α-Amino BODIPY derivatives and their preparation methods and applications

Abstract

The present invention discloses an α-amino BODIPY derivative, a preparation method, and an application thereof. The invention overcomes the defect in the prior art that only alkylamines are feasible in the oxidative cross-dehydrogenation coupling reaction for constructing α-amino BODIPYs, while aniline, as a weak nucleophile, is not suitable for this reaction. The structure of the α-amino BODIPY derivative is shown in Formula 3 and Formula 4, wherein Ar1 is an aryl group, Ar2 is an aryl group or a heterocyclic aryl group, and X is selected from one of C, N, O, and S. The α-amino BODIPY derivative has a novel structure, and can be directly functionalized and synthesized into α-amino BODIPY through base-promoted oxidative cross-dehydrogenation coupling, thereby realizing the installation of weak nitrogen nucleophiles such as aniline and heteroaryl aniline. The synthesis method is simple and efficient, and the preparation method has the advantages of mild conditions and simple operation.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and in particular to an α-amino BODIPY derivative and a preparation method and application thereof. Background Art

[0002] Boron dipyrrolidine (BODIPY) derivatives have become one of the most important organic fluorophores due to their unique photophysical properties, ease of modification, and excellent photostability. They have been applied in many fields, such as photodynamic therapy, fluorescent probes, and sensors. Synthetic chemists have been committed to exploring effective methods for constructing various BODIPYs. Among them, the synthesis of α-functionalized BODIPYs has attracted particular interest, not only because various C-X bonds, such as C-X, C-O, and C-S bonds, have been constructed at the α-position.

[0003] Amino groups represent a key class of functional groups in organic fluorophores because they are strong electron donors for creating push-pull systems and extending π-conjugation via lone electron pairs. Consequently, the synthesis of convenient α-amino BODIPYs has attracted increasing attention in recent years. Traditional methods for amino group installation rely on nucleophilic aromatic substitution (SNAr) reactions of α-bromo / chloro BODIPYs, while the requirement for prefunctionalization of BODIPYs prolongs the synthetic route. Free radical processes offer an alternative to constructing C-N bonds via direct functionalization of BODIPYs. However, most of these protocols require initiation by transition metals or peroxides.

[0004] Ideally, C-N coupling is achieved via direct C-H functionalization of BODIPY without the need for additional oxidants or transition metals. Recently, Dehaen et al. used O₂ as a green oxidant to achieve an oxidative cross-dehydrogenative coupling for the construction of α-amino BODIPYs, showing good atom and step economy. Unfortunately, only alkylamines were feasible in the reaction, while aniline, a weak nucleophile, was unsuitable. Overcoming this limitation is of great value, given the structural diversity of aniline and the potential for new opportunities in the development of BODIPY dyes through the expansion of π-conjugation.

[0005] The addition of a base may be a practical strategy to promote this reaction, which may trap a proton during the process. Therefore, it is valuable to explore the base-promoted oxidative cross-degassing coupling of BODIPY with aniline to prepare a series of novel α-amino BODIPYs. Summary of the Invention

[0006] The present invention aims to overcome the defect in the prior art that only alkylamines are feasible in the oxidative cross-dehydrogenation coupling reaction for constructing α-amino BODIPYs, while aniline, as a weak nucleophile, is not suitable for this reaction. Thus, an α-amino BODIPY derivative and its preparation method and application are provided. The α-amino BODIPY derivative has a novel structure and can be directly functionalized to synthesize α-amino BODIPY through base-promoted oxidative cross-dehydrogenation coupling, thereby achieving the installation of weak nitrogen nucleophiles such as aniline and heteroaryl aniline. The synthesis method is simple and efficient, and the preparation method has the advantages of mild conditions and easy operation.

[0007] In order to achieve the above objectives, in a first aspect, the present invention provides an α-amino BODIPY derivative, the structure of which is shown in Formula 3 and Formula 4.

[0008]

[0009] Wherein, Ar1 is an aryl group, Ar2 is an aryl group or a heterocyclic aryl group, and X is selected from one of C, N, O and S.

[0010] In a second aspect, the present invention provides a method for preparing an α-amino BODIPY derivative, the method comprising: reacting a substrate represented by Formula 1, an aniline derivative, and a base in the presence of a solvent;

[0011] wherein the base is one or more of cesium carbonate, potassium carbonate and potassium tert-butoxide;

[0012] The aniline derivative is an aryl aniline represented by formula 2a and / or a heteroaryl aniline represented by formula 2b;

[0013]

[0014] In a third aspect, the present invention provides an α-amino BODIPY derivative prepared by the preparation method described in the second aspect.

[0015] In a fourth aspect, the present invention provides a use of the α-amino BODIPY derivative described in the first aspect or the third aspect in biological imaging.

[0016] In the above technical solution, the present invention uses oxygen in the air as a green oxidant and uses a base-promoted oxidative cross-dehydrogenation coupling to undergo a substitution reaction of the α-position hydrogen atom of the parent BODIPY with an arylaniline or heteroarylaniline in just one step, thereby synthesizing a series of α-amino BODIPY derivatives. Among them, the direct substitution reaction of the α-position hydrogen atom of the parent BODIPY with aniline or indole is discovered for the first time.

[0017] At the same time, the preparation method of the α-amino BODIPY derivative of the present invention has simple steps, is green and environmentally friendly, does not require additional oxidants or transition metals, and only uses oxygen in the air as an oxidant to directly functionalize and construct a CN bond at the α position of the parent BODIPY.

[0018] Moreover, due to the structural diversity of aniline reagents and the expansion of π-conjugation, the α-amino BODIPY derivatives of the present invention have adjustable photophysical properties, excellent aggregation-induced emission performance, high fluorescence quantum yield and biocompatibility, and have potential applications in the fields of photosensitizers and cell biology.

