CN115850308B - BODIPY near infrared fluorescent probe containing electron donor and acceptor groups for recognizing Abeta fibers and preparation method thereof - Google Patents
BODIPY near infrared fluorescent probe containing electron donor and acceptor groups for recognizing Abeta fibers and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a BODIPY near infrared fluorescent probe (THB) containing electron donor and acceptor groups for identifying Abeta fibers and a preparation method thereof, wherein the THB is synthesized by adopting a BODIPY compound and an aldehyde compound to carry out a nor Wen Geer condensation reaction. The maximum absorption and maximum emission wavelength of the novel compounds formed by the reaction in chloroform are in the near infrared region. Studies have shown that Abeta aggregation and precipitation are the main physiological and pathological manifestations of AD. THB is capable of forming a distorted intramolecular charge transfer (tic) state upon photoexcitation upon free rotation in a non-viscous solution, which reduces its fluorescence intensity. The THB has strong electron donor capability and electron acceptor capability, so that the THB has strong push-pull effect, and therefore has higher TICT tendency than other compounds, and after being combined with the Abeta fiber, the THB has the TICT rotation inhibited, so that the THB emits strong fluorescence to display fluorescence, thereby identifying the Abeta fiber and achieving the purpose of diagnosing AD.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, relates to preparation of a fluorescent probe, and in particular relates to a BODIPY near infrared fluorescent probe containing electron donor and acceptor groups for identifying Abeta fibers and a preparation method thereof.
Background
Alzheimer's Disease (AD) is a neurodegenerative disease, and as known from data statistics, global aging is aggravated, the number of patients suffering from AD is rising year by year, and China is the country with the largest number of patients suffering from AD worldwide. Senile dementia of people over 65 years old in China gradually rises, but the treatment rate is very low. Currently, there are a number of hypotheses about the pathogenesis of AD, of which the beta-amyloid (aβ) cascade hypothesis is most accepted, and this theory suggests that one of the important causative factors of AD is caused by aβ aggregates, which can cause neuronal lesions, ultimately leading to neuronal apoptosis. The aβ aggregates form aβ fibers that eventually deposit in the brain of the human body to form plaques. However, the existing specific diagnosis AD means are only two, one is lumbar puncture cerebrospinal fluid examination and the other is neuroimaging examination, but the two diagnosis methods have obvious limitations, long time consumption, high cost and high misdiagnosis rate.
In recent years, the application of fluorescence technology in the biomedical field has attracted a great deal of attention. The former research on the Aβ cascade hypothesis creates many fluorescent probes for diagnosing Aβ fibers, but these probes have problems in terms of specific recognition and the intensity of fluorescence thereof. Therefore, the research on the near infrared fluorescent probe with high sensitivity and specificity aiming at the Abeta fiber has important significance for diagnosing AD.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a BODIPY near infrared fluorescent probe containing electron donor and acceptor groups for recognizing Abeta fibers, which has the advantages of near infrared long wavelength, high affinity and high selectivity for diagnosing AD; the invention also aims at providing a preparation method of the fluorescent probe.
The invention is realized by the following technical scheme:
a BODIPY near infrared fluorescent probe containing electron donor and acceptor groups recognizing aβ fibers, having the molecular structural formula shown below:
Wherein the dipyrromethene boron complex has a 4- (dimethylamino) phenyl substituent at the 8-position, two alkyl groups at the 1, 7-positions, and a benzothiazole substituent at the 3-position.
