A chiral fluorescent probe and its preparation method and application

Abstract

The invention belongs to the field of fluorescent compounds and relates to a chiral fluorescent probe and a preparation method and application thereof. The method is as follows: Compound R-1, DIPEA and MOMBr are subjected to a substitution reaction to obtain Compound R-2; Compound R-2, anhydrous n-butyl lithium and anhydrous DMF are subjected to a Bouveault aldehyde synthesis reaction to obtain Compound R-3; Compound R-3, anhydrous potassium carbonate and 3-bromopropyne are subjected to a substitution reaction in acetone to obtain a crude product of Compound R-4; Copper sulfate pentahydrate is reduced to active copper by sodium ascorbate in water, and then the active copper is added to a tetrahydrofuran solution of Compound R-4 and methyl azidoacetate to obtain Compound R-5 through a click chemistry reaction; Compound R-5 is subjected to a hydrolysis reaction in trifluoroacetic acid to obtain Compound R-6, which is applied to chiral amino acid recognition, and the chiral amino acid is qualitatively and quantitatively detected under the action of zinc ions, and has good selectivity and repeatability.

Description

Technical Field

[0001] The invention belongs to the field of fluorescent compounds, and in particular relates to a chiral fluorescent probe and a preparation method and application thereof. Background Art

[0002] Chiral amino acids are important components of life, and their enantiomers in free form also show important biological functions. In addition, natural amino acids can be used as versatile synthetic precursors for a variety of functional organic compounds, and can also be used as chiral sources for asymmetric synthesis and catalysis. At present, the main technologies for distinguishing two chiral enantiomers include high performance liquid chromatography, circular dichroism, electrophoresis, and fluorescence spectroscopy (In Vivo Imaging of Endogenously Produced HClO in Zebrafish and Mice Using a Bright, Photostable Ratiometric Fluorescent Probe Chong Duan, Miae Won, Peter Verwilst, Junchao Xu, Hyeong Seok Kim, Lintao Zeng, and Jong Seung Kim Analytical Chemistry 2019 91(6), 4172-4178 DOI: 10.1021 / acs.analchem.9b00224). Enantioselective fluorescence recognition of amino acids has been a hot topic in recent years. Fluorescent probes have potential application value in high-speed analysis of asymmetric reactions and monitoring chiral molecules in biological systems.

[0003] Fluorescent probes have the advantages of being sensitive, rapid, and easy to operate, and have been widely used in various fields. The advantages of traditional fluoresceins, such as fluorescent yellow, rhodamine, and anthocyanins, are that they have a high fluorescence quantum yield, a large difference in fluorescence intensity when identifying different substrates, and a good recognition effect. However, since they cannot recognize enantiomers of the same compound, have poor photostability, small Stokes shift, and low signal-to-noise ratio, their application in chiral recognition of chiral compounds such as amino acids is limited. Summary of the invention

[0004] The present invention aims to solve the problems existing in the prior art and provides a chiral fluorescent probe and a preparation method and application thereof. The chiral fluorescent probe based on binaphthol can detect chiral amino acids qualitatively and quantitatively under the action of zinc ions and has good selectivity and repeatability.

[0005] The objective of the present invention is achieved through the following technical solutions:

[0006] The first purpose is to provide a binaphthol derivative or a stereoisomer thereof, wherein the binaphthol derivative is as shown in Formula I:

[0007]

[0008] (R)-2-(4-((3'-Formyl-2'-hydroxy-[1,1'-dinaphthyl]-2-oxy)methyl)-1H-1,2,3-triazol-1-yl)acetate

[0009] The second purpose is to provide a method for preparing the binaphthol derivatives, and the synthetic route is as follows:

[0010]

[0011] The preparation method comprises the following steps:

[0012] Step (1): Compound (R)-1,1'-bi-2-naphthol, N,N-diisopropylethylamine and bromomethyl methyl ether are subjected to substitution reaction to obtain compound (R)-2'-methoxymethoxy-1,1'-dinaphth-2-ol;

[0013] Step (2): Compound (R)-2'-methoxymethoxy-1,1'-binaphthyl-2-ol, anhydrous n-butyl lithium and anhydrous N,N-dimethylformamide are subjected to Bouveault aldehyde synthesis reaction to obtain compound (R)-2'-hydroxy-2-methoxymethoxy-1,1'-binaphthyl-3-carboxaldehyde;

