CN113233966B

CN113233966B - Chiral fluorescence sensor, preparation method thereof and application thereof in chiral amino acid recognition

Info

Publication number: CN113233966B
Application number: CN202110545651.9A
Authority: CN
Inventors: 戴振亚; 何敬杰; 解妍
Original assignee: China Pharmaceutical University
Current assignee: China Pharmaceutical University
Priority date: 2021-05-19
Filing date: 2021-05-19
Publication date: 2022-03-08
Anticipated expiration: 2041-05-19
Also published as: CN113233966A

Abstract

The invention mainly relates to synthesis of a novel fluorescent sensor, and the novel fluorescent sensor is applied to identification of chiral amino acid. TPE derivative groups with AIE effect are connected with chiral biphenyl naphthol to successfully obtain a series of novel chiral AIE active probes. The probes have good recognition effect on amino acid and have good applicability, selectivity and repeatability. At 1x10^‑5At low mol/L concentration in Zn²⁺Under the action of (3), probe 5 can be used as a fluorescence sensor of arginine, and the enantiomer composition of the arginine can be qualitatively analyzed. Experiments prove that the probe obtained by combining the fragment with the chirality and the fragment with the aggregation-induced emission characteristic can be applied to the field of chiral identification, and a novel, practical and effective means is provided for chiral identification.

Description

Chiral fluorescence sensor, preparation method thereof and application thereof in chiral amino acid recognition

Technical Field

The invention belongs to the field of fluorescent compounds, and particularly relates to a chiral fluorescent sensor, a preparation method thereof and application thereof in chiral amino acid identification.

Background

Molecular recognition is the process by which receptors selectively bind to substrates and produce specific functions. Both the transmission of information in the organism and the synthesis of proteins have strict directionality and selectivity, and here, the binding between the receptor and the substrate has a crucial meaning. Since most of biomolecules are chiral molecules, chiral recognition is very important in the life process. At present, the specific gravity of chiral drugs in the medicines on the market is getting larger and larger. In the asymmetric synthesis of chiral drugs, chiral amino acids are often used as chiral precursors and chiral catalyst ligands. Therefore, chiral recognition of amino acids has attracted a great deal of attention.

Over the last two decades, the research and application of fluorescent probes in enantioselective recognition of chiral compounds has progressed greatly. The fluorescent probe has potential application in the aspects of rapid analysis of asymmetric reaction and monitoring of chiral molecules in a biological system, however, the chiral fluorescent probe has the problems of less number and higher recognition condition.

Disclosure of Invention

The invention aims to connect a derivative with a binaphthol group and tetraphenyl ethylene to obtain a novel chiral fluorescence sensor. Under the action of zinc ions, the chiral fluorescent sensor has a good identification effect on various amino acids, has good applicability, selectivity and repeatability, and can be applied to identification of chiral amino acids.

In order to realize the purpose of the invention, the invention provides the following technical scheme:

the first object of the present invention is to provide a binaphthol derivative or a stereoisomer thereof, wherein the binaphthol derivative is represented by formula I:

the second purpose of the invention is to provide a preparation method of the binaphthol derivative or the stereoisomer thereof, wherein the synthetic route is as follows:

further, the method comprises the following steps:

s1 phenolic hydroxyl protection: dissolving sodium hydride in an anhydrous tetrahydrofuran solution, wherein the concentration of the sodium hydride in the anhydrous tetrahydrofuran solution is 0.03-0.1 g/ml, and preferably, the concentration of the sodium hydride in the anhydrous tetrahydrofuran solution is 0.05 g/ml. And (3) reducing the temperature to 0 ℃, dropwise adding the R/S-binaphthol solution dissolved in anhydrous tetrahydrofuran into the anhydrous tetrahydrofuran solution dissolved in sodium hydride under the protection of nitrogen, wherein the concentration of the R/S-binaphthol in the anhydrous tetrahydrofuran solution is 0.15-0.25 g/ml, preferably, the concentration of the R/S-binaphthol in the anhydrous tetrahydrofuran solution is 0.2g/ml, and after dropwise adding, the concentration of the R/S-binaphthol in the whole anhydrous tetrahydrofuran reaction system is 0.04-0.077 g/ml. Preferably, the concentration of the R/S-binaphthol in the whole anhydrous tetrahydrofuran reaction system is 0.067 g/ml. Stirring for 10 minutes, stirring for 1 hour at room temperature, then reducing the temperature to 0 ℃, slowly adding bromomethyl ether, keeping the temperature for 1 hour, stirring overnight at room temperature, after the reaction is finished, adding water into the reaction liquid, extracting with ethyl acetate, washing with a saturated sodium chloride solution once, drying with anhydrous sodium sulfate, removing the solvent by spin-drying, and purifying by column chromatography, wherein the column chromatography liquid is petroleum ether and ethyl acetate in a volume ratio of 15:1, to obtain white solid R/S-2,2 '-bis (methoxymethoxy) -1, 1' -binaphthyl, and the mass ratio of R/S-binaphthol, sodium hydride and bromomethyl ether is 1: 3.5-4.5: 2.5-3.5;

