reaction was confirmed to be complete by TLC, the mixture was extracted three times with dichloromethane and ice water. The organic layer was dried with anhydrous sodium sulfate, and the product was purified by silica gel column chromatography with petroleum ether / ethyl acetate (20:1) to give the second compound in 86% yield.

[0098] The 1H NMR spectrum and 1C NMR spectrum of the second compound are shown in [reference 1]. Figure 3 and Figure 4 As shown.

[0099] The chemical structural formula of the second compound is shown below:

[0100]

[0101] The NMR data for the second compound are shown below:

[0102] 1 H NMR (401 MHz, CDCl3) δ 7.25 (d, J = 8.4 Hz, 2H), 7.15 (d, J= 2.7Hz, 6H), 7.08 – 7.00 (m, 4H), 6.92 (dd, J = 15.6, 8.5 Hz, 4H), 6.61 (d, J =8.5 Hz, 2H).

[0103] 13 C NMR (101 MHz, CDCl3) δ 154.40, 143.66, 142.93, 140.75, 139.21, 135.71, 133.08, 132.76, 131.30, 130.84, 127.84, 126.53, 120.41, 114.76.

[0104] (3) Preparation of the third compound

[0105] The second compound (500 mg, 1.17 mmol) was dissolved in 10 mL of 1,4-dioxane. After dissolution, N-Boc-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester (905 mg, 1.755 mmol), X-Phos-Pd-G3 (198 mg, 0.117 mmol), and anhydrous potassium phosphate (625 mg, 1.755 mmol) were added sequentially. The atmosphere was then purged with nitrogen three times to maintain a nitrogen atmosphere, and the reaction was carried out at 105 °C for 16 h. After the reaction, the mixture was extracted three times with ethyl acetate and saturated brine. The organic layer was dried over anhydrous sodium sulfate, and the product was purified by silica gel column chromatography with petroleum ether / ethyl acetate (10:1) to give 460 mg of compound (the third compound), with a yield of 73%.

[0106] The 1H NMR spectrum and 1C NMR spectrum of the third compound are shown below. Figure 5 and Figure 6 As shown.

[0107] The chemical structural formula of the third compound is shown below:

[0108]

[0109] The NMR data for the third compound are shown below:

[0110] 1 H NMR (400 MHz, CDCl3) δ 7.10 (dd, J = 11.8, 5.2 Hz, 8H), 7.04 – 7.00(m, 4H), 6.98 (d, J= 8.3 Hz, 2H), 6.87 (d, J = 8.5 Hz, 2H), 6.56 (d, J = 8.5Hz, 2H), 6.00 (s, 1H), 4.04 (s, 2H), 3.59 (t, J = 5.5 Hz, 2H), 2.45 (s, 2H), 1.50 – 1.45 (m, 9H).

[0111] 13 C NMR (101 MHz, CDCl3) δ 154.46, 144.01, 142.98, 140.09, 138.13, 135.96, 132.72, 131.40, 127.67, 126.24, 123.86, 114.65, 79.77, 60.44, 28.49.

[0112] HRMS (ESI): m / z calc. for C 36 H 35 NO3(M+Na+) calc.for: 552.26306; found: 552.28011.

[0113] (4) The fourth compound

[0114] The third compound (400 mg, 0.755 mmol) was added to a reaction flask, along with 5 mL of dichloromethane and triethylamine (0.21 mL, 1.51 mmol). The mixture was stirred thoroughly in an ice bath, and acryloyl chloride (0.13 mL, 1.51 mmol) was slowly added dropwise. The mixture was stirred for another 2.5 h in an ice bath, followed by a reaction at room temperature for 24 h. The organic layer was extracted with saturated brine and dichloromethane, dried over anhydrous sodium sulfate, and purified by silica gel column chromatography with petroleum ether / ethyl acetate (15:1) to give 223 mg of compound (the fourth compound), in 51% yield.

[0115] The hydrogen NMR spectrum and carbon NMR spectrum of the fourth compound are shown below. Figure 7 and Figure 8 As shown.

[0116] The chemical structural formula of the fourth compound is shown below:

[0117]

[0118] The NMR data for the fourth compound are shown below:

[0119] 1 H NMR (400 MHz, CDCl3) δ 7.16 – 7.07 (m, 8H), 7.05 – 6.96 (m, 8H), 6.88 (d, J = 8.6 Hz, 2H), 6.56 (d, J = 17.3 Hz, 1H), 6.27 (dd, J = 17.3, 10.4Hz, 1H), 5.99 (t, J = 9.7 Hz, 2H), 4.04 (s, 2H), 3.59 (t, J = 5.4 Hz, 2H), 2.46 (s, 2H), 1.48 (s, 9H).

[0120] 13 C NMR (101 MHz, CDCl3) δ 164.35, 149.01, 143.59, 142.44, 141.33, 139.54, 138.40, 132.41, 131.58 – 131.02, 128.00, 127.77, 126.56, 124.01, 120.66, 79.65, 60.41, 28.50.

[0121] HRMS (ESI): m / z calc. for C 39 H 37 NO4(M+Na+) calc.for: 606.27159; found: 606.27224.

[0122] (5) Preparation of the fifth compound

[0123] The fourth compound (630 mg, 1.08 mmol) obtained from multiple synthesiss and α-Man-OAc-SH (882 mg, 2.16 mmol) were added to a reaction flask, followed by 5 mL of ultra-dry dichloromethane. After the starting materials were completely dissolved, n-hexylamine (0.108 mmol) was added, and the reaction was carried out at room temperature for 18 h. After the reaction was confirmed to be complete by TLC, the mixture was extracted three times with dichloromethane and saturated brine. The organic layer was dried over anhydrous sodium sulfate, and the product was purified by silica gel column chromatography with petroleum ether / ethyl acetate (3:1) to give 670 mg of compound (i.e., the fifth compound), with a yield of 64%.

[0124] See the 1H NMR and 1C NMR spectra of the fifth compound. Figure 9 and Figure 10 As shown.