[0014] Step (3): Compound (R)-2'-hydroxy-2-methoxymethoxy-1,1'-binaphthyl-3-carboxaldehyde, anhydrous potassium carbonate and 3-bromopropyne are subjected to substitution reaction in acetone to obtain a crude compound (R)-2-methoxymethoxy-2-(propyl-2-yn-1-oxy)-1,1'-binaphthyl-3-carboxaldehyde;

[0015] Step (4): Copper sulfate pentahydrate is reduced to active copper by sodium ascorbate in water, and then added to a tetrahydrofuran solution of compound (R)-2-methoxymethoxy-2-(propyl-2-yn-1-oxy)-1,1'-dinaphthyl-3-carboxaldehyde and methyl azidoacetate to obtain compound (R)-2-(4-((((3'-formyl-2'-methoxymethoxy)-[1,1'-dinaphthyl]-2-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)acetate methyl ester through a click chemistry reaction;

[0016] Step (5): Compound (R)-2-(4-((((3'-formyl-2'-methoxymethoxy)-[1,1'-binaphthyl]-2-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)acetate is subjected to hydrolysis in trifluoroacetic acid to obtain compound (R)-2-(4-((3'-formyl-2'-hydroxy-[1,1'-binaphthyl]-2-oxy)methyl)-1H-1,2,3-triazol-1-yl)acetate, i.e., the compound represented by Formula I.

[0017] Furthermore, the specific steps of step (1) are as follows:

[0018] The compound (R)-1,1'-bi-2-naphthol and N,N-diisopropylethylamine (DIPEA) were dissolved in tetrahydrofuran, and after stirring and dissolving, bromomethyl methyl ether (MOMBr) was slowly added dropwise to protect the phenolic hydroxyl group on the naphthalene ring, so that the subsequent carbonylation reaction could be selective; stirred at 0°C for 10 minutes, and then stirred at room temperature for 30 minutes; after the reaction was completed, water and ethyl acetate were added for extraction, and anhydrous Na 2 SO 4 The mixture was dried, the solvent was removed under reduced pressure, and column chromatography was performed to obtain a white solid (R)-2'-methoxymethoxy-1,1'-dinaphthol-2-ol; wherein the molar ratio of the compound (R)-1,1'-bi-2-naphthol to N,N-diisopropylethylamine was 1:1.5 to 1:2.0; and the molar ratio of the compound (R)-1,1'-bi-2-naphthol to bromomethyl methyl ether was 1:3 to 1:1.5.

[0019] The molar ratio of the compound (R)-1,1'-bi-2-naphthol to N,N-diisopropylethylamine is preferably 1:1.6; the molar ratio of the compound (R)-1,1'-bi-2-naphthol to bromomethyl methyl ether is preferably 1:1.5.

[0020] Furthermore, the specific steps of step (2) are as follows:

[0021] N 2 Under protection, compound (R)-2'-methoxymethoxy-1,1'-dinaphth-2-ol was dissolved in anhydrous tetrahydrofuran (THF), anhydrous n-butyl lithium (n-BuLi) was slowly added dropwise, stirred at 0°C for 30 min, stirred at room temperature for 1 h, anhydrous N,N-dimethylformamide (DMF) was slowly added dropwise, and stirred at room temperature for 45 min; saturated NH 4 The reaction was quenched with Cl, extracted with ethyl acetate, and anhydrous Na 2 SO 4The mixture was dried, concentrated under reduced pressure, and separated by column chromatography to obtain a yellow solid (R)-2'-hydroxy-2-methoxymethoxy-1,1'-binaphthyl-3-carbaldehyde; wherein the molar ratio of the compound (R)-2'-methoxymethoxy-1,1'-binaphthyl-2-ol to anhydrous n-butyl lithium is 1:2 to 1:5; and the molar ratio of the compound (R)-2'-methoxymethoxy-1,1'-binaphthyl-2-ol to anhydrous N,N-dimethylformamide is 1:1 to 1:2.

[0022] The molar ratio of compound (R)-2'-methoxymethoxy-1,1'-dinaphth-2-ol to anhydrous n-butyllithium is preferably 1:3.5; the molar ratio of compound (R)-2'-methoxymethoxy-1,1'-dinaphth-2-ol to anhydrous N,N-dimethylformamide is preferably 1:1.5.