s2 introduction of aldehyde group: under the protection of nitrogen, R/S-2,2 '-bis (methoxymethoxy) -1, 1' -binaphthyl obtained from S1 is dissolved in anhydrous tetrahydrofuran, the concentration of the R/S-2,2 '-bis (methoxymethoxy) -1, 1' -binaphthyl in the anhydrous tetrahydrofuran is 0.04-0.08 g/ml, and preferably, the concentration of the R/S-2,2 '-bis (methoxymethoxy) -1, 1' -binaphthyl in the anhydrous tetrahydrofuran is 0.05 g/ml. Cooling to 0 ℃, slowly adding N-butyllithium, keeping for 30 minutes, removing the ice bath, reacting for 2 hours, cooling to 0 ℃, slowly adding anhydrous N, N-dimethylformamide, keeping for 1 hour, removing the ice bath, stirring at room temperature overnight, after the reaction is finished, quenching a saturated ammonium chloride solution, separating an organic layer, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing a solvent by spinning, purifying by column chromatography, wherein chromatography liquid is petroleum ether and ethyl acetate with a volume ratio of 10:1, and yellow solid R/S-2,2' -bis (methoxymethoxy) - [1,1' -dinaphthalene ] -3,3' -dicarboxaldehyde is obtained; the mass ratio of R/S-2,2 '-bis (methoxy) -1, 1' -binaphthyl, N-butyl lithium and anhydrous N, N-dimethylformamide is 1: 12-13.5: 3-4.5;

s3 introduction of bromine: under the protection of nitrogen, R/S-2,2' -bis (methoxymethoxy) - [1,1' -dinaphthalene ] -3,3' -diformaldehyde obtained in S2 is dissolved in dichloromethane, the concentration of the R/S-2,2' -bis (methoxymethoxy) - [1,1' -dinaphthalene ] -3,3' -diformaldehyde in dichloromethane is 0.02-0.04 g/ml, and the concentration of the R/S-2,2' -bis (methoxymethoxy) - [1,1' -dinaphthalene ] -3,3' -diformaldehyde in dichloromethane is preferably 0.033 g/ml. Dropwise adding liquid bromine, heating and refluxing for 10 hours, after the reaction is finished, quenching with sodium sulfite with the mass fraction of 20%, separating organic layers, extracting with dichloromethane, combining the organic layers, drying with anhydrous sodium sulfate, removing the solvent by spin drying, and purifying by column chromatography, wherein the chromatography liquid is petroleum ether and ethyl acetate with the volume ratio of 10: 1; obtaining yellow solid R/S-6,6 '-dibromo-2, 2' -dihydroxy- [1,1 '-dinaphthalene ] -3,3' -dicarboxaldehyde; the mass ratio of R/S-2,2' -bis (methoxymethoxy) - [1,1' -dinaphthalene ] -3,3' -dicarbaldehyde to bromine is 1: 22-28;

s4suzuki coupling: under the protection of nitrogen, dissolving R/S-6,6 '-dibromo-2, 2' -dihydroxy- [1,1 '-dinaphthalene ] -3,3' -dicarbaldehyde obtained in S3, 1- (4-phenylboronic acid pinacol ester) -1,2, 2-tetraphenylethylene, potassium carbonate and palladium tetratriphenylphosphine in a tetrahydrofuran-water solution, wherein the volume ratio of tetrahydrofuran to water is 5:1, and the concentration of R/S-6,6 '-dibromo-2, 2' -dihydroxy- [1,1 '-dinaphthalene ] -3,3' -dicarbaldehyde in the tetrahydrofuran-water solution is preferably 0.04-0.07 g/ml, and the R/S-6,6 '-dibromo-2, 2' -dihydroxy- [1, the concentration of 1 '-binaphthyl ] -3,3' -dicarboxaldehyde in the tetrahydrofuran aqueous solution was 0.05 g/ml. The weight ratio of R/S-6,6 '-dibromo-2, 2' -dihydroxy- [1,1 '-dinaphthalene ] -3,3' -dicarboxaldehyde, 1- (4-phenylboronic acid pinacol ester) -1,2, 2-tetraphenylethylene, potassium carbonate and tetratriphenylphosphine palladium is 1: 2-3.5: 4.5-6: 0.1. Heating and refluxing for 24 hours at 80 ℃; after the reaction is finished, water quenching is carried out, an organic layer is separated, ethyl acetate is used for extraction, the organic layer is combined, anhydrous sodium sulfate is dried, a solvent is removed by spin drying, column chromatography purification is carried out, and chromatographic solutions are petroleum ether and ethyl acetate with the volume ratio of 5:1, so that a final product, namely a yellow solid, namely R/S-2,2 '-dihydroxy-6, 6' -di (1- (4-phenylboronic acid pinacol ester)) - [1,1 '-binaphthyl ] -3,3' -dicarboxaldehyde, is obtained, namely the binaphthol derivative shown in formula I or a stereoisomer thereof; .