[0019] Other features and advantages of the present invention will be described in detail in the following detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] The accompanying drawings are used to provide a further understanding of the present invention and constitute a part of the specification. Together with the following detailed description, they are used to explain the present invention but do not constitute a limitation of the present invention. In the accompanying drawings:

[0021] Figure 1 The crystal structures of products 3a, 3i, 3f, 3h, 4a, and 5a-5c of the examples of the present invention are shown;

[0022] Figure 2 a is the relative absorption spectrum of the product 3j (10 μM) of Example 9 in acetonitrile / water with different water fractions (fw), b is the fluorescence spectrum of the product 3j (10 μM) of Example 9 in acetonitrile / water with different water fractions (fw), and c is the relationship between the integrated area of ​​fluorescence intensity and different water fractions;

[0023] Figure 3 a is the relative absorption spectrum of the product 5c (10 μM) of Example 15 in acetonitrile / water with different water fractions (fw), b is the fluorescence spectrum of the product 5c (10 μM) of Example 15 in acetonitrile / water with different water fractions (fw), and c is the relationship between the integrated area of ​​fluorescence intensity and different water fractions;

[0024] Figure 4 Wherein, a is the relative absorbance of the product 3j NPs (10 μM) of Example 9 in acetonitrile and water, and b is the fluorescence spectrum of the product 3j NPs (10 μM) of Example 9 in acetonitrile and water;

[0025] Figure 5 a is the relative absorbance of the product 5c NPs (10 μM) of Example 15 in acetonitrile and water, and b is the fluorescence spectrum of the product 5c NPs (10 μM) of Example 15 in acetonitrile and water;

[0026] Figure 6Schematic diagram of organic nanoparticles self-assembled from the product 3j of Example 9 or the product 5c of Example 15 and surfactant F-127;

[0027] Figure 7 are transmission electron micrographs of the product 3j NPs of Example 9 and the product 5c NPs of Example 15;

[0028] Figure 8 is the dark cytotoxicity of HeLa cells treated with different concentrations of the product 3j NPs of Example 9 and the product 5c NPs of Example 15 for 24 hours, and the error bars represent the standard deviation of each group (n=6);

[0029] Figure 9 Cellular uptake diagrams of product 5c of Example 15 in Application Example 1 at different staining times;

[0030] Figure 10 Concentration dependence of HeLa cells in Application Example 1 on product 5c of Example 15;

[0031] Figure 11 is a colocalized fluorescence image of the product 5c of Example 15 in Application Example 1;

[0032] Figure 12 This is a fluorescence image of HeLa cells pretreated with oleic acid (100 μM) and HeLa cells not pretreated with oleic acid after being labeled with product 5c of Example 15 in Application Example 1;

[0033] Figure 13 This is a two-photon fluorescence image of product 5c of Example 15 in Application Example 1. DETAILED DESCRIPTION

[0034] The following is a detailed description of the specific embodiments of the present invention. It should be understood that the specific embodiments described herein are only used to illustrate and explain the present invention and are not intended to limit the present invention.

[0035] The endpoints of the ranges and any values ​​disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoints of each range, the endpoints of each range and individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered to be specifically disclosed herein.

[0036] In a first aspect, the present invention provides an α-amino BODIPY derivative, the structure of which is shown in Formula 3 and Formula 4.

[0037]

[0038] Wherein, Ar1 is an aryl group, Ar2 is an aryl group or a heterocyclic aryl group, and X is selected from one of C, N, O and S.

[0039] The invention realizes the direct functionalization of weak nitrogen nucleophilic reagents to synthesize α-amino BODIPY derivatives through base-promoted oxidative cross-dehydrogenation coupling reaction.

[0040] In a preferred embodiment of the present invention, Ar1 is a monocyclic aromatic group, Ar2 is selected from a monocyclic aromatic group, a thiazolyl group, an oxazolyl group, a pyrimidinyl group, a pyridylpyrazinyl group or a tetraphenylethylene group, and X is C or N.

[0041] In a preferred embodiment of the present invention, the Ar1 is selected from mesitylene or m-dichlorophenyl, the Ar2 is selected from one of phenyl, 2-benzothiazolyl, 2-thiazolyl, 2-oxazolyl, 2-pyrimidinyl, 2-pyridyl, 2-pyrazinyl or tetraphenylethylene, and the X is selected from C or N.

[0042] In a preferred embodiment of the present invention, the structures of the α-amino BODIPY derivatives are shown in Formulas 3a-3j, 4a, 4c and 5a-5c.

[0043]

[0044]

[0045] In a second aspect, the present invention provides a method for preparing an α-amino BODIPY derivative, the method comprising: reacting a substrate represented by Formula 1, an aniline derivative, and a base in the presence of a solvent;

[0046] wherein the base is selected from one or more of cesium carbonate, potassium carbonate and potassium tert-butoxide;

[0047] The aniline derivative is an aryl aniline represented by formula 2a and / or a heteroaryl aniline represented by formula 2b;

[0048]

[0049] The invention obtains an α-amino BODIPY derivative through a simple preparation method. The preparation method is simple and easy to operate, has mild conditions, and is green and environmentally friendly.

[0050] In a preferred embodiment of the present invention, Ar1 is a monocyclic aromatic group, Ar2 is selected from a monocyclic aromatic group, a thiazolyl group, an oxazolyl group, a pyrimidinyl group, a pyridylpyrazinyl group or a tetraphenylethylene group, and X is C or N.

[0051] In a preferred embodiment of the present invention, the Ar1 is selected from mesitylene or m-dichlorophenyl, the Ar2 is selected from one of phenyl, 2-benzothiazolyl, 2-thiazolyl, 2-oxazolyl, 2-pyrimidinyl, 2-pyridyl, 2-pyrazinyl or tetraphenylethylene, and the X is selected from C or N.

[0052] In a preferred embodiment of the present invention, the molar ratio of the substrate represented by Formula 1, the aniline derivative and the base is 1:1-5:1-2, for example, 1:1:1, 1:2:1, 1:3:1, 1:4:1, 1:5:1, 1:1:1.5, 1:1:2, 1:2:1.5, 1:2:2 and 1:5:2.

[0053] In a preferred embodiment of the present invention, the solvent is selected from one or more of acetonitrile, toluene, chloroform, tetrahydrofuran and N,N-dimethylformamide.

[0054] In a preferred embodiment of the present invention, the reaction conditions include: temperature of 40-60° C., time of 4-6 h, and stirring rate of 500-600 rpm.

[0055] In a preferred embodiment of the present invention, the reaction further comprises washing, extraction, drying and purification.

[0056] In a preferred embodiment of the present invention, in order to reduce the solubility of the obtained organic product in water, the washing is performed using an aqueous NaHCO3 solution.

[0057] In a preferred embodiment of the present invention, the extraction solvent used in the extraction is dichloromethane.

[0058] In a preferred embodiment of the present invention, the drying conditions include: first drying with anhydrous Na2SO4, and then removing the organic solvent under vacuum.

[0059] In a preferred embodiment of the present invention, the purification method is column chromatography.

[0060] In a third aspect, the present invention provides an α-amino BODIPY derivative prepared by the preparation method described in the second aspect.

[0061] In a fourth aspect, the present invention provides a use of the α-amino BODIPY derivative described in the first aspect or the third aspect in biological imaging.