[0125] The chemical structural formula of the fifth compound is shown below:

[0126]

[0127] The NMR data for the fifth compound are shown below:

[0128] 1 H NMR (401 MHz, CDCl3) δ 7.18 – 7.09 (m, 8H), 7.02 (dd, J = 17.2, 6.9 Hz, 8H), 6.87 (d, J = 7.1 Hz, 2H), 6.03 (s, 1H), 5.34 (t, J = 12.2 Hz,1H), 5.28 (s, 1H), 4.89 (s, 1H), 4.31 (dd, J = 12.0, 4.9 Hz, 1H), 4.16 (dd, J = 7.1, 1.3 Hz, 1H), 4.07 (s, 2H), 3.89 (dd, J = 15.8, 7.0 Hz, 1H), 3.73 (dd, J = 10.0, 5.3 Hz, 1H), 3.62 (s, 2H), 2.96 (t, J = 7.0 Hz, 2H), 2.90 – 2.79(m, 4H), 2.48 (s, 2H), 2.18 (s, 3H), 2.12 (s, 3H), 2.06 (s, 3H), 2.01 (s,3H), 1.50 (s, 9H).

[0129] 13C NMR (101 MHz, CDCl3) δ 171.22, 170.70, 170.00, 149.00, 143.57, 142.43, 141.38, 139.49, 138.40, 132.38, 132.08 – 130.97 , 127.79 ,126.58 , 124.01 , 120.70 , 97.65 , 79.67 , 69.51 , 69.03 , 68.79 , 68.11 ,66.04 , 62.49 , 60.44 , 35.03, 31.44, 28.51, 27.57, 21.26 – 20.61.

[0130] HRMS (ESI): m / z calc. for C 54 H 59 NO 14 S(M+Na+) calc.for: 1000.37552; found: 1000.37720.

[0131] (6) Preparation of the sixth compound

[0132] Compound 5 (600 mg, 0.625 mmol) was added to a reaction flask, and 5 mL of dichloromethane was added to dissolve it completely. Then, 3 mL of trifluoroacetic acid was added, and the mixture was stirred at room temperature for 6 h. After the reaction was confirmed to be complete by TLC, the reaction solution was diluted with dichloromethane, evaporated to dryness, dissolved in dichloromethane, and finally concentrated to obtain 520 mg of compound 6, with a yield of 96%.

[0133] For the 1H NMR and 1C NMR spectra of the sixth compound, see [link to NMR spectrum]. Figure 11 and Figure 12 As shown.

[0134] The chemical structural formula of the sixth compound is shown below:

[0135]

[0136] The NMR data for the sixth compound are shown below:

[0137] 1 H NMR (401 MHz, CDCl3) δ 7.14 (s, 8H), 7.05 (d, J = 7.6 Hz, 8H), 6.89 (d, J= 8.3 Hz, 2H), 6.00 (s, 1H), 5.40 – 5.33 (m, 1H), 5.30 (s, 1H), 4.94 – 4.85 (m, 1H), 4.32 (dd, J = 12.3, 5.1 Hz, 1H), 4.15 (d, J = 10.9 Hz,3H), 3.95 – 3.82 (m, 1H), 3.79 – 3.67 (m, 1H), 3.35 (d, J = 104.1 Hz, 2H), 3.01 – 2.81 (m, 6H), 2.76 (s, 2H), 2.22 – 1.99 (m, 12H).

[0138] 13 C NMR (101 MHz, CDCl3) δ 170.44 – 169.54, 149.04, 143.32, 141.97, 132.38, 131.69, 131.28, 127.85, 126.76, 124.26, 120.82, 97.62, 70.17 – 69.58, 69.31, 68.74, 68.12, 66.04, 62.57, 53.51, 35.01, 31.44, 27.57, 20.81.

[0139] HRMS (ESI): m / z calc. For C 49 H 51 NO 12 S(M+Na+) calc.for: 900.31012; found: 900.32155.

[0140] (7) Preparation of the seventh compound

[0141] Pentafluorophenol (10.0 g, 54.33 mmol) was dissolved in 250 mL of anhydrous dichloromethane. Ultra-dry triethylamine (7.53 mL, 54.33 mmol) was added dropwise under ice bath conditions. After stirring for 0.5 h, acryloyl chloride (4.42 mL, 54.33 mmol) was added dropwise. The reaction was then maintained at 0 °C and allowed to proceed overnight at room temperature. After the reaction was complete, the mixture was extracted with dichloromethane and saturated brine, washed with saturated brine, and dried over anhydrous sodium sulfate. The crude product was purified by silica gel column chromatography (petroleum ether) to give 8.6 g of a pale yellow liquid (i.e., compound VII), with a yield of 66%.

[0142] See the 1H NMR spectrum of the seventh compound. Figure 13 As shown.

[0143] The chemical structural formula of the seventh compound is shown below:

[0144]

[0145] The NMR data for the seventh compound are shown below:

[0146] 1 H NMR (400 MHz, CDCl3) δ 6.74 (d, J = 16.2 Hz, 1 Hz), 6.40 Hz (dd, J =16.8, 10.5 hz, 1 H), 6.19 (d, J = 11.7 Hz, 1 Hz).

[0147] (8) Preparation of the eighth compound

[0148] Compound VII (3 g, 12.4 mmol) was dissolved in 5 mL of anhydrous 1,4-dioxane, followed by the addition of trithiocarbonate (210 mg, 0.55 mmol) and azobisisobutyronitrile (AIBN) (6 mg, 0.069 mmol). The mixture was purged with nitrogen three times, and then reacted at 85 °C for 24 h. After the reaction was complete, the reaction solution was cooled to room temperature, dissolved in dichloromethane, and precipitated three times with methanol. The solution was then dried to obtain 1.22 g of a pale yellow powder (i.e., compound VIII: pPFPA).

[0149] See the 1H NMR spectrum of pPFPA. Figure 14 As shown.

[0150] The chemical structural formula of pPFPA is shown below:

[0151]

[0152] Where n is 36.

[0153] The NMR data for pPFPA are shown below:

[0154] 1 H NMR (400 M Hz, CDCl3) δ 3.09 (s, 8 H), 2.87 (s, 1 H), 2.50 (s, 4H), 2.11 (s, 8 H), 1.96 (s, 4 H), 1.38 (s, 1 H), 1.25 (s, 1 H).