The third purpose of the invention is to provide the application of the binaphthol derivative or the stereoisomer thereof as a chiral fluorescence sensor in identification of chiral amino acids.

Further, the application comprises the following steps of taking a sample water solution to be detected, adding a dimethyl sulfoxide solution containing the binaphthol derivative shown in the formula I or a stereoisomer thereof, adding zinc ions to obtain a mixed system, wherein the volume ratio of water in the mixed system is 1%, and the mixed system is used for exciting the wavelength lambda _exc460 nm, slit: and identifying whether the sample to be detected contains chiral amino acid or not by using a fluorescence spectrum method at 5/5 nm.

Further, the concentration of the binaphthol derivative represented by the formula I or the stereoisomer thereof in a dimethyl sulfoxide solution is 1X10^-5mol/L～2×10^-5mol/L, concentration of zinc ion is 1X10^-5mol/L～2×10^-5mol/L。

Further, the range of detection of the chiral amino acid by the binaphthol derivative or the stereoisomer thereof is 1 × 10^- ⁵mol/L～3×10^-5mol/L。

Furthermore, when the fluorescence intensity is obviously changed, the sample to be detected comprises chiral amino acid.

Further, the chiral amino acid is one or more of serine, threonine, alanine, valine, arginine and histidine.

The inventor shows through experiments that the temperature is 1 multiplied by 10^-5At low mol/L concentration, the binaphthol derivative shown in the formula I or the stereoisomer thereof can be used as a chiral recognition fluorescence sensor of threonine, and the composition of enantiomers can be qualitatively analyzed.

Compared with the prior art, the technical scheme of the invention has the beneficial effects that:

1. the compound used in the invention is cheap and easy to obtain, the economic benefit is high, and the post-treatment operation is simple and convenient and is easy to repeat.

2. Most preferablyThe final product realizes the ring combination of binaphthol and tetraphenylethylene at low concentration of 1 × 10^-5mol/L, has good selectivity and applicability to chiral amino acid in the presence of zinc ions, and the detection limit reaches 1 multiplied by 10^-5mol/L。

The abbreviations referred to in the present invention have the following meanings:

AIE fluorescence aggregation Induction

TPE tetraphenylethylene

THF tetrahydrofuran

DMSO dimethyl sulfoxide

Drawings

The compound R-5 in FIG. 1 has a fluorescence change curve with fluorescence aggregation induction property;

FIG. 1(a) is a graph showing the water volume fraction (f)_w) Variation, R-5 (1.0X 10)^-5mol/L) in THF-H₂Change curve of fluorescence in O-mixed solution (lambda)_ex＝355nm,ex/em slits 5/5nm)；

FIG. 1 (b). lambda_maxFluorescence curve for R-5 as a function of water volume fraction at 469 nm.

FIG. 2 λ_maxFluorescence change curve of S-5 as a function of water volume fraction at 379 nm.

FIG. 3 shows Zn being contained²⁺In the solution (2), the probe R-5 recognizes the change in fluorescence of the serine enantiomer.

FIG. 4 shows Zn being contained²⁺The probe R-5 recognizes the fluorescence change curve of the threonine enantiomer.

FIG. 5 shows Zn being contained²⁺In the solution (2), the probe R-5 recognizes the fluorescence change curve of the alanine enantiomer.

FIG. 6 shows Zn being contained²⁺In the solution (2), the probe R-5 recognizes the change in the fluorescence of the valine enantiomer.

FIG. 7 shows that Zn is contained²⁺In the solution (2), the probe R-5 recognizes the fluorescence change curve of the arginine enantiomer.