[0062] The present invention will be described in detail below through examples, but the scope of protection of the present invention is not limited thereto. In the following examples, the drugs and pharmaceuticals are all conventional commercial products.

[0063] (1) Structures of substrates BODIPY 1a-1c used in the examples:

[0064]

[0065] (2) Structures of the arylanilines and heteroarylanilines 2a-2k used in the examples:

[0066]

[0067] Example 1

[0068] Synthesis method of compound 3a:

[0069] To a 25 mL round-bottom flask were added the substrate BODIPY 1a (31 mg, 0.1 mmol), 2-aminobenzothiazole 2a (45 mg, 0.3 mmol), and cesium carbonate (49 mg, 0.15 mmol). 5 mL of acetonitrile was added as the solvent and the mixture was stirred at room temperature for 4 hours. The reaction was monitored by TLC. After complete reaction of the substrate BODIPY 1a, the reaction mixture was poured into a separatory funnel containing 100 mL of saturated sodium bicarbonate solution and extracted three times with 30 mL of CHCl. ​​The organic phases were collected and dried over anhydrous NaSO. The organic solvent was then removed by distillation under reduced pressure. The crude product was purified by column chromatography (300-400 mesh silica gel, petroleum ether / dichloromethane = 4 / 1) to afford the desired product 3a as a red solid (36 mg, 78%).

[0070]

[0071] The structure of compound 3a:

[0072] The characterization data of compound 3a are: 1 H NMR (400MHz, CDCl3) δ7.81(d,J=8.0Hz,1H),7.75(d,J=8.0Hz,1H),7.62(s,1H),7.47-7.41(m,2H),7.33-7.28(m,1H ),6.96(s,2H),6.81(d,J=4.8Hz,1H),6.42(d,J=3.6Hz,1H),6.38(dd,J=4.0,2.4Hz,1H),2.37(s,3H),2.13(s,6H). 13 C NMR (100MHz, CDCl3) δ157.8,153.8,151.1,139.9,138.5,136.8,136.3,133.9,133.4,13 2.3,131.5,129.7,128.1,126.6,124.3,124.2,121.5,121.2,115.6,113.3,21.1,19.9.11 B NMR (128MHz, CDCl3) δ0.94 (t, J=33.3Hz, 1B). 19 F NMR (376MHz, CDCl3) δ-147.23 (q, J=33.8Hz, 2F).HRMS calcd.For C 25 H 22 BF2N4S[M+H] + :459.1626,found459.1629.

[0073] Example 2

[0074] Synthesis method of compound 3b:

[0075] The method of Example 1 was followed, except that BODIPY 1b (34 mg, 0.1 mmol) and 2-benzothiazolamine 2a (45 mg, 0.3 mmol) were stirred and reacted at room temperature for 4 hours, and then separated and purified by silica column chromatography (silica, petroleum ether / dichloromethane 2:1, v / v) to obtain the target product 3b (31 mg, 64%).

[0076] The structure of compound 3b:

[0077] The characterization data of compound 3b are: 1 H NMR(400MHz, CDCl3) δ7.82(d,J=8.4Hz,1H),7.76(d,J=7.6Hz,1H),7.63(s,1H) ,7.52-7.37(m,5H),7.32(t,J=7.5Hz,1H),6.83(d,J=4.8Hz,1H),6.41(s,2H). 13 C NMR (100MHz, CDCl3) δ157.4,154.8,151.0,136.6,135.7,133.8,133.2,132.4,132 .3,131.7,131.5,130.9,128.2,126.7,124.5,123.4,121.6,121.2,115.8,114.5. 11 B NMR (128MHz, CDCl3) δ0.90 (t, J=32.9Hz, 1B). 19 F NMR (376MHz, CDCl3) δ-147.01 (q, J=30.1Hz, 2F).HRMS calcd.For C 22 H 13 BCl2F2N4S[M+H] +:485.0377,found485.0386.

[0078] Example 3

[0079] Synthesis method of compound 3c:

[0080] The method of Example 1 was followed, except that BODIPY 1c (36 mg, 0.1 mmol) and 2-benzothiazolamine 2a (45 mg, 0.3 mmol) were stirred and reacted at room temperature for 4 hours, and then separated and purified by silica column chromatography (silica, petroleum ether / dichloromethane 1:1, v / v) to obtain the target product 3c (33 mg, 66%).

[0081] The structure of compound 3c:

[0082] The characterization data of compound 3c are: 1 H NMR (400MHz, CDCl3) δ7.84(d,J=8.4Hz,1H),7.78(d,J=8.0Hz,1H),7.63(s,1H),7.60(d,J=4.8Hz,1H), 7.47(t,J=7.6Hz,1H),7.34(t,J=7.6Hz,1H),6.93(d,J=4.8Hz,1H),6.51(d,J=3.6Hz,1H),6.45(m,1H). 13 C NMR (100MHz, CDCl3) δ157.1,155.8,150.8,146.0,143.4,139.0,137.0,136.5, 132.9,132.2,131.7,124.7,123.5,121.7,121.4,121.3,116.2,115.8,108.3. 11 B NMR (128MHz, CDCl3) δ0.84 (t, J=33.3Hz, 1B). 19 F NMR (376MHz, CDCl3) δ-136.24--137.46(m,2F),-146.74(q,J=33.8Hz,2F),-150.27(t,J=22.6Hz,1F),-159.82--160.29(m,2F).HRMS calcd.For C 22 H 11 BF7N4S[M+H] + :507.0686,found 507.0691.

[0083] Example 4

[0084] Synthesis method of compound 3d:

[0085] The method of Example 1 was followed, except that BODIPY 1a (31 mg, 0.1 mmol) and thiazol-2-amine 2b (30 mg, 0.3 mmol) were stirred and reacted at room temperature for 4 hours, and then separated and purified by silica column chromatography (silica, petroleum ether / dichloromethane 1:1, v / v) to obtain the target product 3d (21 mg, 52%).

[0086] The structure of compound 3d:

[0087] The characterization data of compound 3d are: 1 H NMR (400MHz, CDCl3) δ7.59(s,1H),7.44(d,J=3.6Hz,1H),7.17(d,J=4.8Hz,1H),6.96(d,J=3.6Hz,1H), 6.94(s,2H),6.77(d,J=4.8Hz,1H),6.38(d,J=3.6Hz,1H),6.37-6.33(m,1H),2.36(s,3H),2.11(s,6H). 13 C NMR (100MHz, CDCl3) δ159.5,154.5,139.9,138.8,138.4,136.9,135.4,134.1,132.4,129.8,128.1,123.4,115.3,113.0,112.7,21.1,19.9. 11 B NMR (128MHz, CDCl3) δ0.90 (t, J=33.2Hz, 1B). 19 F NMR (376MHz, CDCl3) δ-147.53 (q, J=34.2Hz, 2F).HRMS calcd.For C 21 H 20 BF2N4S[M+H] + :409.1470,found 409.1472.