[0023] Furthermore, the specific steps of step (3) are as follows:

[0024] N 2 Under protection, compound (R)-2'-hydroxy-2-methoxymethoxy-1,1'-binaphthyl-3-carboxaldehyde and anhydrous potassium carbonate (K 2 CO 3 ) was dissolved in acetone, and then 3-bromopropyne was added dropwise, and refluxed at 55°C overnight; after the reaction was completed, water and ethyl acetate were added for extraction, and anhydrous Na 2 SO 4 The reaction mixture was dried and concentrated under reduced pressure to obtain a pale yellow solid crude product of (R)-2-methoxymethoxy-2-(propyl-2-yn-1-oxy)-1,1'-binaphthyl-3-carboxaldehyde, wherein the molar ratio of the compound (R)-2'-hydroxy-2-methoxymethoxy-1,1'-binaphthyl-3-carboxaldehyde to anhydrous potassium carbonate was 1:1.5 to 1:2.0, and the molar ratio of the compound (R)-2'-hydroxy-2-methoxymethoxy-1,1'-binaphthyl-3-carboxaldehyde to 3-bromopropyne was 1:1.2 to 1:1.5.

[0025] The molar ratio of compound (R)-2'-hydroxy-2-methoxymethoxy-1,1'-binaphthyl-3-carboxaldehyde to anhydrous potassium carbonate is preferably 1:1.8, and the molar ratio of compound (R)-2'-hydroxy-2-methoxymethoxy-1,1'-binaphthyl-3-carboxaldehyde to 3-bromopropyne is preferably 1:1.5.

[0026] Furthermore, the specific steps of step (4) are as follows:

[0027] The crude product of compound (R)-2-methoxymethoxy-2-(propyl-2-yn-1-oxy)-1,1'-dinaphthalene-3-carboxaldehyde was dissolved in tetrahydrofuran and methyl azidoacetate was added dropwise; sodium ascorbate and copper sulfate pentahydrate were dissolved in H 2After O, 55℃ water bath for 5min, sodium ascorbate and copper sulfate pentahydrate mixture were added to the reaction system and reacted at room temperature for 1h. After the reaction, water and ethyl acetate were added for extraction, and anhydrous Na 2 SO 4 The mixture was dried, concentrated under reduced pressure, and separated by column chromatography to obtain a white solid (R)-2-(4-((((3'-formyl-2'-methoxymethoxy)-[1,1'-dinaphthyl]-2-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)acetic acid methyl ester; wherein the molar ratio of copper sulfate pentahydrate to sodium ascorbate is 1:1 to 1:5, the molar ratio of the compound (R)-2-methoxymethoxy-2-(propyl-2-yn-1-oxy)-1,1'-dinaphthyl-3-carboxaldehyde to methyl azidoacetate is 1:1.0 to 1:1.5, and the molar ratio of the compound (R)-2-methoxymethoxy-2-(propyl-2-yn-1-oxy)-1,1'-dinaphthyl-3-carboxaldehyde to sodium ascorbate is 1:1.5 to 1:2.0.

[0028] The molar ratio of copper sulfate pentahydrate to sodium ascorbate is preferably 1:1.5, the molar ratio of compound (R)-2-methoxymethoxy-2-(propyl-2-yn-1-oxy)-1,1'-dinaphthalene-3-carboxaldehyde to methyl azidoacetate is 1:1.3, and the molar ratio of compound (R)-2-methoxymethoxy-2-(propyl-2-yn-1-oxy)-1,1'-dinaphthalene-3-carboxaldehyde to sodium ascorbate is 1:2.0.

[0029] The volume ratio of tetrahydrofuran to solvent water is 1:1 to 1:1.2, preferably 1:1.1.

[0030] In step (5), compound R / S-5 is dissolved in DCM (dichloromethane), and trifluoroacetic acid (CF 3 COOH) and reacted at room temperature for 5 h. After the reaction, saturated NaHCO 3 Quench, add water and ethyl acetate to extract, anhydrous Na 2 SO 4 The mixture was dried and concentrated under reduced pressure. Column chromatography was used to separate the white solid compound (R)-2-(4-((3'-formyl-2'-hydroxy-[1,1'-dinaphthyl]-2-oxy)methyl)-1H-1,2,3-triazol-1-yl)acetate, wherein the volume ratio of the solvent dichloromethane to trifluoroacetic acid was 2:1 to 1:1, preferably 2:1.

[0031] The third purpose is to provide the use of the binaphthol derivative or its stereoisomer as a chiral fluorescent probe in identifying chiral amino acids.

[0032] The chiral amino acids are threonine, methionine, arginine, valine, phenylalanine, tyrosine, tryptophan, leucine and glutamine.