[0155] 19 F NMR (470 MHz, CDCl3): δ = -153.21 (bs, 2F, ortho), -156.76 (bs,1F, para), -162.22 (bs, 2F, meta).

[0156] (9) Preparation of the ninth compound

[0157] Under a nitrogen atmosphere, pPFPA (90.365 mg, 0.38 mmol) was dissolved in 3 mL of DMF, and compound VI (400 mg, 0.456 mmol) and DMAP (23.22 mg, 0.19 mmol) were added. The mixture was reacted at 65 °C for 24 h. After the reaction was complete, the mixture was centrifuged three times in diethyl ether and then dried to obtain 320 mg of a dark yellow-brown powder (i.e., compound VIII), with a yield of 65%.

[0158] See the 1H NMR spectrum of compound 9. Figure 15 As shown.

[0159] The chemical structural formula of the ninth compound is shown below:

[0160]

[0161] Where n is 36.

[0162] The NMR data for compound 9 are shown below:

[0163] 1 H NMR (401 MHz, CDCl3) δ 7.14 (s, 8H), 7.05 (d, J = 7.6 Hz, 8H), 6.89(d, J= 8.3 Hz, 2H), 6.00 (s, 1H), 5.40 – 5.33 (m, 1H), 5.30 (s, 1H), 4.94 –4.85 (m, 1H), 4.32 (dd, J = 12.3, 5.1 Hz, 1H), 4.15 (d, J = 10.9 Hz, 3H), 3.95 – 3.82 (m, 1H), 3.79 – 3.67 (m, 1H), 3.35 (d, J = 104.1 Hz, 2H), 3.01 –2.81 (m, 6H), 2.76 (s, 2H), 2.22 – 1.99 (m, 12H), 1.29 (s, 6H).

[0164] (10) Preparation of tetraphenylethylene monoarm thiol mannose polymers with side chains

[0165] Compound 9 (130 mg, 0.1235 mmol) was dissolved in 1 mL of a mixed solution of anhydrous methanol and anhydrous dichloromethane (MeOH:DCM volume ratio = 1:1). 1 mL of sodium methoxide dichlorosol solution (40 mg, 0.741 mmol) was added dropwise at 25 °C, followed by a reaction at room temperature for 1 h. After the reaction was complete, the solvent was rotary evaporated, and the residue was dissolved in 1 mL of DMF. The polymer solution was transferred to a MWCO 3500Da container and dialyzed against methanol for 24 h. The final homopolymer was lyophilized after dialysis to obtain 92 mg of a pale yellow powder (i.e., a polymer with tetraphenylethylene mono-arm thiomannose side chains), with a yield of 82%.

[0166] See the 1H NMR spectrum of the tetraphenylethylene monoarm thiol mannose polymer with side chain. Figure 16 As shown.

[0167] The chemical structural formula of the polymer containing tetraphenylethylene mono-arm thiol mannose in the side chain is shown below:

[0168]

[0169] Where n is 36.

[0170] The NMR data of the polymer with tetraphenylethylene monoarm thiomannose side chain are shown below:

[0171] 1 H NMR (400 MHz, DMSO) δ 6.78 (dd, J= 181.6, 75.2 Hz, 18H), 6.06 (s,1H), 4.98 (d, J = 268.2 Hz, 3H), 3.48 (dd, J = 60.5, 38.7 Hz, 8H), 2.75 (t, J = 59.4 Hz, 8H), 1.98 (s, 2H), 1.24 (s, 6H).

[0172] The gel permeation chromatography (GPC) characterization of polymers containing tetraphenylethylene mono-arm thiomannose in the side chain is shown in Table 1 below. Test conditions: flow rate: DMF (HPLC grade, containing 50 mmol / L LiBr) as mobile phase, 1 mL / min; temperature: 35 °C; guard column: Waters 4.6 x 30 mm; three Waters columns: WAT054466, WAT044226, and WAT044223; instrument calibrated to 10 PMMA standard.

[0173] Gel permeation chromatography (GPC) characterization is shown in Table 1. It can be seen that the dispersion width of the prepared tetraphenylethylene mono-arm thiol mannose polymer with side chains is 1.08, indicating a relatively small dispersion.

[0174] Table 1. GPC characterization of polymers containing tetraphenylethylene monoarm thiomannose side chains.

[0175]

[0176] The fluorescence emission pattern of the glycopolymer containing tetraphenylethylene monoarm thiomannose with side chains obtained by fluorescence binding assay in HEPES buffer at pH 7.4 with gradually increasing Con A (canavagin A) concentration is shown in the figure below. Figure 18 The testing method was performed according to the literature (Xiaoying Gao, Duo Mao, Xingang Zuo, et al. Specific Targeting, Imaging and Ablation of Tumor-Associated Macrophages by Theranostic Mannose-AIEgen Conjugates. Analytical Chemistry. 2019, 91 (10): 6836-6843.).

[0177] As can be seen, the polymer with tetraphenylethylene mono-arm thiol mannose side chain obtained in this embodiment has good biocompatibility and obvious concentration-dependent fluorescence increase characteristics, and can be used as a sugar-containing fluorescent probe for AIE.

[0178] Example 2

[0179] This embodiment provides a polymer with a side chain containing tetraphenylethylene mono-arm thiol mannose and its preparation method.

[0180] (1) Preparation of the first compound

[0181] Diphenylmethane (1.75 g, 10.4 mmol) was added to a reaction flask, followed by 50 mL of anhydrous tetrahydrofuran. The mixture was stirred in an ice bath under a nitrogen atmosphere. 5 mL of n-butyllithium (2.5 M solution in n-hexane, sealed tightly) was slowly added, resulting in an orange-red reaction solution. Stirring in the ice bath continued for 1 h. 4-Bromo-4'-methoxybenzophenone (2.5 g, 8.63 mmol) was dissolved in 50 mL of anhydrous tetrahydrofuran and slowly added to the mixture using a syringe. The reaction was continued at room temperature for 24 h. After the reaction was complete, the reaction was quenched with saturated ammonium chloride solution, followed by washing with saturated brine. The organic layer was extracted with dichloromethane, dried over anhydrous magnesium sulfate, and concentrated to obtain the crude product. The crude product was dissolved in 50 mL of toluene, and p-toluenesulfonic acid (0.863 mmol) was added. After complete dissolution, the mixture was reacted at 100 °C for 3 h. After the reaction was completed, the mixture was cooled to room temperature, extracted with dichloromethane and saturated brine, dried with anhydrous magnesium sulfate, and purified by silica gel column chromatography with petroleum ether / ethyl acetate (30:1) to give 2.1 g of a pale yellow oil, with a yield of 55%.