Detailed Description

Synthetic route for fluorescent molecules:

EXAMPLE 1 Synthesis of intermediate Compound R-1

Dissolving sodium hydride (1.04g,26mmol) in 20ml of anhydrous tetrahydrofuran, reducing the temperature to 0 ℃, slowly adding a solution of R-0(2g,6.98mmol) dissolved in 10ml of anhydrous tetrahydrofuran, namely an anhydrous tetrahydrofuran solution of (R) -binaphthol under the protection of nitrogen, and mixing to obtain a mixture with the concentration of the (R) -binaphthol in the whole anhydrous tetrahydrofuran reaction system of 0.067 g/ml; stirring was carried out for 10 minutes at 0 ℃ with the ice bath removed and the reaction stirred at room temperature for 1 hour, then cooled to 0 ℃ and bromomethyl ether (2.4g,19.2mmol) was added slowly and the reaction was left for 1 hour with the ice bath removed and stirred at room temperature overnight. After the reaction is finished, water quenching is added, an organic layer is separated, ethyl acetate is extracted for three times, the organic layer is combined, a saturated sodium chloride solution is washed once, dried by anhydrous sodium sulfate and spin-dried to remove the solvent, a light yellow crude product is obtained, and column chromatography purification (the volume ratio of petroleum ether to ethyl acetate is 15:1) is carried out to obtain 2.5g of white solid R-1, wherein the yield is 95.6%. In this example, the ratio of the amounts of (R) -binaphthol, sodium hydride, and bromomethyl methyl ether was 1:3.8: 2.8.

R-1 spectrum data:¹H NMR(300MHz,Chloroform-d)δ8.05～7.88(m,4H),7.63(d,J＝9.0Hz,2H),7.40(ddd,J＝8.1,6.6,1.4Hz,2H),7.29～7.18(m,4H),5.14(d,J＝6.8Hz,2H),5.03(d,J＝6.8Hz,2H),3.20(s,6H).

EXAMPLE 2 Synthesis of intermediate Compound R-2

The compound R-1 from example 1, i.e. (R)2,2 '-bis (methoxymethoxy) -1, 1' -binaphthyl (2.5g,6.68mmol) was dissolved in 50ml of anhydrous tetrahydrofuran under nitrogen protection, reduced to 0 deg.C, N-butyllithium (10.2ml,85mmol) (2.5M in hexanes) was slowly added, maintained for 30 minutes, the ice bath was removed, the reaction was allowed to react for 2 hours, reduced to 0 deg.C, anhydrous DMF (1.92ml,24.9mmol) was slowly added, maintained for 1 hour, the ice bath was removed, and the mixture was stirred at room temperature overnight. After the reaction is finished, quenching with a saturated ammonium chloride solution, separating an organic layer, extracting with ethyl acetate for three times, combining the organic layers, drying with anhydrous sodium sulfate, removing the solvent by rotary drying to obtain a light yellow crude product, and purifying by column chromatography (the volume ratio of petroleum ether to ethyl acetate is 10:1) to obtain 865mg of yellow oily liquid R-2, namely (R) -2,2' -bis (methoxymethoxy) - [1,1' -dinaphthalene ] -3,3' -dicarbaldehyde with the yield of 30.1%. In this example, the ratio of the amounts of (R) -2,2 '-bis (methoxymethoxy) -1, 1' -binaphthyl, N-butyllithium and anhydrous N, N-dimethylformamide was 1:12.8:3.8

R-2 spectrum data:¹H NMR(300MHz,Chloroform-d)δ(ppm)10.60(s,2H),8.66(s,2H),8.16～8.10(m,2H),7.57(ddd,J＝8.2,6.8,1.3Hz,2H),7.48(ddd,J＝8.3,6.8,1.4Hz,2H),7.30–7.23(m,2H),4.78～4.73(d,J＝6.3Hz,4H),2.92(s,6H).

EXAMPLE 3 Synthesis of intermediate Compound R-3

Under nitrogen protection, the compound R-2, i.e. (R) -2,2' -bis (methoxymethyloxy) - [1,1' -bisnaphthalene ] -3,3' -dicarbaldehyde (865mg,2mmol) was dissolved in 26ml of dichloromethane, and liquid bromine (1.3ml,50.6mmol) was added thereto, followed by heating and refluxing for 10 hours. After the reaction is finished, quenching with 20% by mass of sodium sulfite, separating an organic layer, extracting with dichloromethane for three times, combining the organic layers, drying with anhydrous sodium sulfate, removing the solvent by rotary drying to obtain a yellow crude product, and purifying by column chromatography (the volume ratio of petroleum ether to ethyl acetate is 10:1) to obtain 497mg of yellow solid powder R-3, namely, (R) -6,6 '-dibromo-2, 2' -dihydroxy- [1,1 '-dinaphthalene ] -3,3' -dicarboxaldehyde, with the yield of 49.5%. In this example, the ratio of the amounts of (R) -2,2' -bis (methoxymethyloxy) - [1,1' -binaphthyl ] -3,3' -dicarbaldehyde to bromine was 1:25.3

R-3 spectrum data:¹H NMR(300MHz,Chloroform-d)δ(ppm)10.67(s,2H),10.22(s,2H),8.29(s,2H),8.18(d,J＝2.0Hz,2H),7.55(ddd,J＝21.8,9.1,2.0Hz,2H),7.09(d,J＝9.1Hz,2H).