The invention further improves the scheme as follows:
a preparation method of a BODIPY near infrared fluorescent probe containing electron donor and acceptor groups for recognizing Abeta fibers comprises the following steps:
(1) Dimethyl pyrrole and 4- (dimethylamino) benzaldehyde are used as raw materials, methylene dichloride is used as a solvent, 2, 3-dimethyl-5, 6-dicyanobenzoquinone is used as a catalyst, boron trifluoride diethyl etherate is used as a complexing agent, and a BODIPY compound is prepared;
(2) Taking glyoxal and glycol as raw materials, and benzene as a solvent, and reacting to prepare 1, 3-dioxolane-2-formaldehyde under the action of strong acid cation exchange resin of a catalyst 732 #;
(3) 1, 3-dioxolane-2-formaldehyde and 2-aminobenzene mercaptan are taken as raw materials, absolute ethyl alcohol is taken as a solvent, concentrated hydrochloric acid and hydrogen peroxide are taken as catalysts, intermediate products T1 and T1 are prepared, and are placed in a hydrogen chloride aqueous solution to carry out aldehyde deprotection reaction to prepare intermediate products T2, and the intermediate products T2 react with methyl iodide to prepare intermediate products T3;
(4) Taking BODIPY and T3 as raw materials, toluene and piperidine as mixed solvents, and reacting under the action of a catalyst p-toluenesulfonamide to prepare a final product fluorescent probe THB;
the reaction route is shown in the following formula:
The invention further improves the scheme as follows:
The specific process of the step (1) is as follows: mixing and dissolving dimethyl pyrrole and 4- (dimethylamino) benzaldehyde into methylene dichloride, adding triethylamine, stirring at room temperature for 0.5-6 h, slowly dropwise adding boron trifluoride diethyl ether into ice bath, stirring for 0.5-6 h, adding 2, 3-dimethyl-5, 6-dicyanobenzoquinone, extracting with methylene dichloride, drying anhydrous Na 2SO4, removing solvent at 25-60 ℃ in vacuum, and separating and purifying by a chromatographic column to obtain a light yellow solid product of the fluoboric dipyrrole fluorescent dye, namely BODIPY compound.
Further, the molar ratio of the dimethyl pyrrole to the 4- (dimethylamino) benzaldehyde to the triethylamine to the boron trifluoride diethyl etherate to the 2, 3-dimethyl-5, 6-dicyanobenzoquinone is (1-3.3) to (0.3-2.3) to (0.3-4.3) to (0.01-0.43).
Further, the specific process of the step (2) is as follows: placing the mixed solution of glyoxal and glycol into a triangular flask, adding 732 # strong acid cation exchange resin and benzene, heating and starting a stirrer, carrying out acetalation reaction at 70-100 ℃, condensing and refluxing, collecting water generated by the reaction when benzene azeotropes, and ending the reaction after 60-110 min. Slightly cooling, filtering under reduced pressure to remove catalyst, distilling the filtrate under normal pressure to remove low boiling point substances, distilling under reduced pressure, and collecting fraction to obtain 1, 3-dioxolane-2-formaldehyde.
Further, the molar ratio of glyoxal, glycol and 732 # strong acid cation exchange resin is 1-1.5:1-1.75:0.1-0.5.
In the step (1), two aldehyde groups of glyoxal are subjected to acetalization reaction by using one molecule of ethylene glycol, and the aldehyde groups are protected, so that 1, 3-dioxolane-2-formaldehyde is prepared; in the reaction process, the solvent benzene is taken as a water carrying agent at the same time, so that water generated by the reaction is taken away.
Further, the specific process of the step (3) is as follows:
Adding 1, 3-dioxolane-2-formaldehyde and 2-amino benzene thiol into a dried flask, then adding absolute ethanol to dissolve solids, cooling the flask with an ice bath, vigorously stirring, sequentially adding concentrated hydrochloric acid and hydrogen peroxide into the solution, stirring the mixture at room temperature overnight, performing thin layer chromatography to show complete disappearance of starting materials, then filtering the mixture, washing the filtrate with absolute ethanol three times, and drying to obtain a solid product T1;
Placing the obtained product T1 into a hydrogen chloride aqueous solution to carry out deprotection reaction of aldehyde groups, and drying and purifying to finally obtain a pale yellow solid product T2;
Dissolving T2 in a pressure bottle containing anhydrous acetonitrile, adding methyl iodide into the solution, stirring the mixture at 60-100 ℃ for 48 hours, evaporating volatile solvents, purifying the crude product by silica gel column chromatography, and recrystallizing with CH 2Cl2 to obtain an orange solid product T3. In this reaction, the introduction of benzothiazole compounds can enhance the tendency of TCIT of THB, resulting in an increase in fluorescence emission intensity.