[0182] (2) Preparation of the second compound

[0183] The first compound (1.2 g, 2.71 mmol) was dissolved in 20 mL of anhydrous dichloromethane, purged three times with nitrogen, and allowed to dissolve completely in an ice bath. Then, BBr3 (3.6 mL) was slowly injected into the resulting mixture using a syringe, and the reaction continued at room temperature for 24 h. After the starting material was confirmed to be completely reacted by TLC, the mixture was extracted three times with dichloromethane and ice water. The organic layer was dried over anhydrous sodium sulfate, and the product was purified by silica gel column chromatography with petroleum ether / ethyl acetate (20:1) to give compound 0.95 (i.e., the second compound), with a yield of 82%.

[0184] (3) Preparation of the third compound

[0185] The second compound (500 mg, 1.17 mmol) was dissolved in 10 mL of 1,4-dioxane. After dissolution, N-Boc-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester (905 mg, 1.755 mmol), X-Phos-Pd-G3 (198 mg, 0.117 mmol), and anhydrous potassium phosphate (625 mg, 1.755 mmol) were added sequentially. The atmosphere was then purged with nitrogen three times to maintain a nitrogen atmosphere, and the reaction was carried out at 105 °C for 16 h. After the reaction, the mixture was extracted three times with ethyl acetate and saturated brine. The organic layer was dried over anhydrous sodium sulfate, and the product was purified by silica gel column chromatography with petroleum ether / ethyl acetate (10:1) to give 465 mg of compound (the third compound), with a yield of 75%.

[0186] (4) The fourth compound

[0187] The third compound (400 mg, 0.755 mmol) was added to a reaction flask, along with 5 mL of dichloromethane and triethylamine (0.21 mL, 1.51 mmol). The mixture was stirred thoroughly in an ice bath, and acryloyl chloride (0.13 mL, 1.51 mmol) was slowly added dropwise. The mixture was stirred for another 2.5 h in an ice bath, followed by a reaction at room temperature for 24 h. The organic layer was extracted with saturated brine and dichloromethane, dried over anhydrous sodium sulfate, and purified by silica gel column chromatography with petroleum ether / ethyl acetate (15:1) to give 268 mg of compound (the fourth compound), in 61% yield.

[0188] (5) Preparation of the fifth compound

[0189] The fourth compound (630 mg, 1.08 mmol) obtained from multiple synthesiss and α-Man-OAc-SH (882 mg, 2.16 mmol) were added to a reaction flask, followed by 5 mL of ultra-dry dichloromethane. After the starting materials were completely dissolved, n-hexylamine (0.108 mmol) was added, and the reaction was carried out at room temperature for 18 h. After the reaction was confirmed to be complete by TLC, the mixture was extracted three times with dichloromethane and saturated brine. The organic layer was dried over anhydrous sodium sulfate, and the product was purified by silica gel column chromatography with petroleum ether / ethyl acetate (3:1) to give 695 mg of compound (i.e., the fifth compound), with a yield of 65%.

[0190] (6) Preparation of the sixth compound

[0191] Compound 5 (600 mg, 0.625 mmol) was added to a reaction flask, and 5 mL of dichloromethane was added to dissolve it completely. Then, 3 mL of trifluoroacetic acid was added, and the mixture was stirred at room temperature for 6 h. After the reaction was complete, the reaction solution was diluted with dichloromethane, evaporated to dryness, dissolved in dichloromethane, and finally concentrated to give 524 mg of compound 6 (the sixth compound), with a yield of 94%.

[0192] (7) Preparation of the seventh compound

[0193] 10.0 g (54.33 mmol) of pentafluorophenol was dissolved in 250 mL of anhydrous dichloromethane. Ultra-dry triethylamine (7.53 mL, 54.33 mmol) was added dropwise under ice bath conditions. After stirring for 0.5 h, acryloyl chloride (4.42 mL, 54.33 mmol) was added dropwise. The reaction was then maintained at 0 °C and allowed to proceed overnight at room temperature. After the reaction was complete, the mixture was extracted with dichloromethane and saturated brine, washed with saturated brine, and dried over anhydrous sodium sulfate. The crude product was purified by silica gel column chromatography (petroleum ether) to give 8.5 g of a pale yellow liquid (i.e., compound VII), with a yield of 64%.

[0194] (8) Preparation of the eighth compound

[0195] Compound VII (3 g, 12.4 mmol) was dissolved in 5 mL of anhydrous 1,4-dioxane, followed by the addition of trithiocarbonate (210 mg, 0.55 mmol) and azobisisobutyronitrile (AIBN) (6 mg, 0.069 mmol). The mixture was purged with nitrogen three times, and then reacted at 85 °C for 24 h. After the reaction was complete, the reaction solution was cooled to room temperature, dissolved in dichloromethane, and precipitated with methanol three times. The solution was then dried to obtain 1.21 g of a pale yellow powder (i.e., compound VIII: pPFPA).

[0196] (9) Preparation of the ninth compound

[0197] Under a nitrogen atmosphere, pPFPA (90.365 mg, 0.38 mmol) was dissolved in 3 mL of DMF, and compound VI (400 mg, 0.456 mmol) and DMAP (23.22 mg, 0.19 mmol) were added. The mixture was reacted at 65 °C for 24 h. After the reaction was complete, the mixture was precipitated in diethyl ether, centrifuged three times, and then dried to obtain 284 mg of dark yellow-brown powder (i.e., compound IX), with a yield of 58%.