EXAMPLE 4 Synthesis of the end product R-5

Under the protection of nitrogen, the compound R-3, namely (R) -6,6 '-dibromo-2, 2' -dihydroxy- [1,1 '-dinaphthalene ] -3,3' -dicarboxaldehyde (100mg,0.2mmol), the compound 4, namely 1- (4-phenylboronic acid pinacol ester) -1,2, 2-tetraphenylethylene (229mg,0.5mmol), potassium carbonate (146mg,1.06mmol), tetratriphenylphosphine palladium (23.3mg,0.02mmol), is dissolved in 15ml of tetrahydrofuran-water (volume ratio of tetrahydrofuran to water is 5:1) solution, the concentration of (R) -6,6 '-dibromo-2, 2' -dihydroxy- [1,1 '-dinaphthalene ] -3,3' -dicarboxaldehyde in the tetrahydrofuran-water solution is 0.05g/ml, heated to reflux at 80 ℃ for 24 hours. After the reaction is finished, water quenching is carried out, an organic layer is separated, ethyl acetate is extracted for three times, the organic layer is combined, anhydrous sodium sulfate is dried, a solvent is removed by spinning, a dark brown solid is obtained, and 120mg of yellow solid R-5, namely the binaphthol derivative shown in the formula I, is obtained through column chromatography purification (the volume ratio of petroleum ether to ethyl acetate is 5: 1). The yield was 59.8%. In this example, the ratio of the amounts of (R) -6,6 '-dibromo-2, 2' -dihydroxy- [1,1 '-binaphthyl ] -3,3' -dicarboxaldehyde, 1- (4-phenylboronic acid pinacol ester) -1,2, 2-tetraphenylethylene, potassium carbonate, and tetrakistriphenylphosphine palladium was 1:2.5:5.3:0.1

R-5 spectrum data:¹H NMR(300MHz,Chloroform-d)δ(ppm)10.66(s,2H),10.24(s,2H),8.41(s,2H),8.19(d,2H，J＝1.8Hz),7.71-7.66(d,2H J＝1.9Hz),7.49–7.44(m，4H),7.20–7.06(m，38H).

EXAMPLE 5 Synthesis of the final product S-5

Referring to the synthesis of the compound R-5 in examples 1 to 4, the starting material (R) -binaphthol is only replaced with (S) -binaphthol, so as to obtain a target product which is a pale yellow solid S-5, namely, a binaphthol derivative represented by formula i, with a yield of 61.2%.

S-5 spectrogram data:¹H NMR(300MHz,ppm in CDCl₃)δ10.68(s,2H),10.23(s,2H),8.40(s,2H),8.18(d,J＝1.8Hz,2H),7.71-7.66(d,J＝1.9Hz,2H),7.49–7.44(m，4H),7.23–7.08(m,38H).

example 6 fluorescence aggregation induction property test:

a test solution for fluorescence aggregation inducing property of compound R-5 prepared in example 4 was prepared as an example: accurately weighing compound R-54.01 mg, placing in a 5ml centrifuge tube, adding 4ml THF solution to prepare 1x10^-3mol/L solution. 400 μ l of the solution was put into a 5ml centrifuge tube and 3.6ml THF was added to prepare 1X10^-4mol/L solution. Then respectively placing 300 mul of the solution into ten 5ml centrifuge tubes, respectively adding 2.7, 2.4, 2.1, 1.8, 1.5, 1.2, 0.9, 0.6, 0.3 and 0ml of THF solution, then adding deionized water until the total liquid volume in each centrifuge tube is 3ml, and oscillating the centrifuge tubes to uniformly mix the solution, namelyObtaining mixed solution with water content of 0, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80% and 90%, respectively, and the solution concentration is 1x10^-5mol/L. And finally, pouring the mixed solutions into quartz cuvettes respectively for fluorescence spectrum test.

The results show that: to compound R-5(1X 10)^-5mol/L) of the compound R-5, and the poor solvent water is continuously added into the THF solution, and as the volume fraction of water is continuously increased, the compound R-5 starts to be continuously aggregated in the mixed solvent due to the hydrophobicity of the structure of the compound, the solution gradually becomes turbid from clarification, the fluorescence intensity of the mixed solution also shows remarkable change, and the compound R-5 has AIE properties (figure 1).