Further, the molar ratio of the 1, 3-dioxolane-2-formaldehyde to the 2-aminobenzene mercaptan to the methyl iodide is (1-1.75) to (1-1.78) to (3-12).
Further, the specific process of the step (4) is as follows: dissolving BODIPY, T3 and p-toluenesulfonamide in a mixed solution of toluene and piperidine, placing the mixed solution in a round bottom flask with a Dean-Stark device, heating and refluxing at 100-150 ℃ until all solvents are collected by the Dean-Stark device, adding toluene and piperidine into a reaction medium, repeating at least once, tracking until the raw materials react completely by TLC, performing column chromatography, and removing the solvents by reduced pressure distillation to obtain a black solid product, namely the fluorescent probe THB.
Further, the molar ratio of BODIPY to T3 to p-toluenesulfonamide is 0.1-1:0.1-1.3:0.01-0.13; the volume ratio of benzene to piperidine is (1-3) to (0.1-0.3).
Compared with the prior art, the invention has the beneficial effects that:
The invention firstly uses dimethyl pyrrole and 4- (dimethylamino) benzaldehyde to generate a Noruge condensation reaction, synthesizes a near infrared BODIPY compound fluorescent dye, and then carries out condensation reaction with aldehydes to finally obtain THB. The THB is capable of forming a distorted intramolecular charge transfer (TICT) state upon photoexcitation upon free rotation in a non-viscous solution, which reduces its fluorescence intensity. The THB has strong electron donor capability and electron acceptor capability, so that the THB has strong push-pull effect, and therefore has higher TICT tendency than other compounds, and after being combined with the Abeta fiber, the THB has the TICT rotation inhibited, so that the THB emits strong fluorescence to display fluorescence, thereby identifying the Abeta fiber and achieving the purpose of diagnosing AD. Studies have shown that misfolding and aggregation of Abeta is closely related to the occurrence of Alzheimer's disease, and thus the invention has potential value in diagnosing AD.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of THB obtained in example 1 of the present invention;
FIG. 2 is a fluorescent staining presentation of brain sections of Alzheimer's disease mice by THB obtained in example 1 of the present invention.
Detailed Description
The invention is further described in connection with the following detailed description, in order to make the technical means, the creation characteristics, the achievement of the purpose and the effect of the invention easy to understand.
The preparation method of the BODIPY fluorescent dye used in the following examples is as follows:
298mg (2.0 mmol) of 4- (dimethylamino) benzaldehyde is weighed and dissolved in 200mL of freshly distilled dichloromethane, 412mg (4.4 mmol) of 2, 4-dimethylpyrrole (3 mL of triethylamine) is injected by a syringe, the mixture is stirred rapidly and magnetically, and is protected from light, 3mL of boron trifluoride diethyl ether is slowly added dropwise into ice bath under nitrogen protection, stirring is carried out for 10 minutes, then 45.4mg (0.2 mmol) of 2, 3-dimethyl-5, 6-dicyanobenzoquinone is added under stirring, after TLC tracking is carried out until the reaction of the raw materials is completed, column chromatography, after the solvent is distilled off under reduced pressure, dichloromethane extraction, anhydrous Na 2SO4 is dried, the solvent is removed in vacuo at 50 ℃, and the green fluorescent boron difluoride fluorescent dye, namely BODIPY compound, is obtained after separation and purification by a chromatographic column.
Example 1
(1) 232Mg (4.0 mmol) glyoxal and 248mg (4.0 mmol) glycol are added into a triangular flask, 50mg 732 # strong acid cation exchange resin and 40ml benzene are added as water carrying agents, the temperature is 90 ℃ and a stirrer is started for acetalation reaction, condensation reflux is carried out, water generated by the reaction is carried to a water separator when the water carrying agents are azeotroped, and the reaction is finished after 90 minutes. The reaction product was filtered (the catalyst was removed by filtration under reduced pressure), the low boiling point substances were removed by distillation from the filtrate under normal pressure, and the fractions were collected by distillation under reduced pressure to give 1, 3-dioxolane-2-carbaldehyde.
