JP7138887B2 - Compound, and material and method for detecting sugar compound using the same - Google Patents

Description

TECHNICAL FIELD The present invention relates to a compound, and a material and method for detecting a sugar compound using the compound.

π-conjugated oligomers are a general term for compounds with repeating multiple bonds such as double and triple bonds and single bonds. Therefore, it is applied as a material for organic light-emitting devices, nanodevices, and the like. As an example of such applications, for example, Patent Document 1 discloses a compound in which an aromatic ring and a butadiene skeleton are alternately bonded to form a main chain as a π-conjugated polymer useful for forming a polymeric organic semiconductor. Proposed.

Such a π-conjugated oligomer not only controls the luminescent properties and electronic properties but also imparts molecular recognition ability depending on the introduced side chain. For example, well-designed π-conjugated oligomers are expected to exhibit fluorescence quenching upon strong interaction with biopolymers and metal ions. For this reason, various π-conjugated oligomers have been synthesized and applied to chemical sensor materials.

By the way, sugars such as glucose are widely known as important substances in living organisms, and are said to be involved in various life phenomena such as skeletal formation and immunity, in addition to being an energy source for living organisms. In addition, in the study of the behavior of substances in vivo, including the examination of specific diseases such as diabetes, there is a demand for means for detecting sugar compounds from biological samples such as blood and urine. Against this background, many methods for detecting sugar compounds have been proposed, including Patent Document 2, for example.

JP 2016-65112 A JP-A-06-229925

The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a novel compound suitable for detecting sugar compounds and a method for detecting sugar compounds using the same.

The present inventors have made intensive studies to solve the above problems, and found that p-phenyleneethenylene (also referred to as p-phenylenevinylene) derivatives, which are π-conjugated oligomers themselves having fluorescence emission properties, and It was found that a p-phenyleneethynylene derivative having a phenylboronic acid moiety bound thereto changes its fluorescence significantly in the presence of sugar compounds such as glucose and fructose, and is useful as a reagent for detecting sugar compounds. rice field. The present invention has been completed based on such findings, and provides the following.

（上記一般式（Ａ４）中、各Ｒはそれぞれ独立に炭素数１２～２０のアルキルオキシ基であり、Ｘ^－はピリジニウムカチオンの対イオンであり、Ｒ^１は水素原子、又は炭素数１２～２０のアルキルオキシ基であり、各ｍは、それぞれ独立に、上記Ｒ ^１ が炭素数１２～２０のアルキルオキシ基である場合には０～４の整数、その他の場合には１～４の整数であり、ｎは１～５の整数である。上記一般式（Ｂ４）中、各Ｒはそれぞれ独立に炭素数１２～２０のアルキルオキシ基であり、Ｘ^－はピリジニウムカチオンの対イオンであり、各ｍはそれぞれ独立に１～４の整数であり、ｎは１～５の整数である。）
(1) The present invention is a compound represented by the following general formula (A4) or (B4).

(In the above general formula (A4), each R is independently an alkyloxy group having 12 to 20 carbon atoms , X ^- is a counter ion of a pyridinium cation, R ¹ is a hydrogen atom, or and each m is independently an integer of 0 to 4 when R ¹ is an alkyloxy group having 12 to 20 carbon atoms, and an integer of 1 to 4 in other cases. and n is an integer of 1 to 5. In the general formula (B4), each R is independently an alkyloxy group having 12 to 20 carbon atoms , X ^- is a counterion of a pyridinium cation, and each m is each independently an integer of 1 to 4, and n is an integer of 1 to 5.)

(2) The present invention also provides a detection material for sugar compounds comprising the compound described in (1) above.

( 3) The present invention also provides a method for adding a sample to be measured to a solution containing the compound described in (1) above, and examining a change in fluorescence emission caused by the compound to detect the sugar compound contained in the sample to be measured. It is also a method for detecting a sugar compound characterized by detecting its presence.

INDUSTRIAL APPLICABILITY According to the present invention, a novel compound suitable for detection of sugar compounds, and means for detecting sugar compounds using the novel compounds suitable for detecting sugar compounds, and means for detecting sugar compounds using the same are provided. be done.