The fluorescence aggregation inducing property of S-5 was tested by preparing a solution for testing the fluorescence aggregation inducing property of the reference compound R-5. The results are shown in FIG. 2, which shows that compound S-5(1X 10)^-5mol/L) THF solution, adding poor solvent water continuously, with the increasing of the volume fraction of water, the compound S-5 begins to gather continuously in the mixed solvent due to the hydrophobicity of the compound structure, the solution gradually becomes turbid from clarification, the fluorescence intensity of the mixed solution also shows obvious change, and the compound S-5 has AIE property.

Example 7 chiral identification solution formulation

1. Preparing a mixed solution of a compound R-5 and D/L arginine:

1) accurately weighing compound R-54.01 mg, placing in a 5ml centrifuge tube, adding 4ml DMSO solution to prepare 1x10^-3The mol/L solution is designated as tube A.

2) Accurately weighing 6.97mg of arginine enantiomer respectively, placing in a 5ml centrifuge tube, adding 4ml of water to prepare 1x10^-2The mol/L solutions were designated as bottle B1 and bottle B2. 400. mu.l of each of bottles B1 and B2 was placed in a 5ml centrifuge tube, and 3.6ml of water was added to prepare a 1X10^-3The mol/L solution is designated as tube B1-1 and tube B2-1.

3) Accurately weighing anhydrous zinc acetate 7.34mg, placing in 5ml centrifuge tube, adding 4ml water to obtain a mixture of 1 × 10^-2The mol/L solution is designated as tube C. 400. mu.l of each of the obtained solutions was put into a 5ml centrifuge tube and 3.6ml of water was added to prepare a 1 Xtube10^-3mol/L solution, denoted as tube C-1

4) Taking 5ml two centrifuge tubes, adding 30 mul of solution in tube A and 60 mul of solution in tube C-1 into each tube, adding 30 mul of solution in tube B1-1 and tube B2-1 respectively, and adding DMSO into each centrifuge tube until the total liquid volume is 3ml to prepare 1x10^-5The test system of mol/L is characterized in that a centrifugal tube is oscillated to uniformly mix the solution, the solution is kept stand for 3 hours and is subjected to excitation wavelength lambda _exc460 nm, slit: the fluorescence spectrum test was carried out at 5/5 nm.

2. Referring to the preparation of the mixed solution of the compound R-5 and the D/L-arginine, the chiral recognition mixed solution of the compound R-5 and the serine enantiomer (D/L-serine), the alanine enantiomer (D/L-alanine) and the valine enantiomer (D/L-valine) is respectively prepared, and the rest is not changed except for different types of amino acids.

3. Referring to the preparation of the mixed solution of the compound R-5 and the D/L-arginine, chiral recognition mixed solutions of the compound S-5 and a histidine enantiomer (D/L-histidine) valine enantiomer (D/L-valine) are respectively prepared for fluorescence spectrum test.

Example 8 results of chiral identification

The details of the chiral discrimination are shown in Table 1.

TABLE 1 results of chiral recognition

^aRatio of fluorescence intensity of amino acid enantiomer 1/enantiomer 2(λ 570nm)

^b[ Probe]Is ═ enantiomer]

As can be seen from Table 1, probe R-5 has a certain recognition effect on chiral amino acids at low concentrations, and has the advantages of high sensitivity and wide recognition range (FIGS. 3 to 7).

Under the same conditions, probe S-5 also had a recognition effect on the chiral amino acids histidine, alanine, valine and arginine, probe S-5 had a recognition effect on D/L histidine, the ratio of the fluorescence intensity of D-histidine to that of L-histidine was 2.7, and the recognition effect on D-histidine was higher than that of L-histidine. For the valine enantiomer, the probe S-5 also had a recognition effect on D/L valine, wherein the ratio of the fluorescence intensity of D-valine to that of L valine was 3.0, and the recognition effect on D valine was higher than that of L valine.

The invention discloses a binaphthol derivative shown as a formula I or a stereoisomer thereof. The binaphthol derivative is obtained by coupling reaction of a chiral binaphthol derivative and tetraphenylethylene. The invention also discloses an application of the binaphthol derivative shown as the formula I or a stereoisomer thereof as a chiral fluorescence sensor in chiral amino acid recognition, the binaphthol derivative can be applied to the field of chiral recognition under the action of zinc ions, has a good recognition effect on various amino acids, and has good applicability, selectivity and repeatability. At low concentrations, the binaphthol derivatives of the present invention can be used as fluorescence sensors for arginine to perform qualitative analysis on the enantiomeric composition thereof.