[0088] Example 5

[0089] Synthesis method of compound 3e:

[0090] The method of Example 1 was followed, except that BODIPY 1a (31 mg, 0.1 mmol) and oxazol-2-amine 2c (26 mg, 0.3 mmol) were stirred and reacted at room temperature for 4 hours, and then separated and purified by silica column chromatography (silica, petroleum ether / dichloromethane 1:1, v / v) to obtain the target product 3e (26 mg, 66%).

[0091] The structure of compound 3e:

[0092] The characterization data of compound 3e are: 1 H NMR (400MHz, CDCl3) δ7.59(s,1H),7.43(s,1H),7.15(d,J=4.8Hz,1H),7.02(s,1H),6.94(s,2 H),6.77(d,J=4.8Hz,1H),6.39(d,J=3.6Hz,1H),6.37-6.31(m,1H),2.35(s,3H),2.11(s,6H). 13 C NMR (100MHz, CDCl3) δ153.1,139.8,138.5,136.8,136.1,134.8,134.0,133.3,129.7,128.1,127.3,124.1,115.5,112.2,21.1,19.9. 11 B NMR (128MHz, CDCl3) δ0.85 (t, J=33.3Hz, 1B). 19 F NMR (376MHz, CDCl3) δ-147.91 (q, J=31.9Hz, 2F).HRMS calcd.For C 21 H 20 BF2N4O[M+H] + :393.1698,found393.1690.

[0093] Example 6

[0094] Synthesis method of compound 3f:

[0095] The method of Example 1 was followed, except that BODIPY 1a (31 mg, 0.1 mmol) and 2-aminopyridine 2d (28 mg, 0.3 mmol) were stirred and reacted at room temperature for 4 hours, and then separated and purified by silica column chromatography (silica, petroleum ether / dichloromethane 1:1, v / v) to obtain the target product 3f (27 mg, 68%).

[0096] The structure of compound 3f:

[0097] The characterization data of compound 3f are: 1H NMR (400MHz, CDCl3) δ8.40(s,1H),8.37(d,J=4.0Hz,1H),7.72-7.66(m,1H),7.52(s,1H),7.45(d,J=4.8Hz,1H),7.03(dd,J=7 .2,5.2Hz,1H),6.99-6.91(m,3H),6.76(d,J=4.8Hz,1H),6.34-6.30(m,1H),6.29(d,J=3.6Hz,1H),2.36(s,3H),2.12(s,6H). 13 C NMR (100MHz, CDCl3) δ156.0,151.2,148.4,138.3,138.2,137.0,136.4,134.1,13 3.7,132.9,132.5,130.1,128.0,121.6,118.9,114.7,114.5,112.9,21.1,19.9. 11 B NMR (128MHz, CDCl3) δ1.07 (t, J=33.3Hz, 1B). 19 F NMR (376MHz, CDCl3) δ-147.82 (q, J=33.8Hz, 2F).HRMS calcd.For C 23 H 22 BF2N4[M+H] + :403.1906,found403.1914.

[0098] Example 7

[0099] Synthesis method of compound 3g:

[0100] The method of Example 1 was followed, except that BODIPY 1a (31 mg, 0.1 mmol) and 2-aminopyrimidine 2e (29 mg, 0.3 mmol) were stirred and reacted at room temperature for 4 hours, and then separated and purified by silica gel column chromatography (silica gel, petroleum ether / dichloromethane 1:1, v / v) to obtain 3 g (33 mg, 82%) of the desired product.

[0101] The structure of compound 3g:

[0102] The characterization data of compound 3g are: 1H NMR (400MHz, CDCl3) δ8.87 (s, 1H), 8.58 (s, 2H), 7.59 (s, 1H), 7.49 (d, J = 3.6Hz, 1H), 6. 99(s,1H),6.95(s,2H),6.76(d,J=3.6Hz,1H),6.34(s,2H),2.36(s,3H),2.12(s,6H). 13 C NMR (100MHz, CDCl3) δ158.4,157.4,154.9,138.5,138.3,136.9,135.2,133.7,133.1,129.9,128.0,123.0,115.8,115.0,114.3,21.1,20.0. 11 BNMR (128MHz, CDCl3) δ0.97 (t, J = 33.3Hz, 1B). 19 F NMR (376MHz, CDCl3) δ-147.71 (q, J=33.8Hz, 2F).HRMS calcd.For C 22 H 21 BF2N5[M+H] + :404.1858,found 404.1850.

[0103] Example 8

[0104] Synthesis method of compound 3h:

[0105] The method of Example 1 was followed, except that BODIPY 1a (31 mg, 0.1 mmol) and 2-aminopyrazine 2f (29 mg, 0.3 mmol) were stirred and reacted at room temperature for 4 hours, and then separated and purified by silica column chromatography (silica, petroleum ether / dichloromethane 1:1, v / v) to obtain the target product 3h (33 mg, 82%).

[0106] The structure of compound 3h:

[0107] The characterization data of compound 3h are: 1 H NMR (400MHz, CDCl3) δ8.45(s,1H),8.41(s,1H),8.28(d,J=7.2Hz,2H),7.58(s,1H),7.37(d,J =4.8Hz,1H),6.95(s,2H),6.78(d,J=4.4Hz,1H),6.37-6.34(m,2H),2.36(s,3H),2.12(s,6H). 13C NMR (100MHz, CDCl3) δ154.6,148.1,141.9,138.7,138.5,138.4,136.9,135.5 ,135.3,133.9,133.2,132.2,129.8,128.1,123.3,115.2,113.6,21.1,19.9. 11 B NMR (128MHz, CDCl3) δ1.02 (t, J = 33.3Hz, 1B). 19 F NMR (376MHz, CDCl3) δ-147.43 (q, J=33.8Hz, 2F).HRMS calcd.For C 22 H 21 BF2N5[M+H] + :404.1858,found 404.1854.

[0108] Example 9

[0109] Synthesis method of compound 3i:

[0110] The method of Example 1 was followed, except that BODIPY 1a (31 mg, 0.1 mmol) and aniline 2 g (28 mg, 0.3 mmol) were stirred and reacted at room temperature for 6 hours, and then separated and purified by silica gel column chromatography (silica gel, petroleum ether / dichloromethane 1:1, v / v) to obtain the target product 3i (16 mg, 39%).