FIG. 1 is a chart showing changes in the fluorescence spectrum of Compound 1 upon addition of sugar when glucose is used as the sugar compound. FIG. 2 is a chart showing changes in the fluorescence spectrum of compound 1 with the addition of sugar when fructose is used as the sugar compound. FIG. 3 is a chart showing changes in the fluorescence spectrum of Compound 2 with the addition of sugar when glucose is used as the sugar compound. FIG. 4 is a chart showing changes in the fluorescence spectrum of compound 2 with the addition of sugar when fructose is used as the sugar compound. FIG. 5 is a chart showing changes in the fluorescence spectrum of compound 2 with the addition of sugar when γ-cyclodextrin is used as the sugar compound. FIG. 6 is a chart showing changes in the fluorescence spectrum of compound 4 with the addition of sugar when glucose is used as the sugar compound.

An embodiment of the compound of the present invention, a material for detecting a sugar compound, and an embodiment of a method for detecting a sugar compound of the present invention are described below. It should be noted that the present invention is not limited to the following embodiments and modes, and can be implemented with appropriate modifications within the scope of the present invention.

[Compound]
First, one embodiment of the compound of the present invention is described. The compound of the present invention is a phenyleneethynylene derivative or a phenyleneethynylene derivative represented by the following general formula (A1) or (B1). π-conjugated oligomers, such as phenyleneethynylene and phenyleneethynylene, have well-developed π-conjugated systems and exhibit fluorescence emission. In the compounds of the present invention, Ar ³ in the general formulas (A1) and (B1) may have a phenylboronic acid group (as an example for understanding, —C ₆ H ₄ B(OH) ₂ is include.). A phenylboronic acid group has two hydroxyl groups bonded to a boron atom, and since these two hydroxyl groups form a covalent cyclic ester structure with polyol compounds such as sugar compounds, it can be used as a sensor unit for sugar compounds. Function. On the other hand, when a sugar compound binds to the phenylboronic acid group in the compound of the present invention, the state of fluorescence emission of the compound of the present invention changes greatly. This is thought to be caused by a change in the electronic state of the π-conjugated system or by the distortion of the conjugated system caused by cross-linking of the compound of the present invention due to many hydroxyl groups contained in the sugar compound. The present invention was completed by paying attention to such properties, and the compounds of the present invention are useful as sensors for sugar compounds.

Among the compounds represented by the general formulas (A1) and (B1), the compound represented by the general formula (A1) will be described first.

In general formula (A1) above, Ar ¹ is a substituent and/or an aromatic ring which may have a heteroatom in the ring. “The substituent and/or the ring may have a heteroatom” means that the aromatic ring represented by Ar ¹ (condition A) is bound to a substituent and (condition B) constitutes a ring If there is a condition that one or more of the carbon atoms is replaced with a heteroatom, one or both of the above (Condition A) and (Condition B) may be satisfied, or both may be satisfied. It means that you don't have to. When Ar ¹ has a substituent, examples thereof include an alkyl group having 1 to 20 carbon atoms, an oxyalkyl group, an alkyl alcohol group, and a benzyl group. The heteroatom substituting the carbon atom constituting the aromatic ring of Ar ¹ includes a nitrogen atom, an oxygen atom, a sulfur atom and the like, and among these, a nitrogen atom is preferred. When Ar ¹ contains such a heteroatom, it is preferred that the methylene chain linking Ar ³ and Ar ¹ is attached to this heteroatom. As a result, this heteroatom becomes a cation center and improves the solubility of the compound represented by the general formula (A1). However, even if this compound does not have such a cation center and does not have sufficient solubility, if this compound can be present on the substrate surface by means of vapor deposition on the substrate, it can be used as a sugar compound sensor. It is possible to utilize this compound. Ar ¹ , which is an aromatic ring, includes a pyridine ring, a benzene ring, a naphthalene ring and the like, and among these, a pyridine ring is preferred.

In the general formula (A1), the number of Ar ² is plural depending on the value of n, which will be described later. In this case, each Ar ² is independent and may be the same or different. Ar ² is an aromatic ring optionally having a substituent. Phenyleneethynylene derivatives and phenyleneethynylene derivatives generally have poor solubility, but the solubility can be increased by introducing a relatively long-chain substituent to Ar ² . Examples of such substituents include alkyl groups and alkyloxy groups having 1 to 20 carbon atoms. In addition, a hetero atom may be included in the middle of the carbon chain of these substituents. Among these, -OC ₁₂ H ₂₅ , which is an alkyloxy group having 12 carbon atoms, and -OC ₁₈ H ₃₇ , which is an alkyloxy group having 18 carbon atoms, are preferable. Examples of the aromatic ring constituting Ar ² include a benzene ring and a naphthalene ring, and among these, a benzene ring is preferred. n represents the number of repetitions of Ar ² and is an integer of 1-5. Among these, it is preferable that n is 1.