[0033] The fluorescence detection conditions are as follows: a 4% water / methanol solution mixed solution is used as the system, and the concentration of the binaphthol derivative or its stereoisomer represented by formula I in the system is 1×10 -5 mol / L, zinc ion concentration is 1×10 -5 mol / L, in the presence of zinc ions, at the excitation wavelength λ ex =270 nm, slit: 5 / 5 nm for identification of chiral amino acids by fluorescence spectroscopy.

[0034] The fourth purpose is to provide the application of the chiral fluorescence sensor of the binaphthol derivative or its stereoisomer in the quantitative analysis of chiral amino acids.

[0035] The present invention has the following technical effects: The inventors have shown through experiments that at 1×10 -5 At a low concentration of 1.5 mol / L, the binaphthol derivative or its stereoisomers shown in Formula I can be used as a chiral recognition fluorescent probe for valine to perform qualitative and quantitative analysis of the enantiomeric composition.

[0036] Compared with a chiral fluorescence sensor and its preparation method and application with publication number CN 115745873 A, the probe of the present invention has better discrimination of chiral amino acids during detection, more obvious fluorescence enhancement effect of the probe, and is less susceptible to interference by background noise; the probe can perform quantitative detection of amino acid enantiomeric excess.

[0037] The present invention has a good recognition effect on the two enantiomers of valine, and can be used for the determination of the enantiomeric composition of valine. Among them, the fluorescence intensity of compound R-6 for L-valine reaches 6.35 times that of D-valine. In addition, compound R-6 can also perform chiral recognition on threonine (D / L-threonine) enantiomers, methionine (D / L-methionine) enantiomers, arginine (D / L-arginine) enantiomers, phenylalanine (D / L-phenylalanine) enantiomers, tyrosine (D / L-tyrosine) enantiomers, tryptophan (D / L-tryptophan) enantiomers, leucine (D / L-leucine) enantiomers, and glutamine (D / L-glutamine) enantiomers, and has the advantages of high sensitivity and wide recognition range. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 In the presence of Zn 2+ Fluorescence change curve of chiral fluorescent probe (fluorescent probe) R-6 recognizing valine enantiomer in a solution.

[0039] Figure 2 In the presence of Zn 2+ Fluorescence change curve of chiral fluorescent probe (fluorescent probe) R-6 recognizing threonine enantiomer in a solution.

[0040] Figure 3 In the presence of Zn 2+ Fluorescence change curve of chiral fluorescent probe (fluorescent probe) R-6 recognizing methionine enantiomer in a solution.

[0041] Figure 4 In the presence of Zn 2+ Fluorescence change curve of chiral fluorescent probe (fluorescent probe) R-6 recognizing arginine enantiomer in a solution.

[0042] Figure 5 In the presence of Zn 2+ Fluorescence change curve of chiral fluorescent probe (fluorescent probe) R-6 recognizing phenylalanine enantiomer in a solution.

[0043] Figure 6 In the presence of Zn 2+ Fluorescence change curve of chiral fluorescent probe (fluorescent probe) R-6 recognizing tyrosine enantiomer in a solution.

[0044] Figure 7 In the presence of Zn 2+ Fluorescence change curve of chiral fluorescent probe (fluorescent probe) R-6 recognizing tryptophan enantiomer in a solution.

[0045] Figure 8 In the presence of Zn 2+ Fluorescence change curve of chiral fluorescent probe (fluorescent probe) R-6 recognizing leucine enantiomer in a solution.

[0046] Fig. 9 In the presence of Zn 2+ Fluorescence change curve of chiral fluorescent probe (fluorescent probe) R-6 recognizing glutamine enantiomer in a solution.

[0047] Fig.10 ee value curve of chiral fluorescent probe R-6 for D / L-valine recognition. DETAILED DESCRIPTION

[0048] The present invention is further described in detail below with reference to the examples. The reagents or instruments used without indicating the manufacturer are all regarded as conventional products that can be purchased on the market.