Claims

1. A binaphthol derivative or a stereoisomer thereof, wherein the binaphthol derivative is represented by formula i:

2. the process for producing a binaphthol derivative or a stereoisomer thereof according to claim 1, wherein the synthesis route is as follows:

3. a process for the preparation of a binaphthol derivative or a stereoisomer thereof according to claim 2, comprising the steps of:

s1 phenolic hydroxyl protection: dissolving sodium hydride in an anhydrous tetrahydrofuran solution, wherein the concentration of the sodium hydride in the anhydrous tetrahydrofuran solution is 0.03-0.1 g/ml; reducing the temperature to 0 ℃, and dropwise adding an R/S-binaphthol solution dissolved in anhydrous tetrahydrofuran into a tetrahydrofuran solution dissolved in anhydrous sodium hydride under the protection of nitrogen, wherein the concentration of R/S-binaphthol in the R/S-binaphthol solution dissolved in anhydrous tetrahydrofuran is 0.15-0.25 g/ml; after the dropwise addition is finished, the concentration of the R/S binaphthol in the whole anhydrous tetrahydrofuran reaction system is 0.04-0.067 g/ml; stirring for 10 minutes at 0 ℃, stirring for 1 hour at room temperature, then reducing the temperature to 0 ℃, slowly adding bromomethyl ether, keeping the temperature for 1 hour, stirring overnight at room temperature, after the reaction is finished, adding water into the reaction liquid, extracting with ethyl acetate, washing with a saturated sodium chloride solution once, drying with anhydrous sodium sulfate, removing the solvent by spin-drying, and purifying by column chromatography, wherein the column chromatography liquid is petroleum ether and ethyl acetate with the volume ratio of 15:1 to obtain a white solid R/S-2,2 '-bis (methoxymethoxy) -1, 1' -binaphthol, and the mass ratio of the R/S-binaphthol, sodium hydride and bromomethyl ether is 1: 3.5-4.5: 2.5-3.5;

s2 introduction of aldehyde group: under the protection of nitrogen, dissolving R/S-2,2 '-bis (methoxymethoxy) -1, 1' -binaphthyl obtained from S1 in anhydrous tetrahydrofuran, wherein the concentration of the R/S-2,2 '-bis (methoxymethoxy) -1, 1' -binaphthyl in the anhydrous tetrahydrofuran is 0.04-0.08 g/ml, reducing the temperature to 0 ℃, slowly adding N-butyllithium, keeping for 30 minutes, removing the ice bath, reacting for 2 hours, reducing the temperature to 0 ℃, slowly adding anhydrous N, N-dimethylformamide, keeping for 1 hour, removing the ice bath, stirring at room temperature overnight, after the reaction is finished, quenching with a saturated ammonium chloride solution, separating an organic layer, extracting with ethyl acetate, drying with anhydrous sodium sulfate, spin-drying to remove a solvent, purifying by column chromatography, wherein a chromatographic solution comprises petroleum ether and ethyl acetate in a volume ratio of 10:1, obtaining yellow solid R/S-2,2' -bis (methoxyl group) - [1,1' -dinaphthalene ] -3,3' -dicarboxaldehyde; the mass ratio of R/S-2,2 '-bis (methoxy) -1, 1' -binaphthyl, N-butyl lithium and anhydrous N, N-dimethylformamide is 1: 12-13.5: 3-4.5;

s3 introduction of bromine: under the protection of nitrogen, dissolving R/S-2,2 '-bis (methoxymethoxy) - [1,1' -dinaphthalene ] -3,3 '-diformaldehyde obtained from S2 in dichloromethane, wherein the concentration of the R/S-2,2' -bis (methoxymethoxy) - [1,1 '-dinaphthalene ] -3,3' -diformaldehyde in dichloromethane is 0.02-0.04 g/ml; dropwise adding liquid bromine, heating and refluxing for 10 hours, after the reaction is finished, quenching with sodium sulfite with the mass fraction of 20%, separating organic layers, extracting with dichloromethane, combining the organic layers, drying with anhydrous sodium sulfate, spin-drying to remove the solvent, and purifying by column chromatography, wherein the chromatographic solution is petroleum ether and ethyl acetate with the volume ratio of 10: 1; obtaining yellow solid R/S-6,6 '-dibromo-2, 2' -dihydroxy- [1,1 '-dinaphthalene ] -3,3' -dicarboxaldehyde; the ratio of the amount of R/S-2,2' -bis (methoxymethyloxy) - [1,1' -dinaphthalene ] -3,3' -dicarbaldehyde to the amount of bromine is 1:22 to 28,