The bond between Ar ¹ and Ar ² is an ethenylene group (--CH=CH--; also called a vinylene group) or an ethynylene group (--C.ident.C--). The following bond represented by a combination of a double bond and a dashed line between carbon atoms present between Ar ¹ and Ar ² in general formula (A1) represents a double bond or a triple bond.

A plurality of such bonds are present depending on the value of n, and in such cases, each bond is independently arbitrarily selected from double bonds and triple bonds. When this bond is a double bond, the bond is either cis-type or trans-type, preferably trans-type. In the above general formula (A1), this bond is represented by a trans-type bond angle for convenience, but this bond may be a cis-type bond, and when this bond is a triple bond, the bond angle is 180 °. This also applies to (A2), (B1) and (B2) described later.

In general formula (A1) above, R ¹ is a hydrogen atom, an alkyl group having 1 to 20 carbon atoms which may contain a hetero atom in the middle of the carbon chain, or an alkyloxy group. When R ¹ is an alkyl group having 1 to 20 carbon atoms or an alkyloxy group, the solubility of the compound represented by the general formula (A1) can be enhanced.

In general formula (A1) above, Ar ³ is an optionally substituted aromatic ring having at least one —B(OH) ₂ . This —B(OH) ₂ is called a boronic acid group for convenience. A boronic acid group has high reactivity with a sugar compound having multiple hydroxyl groups, and forms a cyclic ester by forming a covalent bond with the sugar compound. That is, Ar ³ serves as a sugar compound detection unit in the compounds of the present invention. The aromatic ring for Ar ³ includes a benzene ring, a naphthalene ring and the like, and among these, a benzene ring is preferred. The aromatic ring in Ar ³ may have a substituent, and examples of such substituents are the same as those for Ar ¹ above. More specifically, Ar ³ preferably includes the following phenylboronic acid units.

Among these phenylboronic acid units, the following p-phenylboronic acid units are particularly preferred as Ar ³ .

More specifically, the compound represented by the general formula (A1) includes a compound represented by the following general formula (A2).

In general formula (A2) above, Ar ² , Ar ³ , R ¹ and n are the same as described for general formula (A1) above.

In general formula (A2) above, Ar ¹ is an optionally substituted aromatic ring in which at least one atom constituting the skeleton of the aromatic ring is nitrogen. Such Ar ¹ can include a pyridine ring. In general formula (A2) above, the bond represented by the wavy line is a single bond to the nitrogen atom contained in the aromatic ring skeleton of ^Ar1 . That is, Ar ³ will be attached to the nitrogen atom contained in the ring of Ar ¹ via a methylene group. Therefore, the nitrogen atom contained in Ar ¹ becomes a cation center and improves the solubility of the compound represented by the general formula (A2). The compound represented by (A2) also includes an anion that serves as a counterion for this cation.

More specifically, the compound represented by the general formula (A2) includes a compound represented by the following general formula (A3).

In general formula (A3), Ar ¹ , Ar ² , Ar ³ , R ¹ , n, and bonds represented by wavy lines are the same as those described for general formulas (A1) and (A2).

This general formula (A3) specifies that the double bond or triple bond in the above general formula (A2) is a double bond. This double bond is trans-type.

More specifically, the compound represented by the general formula (A3) includes a compound represented by the following general formula (A4).

In general formula (A4) above, R ¹ and n are the same as those described in general formulas (A1) to (A3) above. In the above general formula (A4), when there are a plurality of R, each independently represents an alkyl group or an alkyloxy group having 1 to 20 carbon atoms which may contain a heteroatom in the middle of the carbon chain. Phenyleneethenylene derivatives are generally poorly soluble compounds, but the presence of R makes it possible to improve their solubility. n benzene rings are each independent when there are a plurality of them. That is, these benzene rings may be the same or different. m is an integer of 0 to 4, and when n is 2 or more, each m is independently determined. Preferably m is 0 or 2.