[0049] The chiral fluorescent probe synthesis route of the present invention is:

[0050]

[0051] Example 1 Synthesis of Compound (R)-2'-methoxymethoxy-1,1'-dinaphth-2-ol

[0052] Compound R-1 (10 g, 35 mmol) and N,N-diisopropylethylamine (DIPEA) (10 mL, 56 mmol) were dissolved in tetrahydrofuran (THF), stirred and dissolved, and bromomethyl methyl ether (MOMBr) (4.3 mL, 52.5 mmol) was slowly added dropwise, stirred at 0 ° C for 10 min, and then stirred at room temperature for 30 min. After the reaction was completed, water and ethyl acetate were added for extraction, and anhydrous Na 2 SO 4 , dried, and the solvent was removed under reduced pressure. The residue was separated by column chromatography (petroleum ether: ethyl acetate = 25:1) to obtain a white solid R-2 with a yield of 71%. 1 H NMR (300 MHz, DMSO-d 6 )δ9.38(s,1H),8.01(d,J=9.0Hz,1H),7.94(d,J=8.2Hz,1H),7.87(dd,J=8.6,6.8Hz,2H),7.60(d,J=9.1Hz,1H),7.36–7.30(m,2H),7.24(ddd ,J=8.1,7.0,1.4Hz,2H),7.17(ddd,J=8.2,6.8,1.5Hz,1H),7.03–6.98(m,1H),6.88(dd,J=8.2,1.4Hz,1H),5.08(q,=6.7Hz,2H),3.10(s,3H).

[0053] Example 2 Synthesis of Compound (R)-2'-Hydroxy-2-methoxymethoxy-1,1'-binaphthyl-3-carboxaldehyde

[0054] N 2 Under protection, compound R-2 (4.5 g, 13.5 mmol) was dissolved in 50 mL of anhydrous THF, anhydrous n-butyl lithium (n-BuLi) (19 mL, 47.25 mmol) was slowly added dropwise, stirred at 0 ° C for 30 min, stirred at room temperature for 1 h, anhydrous N, N-dimethylformamide (DMF) (1.55 mL, 20 mmol) was slowly added dropwise, and stirred at room temperature for 45 min. Saturated NH 4 The reaction was quenched with Cl, extracted with ethyl acetate, and anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and separated by column chromatography (petroleum ether:ethyl acetate=15:1) to obtain yellow solid R-3 with a yield of 56%. 1 H NMR (300 MHz, DMSO-d 6)δ10.46(s,1H),9.74(s,1H),8.58(s,1H),8.26–8.20(m,1H),7.96(d,J=8.9Hz,1H),7.8 9(dd,J=8.1,1.4Hz,1H),7.53(ddd,J=8.1,6.8,1.3Hz,1H),7.45(ddd,J=8.3,6.8,1.4Hz ,1H),7.38(d,J=8.9Hz,1H),7.25(dddd,J=17.8,8.2,6.8,1.4Hz,2H),7.15–7.10(m,1H) ,6.91(dd,J=8.2,1.5Hz,1H),4.82(d,J=5.8Hz,1H),4.64(d,J=5.8Hz,1H),2.97(s,3H).

[0055] Example 3 Synthesis of Compound (R)-2-methoxymethoxy-2-(propyl-2-yn-1-oxy)-1,1'-dinaphthalene-3-carboxaldehyde

[0056] N 2 Under protection, compound R-3 (200 mg, 0.56 mmol), anhydrous K 2 CO 3 (150 mg, 1 mmol) was dissolved in 5 mL of acetone, and then 3-bromopropyne (100 mg, 0.84 mmol) was added dropwise and refluxed at 55 °C overnight. After the reaction was completed, water and ethyl acetate were added for extraction, and anhydrous Na 2 SO 4 The product was dried and concentrated under reduced pressure to obtain 220 mg of crude pale yellow solid R-4, which was directly used for the next step.

[0057] Example 4 Synthesis of Compound (R)-2-(4-((((3'-formyl-2'-methoxymethoxy)-[1,1'-dinaphthyl]-2-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)acetate

[0058] The crude product of compound R-4 (220 mg, 0.56 mmol) was dissolved in 3 mL THF and then methyl azidoacetate (85 mg, 0.73 mmol) was added dropwise. Sodium ascorbate (NaVC (2.0 eq) (220 mg, 1.12 mmol) and copper sulfate pentahydrate (180 mg, 0.73 mmol) were dissolved in 3.3 mL H 2 After O, the mixture was added to the reaction system after 55°C water bath for 5 min and reacted at room temperature for 1 h. After the reaction was completed, water and ethyl acetate were added for extraction, and anhydrous Na 2 SO 4The residue was dried, concentrated under reduced pressure, and separated by column chromatography (petroleum ether:ethyl acetate=15:1) to obtain 200 mg of white solid R-5 with a yield of 77%. 1 H NMR (300 MHz, DMSO-d 6 )δ10.42(s,1H),8.58(s,1H),8.18(dd,J=16.7,8.6Hz,2H),7.98(d,J=8.1Hz,1 H),7.90(d,J=9.1Hz,1H),7.81(s,1H),7.52(ddd,J=8.1,6.7,1.2Hz,1H),7.42 –7.36(m,2H),7.29–7.24(m,1H),6.95(dd,J=18.5,8.5Hz,2H),5.31(d,J=6.7H z,4H),4.72(d,J=5.9Hz,1H),4.58(d,J=5.9Hz,1H),3.66(s,3H),2.85(s,3H).