(2) To the dried flask were added 179mg (1.75 mmol) of 1, 3-dioxolane-2-carbaldehyde and 224mg (1.78 mmol) of 2-aminobenzenethiol, followed by 80 ml of absolute ethanol to dissolve the solid. The flask was cooled with an ice bath. Concentrated hydrochloric acid (0.14 ml, 2.6 eq) and hydrogen peroxide (0.24 ml, 4.5 eq) were added sequentially to the solution with vigorous stirring. The mixture was stirred at room temperature overnight. Thin Layer Chromatography (TLC) showed complete disappearance of starting material. The mixture was then filtered. The filtrate was washed three times with absolute ethanol and dried to give the solid product T1.
And (3) placing the T1 in a hydrochloric acid solution (2 ml, 6 equivalent) for stirring reaction for 6 hours, carrying out deprotection reaction of aldehyde groups, extracting the obtained crude product with ethyl acetate, evaporating a liquid solvent, recrystallizing a solid, and drying to obtain a pale yellow product T2.
T2 was dissolved in a pressure bottle containing anhydrous acetonitrile (20 ml), methyl iodide (0.16 ml, 10 eq) was added to the solution, the mixture was stirred at 85 ℃ for 48 hours, and after evaporation of the volatile solvents, the crude product was first purified by silica gel column chromatography (CH 2Cl2 -MeOH 20:1) and then recrystallized from CH 2Cl2 to give the final product as an orange solid, T3.
(3) 198Mg (0.54 mmol) of BODIPY fluorescent dye, 96mg (0.54 mmol) of T3, 1.7mg (0.01 mmol) of p-toluenesulfonamide are dissolved in a mixed solution of toluene (25 mL) and piperidine (1 mL), placed in a round bottom flask equipped with a Dean-Stark apparatus, heated under reflux at 142℃until all solvents were collected by the Dean-Stark apparatus, toluene (25 mL) and piperidine (1 mL) were added to the reaction medium, heated under reflux at 142℃until all solvents were collected by the Dean-Stark apparatus was continued, toluene (25 mL) and piperidine (1 mL) were repeatedly added and the heated reflux process was repeated 4 times, which was followed by TLC tracing after completion of the reaction of the starting materials, column chromatography was carried out after removal of the solvent by distillation under reduced pressure to give a black solid product THB (199 mg, yield 70%) which was confirmed by nuclear magnetic 1H NMR spectrum.
Example 2
(1) 116Mg (2.0 mmol) glyoxal and 217mg (3.5 mmol) glycol are added into a triangular flask, 20mg 732# strong acid cation exchange resin and 40ml benzene are added as water carrying agents, the temperature is 90 ℃ and a stirrer is started for acetalation reaction, condensation reflux is carried out, water generated by the reaction is carried to a water separator when the water carrying agents are azeotroped, and the reaction is finished after 90 minutes. The reaction product was filtered (the catalyst was removed by filtration under reduced pressure), the low boiling point substances were removed by distillation from the filtrate under normal pressure, and the fractions were collected by distillation under reduced pressure to give 1, 3-dioxolane-2-carbaldehyde.
(2) To the oven dried flask were added 204mg (2.0 mmol) of 1, 3-dioxolane-2-carbaldehyde and 224mg (2.0 mmol) of 2-aminobenzenethiol, followed by 80 ml of absolute ethanol to dissolve the solid. The flask was cooled with an ice bath. Concentrated hydrochloric acid (0.14 ml, 2.6 eq) and hydrogen peroxide (0.24 ml, 4.5 eq) were added sequentially to the solution with vigorous stirring. The mixture was stirred at room temperature overnight. Thin Layer Chromatography (TLC) showed complete disappearance of starting material. The mixture was then filtered. The filtrate was washed three times with absolute ethanol and dried to give the solid product T1.
And (3) placing the T1 in a 6-equivalent hydrochloric acid solution, stirring and reacting for 6 hours, carrying out deprotection reaction of aldehyde groups, extracting the obtained crude product with ethyl acetate, evaporating a liquid solvent, recrystallizing a solid, and drying to obtain a pale yellow product T2.