[0198] (10) Preparation of tetraphenylethylene monoarm thiol mannose polymers with side chains

[0199] Compound 9 (130 mg, 0.1235 mmol) was dissolved in 1 mL of a mixed solution of anhydrous methanol and anhydrous dichloromethane (MeOH:DCM volume ratio = 1:1). 1 mL of sodium methoxide dichlorosol solution (40 mg, 0.741 mmol) was added dropwise at 25 °C, followed by a reaction at room temperature for 1 h. After the reaction was complete, the solvent was rotary evaporated, and the residue was dissolved in 1 mL of DMF. The polymer solution was transferred to a MWCO3500Da container and dialyzed against methanol for 24 h. The final homopolymer P3 was lyophilized after dialysis to obtain 96 mg of a pale yellow powder (i.e., a polymer with tetraphenylethylene mono-arm thiomannose side chains), with a yield of 85%.

[0200] Example 3

[0201] This embodiment provides a polymer with a side chain containing tetraphenylethylene mono-arm thiol mannose and its preparation method.

[0202] (1) Preparation of the first compound

[0203] Diphenylmethane (1.75 g, 10.4 mmol) was added to a reaction flask, followed by 50 mL of anhydrous tetrahydrofuran. The mixture was stirred in an ice bath under a nitrogen atmosphere. 5 mL of n-butyllithium (2.5 M solution in n-hexane, sealed tightly) was slowly added, resulting in an orange-red reaction solution. Stirring in the ice bath continued for 1 h. 4-Bromo-4'-methoxybenzophenone (2.5 g, 8.63 mmol) was dissolved in 40 mL of anhydrous tetrahydrofuran and slowly added to the resulting mixture using a syringe. The reaction was continued at room temperature for 24 h. After the reaction was complete, the reaction was quenched with saturated ammonium chloride solution, followed by washing with saturated brine. The organic layer was extracted with dichloromethane, dried over anhydrous magnesium sulfate, and concentrated to obtain the crude product. The crude product was dissolved in 50 mL of toluene, and p-toluenesulfonic acid (0.104 mmol) was added. After complete dissolution, the mixture was reacted at 100 °C for 3 h. After the reaction was completed, the mixture was cooled to room temperature, extracted with dichloromethane and saturated brine, dried with anhydrous magnesium sulfate, and purified by silica gel column chromatography with petroleum ether / ethyl acetate (30:1) to give 2.3 g of a pale yellow oil, with a yield of 61%.

[0204] (2) Preparation of the second compound

[0205] The first compound (1.2 g, 2.71 mmol) was dissolved in 20 mL of anhydrous dichloromethane, purged three times with nitrogen, and allowed to dissolve completely in an ice bath. Then, BBr3 (3.6 mL) was slowly injected into the mixture using a syringe, and the reaction was continued at room temperature for 24 h. After the reaction was confirmed to be complete by TLC, the mixture was extracted three times with dichloromethane and ice water. The organic layer was dried with anhydrous sodium sulfate, and the product was purified by silica gel column chromatography with petroleum ether / ethyl acetate (20:1) to give compound 1.05 (i.e., the second compound), with a yield of 93%.

[0206] (3) Preparation of the third compound

[0207] The second compound (500 mg, 1.17 mmol) was dissolved in 10 mL of 1,4-dioxane. After dissolution, N-Boc-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester (905 mg, 1.755 mmol), X-Phos-Pd-G3 (198 mg, 0.117 mmol), and anhydrous potassium phosphate (625 mg, 1.755 mmol) were added sequentially. The atmosphere was then purged with nitrogen three times to maintain a nitrogen atmosphere, and the reaction was carried out at 105 °C for 16 h. After the reaction, the mixture was extracted three times with ethyl acetate and saturated brine. The organic layer was dried over anhydrous sodium sulfate, and the product was purified by silica gel column chromatography with petroleum ether / ethyl acetate (10:1) to give 483 mg of compound (the third compound), with a yield of 78%.

[0208] (4) The fourth compound

[0209] The third compound (400 mg, 0.755 mmol) was added to a reaction flask, along with 5 mL of dichloromethane and triethylamine (0.21 mL, 1.51 mmol). The mixture was stirred thoroughly in an ice bath, and acryloyl chloride (0.13 mL, 1.51 mmol) was slowly added dropwise. The mixture was stirred for another 2.5 h in an ice bath, followed by reaction at room temperature for 24 h. The organic layer was extracted with saturated brine and dichloromethane, dried over anhydrous sodium sulfate, and purified by silica gel column chromatography with petroleum ether / ethyl acetate (15:1) to give 255 mg of compound (the fourth compound), in 58% yield.

[0210] (5) Preparation of the fifth compound

[0211] The fourth compound (630 mg, 1.08 mmol) obtained from multiple synthesiss and α-Man-OAc-SH (882 mg, 2.16 mmol) were added to a reaction flask, followed by 5 mL of ultra-dry dichloromethane. After the starting materials were completely dissolved, n-hexylamine (0.162 mmol) was added, and the reaction was carried out at room temperature for 20 h. After the reaction was confirmed to be complete by TLC, the mixture was extracted three times with dichloromethane and saturated brine. The organic layer was dried over anhydrous sodium sulfate, and the product was purified by silica gel column chromatography with petroleum ether / ethyl acetate (3:1) to give 645 mg of compound (i.e., the fifth compound), with a yield of 60%.

[0212] (6) Preparation of the sixth compound

[0213] Compound 5 (600 mg, 0.625 mmol) was added to a reaction flask, and 5 mL of dichloromethane was added to dissolve it completely. Then, 3 mL of trifluoroacetic acid was added, and the mixture was stirred at room temperature for 6 h. After the reaction was confirmed to be complete by TLC, the reaction solution was diluted with dichloromethane, evaporated to dryness, dissolved in dichloromethane, and finally concentrated to give 513 mg of compound 6 (i.e., compound 6), with a yield of 92%.