X ^- is the counterion of the pyridinium cation. Examples of such counterions include chloride ion, bromide ion, hexafluorophosphate ion, nitrate ion, sulfate ion, and phosphate ion.

Specific examples of the compound represented by the general formula (A4) include those represented by the following chemical formula. Needless to say, the compounds of the present invention are not limited to these examples.

Using the compound represented by the above chemical formula as an example, the chemical formula below shows an example of the reaction between the sugar compound and the compound of the present invention. As shown in the chemical formula below, two molecules of the compound represented by the above general formula (A1) can bind to one molecule of a sugar compound, which causes energy transfer from the conjugated skeleton to the sugar compound, resulting in a change in fluorescence. do.

As an example of a route for synthesizing the compounds described above, the scheme shown below can be shown.

Next, the compound represented by the general formula (B1) will be described.

In general formula (B1) above, Ar ¹ is a substituent and/or an aromatic ring which may have a heteroatom in the ring. “The substituent and/or the ring may have a heteroatom” means that the aromatic ring represented by Ar ¹ (condition A) is bound to a substituent and (condition B) constitutes a ring If there is a condition that one or more of the carbon atoms is replaced with a heteroatom, one or both of the above (Condition A) and (Condition B) may be satisfied, or both may be satisfied. It means that you don't have to. When Ar ¹ has a substituent, examples thereof include an alkyl group having 1 to 20 carbon atoms, an oxyalkyl group, an alkyl alcohol group, and a benzyl group. The heteroatoms substituting the carbon atoms constituting the aromatic ring of Ar ¹ include nitrogen, oxygen and sulfur atoms, among which nitrogen atoms are preferred. When Ar ¹ contains such a heteroatom, it is preferred that the methylene chain linking Ar ³ and Ar ¹ is attached to this heteroatom. As a result, this heteroatom becomes a cation center and improves the solubility of the compound represented by the general formula (B1). However, even if this compound does not have such a cation center and does not have sufficient solubility, it can be used as a sugar compound sensor, etc., if it is possible to make this compound exist on the substrate surface by means such as vapor deposition on the substrate. It is possible to utilize this compound. Ar ¹ , which is an aromatic ring, includes a pyridine ring, a benzene ring, a naphthalene ring, etc. Among them, a pyridine ring is preferred.

In the above general formula (B1), the number of Ar ² is plural depending on the value of n. In this case, each Ar ² is independent and may be the same or different. Ar ² is an aromatic ring optionally having a substituent. Phenyleneethynylene derivatives and phenyleneethynylene derivatives generally have poor solubility, but their solubility can be increased by introducing a relatively long-chain substituent to Ar ² . Examples of such substituents include alkyl groups and alkyloxy groups having 1 to 20 carbon atoms. In addition, a hetero atom may be included in the middle of the carbon chain of these substituents. Among these, -OC ₁₂ H ₂₅ , which is an alkyloxy group having 12 carbon atoms, and -OC ₁₈ H ₃₇ , which is an alkyloxy group having 18 carbon atoms, are preferable. Examples of the aromatic ring constituting Ar ² include a benzene ring and a naphthalene ring, and among these, a benzene ring is preferred. n represents the number of repetitions of Ar ² and is an integer of 1-5. Among these, it is preferable that n is an integer of 1 to 3.

It is an ethenylene group (--CH=CH--) or an ethynylene group (--C.ident.C--) that binds Ar ¹ and Ar ² together. The following bond represented by a combination of a double bond and a dashed line between carbon atoms present between Ar ¹ and Ar ² in general formula (B1) represents a double bond or a triple bond.

A plurality of such bonds are present depending on the value of n, and in such cases, each bond is independently arbitrarily selected from double bonds and triple bonds. When this bond is a double bond, the bond is either cis-type or trans-type, preferably trans-type.

In general formula (B1) above, Ar ³ is an optionally substituted aromatic ring having at least one —B(OH) ₂ . That is, Ar ³ serves as a sugar compound detection unit in the compound of the present invention, as in the general formula (A1). The aromatic ring for Ar ³ includes a benzene ring, a naphthalene ring and the like, and among these, a benzene ring is preferred. The aromatic ring in Ar ³ may have a substituent, and examples of such substituents are the same as those for Ar ¹ above. More specifically, Ar ³ preferably includes the following phenylboronic acid units.