s4, suzuki coupling: under the protection of nitrogen, dissolving R/S-6,6 '-dibromo-2, 2' -dihydroxy- [1,1 '-dinaphthalene ] -3,3' -dicarboxaldehyde obtained from S3, 1- (4-phenylboronic acid pinacol ester) -1,2, 2-tetraphenylethylene, potassium carbonate and palladium tetratriphenylphosphine in a tetrahydrofuran-water solution, wherein the volume ratio of tetrahydrofuran to water is 5:1, and the concentration of R/S-6,6 '-dibromo-2, 2' -dihydroxy- [1,1 '-dinaphthalene ] -3,3' -dicarboxaldehyde in the tetrahydrofuran-water solution is 0.04-0.07 g/ml; the mass ratio of R/S-6,6 '-dibromo-2, 2' -dihydroxy- [1,1 '-dinaphthalene ] -3,3' -dicarboxaldehyde, 1- (4-phenylboronic acid pinacol ester) -1,2, 2-tetraphenylethylene, potassium carbonate and tetratriphenylphosphine palladium is 1: 2-3.5: 4.5-6: 0.1; heating and refluxing for 24 hours at 80 ℃; after the reaction is finished, water quenching is carried out, an organic layer is separated, ethyl acetate is used for extraction, the organic layer is combined, anhydrous sodium sulfate is dried, a solvent is removed by spin drying, column chromatography purification is carried out, and chromatographic solutions are petroleum ether and ethyl acetate with the volume ratio of 5:1, so that a final product, namely a yellow solid, namely R/S-2,2 '-dihydroxy-6, 6' -di (1- (4-phenylboronic acid pinacol ester)) - [1,1 '-dinaphthalene ] -3,3' -dicarboxaldehyde, is obtained, namely the binaphthol derivative shown in formula I or a stereoisomer thereof.

4. The process for producing a binaphthol derivative or a stereoisomer thereof according to claim 3, wherein the concentration of sodium hydride in the anhydrous tetrahydrofuran solution is 0.05g/ml in S1.

5. The process for producing a binaphthol derivative or a stereoisomer thereof according to claim 3, wherein the concentration of R/S-binaphthol in the R/S-binaphthol solution dissolved in anhydrous tetrahydrofuran is 0.2g/ml in S1.

6. The process for producing a binaphthol derivative or a stereoisomer thereof according to claim 3, wherein the concentration of R/S-binaphthol in S1 is 0.05g/ml in the whole reaction system of anhydrous tetrahydrofuran.

7. The process for producing a binaphthol derivative or a stereoisomer thereof according to claim 3, wherein the concentration of R/S-2,2 '-bis (methoxymethoxy) -1, 1' -binaphthyl in anhydrous tetrahydrofuran is 0.05g/ml in S2.

8. The process for producing a binaphthol derivative or a stereoisomer thereof according to claim 3, wherein the concentration of R/S-2,2' -bis (methoxymethoxy) - [1,1' -binaphthyl ] -3,3' -dicarbaldehyde in methylene chloride is 0.033 g/ml.

9. The process for producing a binaphthol derivative or a stereoisomer thereof according to claim 3, wherein the concentration of the R/S-6,6 '-dibromo-2, 2' -dihydroxy- [1,1 '-binaphthyl ] -3,3' -dicarbaldehyde in the tetrahydrofuran-water solution is 0.05 g/ml.

10. Use of the binaphthol derivative or a stereoisomer thereof according to claim 1 as a chiral fluorescence sensor for identifying chiral amino acids.

11. The application according to claim 10, characterized in that it comprises the following steps: taking a sample water solution to be detected, adding dimethyl sulfoxide solution containing binaphthol derivative shown in formula I or stereoisomer thereof, adding zinc ions to obtain a mixed system, wherein the volume ratio of water in the mixed system is 1%, and mixing the mixed system at an excitation wavelength lambda_exc460 nm, slit: and identifying whether the sample to be detected contains chiral amino acid or not by using a fluorescence spectrum method at 5/5 nm.

12. The use according to claim 10, characterized in that the compound of formula IThe concentration of binaphthol derivative or its stereoisomer in dimethyl sulfoxide solution is 1 × 10^-5mol/L～2×10^-5mol/L, concentration of zinc ion is 1X10^-5mol/L～2×10^-5mol/L。

13. The use according to claim 10, wherein the binaphthol derivative or a stereoisomer thereof detects a chiral amino acid in a range of 1x10^-5mol/L～3×10^-5mol/L。

14. The use according to claim 10, wherein a significant change in fluorescence intensity indicates the presence of a chiral amino acid in the sample.

15. Use according to claim 10, characterized in that the chiral amino acid is a combination of one or more of serine, threonine, alanine, valine, arginine, histidine.