T2 was dissolved in a pressure bottle containing anhydrous acetonitrile (20 ml), methyl iodide (0.16 ml, 10 eq) was added to the solution, the mixture was stirred at 80 ℃ for 48 hours, and after evaporation of the volatile solvents, the crude product was first purified by silica gel column chromatography (CH 2Cl2 -MeOH 20:1) and then recrystallized from CH 2Cl2 to give the final product as an orange solid, T3.
(3) 184Mg (0.5 mmol) of BODIPY fluorescent dye, 178mg (1.0 mmol) of T3, 1.7mg (0.01 mmol) of p-toluenesulfonamide were dissolved in a mixed solution of toluene (25 mL) and piperidine (1 mL), placed in a round bottom flask equipped with a Dean-Stark apparatus, heated under reflux at 142℃until all solvents were collected by the Dean-Stark apparatus, toluene (25 mL) and piperidine (1 mL) were added to the reaction medium, heated under reflux at 142℃was continued until all solvents were collected by the Dean-Stark apparatus, toluene (25 mL) and piperidine (1 mL) were repeatedly added and the heated reflux procedure was repeated 4 times, which was followed by TLC tracing after completion of the reaction of the starting materials, column chromatography was carried out after removal of the solvents by distillation under reduced pressure to give a black solid product THB (198 mg, 75% yield) which was confirmed by nuclear magnetic 1H NMR spectrum.
Example 3
(1) 116Mg (2.0 mmol) glyoxal and 186mg (3.0 mmol) glycol are added into a triangular flask, 20mg 732# strong acid cation exchange resin and 40ml benzene are added as water carrying agents, the temperature is 85 ℃ and a stirrer is started for acetalation reaction, condensation reflux is carried out, water generated by the reaction is carried to a water separator when the water carrying agents are azeotroped, and the reaction is finished after 90 minutes. The reaction product was filtered (the catalyst was removed by filtration under reduced pressure), the low boiling point substances were removed by distillation from the filtrate under normal pressure, and the fractions were collected by distillation under reduced pressure to give 1, 3-dioxolane-2-carbaldehyde.
(2) To the oven dried flask were added 204mg (2.0 mmol) of 1, 3-dioxolane-2-carbaldehyde and 375mg (3.0 mmol) of 2-aminobenzenethiol, followed by 60 ml of absolute ethanol to dissolve the solid. The flask was cooled with an ice bath. Concentrated hydrochloric acid (0.14 ml, 2.6 eq) and hydrogen peroxide (0.24 ml, 4.5 eq) were added sequentially to the solution with vigorous stirring. The mixture was stirred at room temperature overnight. Thin Layer Chromatography (TLC) showed complete disappearance of starting material. The mixture was then filtered. The filtrate was washed three times with absolute ethanol and dried to give the solid product T1.
And (3) placing the T1 in a 6-equivalent hydrochloric acid solution to react for 10 hours under stirring, carrying out deprotection reaction of aldehyde groups, extracting the obtained crude product with ethyl acetate, evaporating a liquid solvent to dryness, recrystallizing a solid, and drying to obtain a pale yellow product T2.
T2 was dissolved in a pressure bottle containing anhydrous acetonitrile (20 ml), methyl iodide (0.16 ml, 10 eq) was added to the solution, the mixture was stirred at 90 ℃ for 48 hours, and after evaporation of the volatile solvents, the crude product was first purified by silica gel column chromatography (CH 2Cl2-MeOH 20:1) and then recrystallized from CH2Cl2 to give the final product as an orange solid, T3.
(3) 367Mg (1.0 mmol) of BODIPY fluorescent dye, 178mg (1.0 mmol) of T3, 1.7mg (0.01 mmol) of p-toluenesulfonamide were dissolved in a mixed solution of toluene (25 mL) and piperidine (1 mL), placed in a round bottom flask equipped with a Dean-Stark apparatus, heated under reflux at 142℃until all solvents were collected by the Dean-Stark apparatus, toluene (25 mL) and piperidine (1 mL) were further added to the reaction medium, heated under reflux at 142℃until all solvents were collected by the Dean-Stark apparatus, toluene (25 mL) and piperidine (1 mL) were repeatedly added and the heated reflux procedure was repeated 4 times, which was followed by TLC tracing, column chromatography after completion of the raw materials, and after removal of the solvent by distillation under reduced pressure, a black solid product THB (369 mg, yield 70%) was obtained, which was confirmed by nuclear magnetic 1H NMR spectrum.