[0214] (7) Preparation of the seventh compound

[0215] 10.0 g (54.33 mmol) of pentafluorophenol was dissolved in 250 mL of anhydrous dichloromethane. Ultra-dry triethylamine (7.53 mL, 54.33 mmol) was added dropwise under ice bath conditions. After stirring for 0.5 h, acryloyl chloride (4.42 mL, 54.33 mmol) was added dropwise. The reaction was then maintained at 0 °C and allowed to proceed overnight at room temperature. After the reaction was complete, the mixture was extracted with dichloromethane and saturated brine, washed with saturated brine, and dried over anhydrous sodium sulfate. The crude product was purified by silica gel column chromatography (petroleum ether) to give 8.7 g of a pale yellow liquid (i.e., compound VII), with a yield of 67%.

[0216] (8) Preparation of the eighth compound

[0217] Compound VI (3 g, 12.4 mmol) was dissolved in 5 mL of anhydrous 1,4-dioxane, followed by the addition of trithiocarbonate (210 mg, 0.55 mmol) and azobisisobutyronitrile (AIBN) (6 mg, 0.069 mmol). Nitrogen gas was purged three times, and the reaction mixture was then incubated at 85 °C for 24 h. After the reaction was complete, the reaction solution was cooled to room temperature, dissolved in dichloromethane, and precipitated three times with methanol. The solution was then dried to obtain 1.25 g of a pale yellow powder (i.e., compound VIII: pPFPA).

[0218] (9) Preparation of the ninth compound

[0219] Under a nitrogen atmosphere, pPFPA (90.365 mg, 0.38 mmol) was dissolved in 3 mL of DMF, and compound VI (400 mg, 0.456 mmol) and DMAP (23.22 mg, 0.19 mmol) were added. The mixture was reacted at 65 °C for 24 h. After the reaction was complete, the mixture was centrifuged three times in diethyl ether and then dried to obtain 304 mg of a dark yellow-brown powder (i.e., compound IX), with a yield of 62%.

[0220] (10) Preparation of tetraphenylethylene monoarm thiol mannose polymers with side chains

[0221] Compound 9 (130 mg, 0.1235 mmol) was dissolved in 1 mL of a mixed solution of anhydrous methanol and anhydrous dichloromethane (MeOH:DCM volume ratio = 1:1). 1 mL of sodium methoxide dichlorosol solution (40 mg, 0.741 mmol) was added dropwise at 25 °C, followed by a reaction at room temperature for 1 h. After the reaction was complete, the solvent was rotary evaporated, and the residue was dissolved in 1 mL of DMF. The polymer solution was transferred to a MWCO3500Da container and dialyzed against methanol for 24 h. The final homopolymer P3 was lyophilized after dialysis to obtain 100 mg of a pale yellow powder (i.e., a polymer with tetraphenylethylene mono-arm thiomannose side chains), with a yield of 90%.

[0222] Comparative Example 1

[0223] Figure 19 This is a flowchart illustrating an exemplary preparation method for Comparative Example 1. The specific preparation process is as follows:

[0224]

[0225] Step 1: At 25 °C, N-BOC-1,2,3,6-tetrahydropyridine-4-boronic acid pinacol ester (0.7 g, 2.56 mmol), potassium phosphate (3.59 g, 1.69 mmol), X-Phos-Pd-G3 (20 mg, 0.03 mmol), SPHOS (20 mg, 0.05 mmol), and tetrabutylammonium bromide (10 mg, 0.03 mmol) were added sequentially to a mixture of 4-(1-(4-bromophenyl)-2,2-diphenylvinyl)phenol (0.5 g, 1.13 mmol) in 1,4-dioxane (50 mL) and water (5 mL). The resulting mixture was stirred at 105 °C under a nitrogen atmosphere for 16 hours. After the reaction was completed, 50 mL of dichloromethane was added to the reaction solution to dilute it and filter it. The filtrate was washed with brine (50 mL x 3), the organic phase was dried and concentrated, and the crude product was purified by normal column chromatography (n-hexane / ethyl acetate = 60:40) to give white compound 2 (0.52 g, yield 85.4%).

[0226] 1 H NMR (400 MHz, DMSO) δ 9.34 (s, 1H), 7.20 (d, J = 8.3 Hz, 2H), 7.17– 7.06 (m, 6H), 6.98 – 6.90 (m, 6H), 6.73 (d, J = 8.5 Hz, 2H), 6.50 (d, J =8.6 Hz, 2H), 6.11 (s, 1H), 3.96 (s, 2H), 3.48 (t, J = 5.5 Hz, 2H), 2.37 (d, J = 5.7 Hz, 2H), 1.41 (s, 9H).

[0227] MS (ESI): m / z calc. for C 36 H 34 NO3 (MH)-: 528.3; found: 528.4.

[0228] Step 2: At 0°C, potassium carbonate (0.39 g, 2.83 mmol) and bromopropyne (0.34 mL, 2.83 mmol) were added to a mixture of compound 2 (0.50 g, 0.95 mmol) in acetonitrile (50 mL). The resulting mixture was stirred at 75°C under a nitrogen atmosphere for 12 hours. After the reaction was complete, the reaction solution was diluted with 50 mL of dichloromethane, washed with brine (50 mL x 3), dried, and the concentrated organic phase was purified by normal column chromatography (n-hexane / ethyl acetate = 70:30) to give compound 3 (0.45 g, yield 71.79%) as a yellow solid.

[0229] 1 H NMR (400 MHz, DMSO) δ 7.21 (d, J = 8.4 Hz, 2H), 7.17 – 7.08 (m,6H), 7.00 – 6.91 (m, 6H), 6.90 – 6.84 (m, 2H), 6.74 (d, J = 8.8 Hz, 2H), 6.12(s, 1H), 4.71 (d, J = 2.3 Hz, 2H), 3.96 (s, 2H), 3.54 (t, J = 2.3 Hz, 1H), 3.48 (t, J = 5.5 Hz, 2H), 2.37 (s, 2H), 1.41 (s, 9H).

[0230] MS (ESI): m / z calc. for C 39 H 38 NO3 (M+H) + : 568.3; found: 567.5.