Among these phenylboronic acid units, the following p-phenylboronic acid units are particularly preferred as Ar ³ .

More specifically, the compound represented by the general formula (B1) includes a compound represented by the following general formula (B2).

In general formula (B2) above, Ar ² , Ar ³ and n are the same as described for general formula (B1) above.

In general formula (B2) above, Ar ¹ is an optionally substituted aromatic ring in which at least one atom constituting the skeleton of the aromatic ring is nitrogen. Such Ar ¹ can include a pyridine ring. In general formula (B2) above, the bond represented by the wavy line is a single bond to the nitrogen atom contained in the aromatic ring skeleton of ^Ar1 . That is, Ar ³ will be attached to the nitrogen atom contained in the ring of Ar ¹ via a methylene group. Therefore, the nitrogen atom contained in Ar ¹ becomes a cation center and improves the solubility of the compound represented by the general formula (B2). The compound represented by (B2) also includes an anion that serves as a counterion for this cation.

More preferably, the compound represented by the general formula (B2) is a compound represented by the following general formula (B3).

In general formula (B3) above, Ar ¹ , Ar ² , Ar ³ , n, and bonds represented by wavy lines are the same as those described for general formulas (B1) and (B2) above.

This general formula (B3) specifies that the double bond or triple bond in the above general formula (B2) is a double bond. This double bond is trans-type. Thus, when a compound having two Ar ^3s and a bent structure due to the presence of a trans-type double bond is reacted with a sugar compound, one molecule of the compound is converted to the following per molecule of the sugar compound. and the accompanying distortion of the π-conjugated system strongly quenches the fluorescence of this compound. Thus, such compounds can be expected to have higher sensitivity in detecting sugar compounds. The compounds represented by the reaction formulas below are examples of the compounds of the present invention, and the present invention is not limited thereto.

More specific examples of the compound represented by the general formula (B3) include compounds represented by the following general formula (B4).

In the above general formula (B4), R, when there are more than one, is each independently an alkyl group or an alkyloxy group having 1 to 20 carbon atoms which may contain a heteroatom in the middle of the carbon chain. Phenyleneethenylene derivatives are generally poorly soluble compounds, but the presence of R makes it possible to improve their solubility. n benzene rings are each independent when there are a plurality of them. That is, these benzene rings may be the same or different. n is an integer of 1-5, preferably an integer of about 1-3. m is an integer of 0 to 4, and when n is 2 or more, each m is independently determined. Preferably m is two.

X ^- is the counterion of the pyridinium cation. Examples of such counterions include chloride ion, bromide ion, hexafluorophosphate ion, nitrate ion, sulfate ion, and phosphate ion.

Specific examples of the compound represented by the general formula (B4) include those represented by the following chemical formula. Needless to say, the compounds of the present invention are not limited to these examples.

As an example of a route for synthesizing the compounds described above, the scheme shown below can be shown. In the scheme below, R in compounds 2, 4, 10, 11, 14, 15, 16 and 17 is —C ₁₂ H ₂₅ , and compounds 3, 5, 12, 13, 18, 19, 20, 21 R in is -C ₁₈ H ₃₇ .

[Saccharide compound detection material]
Next, one embodiment of the detection material for sugar compounds of the present invention will be described. The material for detecting sugar compounds of the present invention comprises the compound of the present invention.

The detection material of the present invention may be of any form as long as it contains the compound of the present invention. Examples of the form of such a detection material include, but are not particularly limited to, a solution containing the compound of the present invention, a substrate on which a thin film containing the compound of the present invention is formed, and the like.

As the solution containing the compound of the present invention, an alcohol solution, an alcohol/water mixed solution, and the like are preferable, and examples of such alcohol include methanol, ethanol, propanol, and the like. The concentration of the compound of the present invention in the solution is on the order of 10 ^-7 to 10 ^-4 mol/L. The liquid property of the solution is preferably neutral or basic. By making the solution basic, the reactivity between the sugar compound and the compound of the present invention can be improved.

The thin film containing the compound of the present invention is formed by applying the solution of the present invention to the surface of a substrate and then evaporating the solvent to form a film, or by melting the compound of the present invention and applying it to the surface of the substrate. Examples include those obtained by vapor-depositing the compound of the invention on the surface of a substrate. Such thin films may consist of the compounds of the invention themselves or mixtures of the compounds of the invention with other substances.