[0059] Example 5 Synthesis of Compound (R)-2-(4-((3'-formyl-2'-hydroxy-[1,1'-dinaphthyl]-2-oxy)methyl)-1H-1,2,3-triazol-1-yl)acetate

[0060] Compound R-5 (200 mg, 0.39 mmol) was dissolved in 2 mL DCM, and 1 mL trifluoroacetic acid (CF) was added dropwise to the solution. 3 COOH) and reacted at room temperature for 5 h. After the reaction, saturated NaHCO 3 Quench, add water and ethyl acetate to extract, anhydrous Na 2 SO 4 The residue was dried, concentrated under reduced pressure, and separated by column chromatography (petroleum ether: ethyl acetate: triethylamine = 5:1:0.05) to obtain 150 mg of white solid R-6 with a yield of 82%. 1 H NMR (300 MHz, DMSO-d 6 )δ10.31(s,1H),10.14(s,1H),8.61(s,1H),8.13–8.07(m,2H),7.97(d,J=8.1Hz,1H),7.79(d,J=9.1Hz,1H),7.73(s,1H), 7.40–7.33(m,3H),7.25(ddd,J=8.2,6.7,1.4Hz,1H),7.00–6.83(m,2H),5.31(s,2H),5.24(d,J=1.8Hz,2H),3.67(s,3H).

[0061] Example 6 Preparation of Chiral Recognition Solution

[0062] 1. Preparation of chiral recognition solution

[0063] (1) Accurately weigh 1.4 mg of compound R-6 into a 5 mL centrifuge tube and add 3 mL of methanol solution to make 1×10 -3 mol / L solution is recorded as solution A.

[0064] (2) Accurately weigh 2.43 mg of valine enantiomers into 5 mL centrifuge tubes and add 3 mL of water to make 1×10 - 3 mol / L solutions are recorded as solution B1 and solution B2.

[0065] (3) Accurately weigh 7.34 mg of anhydrous zinc acetate and place it in a 5 ml centrifuge tube. Add 3 mL of water to make 1×10 - 3 mol / L solution is recorded as solution C.

[0066] (4) Add 10 μL of solution A and 10 μL of solution C to two 1.5 mL centrifuge tubes, respectively. Add 30 μL of solution B1 to one of them and 30 μL of solution B2 to the other. Then add methanol to both centrifuge tubes to make the total liquid volume 1 mL. This is the chiral recognition solution. Oscillate the centrifuge tubes to mix the solutions evenly. Let stand for 3 h. ex =270 nm, slit: 5 / 5 nm for identification of chiral amino acids by fluorescence spectroscopy.

[0067] The chiral recognition mixed solution of (D / L-threonine) enantiomers, methionine (D / L-methionine) enantiomers, arginine (D / L-arginine) enantiomers, phenylalanine (D / L-phenylalanine) enantiomers, tyrosine (D / L-tyrosine) enantiomers, tryptophan (D / L-tryptophan) enantiomers, leucine (D / L-leucine) enantiomers, and glutamine (D / L-glutamine) enantiomers remains unchanged except for the different types of amino acids.

[0068] Example 7 Chiral Recognition Results

[0069] Table 1 Detailed information of chiral recognition results

[0070]

[0071] As can be seen from Table 1, the chiral fluorescent probe R-6 has a certain recognition effect on amino acids at low concentrations, and has the advantages of high sensitivity and wide recognition range.

[0072] Example 8 Quantitative Analysis of Enantiomeric Composition Using Chiral Fluorescent Probe

[0073] Take the above solutions A, B1, B2 and C, add methanol and water to dilute, and prepare 1mL of 4% water / methanol mixed solution, in which compound R-6 (1×10 -5 mol / L, 1 equivalent), total amount of L- / D-valine (1×10 -5 mol / L, 1 equivalent), zinc acetate (1×10 -5 mol / L, 1 equivalent). Then, fluorescence spectroscopy test was performed to explore the quantitative analysis results of the composition of valine enantiomers by probe R-6.