Example 4: application of the substances prepared in example 1
THB detection and analysis of brain tissue sections of mice with alzheimer's disease:
Histological analysis was performed using adult Alzheimer's disease model mouse APPswe/PS1dE9 brain tissue. Paraffin-embedded parts of the tissue of the hippocampus, sections 10 μm thick. Sections were stained with 50% ethanol THB solution (100 uM) for 2 hours, washed with 50% ethanol for 20 minutes, washed under a confocal laser microscope (nikon A1R) at 640nm, histologically evaluated using a fluorescence preservation reagent (Merck Millipore company) and covering all sections, and THB was found to render beta-amyloid fibers red fluorescent, indicating that THB has potential application value for diagnosis of alzheimer's disease.
The foregoing has shown and described the basic principles and main features of the present invention and the advantages of the present invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, and that the above embodiments and descriptions are merely illustrative of the principles of the present invention, and various changes and modifications may be made without departing from the spirit and scope of the invention, which is defined in the appended claims. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (10)
1.A BODIPY near infrared fluorescent probe comprising electron donor and acceptor groups recognizing aβ fibers, characterized in that said fluorescent probe THB has the molecular structural formula shown below:
2. the method for preparing the BODIPY near infrared fluorescent probe containing electron donor and acceptor groups for recognizing aβ fibers according to claim 1, comprising the following steps:
(1) Dimethyl pyrrole and 4- (dimethylamino) benzaldehyde are used as raw materials, methylene dichloride is used as a solvent, 2, 3-dimethyl-5, 6-dicyanobenzoquinone is used as a catalyst, boron trifluoride diethyl etherate is used as a complexing agent, and a BODIPY compound is prepared;
(2) Taking glyoxal and glycol as raw materials, and benzene as a solvent, and reacting to prepare 1, 3-dioxolane-2-formaldehyde under the action of strong acid cation exchange resin of a catalyst 732 #;
(3) 1, 3-dioxolane-2-formaldehyde and 2-aminobenzene mercaptan are taken as raw materials, absolute ethyl alcohol is taken as a solvent, concentrated hydrochloric acid and hydrogen peroxide are taken as catalysts, intermediate products T1 are prepared, the intermediate products T1 are placed in a strong acid solution, water is added for aldehyde deprotection reaction, intermediate products T2 are prepared, and the intermediate products T2 react with methyl iodide to prepare intermediate products T3;
(4) Taking BODIPY and T3 as raw materials, toluene and piperidine as mixed solvents, and reacting under the action of a catalyst p-toluenesulfonamide to prepare a final product fluorescent probe THB;
the reaction route is shown in the following formula:
。
3. The method for preparing the BODIPY near infrared fluorescent probe containing electron donor and acceptor groups for recognizing aβ fibers according to claim 2, wherein the method comprises the following steps: the specific process of the step (1) is as follows: mixing and dissolving dimethyl pyrrole and 4- (dimethylamino) benzaldehyde into methylene dichloride, adding triethylamine, stirring at room temperature for 0.5-6 h, slowly dropwise adding boron trifluoride diethyl ether into ice bath, stirring for 0.5-6 h, adding 2, 3-dimethyl-5, 6-dicyanobenzoquinone, extracting with methylene dichloride, drying anhydrous Na 2SO4, removing solvent at 25-60 ℃ in vacuum, and separating and purifying by a chromatographic column to obtain a light yellow solid product of the fluoboric dipyrrole fluorescent dye, namely BODIPY compound.