[0111] The structure of compound 3i:

[0112] The characterization data of compound 3i are: 1 H NMR (400MHz, CDCl3) δ8.00 (s, 1H), 7.48 (s, 1H), 7.42 (t, J = 7.6Hz, 2H), 7.32-7.24 (m, 3H), 6. 93(s,2H),6.68(d,J=4.4Hz,1H),6.36-6.27(m,2H),6.23(s,1H),2.34(s,3H),2.12(s,6H). 13 C NMR (100MHz, CDCl3) δ158.7,138.1,137.5,137.1,134.4,133.3,132.7,13 2.6,130.2,129.7,128.0,126.1,122.7,120.5,114.0,111.0,21.1,19.9. 11 B NMR (128MHz, CDCl3) δ1.11 (t, J = 33.5Hz, 1B). 19F NMR (376MHz, CDCl3) δ-148.62 (q, J=30.8Hz, 2F).HRMS calcd.For C 24 H 23 BF2N3[M+H] + :402.1953,found402.1946.

[0113] Example 10

[0114] Synthesis method of compound 3j:

[0115] The method of Example 1 was followed, except that BODIPY 1a (31 mg, 0.1 mmol) and 4-(1,2,2-triphenylvinyl)aniline 2h (104 mg, 0.3 mmol) were stirred and reacted at room temperature for 4 hours, and then separated and purified by silica column chromatography (silica, petroleum ether / dichloromethane 3:1, v / v) to obtain the target product 3j (288 mg, 44%).

[0116] The structure of compound 3j:

[0117] The characterization data of compound 3j are: 1 H NMR(400MHz, CDCl3)δ7.92(s,1H),7.47(s,1H),7.15-7.09(m,9H),7.08-6.97(m,10H),6.9 3(s,2H),6.67(d,J=4.8Hz,1H),6.33-6.25(m,2H),6.22(s,1H),2.34(s,3H),2.11(s,6H). 13 C NMR (100MHz, CDCl3) δ158.2, 143.7, 143.3, 143.2, 141.7, 141.5, 139.7, 138.0, 137.1, 135.6, 134.3, 132.6 ,132.5,131.3,131.2,130.1,128.0,127.8,127.7,126.7,129.6,121.4,120.4,114.0,111.2,21.1,20.0. 11 B NMR (128MHz, CDCl3) δ1.09 (t, J = 28.2Hz, 1B). 19 F NMR (376MHz, CDCl3) δ-148.52 (dd, J=59.5, 22.0Hz, 2F).HRMS calcd.For C 44 H 37 BF2N3[M+H] +:656.3043,found 656.3040.

[0118] Example 11

[0119] Synthesis method of compound 4a:

[0120] The method of Example 1 was followed, except that BODIPY 1a (31 mg, 0.1 mmol) and pyrazole 2i (20 mg, 0.3 mmol) were stirred and reacted at room temperature for 4 hours, and then separated and purified by silica column chromatography (silica, petroleum ether / dichloromethane 1:1, v / v) to obtain the target product 4a (24 mg, 62%).

[0121] The structure of compound 4a:

[0122] The characterization data of compound 4a are: 1 H NMR (400MHz, CDCl3) δ8.96 (d, J = 2.4Hz, 1H), 7.82 (s, 1H), 7.77 (s, 1H), 7.01 (d, J = 4.8Hz, 1H), 6.96 (s,2H),6.76(d,J=4.4Hz,1H),6.57(d,J=3.2Hz,2H),6.48-6.42(m,1H),2.37(s,3H),2.13(s,6H). 13 C NMR (101MHz, CDCl3) δ153.0,144.5,143.8,140.6,138.8,136.7,134.2,133.6 ,132.4,132.3,132.1,129.6,128.2,127.1,117.6,114.2,109.7,21.2,20.0. 11 B NMR (128MHz, CDCl3) δ0.94 (t, J=31.5Hz, 1B). 19 FNMR (376MHz, CDCl3) δ-141.91 (q, J=30.8Hz, 2F).HRMS calcd.For C 21 H 20 BF2N4[M+H] + :377.1749,found 377.1753.

[0123] Example 12

[0124] Synthesis method of compound 4c:

[0125] The method of Example 1 was followed, except that BODIPY 1a (31 mg, 0.1 mmol) and indole 2k (35 mg, 0.3 mmol) were stirred and reacted at room temperature for 4 hours, and then separated and purified by silica gel column chromatography (silica gel, petroleum ether / dichloromethane 1:1, v / v) to obtain the target product 4c (29 mg, 69%).

[0126] The structure of compound 4c:

[0127] The characterization data of compound 4c are: 1 H NMR (400MHz, CD2Cl2) δ8.05(d,J=3.2Hz,1H),7.70(s,1H),7.61(d,J=7.6Hz,1H),7.54(d,J=8.0Hz,1H),7.25-7.14(m ,2H),6.94(s,2H),6.77(d,J=4.0Hz,1H),6.71(d,J=3.2Hz,2H),6.53(s,1H),6.41(s,1H),2.31(s,3H),2.09(s,6H). 13 C NMR(100MHz,CD2Cl2)δ151.6,144.5,141.1,139.0,136.7,134.2,133.8,130.2,1 29.5, 128.2, 127.6, 123.3, 122.3, 121.4, 117.8, 114.6, 112.2, 106.4, 20.9, 19.7. 11 B NMR (128MHz, CD2Cl2) δ0.79 (t, J=30.5Hz, 1B). 19 F NMR(376MHz,CD2Cl2)δ-141.50(q,J=30.8Hz,2F).HRMS calcd.For C 26 H 23 BF2N3[M+H] + :426.1953,found 426.1947.

[0128] Example 13

[0129] Synthesis method of compound 5a:

[0130] The method of Example 1 was followed, except that BODIPY 1a (31 mg, 0.1 mmol) and pyrazole 2i (34 mg, 0.5 mmol) were stirred and reacted at room temperature for 6 hours, and then separated and purified by silica column chromatography (silica, petroleum ether / dichloromethane 2:1, v / v) to obtain the target product 5a (34 mg, 78%).