[0231] Step 3: To an anhydrous DCM and MeOH mixed solution of compound 3 (250 mg, 0.441 mmol) and azidoacetylmannose Man-OAc-N3 (180 mg, 0.485 mmol) (1 v: 1 v, 5 mL), sodium L-ascorbate (174.6 mg, 0.882 mmol) and copper sulfate pentahydrate (110 mg, 0.441 mmol) were added. The resulting mixture was stirred at room temperature under a nitrogen atmosphere for 12 hours. After the reaction was complete, the reaction solution was filtered and evaporated to dryness. The crude product was purified by normal column chromatography (n-hexane / ethyl acetate = 30:70) to give compound 4 (0.37 g, yield 89.37%) as a white solid.

[0232] 1 H NMR (400 MHz, DMSO-d6) δ 8.41 (s, 1H), 7.21 (d, J = 8.3 Hz, 2H),7.20 – 7.05 (m, 7H), 6.97 (d, J = 6.6 Hz, 4H), 6.91 (dd, J = 17.5, 8.5 Hz,4H), 6.88 – 6.75 (m, 3H), 6.45 (d, J = 1.8 Hz, 1H), 6.12 (s, 1H), 5.81 (dd, J = 9.4, 3.8 Hz, 1H), 5.76 (s, 1H), 5.25 (t, J = 9.4 Hz, 1H), 5.12 (s, 2H), 4.23 (dd, J = 12.6, 4.9 Hz, 1H), 4.02 (dt, J = 9.4, 4.6 Hz, 2H), 3.96 (s,2H), 3.90 – 3.82 (m, 1H), 3.49 (t, J = 5.2 Hz, 2H), 2.38 (s, 2H), 2.15 (s,3H), 2.04 (s, 3H), 1.99 (d, J = 3.1 Hz, 7H), 1.41 (s, 9H).

[0233] MS (ESI): m / z calc. for C 53 H 56 N4O 12 (M+H) + : 941.4; found: 941.3.

[0234] Step 4: Compound 4 (370 mg, 0.397 mmol) was dissolved in anhydrous DCM (4 mL), and trifluoroacetic acid (2 mL) was added under ice bath conditions. The resulting mixture was stirred at room temperature under a nitrogen atmosphere for 3 hours. After the reaction was complete, the reaction solution was diluted with ethyl acetate, neutralized to a weak base with saturated sodium bicarbonate solution, extracted three times with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by normal column chromatography (n-hexane / ethyl acetate = 60:40) to give compound 5 (0.27 g, yield 81.82%) as a white solid.

[0235] 1 H NMR (400 MHz, DMSO) δ 8.42 (s, 1H), 7.26 (d, J = 8.4 Hz, 2H), 7.20– 7.06 (m, 6H), 6.98 (dd, J = 9.1, 4.8 Hz, 5H), 6.89 (d, J = 8.8 Hz, 2H), 6.83 (d, J = 8.9 Hz, 2H), 6.45 (d, J = 2.1 Hz, 1H), 6.16 (s, 1H), 5.81 (dd, J = 9.4, 3.9 Hz, 1H), 5.76 (s, 1H), 5.25 (t, J = 9.4 Hz, 1H), 5.12 (s, 2H), 4.23 (dd, J = 12.6, 5.0 Hz, 1H), 4.07 – 3.96 (m, 1H), 3.90 – 3.80 (m, 1H), 3.71 (s, 2H), 3.27 (t, J = 6.0 Hz, 3H), 2.58 (s, 2H), 2.15 (s, 3H), 2.04 (s,3H), 1.99 (d, J = 3.2 Hz, 6H).

[0236] MS (ESI): m / z calc. for C 48 H 48 N4O 10 (M+H) + : 841.3; found: 841.3.

[0237] Step 5: Compound 5 (270 mg, 0.321 mmol), pPFPA (70 mg, 0.2922 mmol), and 4-dimethylaminopyridine (23.2 mg, 0.1894 mmol) were added to a reaction flask under a nitrogen atmosphere, followed by the addition of anhydrous DMF (3 mL). The resulting mixture was subjected to RAFT polymerization at 65 °C for 20 hours under a nitrogen atmosphere. After the reaction was completed, the reaction solution was precipitated three times (45 mL of diethyl ether × 3), and the resulting solid was lyophilized to obtain polymer OAc (220 mg, yield 81%).

[0238] 1H NMR (400 MHz, CDCl3) δ 7.75 (s, 1H), 7.02 (d, J = 36.8 Hz, 16H), 6.65 (s, 2H), 6.01 – 5.86 (m, 3H), 5.37 (t, J = 8.9 Hz, 1H), 5.30 (s, 1H), 5.04 (s, 2H), 4.33 (s, 1H), 4.04 (s, 1H), 3.88 (s, 1H), 3.48 (q, J = 7.0 Hz, 1H), 2.92 (d, J = 29.2 Hz, 1H), 2.16 (s, 3H), 2.05 (s, 9H), 1.21 (t, J = 7.0Hz, 2H).

[0239] Step 6: Dissolve OAc-P1 (220 mg) in a mixed solution of dichloromethane and methanol (v / v=1 / 1). After dissolution, add excess sodium methoxide and check the pH of the solution. Stir at room temperature for two hours, evaporate to dryness, dissolve in a small amount of DMF solution, dialyze in methanol system for 48 h, and freeze dry to obtain white solid P1 (65 mg, yield, 46%).

[0240] 1 H NMR (400 MHz, DMSO) δ 8.27 (s, 1H), 7.21 – 6.65 (m, 18H), 5.91 (s,1H), 5.28 (s, 1H), 5.00 (s, 3H), 4.61 (s, 1H), 4.41 (s, 1H), 3.84 (s, 1H), 3.60 (s, 3H), 3.33 (s, 9H), 1.24 (s, 1H).

[0241] Turbidimetry is a method for determining the concentration of suspended substances by measuring the light intensity transmitted through a medium containing suspended particles. Using a UV spectrophotometer, the recognition effect between glycopolymers and Con A can be qualitatively analyzed. Since the initial rate of change in absorbance is related to the binding rate of the glycopolymer and lectin, the initial slope (K0) of the curve can be determined. i The binding ratio of polymers is compared using (Abs / s).