In order to detect the presence of a sugar compound using the sugar compound detection material of the present invention, the sample to be measured is brought into contact with or mixed with the detection material, and the compound of the present invention is irradiated with excitation light. Since the compound of the present invention changes fluorescence emission by reacting with a sugar compound, the presence of the sugar compound in the sample to be measured can be detected by observing the change in fluorescence when irradiated with excitation light. .

According to the sugar compound detection material of the present invention, it becomes possible to detect the presence of a sugar compound in a sample to be measured by a simple observation technique of change in fluorescence. In addition, its detection sensitivity is high, and even if the concentration of the sugar compound to be detected is low, it is possible to sufficiently detect it. Therefore, the material for detecting sugar compounds of the present invention is preferably applied, for example, to highly sensitive determination of whether urine or the like contains sugar.

[Method for detecting sugar compound]
Next, one embodiment of the method for detecting sugar compounds of the present invention will be described. The method for detecting a sugar compound of the present invention is performed by adding a sample to be measured to a solution containing the compound of the present invention, and examining the change in fluorescence caused by the compound to detect the presence of the sugar compound contained in the sample to be measured. is detected. Since the details have already been described, the description is omitted here.

EXAMPLES The present invention will be described in more detail with reference to Examples below, but the present invention is not limited to these Examples. The compound numbers shown in the chemical reaction formulas shown in the following synthesis examples correspond to the compound numbers shown in the synthesis schemes of the compounds of the present invention.

[Synthesis Example 1]
・Synthesis of 1-bromo-4-(dodecyloxy)benzene (6)

4-bromophenol (0.5 g, 2.89×10 ⁻³ mol) was dissolved in N,N-dimethylformamide (DMF) to form a solution. 1-bromododecane (0.83 mL, 3.47×10 ⁻³ mol) and potassium carbonate (2.00 g, 1.45×10 ⁻² mol) were added to the solution and stirred at 70° C. overnight. After adding dichloromethane to the reaction mixture for extraction, the organic phase was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (CH ₂ Cl ₂ :hexane=1:2) to obtain compound 6 as a white solid (yield 0.94 g, yield 95.3%).
FT-IR (ATR): 2918 cm ⁻¹ (ν, —CH ₃ ), 1474 cm ⁻¹ (ν, —CH ₂ —CH ₂ —CH ₂ —)

[Synthesis Example 2]
Synthesis of (E)-4-(4-(dodecyloxy)styryl)pyridine (7)

Tris(2-methylphenyl)phosphine was added to a toluene solution (5 mL) of compound 6 (0.3 g, 8.79×10 ⁻⁴ mol) and 4-vinylpyridine (0.11 mL, 1.05×10 ⁻³ mol). (8.0 mg, 2.64×10 ⁻⁵ mol) was added and stirred for 30 minutes under a nitrogen stream. Thereafter, palladium acetate (5.9 mg, 2.64×10 ⁻⁵ mol) and 5 mL of triethylamine (TEA) were added to the reaction solution, and the mixture was stirred and refluxed at 100° C. overnight. After completion of the reaction, the solvent was distilled off under reduced pressure, and purification was performed by silica gel column chromatography (CH ₂ Cl ₂ : methanol = 19:1) to obtain compound 7 as a pale yellow solid (yield: 0.10 g, yield: 31 .3%).
FT-IR (ATR): 2918 cm ⁻¹ (ν, —CH ₃ ), 1408 cm ⁻¹ (ν, —CH ₂ —CH ₂ —CH ₂ —)

[Synthesis Example 3]
Synthesis of (E)-1-(4-bromobenzyl)-4-(4-(dodecyloxy)styryl)pyridin-1-ium bromide (1)

A toluene solution (7 mL) of compound 7 (0.08 g, 2.19×10 ⁻⁴ mol) and p-(bromomethyl)phenylboronic acid (57 mg, 2.64×10 ⁻⁴ mol) was stirred at 120° C. overnight. did. After completion of the reaction, the solvent was distilled off under reduced pressure, acetone was added for purification, and a solid was obtained by filtration. After dissolving this solid in methanol, the solvent was distilled off under reduced pressure to obtain compound 1 as a yellow solid (yield: 0.11 g, yield: 86.6%).
FT-IR (ATR): 3383 cm ⁻¹ (ν, —OH), 2918 cm ⁻¹ (ν, —CH ₃ ), 1598 cm ⁻¹ (ν, pyridine)