4. The method for preparing the BODIPY near infrared fluorescent probe containing electron donor and acceptor groups for recognizing aβ fibers according to claim 3, wherein the method comprises the following steps: the molar ratio of the dimethyl pyrrole to the 4- (dimethylamino) benzaldehyde to the triethylamine to the boron trifluoride diethyl etherate to the 2, 3-dimethyl-5, 6-dicyanobenzoquinone is (1-3.3) to (0.3-2.3) to (0.3-4.3) to (0.3-3) to (0.01-0.43).
5. The method for preparing the BODIPY near infrared fluorescent probe containing electron donor and acceptor groups for recognizing aβ fibers according to claim 2, wherein the method comprises the following steps: the specific process of the step (2) is as follows: placing the mixed solution of glyoxal and glycol into a triangular flask, adding 732 # strong acid cation exchange resin and benzene, heating and starting a stirrer, carrying out acetalation reaction at 70-100 ℃, condensing and refluxing, collecting water generated by the reaction by a water separator when benzene azeotropes, ending the reaction after 60-100 min, slightly cooling, decompressing and filtering to remove a catalyst, distilling the filtrate at normal pressure to remove low boiling point substances, distilling under pressure, and collecting fractions to obtain the 1, 3-dioxolane-2-formaldehyde.
6. The method for preparing the BODIPY near infrared fluorescent probe containing the electron donor and the acceptor groups for recognizing the Abeta fiber, which is characterized in that: the molar ratio of glyoxal, glycol and 732 # strong acid cation exchange resin is 1-1.5:1-1.75:0.1-0.5.
7. The method for preparing the BODIPY near infrared fluorescent probe containing electron donor and acceptor groups for recognizing aβ fibers according to claim 2, wherein the method comprises the following steps: the specific process of the step (3) is as follows: adding 1, 3-dioxolane-2-formaldehyde and 2-amino benzene thiol into a dried flask, then adding absolute ethanol to dissolve solids, cooling the flask with an ice bath, vigorously stirring, sequentially adding concentrated hydrochloric acid and hydrogen peroxide into the solution, stirring the mixture at room temperature overnight, performing thin layer chromatography to show complete disappearance of starting materials, then filtering the mixture, washing the filtrate with absolute ethanol three times, and drying to obtain a solid product T1; placing the obtained product T1 into a hydrogen chloride aqueous solution to carry out deprotection reaction of aldehyde groups, and drying and purifying to finally obtain a pale yellow solid product T2; dissolving T2 in a pressure bottle containing anhydrous acetonitrile, adding methyl iodide into the solution, stirring the mixture at 60-100 ℃ for 48 hours, evaporating volatile solvents, purifying the crude product by silica gel column chromatography, and recrystallizing with CH 2Cl2 to obtain an orange solid product T3.
8. The method for preparing the BODIPY near infrared fluorescent probe containing electron donor and acceptor groups for recognizing aβ fibers according to claim 7, wherein the method comprises the following steps: the molar ratio of the 1, 3-dioxolane-2-formaldehyde to the 2-amino benzene mercaptan to the methyl iodide is (1-1.75) to (1-1.78) to (3-12).
9. The method for preparing the BODIPY near infrared fluorescent probe containing electron donor and acceptor groups for recognizing aβ fibers according to claim 2, wherein the method comprises the following steps: the specific process of the step (4) is as follows: dissolving BODIPY, T3 and p-toluenesulfonamide in a mixed solution of toluene and piperidine, placing the mixed solution in a round bottom flask with a Dean-Stark device, heating and refluxing at 100-150 ℃ until all solvents are collected by the Dean-Stark device, adding toluene and piperidine into a reaction medium, repeating at least once, tracking until the raw materials react completely by TLC, performing column chromatography, and removing the solvents by reduced pressure distillation to obtain a black solid product, namely the fluorescent probe THB.
10. The method for preparing the BODIPY near infrared fluorescent probe containing electron donor and acceptor groups for recognizing aβ fibers according to claim 9, wherein the method comprises the following steps: the molar ratio of BODIPY to T3 to p-toluenesulfonamide is 0.1-1:0.1-1.3:0.01-0.13; the volume ratio of benzene to piperidine is (1-3) to (0.1-0.3).
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