[0131] The structure of compound 5a:

[0132] The characterization data of compound 5a are: 1 H NMR (400MHz, CDCl3) δ8.82(s,2H),7.80(s,2H),6.97(s,2H),6.93(s,2H),6.67(s,2H),6.55(s,2H),2.37(s,3H),2.16(s,6H). 13 C NMR (100MHz, CDCl3) δ150.6,143.2,142.8,138.9,136.9,132.4,132.1,132.0,131.9,129.6,128.3,113.5,109.1,21.1,19.9. 11 B NMR (128MHz, CDCl3) δ1.43 (t, J = 33.8Hz, 1B). 19 F NMR (376MHz, CDCl3) δ-137.46 (q, J=33.8Hz, 2F).HRMS calcd.For C 22 H 28 BF2N6[M+H] + :443.1967,found 443.1975.

[0133] Example 14

[0134] Synthesis method of compound 5b:

[0135] The method of Example 1 was followed, except that BODIPY 1a (31 mg, 0.1 mmol) and pyrrole 2j (34 mg, 0.5 mmol) were stirred and reacted at room temperature for 6 hours, and then separated and purified by silica column chromatography (silica, petroleum ether / dichloromethane 3:1, v / v) to obtain the target product 5b (33 mg, 75%).

[0136] The structure of compound 5b:

[0137] The characterization data of compound 5b are: 1 H NMR (400MHz, CDCl3) δ7.51-7.42(m,4H),6.97(s,2H),6.61(d,J=4.4Hz,2H),6.40(d,J=4.4Hz,2H),6.39-6.34(m,4H),2.37(s,3H),2.16(s,6H). 13C NMR (100MHz, CDCl3) δ151.1,141.6,138.7,137.0,132.2,129.5,129.2,128.2,122.7,122.6,122.5,112.3,111.9,21.1,19.9. 11 B NMR (128MHz, CDCl3) δ1.31 (t, J=32.0Hz, 1B). 19 F NMR (376MHz, CDCl3) δ-136.5 (q, J=33.8Hz, 2F).HRMS calcd.ForC 26 H 24 BF2N4[M+H] + :441.2057,found 441.2054.

[0138] Example 15

[0139] Synthesis method of compound 5c:

[0140] The method of Example 1 was followed, except that BODIPY 1a (31 mg, 0.1 mmol) and indole 2k (59 mg, 0.5 mmol) were stirred and reacted at room temperature for 6 hours, and then separated and purified by silica column chromatography (silica, petroleum ether / dichloromethane 2:1, v / v) to obtain the target product 5c (44 mg, 82%).

[0141] The structure of compound 5c:

[0142] The characterization data of compound 5c are: 1 H NMR(400MHz, CDCl3) δ7.99(d,J=3.2Hz,2H),7.63(d,J=7.6Hz,2H),7.55(d,J=8.0Hz,2H),7.25 -7.16(m,4H),7.03(s,2H),6.76(d,J=4.4Hz,2H),6.72-6.66(m,4H),2.41(s,3H),2.26(s,6H). 13 C NMR (100MHz, CDCl3) δ149.6,142.1,138.9,137.1,136.8,132.6,130.0,129.8,12 9.7,129.4,129.3,128.3,122.9,121.8,121.4,114.1,112.0,106.1,21.2,20.2. 11 B NMR (128MHz, CDCl3) δ1.21 (t, J = 31.6Hz, 1B). 19FNMR(376MHz,CDCl3)δ-137.32(q,J=31.6Hz,2F).HRMS calcd.For C 34 H 28 BF2N4[M+H] + :541.2375,found 541.2370.

[0143] Test Example 1

[0144] The photophysical properties of substrate 1a in dichloromethane at room temperature, as well as the photophysical properties of α-amino BODIPY derivatives 3a-3j, 4a, 4c and 5a-5c prepared in Examples 1-15 in different solvents were tested. The results are shown in Table 1.

[0145] Table 1 Spectral and photophysical data of compounds 5a-5j in different organic solvents at room temperature.

[0146]

[0147]

[0148]

[0149]

[0150] It can be observed from Table 1 that the α-amino BODIPY derivatives 3a-3j, 4a, 4c and 5a-5c prepared in Examples 1-15 of the present invention all showed significant absorption in the range of 502-584 nm. Compared with the substrate BODIPY1a at 501 nm in dichloromethane, 3a showed a significant red shift to 534 nm. Different meso-substituted 3b and 3c and heteroaryl-substituted amino groups 3d–3h also showed similar absorption in the range of 522–546 nm, but with phenyl-substituted aniline 3i, only a slightly red-shifted absorption was observed at 502 nm. In addition, 3j also showed an absorption peak only at 510 nm. Compared with 3-anilino BODIPY 3i, monopyrazole- or indole-substituted BODIPY 4a and 4c showed maximum red-shifted absorption at 528 nm and 546 nm, respectively, and disubstituted BODIPY 5a–5c were significantly red-shifted to 562 nm, 558 nm, and 584 nm, respectively, indicating that pyrazole, pyrrole, and indole rings conjugated with the BODIPY π-system more effectively than the aniline ring.

[0151] Similar to absorption, most of these meso-substituted BODIPYs 3a-3c and heteroaryl-substituted amino BODIPYs 3d-3h displayed similar emissions in the 540-574 nm range. For example, the emission of 3a showed a red-shift to 552 nm. Interestingly, 3i and 3j also displayed red-shifted emission maxima at 554 and 597 nm, respectively. Similarly, BODIPYs 5a-5c showed a significant red-shift at 577-614 nm.

[0152] The α-amino BODIPY derivatives of the present invention exhibit slightly blue-shifted absorption in polar solvents, while the emission maximum varies slightly in different solvents. The fluorescence quantum yield is generally higher in the non-polar solvent hexane and decreases in polar solvents such as acetonitrile. For example, most of these α-amino BODIPY derivatives show good to excellent fluorescence quantum yields (0.43-0.94) in dichloromethane. However, 3j, 4c, and 5c show very low fluorescence quantum yields (0.02, 0.01, and 0.04, respectively, in dichloromethane). It is worth noting that their fluorescence quantum yields in hexane increase to 0.10, 0.87, and 0.89, respectively. A plausible reason for the quenching of emission in polar solvents may be the photoinduced electron transfer (PET) process from the electron-rich aromatic substituents (TPE and indolyl) to the electron-deficient BODIPY core.

[0153] Test Example 2

[0154] The crystal data and structure refinement of 3a, 3i, 3f, 3h, 4a, 5a, 5b, and 5c are shown in Tables 2 and 3.