[0242] Figure 20This is a recognition effect diagram between the tetraphenylethylene mono-arm thiomannose polymer with side chains in Example 1 of this invention and Con A. It can be seen that the turbidity change (absorbance change) after mixing the TPE glycopolymer and Con A is significant. The initial rate of change in the absorbance curves of the TPE mannose polymers P1 (n = 36) and P2 (P2 is the compound from Example 1) is very large, gradually becoming stable. The binding rate of P1 is K. i = 0.01668; the binding rate of P2 is K i = 0.02776. Dendritic sugar polymers with flexible thioether linkages in their side chains, achieved through the Thiol-ene reaction, exhibit better protein recognition ability compared to those with rigid triazole linkages achieved through the CuAAC reaction. This is because the flexible geometry in the polymer side chains provides more space for Con A binding; on the other hand, the flexible linkages may also have a synergistic effect in the recognition of lectin Con A by the sugar polymers.

[0243] The above description of the embodiments is provided to enable those skilled in the art to understand and use the invention. It will be apparent to those skilled in the art that various modifications can be made to these embodiments, and the general principles described herein can be applied to other embodiments without inventive effort. Therefore, the present invention is not limited to the above embodiments, and any improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the invention should be within the protection scope of the present invention.

Claims

1. A polymer with a side chain containing tetraphenylethylene mono-arm thiomannose, characterized in that, The chemical structural formula of the polymer containing tetraphenylethylene monoarm thiomannose in the side chain is shown in formula (I): ； Where n is an integer ≥ 2.

2. A method for preparing a tetraphenylethylene monoarm thiol-mannose polymer with a side chain according to claim 1, characterized in that, Includes the following steps: (1) 4-Bromo-4'-methoxybenzophenone reacts with diphenylmethane via a nucleophilic addition-elimination reaction to give the first compound; (2) The first compound reacts with boron tribromide via a demethylation reaction to yield the second compound; (3) The second compound and N-Boc-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester were coupled via a Suzuki reaction to give the third compound; (4) The third compound is reacted with acryloyl chloride and anhydrous triethylamine by esterification to obtain the fourth compound; (5) The fourth compound, acetyl-protected thiol mannose, and n-hexylamine undergo a Thiol-ene click chemistry reaction to obtain the fifth compound; (6) The fifth compound reacts with trifluoroacetic acid via a substitution reaction to yield the sixth compound; (7) Pentafluorophenol reacts with triethylamine and acryloyl chloride via esterification to give compound VII; (8) The seventh compound, together with a chain transfer agent and an initiator, undergoes a RAFT polymerization reaction to obtain the eighth compound; (9) The eighth compound, the sixth compound, and 4-diaminopyridine undergo an ammonolysis reaction to obtain the ninth compound; (10) The ninth compound was reacted with sodium methoxide via a substitution reaction to obtain a thiomannose polymer with a tetraphenylethylene monoarm side chain; The chemical structural formulas of the tetraphenylethylene mono-arm thiol mannose polymer, compound 1, compound 2, compound 3, compound 4, compound 5, compound 6, compound 7, compound 8, and compound 9 are shown in formulas (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), and (X), respectively: ； Where n is an integer ≥ 2.

3. The preparation method according to claim 2, characterized in that, In the nucleophilic addition-elimination reaction of step (1), the molar ratio of 4-bromo-4'-methoxybenzophenone to diphenylmethane is 1:(1.1~1.3); the reaction temperature is 0 ℃~100℃, and the reaction time is 3 h~24 h.

4. The preparation method according to claim 2, characterized in that, In the demethylation reaction of step (2), the ratio of the first compound to boron tribromide is 1 g: (2~3) mL; the reaction temperature is 10 ℃~30 ℃; and the reaction time is 18 h~30 h.

5. The preparation method according to claim 2, characterized in that, In step (3) of the Suzuki coupling reaction, the molar ratio of the second compound and N-Boc-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester is 1:(1~3); the reaction temperature is 105 ℃~115 ℃, and the reaction time is 16 h~20 h.

6. The preparation method according to claim 2, characterized in that, In the esterification reaction of step (4), the molar ratio of the third compound, acryloyl chloride and anhydrous triethylamine is 1:(1~3):(1~3); the reaction temperature is 0 ℃~25 ℃, and the reaction time is 18 h~24 h.

7. The preparation method according to claim 2, characterized in that, In the Thiol-ene click chemical reaction in step (5), the molar ratio of the fourth compound, acetyl-protected thiol mannose, and n-hexylamine is 1:(1~3):(0.1~0.15); the reaction temperature is 15 ℃~30 ℃, and the reaction time is 18 h~24 h.

8. The preparation method according to claim 2, characterized in that, In the substitution reaction of step (6), the ratio of the fifth compound to trifluoroacetic acid is 1 mmol: (1~6) ml; the reaction temperature is 15 ℃~25 ℃, and the reaction time is 4 h~6 h.

9. The preparation method according to claim 2, characterized in that, In the esterification reaction of step (7), the molar ratio of pentafluorophenol, triethylamine and acryloyl chloride is 1:(0.5~2):(0.5~2); the reaction temperature is 0 ℃~25 ℃ and the reaction time is 16 h~36 h.

10. The preparation method according to claim 2, characterized in that, In the RAFT polymerization reaction of step (8), the molar ratio of the seventh compound, the chain transfer agent, and the initiator is (150~220):(7~10):1; the chain transfer agent is trithiocarbonate, and the initiator is azobisisobutyronitrile; the reaction temperature is 70 ℃~90 ℃, and the reaction time is 20 h~30 h.

11. The preparation method according to claim 2, characterized in that, In the ammonolysis reaction of step (9), the molar ratio of compound 8, compound 6, and 4-diaminopyridine is (1~3):(2~5):1; the reaction temperature is 50℃~70℃, and the reaction time is 18 h~24 h.

12. The preparation method according to claim 2, characterized in that, In the substitution reaction of step (10), the ratio of compound 9 to sodium methoxide is 0.1 g: (30~60) mg; the reaction temperature is 15 ℃~30 ℃, and the reaction time is 1 h~3 h.

13. The application of a tetraphenylethylene monoarm thiol mannose polymer with a side chain as described in claim 1 in the preparation of a fluorescent probe.

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