[0074] Fluorescence test conditions: SpectraMax iD5 microplate detection system (ELISA reader), room temperature, excitation wavelength λ ex =270nm, slit: 5 / 5nm, emission wavelength λ em =570nm,

[0075] like Fig.10 As shown in the figure, compound R-6 is mixed with valine enantiomers, and the change in fluorescence intensity of the mixed system at 570 nm is related to a certain concentration (1×10 -5 mol / L) of the valine enantiomer mixture solution showed a linear relationship. This indicates that under certain conditions, the fluorescent probe R-6 can accurately detect the mixture ratio of valine enantiomers. It further indicates that compound R-6 has a high sensitivity and can be used to determine the enantiomeric purity at a very low concentration, which has broad application prospects in real life.

[0076] The protection content of the present invention is not limited to the above embodiments. Without departing from the spirit and scope of the inventive concept, changes and advantages that can be thought of by those skilled in the art are included in the present invention and are protected by the attached claims.

Claims

1. A binaphthol derivative, characterized in that, the binaphthol derivative is shown as formula I:

2. A preparation method of the binaphthol derivative according to claim 1, characterized in that, the preparation method comprises the following steps: Step (1): The compound (R)-1,1'-bi-2-naphthol, N,N-diisopropylethylamine, and bromomethyl methyl ether undergo a substitution reaction to obtain the compound (R)-2'-methoxymethoxy-1,1'-dinaphthalen-2-ol; Step (2): The compound (R)-2'-methoxymethoxy-1,1'-dinaphthalen-2-ol, anhydrous n-butyllithium, and anhydrous N,N-dimethylformamide undergo a Bouveault aldehyde synthesis reaction to obtain the compound (R)-2'-hydroxy-2-methoxymethoxy-1,1'-binaphthalene-3-carbaldehyde; Step (3): The compound (R)-2'-hydroxy-2-methoxymethoxy-1,1'-binaphthalene-3-carbaldehyde, anhydrous potassium carbonate, and 3-bromopropyne undergo a substitution reaction in acetone to obtain the crude product of the compound (R)-2-methoxymethoxy-2-(prop-2-yn-1-yloxy)-1,1'-dinaphthalene-3-carbaldehyde; Step (4): Copper sulfate pentahydrate is reduced to active copper by sodium ascorbate in water, and then it is added to the tetrahydrofuran solution of the compound (R)-2-methoxymethoxy-2-(prop-2-yn-1-yloxy)-1,1'-dinaphthalene-3-carbaldehyde and methyl azidoacetate to undergo a click chemical reaction to obtain the compound (R)-methyl 2-(4-((((3'-formyl-2'-methoxymethoxy)-[1,1'-binaphthalene]-2-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)acetate; Step (5): The compound (R)-methyl 2-(4-((((3'-formyl-2'-methoxymethoxy)-[1,1'-binaphthalene]-2-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)acetate undergoes a hydrolysis reaction in trifluoroacetic acid to obtain the compound (R)-methyl 2-(4-((3'-formyl-2'-hydroxy-[1,1'-binaphthalene]-2-yloxy)methyl)-1H-1,2,3-triazol-1-yl)acetate, which is the compound shown as formula I.

3. According to the preparation method of the binaphthol derivative described in claim 2, characterized in that, the specific steps of step (1) are as follows: The compound (R)-1,1'-bi-2-naphthol and N,N-diisopropylethylamine were dissolved in tetrahydrofuran, and after stirring and dissolving, bromomethyl methyl ether was slowly added dropwise thereto, and stirred at 0°C for 10 minutes, and then stirred at room temperature for 30 minutes; after the reaction was completed, water and ethyl acetate were added for extraction, and anhydrous Na 2 SO 4 After drying, the solvent was removed under reduced pressure and separated by column chromatography to obtain a white solid (R)-2'-methoxymethoxy-1,1'-dinaphth-2-ol; Among them, the molar ratio of the compound (R)-1,1'-bi-2-naphthol to N,N-diisopropylethylamine is 1:1.5 to 1:2.0; the molar ratio of the compound (R)-1,1'-bi-2-naphthol to bromomethyl methyl ether is 1:3 to 1:1.

5.