[0155] Table 2

[0156]

[0157]

[0158] Table 3

[0159]

[0160]

[0161] Depend on Figure 1 From the data in Tables 2 and 3, we can see that the bond lengths of the newly formed C-NH bonds in 3a, 3i, 3f, and 3h are and However, the lengths of the newly formed C-N bonds in 4a, 5a, 5b, and 5c were measured to be ca. The C-NH bond in 3a, 3i, 3f, and 3h is slightly longer than that in 3a, 3i, 3f, and 3h. The middle aromatic group is almost orthogonal to the BODIPY core, with dihedral angles ranging from 72.8° to 82.3°. In addition, the average NH·F distances of 3a, 3i, 3f, and 3h and the CH··F distances of 4a, 5a, 5b, and 5c are and The CH··N interaction distances of 3a, 3f, 3h, 4a, and 5a are and The dihedral angles between the BODIPY core and the α-substituent aromatic ring are 2.6°, 18.8°, 6.5°, 0.8°, and 17.6°, respectively. However, no CH··N interaction was observed in 3i, 5b, and 5c, and the dihedral angles between the BODIPY core and the α-substituent aromatic ring are significantly larger than those of the aforementioned α-amino BODIPY derivatives with CH··N interactions (57.2°, 40.1°, and 46.2°, respectively). These results suggest that the molecular conformation may be restricted by these intramolecular hydrogen bonding interactions, which is conducive to extended conjugation and radiative decay of the excited state.

[0162] Test Example 3

[0163] Aggregation-induced fluorescence (AIE) property detection:

[0164] Compounds 3j (10 μM) and 5c (10 μM) were added to different proportions of binary mixed solvents of acetonitrile and water, and then their UV absorption and fluorescence emission spectra were measured. When measuring the UV absorption spectrum, the receiving wavelength was 300-750 nm. For the fluorescence emission spectrum, the excitation wavelength of 3j was 480 nm and the receiving wavelength was 490-850 nm; the excitation wavelength of 5c was 520 nm and the receiving wavelength was 530-850 nm. The results are shown in Figure 2. Figure 2 and Figure 3 .

[0165] Depend on Figure 2 As shown in Figure a, with the gradual increase of the water ratio in the binary solvent of acetonitrile and water, the solubility of 3j decreases, which promotes the formation of 3j aggregates of different sizes and causes the absorption peak to gradually decrease and broaden, accompanied by a red shift; Figure 2 b and Figure 2 As shown in c, when the water fraction is in the range of 0-30%, a slight red shift appears in the emission spectrum. When the water fraction increases from 30% to 96%, the fluorescence intensity of 3j increases significantly, and a new strong red-shifted emission band appears near 650nm. Figure 3The AIE process of 5c is similar to that of 3j, but the degree of light enhancement is slightly lower. This is likely due to the presence of a core AIE molecule, tetraphenylethylene (TPE), with a propeller structure, in the structure of 3j. When these molecules aggregate, they stack in a staggered manner, leaving insufficient space for the propellers. This restricts intramolecular motion (RIM), forcing energy to radiate and emit fluorescence. Consequently, the more they aggregate, the more luminescent they become. These molecular aggregates can restrict molecular rotation and inhibit the photoinduced electron transfer (PET) process, thereby releasing more excited-state energy through radiative transitions, leading to the aggregation-induced fluorescence of 3j and 5c.

[0166] Test Example 4

[0167] Cytotoxicity was determined by CCK-8 assay:

[0168] First, we encapsulated the compound. The encapsulation method was to take a 50mL round-bottom flask, add 1mL of chloroform as the base solution, then add the sample of 3j (10μM), and then add 20 equivalents of surfactant F-127. After drying, the encapsulation was completed. The encapsulation method of 5c was the same as above. In order to test the photophysical properties of the nanoparticles after encapsulation, 3mL of water was added and their UV absorption and fluorescence emission spectra were measured respectively. The results are shown in Figure 4 and Figure 5 .

[0169] HeLa cells (5000) were seeded in each well of a 96-well plate and incubated in 1640 complete medium at 37°C for 24 hours. 3j NPs (100 μM) and 5c NPs (100 μM) were prepared as described above, then dissolved in fresh culture medium and prepared into gradient concentrations from 0 to 100 μM, added to a 96-well plate, and the cells with probes were incubated at 37°C. Each experiment was performed at least six times. After 24 hours, the working solution was removed and the cells were washed with PBS buffer. A total of 100 μL of CCK-8 (diluted 10 times, Cell Counting Kit-8, BIOMIKY) was added to each well, and the cells were further incubated at 37°C in a humidified atmosphere of 5% CO2 for 30 minutes. The plate was shaken for 5 minutes, and the absorbance was measured at 450 nm using a microplate reader (Multiskan-Sky). The results are shown in Table 1. Figure 8 .

[0170] Depend on Figure 4 and Figure 5 ,The fluorescence emission spectra of 3j NPs and 5c NPs show that both have good AIE properties after encapsulation, so the encapsulation is successful.

[0171] Depend on Figure 6As can be seen from the contents of the present invention, the classic surfactant F-127 is used to encapsulate 3j and 5c to form corresponding nanoparticles (NPs); Figure 7 The transmission electron microscopy images of 3j NPs and 5c NPs show that both have nanoflower structures with diameters of 41 nm and 44 nm, respectively;

[0172] Depend on Figure 8 It can be seen that at a high concentration of 100 μM, neither 3j nanoparticles nor 5c nanoparticles showed significant cytotoxicity, and after 24 hours of incubation, the cell viability of HeLa cells was higher than 90%, indicating that the α-amino BODIPY derivatives of the present invention have good biosafety.

[0173] Application Example 1

[0174] Cell imaging studies, the specific steps are as follows:

[0175] (1) Cell culture: HeLa cells were cultured in culture medium (RPMI-1640 containing 10% FBS and 1% penicillin / streptomycin solution) at 37°C in a 5% CO2 and 95% humidified atmosphere.

[0176] (2) Cellular uptake: A total of 30,000 HeLa cells were seeded into glass-bottomed dishes and cultured at 37°C in a 5% CO2 and 95% humidified atmosphere in a culture medium (RPMI-1640, containing 10% FBS and 1% penicillin / streptomycin solution) for 24 hours. HeLa cells were then stained with 5c NPs (5 μM) for 10, 20, 30, 40, 50, and 60 minutes. 5c NPs were excited at 552 nm using a confocal fluorescence microscope (CLSM, Leica Microsystems SP8MP) to monitor the uptake of HeLa cells. The results are shown in Figure 3. Figure 9 .

[0177] (3) Concentration dependence: A total of 30,000 HeLa cells were seeded into glass-bottomed dishes and cultured at 37°C in a 5% CO2 and 95% humidified atmosphere in RPMI-1640 medium (containing 10% FBS and 1% penicillin / streptomycin solution) for 24 hours. HeLa cells were then stained with 5c NPs (0.5, 1, and 2 μM) for 60 minutes. 5c NPs were excited at 552 nm using a confocal fluorescence microscope (CLSM, Leica Microsystems SP8 MP) to monitor the concentration dependence of HeLa cells. The results are shown in Figure 2. Figure 10 .