[Synthesis Example 4]
・Synthesis of 1,4-diiodo-2,5-dimethoxybenzene (8)

1,4-dimethoxybenzene (2.0 g, 1.45×10 ⁻² mol), iodine (3.68 g, 1.45×10 ⁻² mol) and H ₅ IO ₆ (1.98 g, 8.70× 10 ⁻³ mol) was added to a mixed solution of 30% aqueous sulfuric acid (10 mL), carbon tetrachloride (20 mL) and acetic acid 30 mL, and the mixture was stirred and refluxed at 100° C. for 3 hours. The reaction mixture was then added to ice and stirred overnight. Thereafter, recrystallization was performed twice in ethanol to obtain Compound 8 as a flesh-colored solid (yield: 3.42 g, yield: 60.5%).

[Synthesis Example 5]
・Synthesis of 2,5-diiodobenzene-1,4-diol (9)

Compound 8 (1.0 g, 2.56×10 ⁻³ mol) was dissolved in dichloromethane (20 mL) and stirred in an ice-salt bath for 30 minutes. A solution of 1.0 M BBr ₃ in dichloromethane (6.14 mL, 6.14×10 ⁻³ mol) was added to the solution and stirred overnight. Thereafter, deionized water was added to the reaction mixture until white smoke was no longer produced, and then suction filtration was performed. The obtained solid was vacuum-dried to obtain compound 9 as a white solid (yield: 0.81 g, yield: 87.1%).

[Synthesis Example 6]
・Synthesis of 1,4-bis(dodecyloxy)-2,5-diiodobenzene (10)

1 ^{-bromododecane (0.79 g, 3.31×10 −3 mol} ) and potassium carbonate (1.91 g, 1 .38×10 ⁻² mol) was added and stirred at 70° C. overnight. After adding dichloromethane to the reaction mixture for extraction, the organic phase was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (CH ₂ Cl ₂ :hexane=1:2) to obtain compound 10 as a white solid (0.88 g, 91.7% yield).
FT-IR (ATR): 2920 cm ⁻¹ (ν, —CH ₃ ), 1464 cm ⁻¹ (ν, —CH ₂ —CH ₂ —CH ₂ —)

[Synthesis Example 7]
Synthesis of 4,4′-((1E,1′E)-(2,5-bis(dodecyloxy)-1,4-phenylene)bis(ethene-2,1-diyl))dipyridine (11)

Tris(2-methylphenyl)phosphine was added to a toluene solution (5 mL) of compound 10 (0.2 g, 2.86×10 ⁻⁴ mol) and 4-vinylpyridine (0.073 mL, 6.86×10 ⁻⁴ mol). (2.6 mg, 8.58×10 ⁻⁶ mol) was added and stirred for 30 minutes under a nitrogen stream. After that, palladium acetate (1.9 mg, 8.58×10 ⁻⁶ mol) and 5 mL of TEA were added to the reaction solution, and the mixture was stirred and refluxed at 100° C. overnight. After completion of the reaction, the solvent was distilled off under reduced pressure, and purification was performed by silica gel column chromatography (CH ₂ Cl ₂ : methanol = 19:1) to obtain compound 11 as a yellowish-orange solid (yield: 0.10 g, yield: 53.5%).
FT-IR (ATR): 2916 cm ⁻¹ (ν, —CH ₃ ), 1470 cm ⁻¹ (ν, —CH ₂ —CH ₂ —CH ₂ —)

[Synthesis Example 8]
・4,4′-((1E,1′E)-(2,5-bis(dodecyloxy)-1,4-phenylene)bis(ethene-2,1-diyl)bis(1-(4-boronobenzyl) - synthesis of pyridin-1-ium) bromide (2)