4. According to the preparation method of the binaphthol derivative described in claim 2, characterized in that, the specific steps of step (2) are as follows: N 2 Under protection, compound (R)-2'-methoxymethoxy-1,1'-dinaphth-2-ol was dissolved in anhydrous tetrahydrofuran, anhydrous n-butyl lithium was slowly added dropwise, stirred at 0°C for 30 min, stirred at room temperature for 1 h, anhydrous N,N-dimethylformamide was slowly added dropwise, and stirred at room temperature for 45 min; saturated NH 4 The reaction was quenched with Cl, extracted with ethyl acetate, and anhydrous Na 2 SO 4 The product was dried, concentrated under reduced pressure, and separated by column chromatography to obtain a yellow solid (R)-2'-hydroxy-2-methoxymethoxy-1,1'-binaphthyl-3-carboxaldehyde; Among them, the molar ratio of the compound (R)-2'-methoxymethoxy-1,1'-dinaphthalen-2-ol to anhydrous n-butyllithium is 1:2 to 1:5; the molar ratio of the compound (R)-2'-methoxymethoxy-1,1'-dinaphthalen-2-ol to anhydrous N,N-dimethylformamide is 1:1 to 1:

2.

5. The method for preparing the binaphthol derivative according to claim 2, It is characterized in that The specific steps of step (3) are as follows: N 2 Under protection, compound (R)-2'-hydroxy-2-methoxymethoxy-1,1'-binaphthyl-3-carboxaldehyde and anhydrous potassium carbonate were dissolved in acetone, and then 3-bromopropyne was added dropwise, and refluxed at 55°C overnight; after the reaction was completed, water and ethyl acetate were added for extraction, and anhydrous Na 2 SO 4 The mixture was dried and concentrated under reduced pressure to obtain a pale yellow solid crude product of (R)-2-methoxymethoxy-2-(propyl-2-yn-1-oxy)-1,1'-dinaphthalene-3-carboxaldehyde; Among them, the molar ratio of compound (R)-2'-hydroxy-2-methoxymethoxy-1,1'-binaphthyl-3-carboxaldehyde to anhydrous potassium carbonate is 1:1.5 to 1:2.0, and the molar ratio of compound (R)-2'-hydroxy-2-methoxymethoxy-1,1'-binaphthyl-3-carboxaldehyde to 3-bromopropyne is 1:1.2 to 1:1.

5.

6. The method for preparing the binaphthol derivative according to claim 2, It is characterized in that The specific steps of step (4) are as follows: The crude product of compound (R)-2-methoxymethoxy-2-(propyl-2-yn-1-oxy)-1,1'-dinaphthalene-3-carboxaldehyde was dissolved in tetrahydrofuran and methyl azidoacetate was added dropwise; sodium ascorbate and copper sulfate pentahydrate were dissolved in H 2 After O, the mixture was added into the reaction system at 55°C water bath for 5 min, and the reaction was continued at room temperature for 1 h. After the reaction was completed, water and ethyl acetate were added for extraction, and anhydrous Na 2 SO 4 The mixture was dried, concentrated under reduced pressure, and separated by column chromatography to obtain a white solid (R)-2-(4-((((3'-formyl-2'-methoxymethoxy)-[1,1'-dinaphthyl]-2-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)acetic acid methyl ester; wherein the molar ratio of copper sulfate pentahydrate to sodium ascorbate is 1:1 to 1:5, the molar ratio of the compound (R)-2-methoxymethoxy-2-(propyl-2-yn-1-oxy)-1,1'-dinaphthyl-3-carboxaldehyde to methyl azidoacetate is 1:1.0 to 1:1.5, and the molar ratio of the compound (R)-2-methoxymethoxy-2-(propyl-2-yn-1-oxy)-1,1'-dinaphthyl-3-carboxaldehyde to sodium ascorbate is 1:1.5 to 1:2.

0.

7. Use of the binaphthol derivative according to claim 1 as a chiral fluorescent probe in identifying chiral amino acids, It is characterized in that The chiral amino acids are threonine, methionine, arginine, valine, phenylalanine, tyrosine, tryptophan, leucine and glutamine.

8. The use according to claim 7, It is characterized in that The fluorescence detection conditions are as follows: a 4% water / methanol solution mixed solution is used as the system, and the concentration of the binaphthol derivative or its stereoisomer represented by formula I in the system is 1×10 -5 mol / L, zinc ion concentration is 1×10 -5 mol / L, in the presence of zinc ions, at the excitation wavelength λ ex =270 nm, slit: 5 / 5 nm for identification of chiral amino acids by fluorescence spectroscopy.

9. Use of the binaphthol derivative according to claim 1 as a chiral fluorescence sensor in the quantitative analysis of chiral amino acids, It is characterized in that The chiral amino acids are threonine, methionine, arginine, valine, phenylalanine, tyrosine, tryptophan, leucine and glutamine.

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