[0178] (4) Cell colocalization: A total of 30,000 HeLa cells were seeded into glass-bottomed dishes and cultured at 37°C in a culture medium (RPMI-1640, containing 10% FBS and 1% penicillin / streptomycin solution) in a humidified atmosphere of 5% CO2 and 95% CO2 for 24 hours. HeLa cells were then stained with 5c NPs (0.5 μM) for 15 minutes, and finally BODIPY 493 / 503 (5 μM) was added and incubated for 15 minutes. The commercial lipid droplet dye BODIPY 493 / 503 and 5c NPs were excited at 488 nm and 552 nm, respectively, using a confocal fluorescence microscope (CLSM, Leica Microsystems SP8 MP), and colocalization images of HeLa cells were collected. The results are shown in Figure 3. Figure 11 .

[0179] (5) Oleic acid-induced imaging: A total of 30,000 HeLa cells were seeded into glass-bottomed dishes and cultured at 37°C in a 5% CO2 and 95% humidified atmosphere for 24 hours. HeLa cells were then pretreated with oleic acid (100 μM) for 4 hours and then incubated with 5c NPs (0.5 μM) for 30 minutes. 5c NPs were excited at 552 nm using a confocal fluorescence microscope (CLSM, Leica Microsystems SP8 MP) to capture oleic acid-induced images of HeLa cells. The results are shown in Figure 2. Figure 12 .

[0180] (6) Two-photon imaging: A total of 30,000 HeLa cells were seeded into glass-bottomed dishes and cultured at 37°C in a humidified atmosphere of 5% CO2 and 95% CO2 for 24 hours. HeLa cells were stained with 5c NPs (0.5 μM) for 30 minutes, washed twice with PBS, fixed with 4% paraformaldehyde for 30 minutes at room temperature, and then washed twice with PBS. DAPI (1 μg / mL) was added to stain the cell nuclei for 30 minutes. Finally, a confocal fluorescence microscope (CLSM, Leica Microsystems SP8 MP) was used to excite the commercial cell nuclear dye DAPI and 5c NPs at 700 nm and 552 nm / 860 nm, respectively, to acquire single- and double-photon fluorescence images. The results are shown in Figure 3. Figure 13 .

[0181] Depend on Figure 9It can be seen that the α-amino BODIPY derivative 5c NPs of the present invention almost completed cellular uptake in 30 minutes, indicating that the α-amino BODIPY derivative 5c NPs of the present invention has good lipophilicity.

[0182] Depend on Figure 10 It can be seen that the α-amino BODIPY derivative 5c NPs of the present invention can exhibit bright red fluorescence at 0.5 μM, indicating that its aggregation-induced emission property further promotes its fluorescence imaging potential in HeLa cells.

[0183] Depend on Figure 11 It can be seen that the α-amino BODIPY derivative 5c NPs of the present invention has good overlap with the commercial lipid droplet dye BODIPY 493 / 503, with a Pearson correlation coefficient of 0.85, indicating that the α-amino BODIPY derivative of the present invention has good lipid droplet localization ability.

[0184] Depend on Figure 12 It can be seen that cells pretreated with oleic acid have more fluorescent beads, indicating that oleic acid can induce cells to produce excessive endogenous lipid droplets, and the α-amino BODIPY derivative 5c NPs of the present invention can track this phenomenon in real time.

[0185] Depend on Figure 13 It can be seen that under 860nm two-photon femtosecond laser excitation, 5c NPs exhibit bright two-photon fluorescence, which overlaps well with its single-photon fluorescence imaging, indicating that the α-amino BODIPY derivative 5c NPs of the present invention have good two-photon imaging potential.

[0186] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the scope of protection of the present invention.

[0187] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any appropriate manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

[0188] In addition, the various embodiments of the present invention may be arbitrarily combined, and as long as they do not violate the concept of the present invention, they should also be regarded as the contents disclosed by the present invention.

Claims

1. An α-amino BODIPY derivative, characterized in that: The structures of the α-amino BODIPY derivatives are shown in Formula 3 and Formula 4. or ; Wherein, Ar1 is a monocyclic aromatic group, Ar2 is selected from a monocyclic aromatic group, a pyrimidinyl group, a pyridinyl group, a pyrazinyl group or a tetraphenylethylene group, and X is C or N.

2. The α-amino BODIPY derivative according to claim 1, characterized in that The Ar1 is selected from mesitylene or m-dichlorophenyl, the Ar2 is selected from phenyl, 2-pyrimidinyl, 2-pyridyl, 2-pyrazinyl or tetraphenylethylene, and X is C or N.

3. The α-amino BODIPY derivative according to claim 1 or 2, characterized in that The structures of the α-amino BODIPY derivatives are shown in Formulas 3a-3j, 4c and 5c. 。 4. A method for preparing an α-amino BODIPY derivative according to any one of claims 1 to 3, characterized in that: The preparation method comprises: reacting a substrate represented by formula 1, an aniline derivative and a base in the presence of a solvent; wherein the base is selected from one or more of cesium carbonate, potassium carbonate and potassium tert-butoxide; The aniline derivative is an aryl aniline represented by formula 2a and / or a heteroaryl aniline represented by formula 2b; ， ， 。 5. The preparation method according to claim 4, characterized in that Ar1 is a monocyclic aromatic group, Ar2 is selected from a monocyclic aromatic group, a pyrimidinyl group, a pyridinyl group, a pyrazinyl group or a tetraphenylethylene group, and X is C or N.

6. The preparation method according to claim 4 or 5, characterized in that The Ar1 is selected from mesitylene or m-dichlorophenyl, the Ar2 is selected from phenyl, 2-pyrimidinyl, 2-pyridyl, 2-pyrazinyl or tetraphenylethylene, and X is C or N.

7. The preparation method according to claim 4, characterized in that The molar ratio of the substrate represented by formula 1, the aniline derivative and the base is 1:1-5:1-2.

8. The preparation method according to claim 4, characterized in that The solvent is selected from one or more of acetonitrile, toluene, chloroform, tetrahydrofuran and N,N-dimethylformamide.

9. The preparation method according to claim 4, characterized in that The reaction conditions include: temperature of 40-60° C., time of 4-6 h, and stirring rate of 500-600 rpm.

10. Use of the α-amino BODIPY derivative according to any one of claims 1 to 3 in the preparation of a bioimaging agent.

Images