A toluene solution (7 mL) of compound 11 (0.027 g, 4.13×10 ⁻⁵ mol) and p-(bromomethyl)phenylboronic acid (0.021 g, 9.91×10 ⁻⁵ mol) was heated at 120° C. Stir overnight. After completion of the reaction, the solvent was distilled off under reduced pressure, acetone was added for purification, and a solid was obtained by filtration. This solid was recrystallized with ethanol, and the solvent was distilled off under reduced pressure to obtain compound 2 as a red solid (yield: 0.03 g, yield: 66.7%).
FT-IR (KBr): 3380 cm ⁻¹ (ν, —OH), 2924 cm ⁻¹ (ν, —CH ₃ ), 1604 cm ⁻¹ (ν, pyridine)
¹ H-NMR (DMSO-d ₆ , 300.13 MHz): δ = 7.32-8.31 (s, 15H, Ar- H , Py- H , -C H =C H -), 5.75- 5.82 (s, 3H, Ar- H ), 4.00-4.47 (s, 8H, -OC H ₂ -, -OH), 2.50-2.52 (m, 4H, -C H ₂ —), 1.58-1.90 (m, 4H, —OCH ₂ CH ₂ —), 1.40-1.56 (m, 4H, —OCH ₂ CH ₂ CH ₂ —), 1 .18-1.38 (m, 32H, -C H ₂ -), 0.80-0.83 (t, J = 6.00 Hz, 6H, -C H ₃ )

[Synthesis Example 9]
Synthesis of ((2,5-bis(dodecyloxy)-1,4-phenylene)bis(ethylene-2,1-diyl))bis(trimethylsilane) (14)

Compound 10 (0.2 g, 2.86×10 ⁻⁴ mol) was dissolved in TEA (10 mL), copper iodide (1.6 mg, 8.58×10 ⁻⁶ mol) was added to the solution, and nitrogen flow was performed. Stirred for 30 minutes on low. After that, Pd(PPh ₃ ) ₂ Cl ₂ (6.0 g, 8.58×10 ⁻⁶ mol) and trimethylsilylacetylene (0.094 mL, 6.86×10 ⁻⁴ mol) were added to the reaction solution, and Stirring and refluxing was carried out overnight. After the reaction, the solvent was distilled off under reduced pressure, and purification was performed twice by silica gel column chromatography (CH ₂ Cl ₂ : hexane = 1:4) to obtain compound 14 as a pale yellow solid (yield: 0.21 g, yield: 116.6%).
FT-IR (ATR): 2920 cm ⁻¹ (ν, —CH ₃ ), 2359 cm ⁻¹ (ν, —C≡C—), 1458 cm ⁻¹ (ν, —CH ₂ —CH ₂ —CH ₂ —)

[Synthesis Example 10]
・Synthesis of 1,4-bis(dodecyloxy)-2,5-diethynylbenzene (15)

Compound 14 (0.21 g, 3.29×10 ⁻⁴ mol) was dissolved in THF (5 mL) and tetrabutylammonium fluoride (TBAF) (0.79 mL, 7.89×10 ⁻⁴ mol) was added to the solution. was added, and the mixture was stirred for 30 minutes at room temperature in the dark. After the reaction, the solvent was distilled off under reduced pressure, and purification was performed twice by silica gel column chromatography (CH ₂ Cl ₂ : hexane = 1:3) to obtain compound 15 as a pale yellow solid (yield: 0.12 g, yield: 75.0%).
FT-IR (ATR): 3285 cm ⁻¹ (ν, —C≡CH), 2919 cm ⁻¹ (ν, —CH ₃ ), 1499 cm ⁻¹ (ν, —CH ₂ —CH ₂ —CH ₂ —)

[Synthesis Example 11]
・5,5′-((2,5-bis(dodecyloxy)-1,4-phenylene)bis(ethyne-2,1-diyl))bis(1,4-bis(dodecyloxy)-2-iodobenzene ( 16) synthesis

Compound 15 (0.12 g, 2.43×10 ⁻⁴ mol) and compound 10 (0.41 g, 5.82×10 ⁻⁴ mol) were dissolved in toluene (7 mL), and copper iodide (1 .4 mg, 7.29×10 ⁻⁶ mol) was added and stirred for 30 minutes under a nitrogen stream. After that, Pd(PPh ₃ ) ₄ (8.4 mg, 7.29×10 ⁻⁶ mol) and 7 mL of TEA were added to the reaction solution, and the mixture was stirred and refluxed at 90° C. overnight. After the reaction, the solvent was distilled off under reduced pressure, and purification was performed twice by silica gel column chromatography (CH ₂ Cl ₂ : hexane = 1:2) to obtain compound 16 as a yellow solid (yield: 0.14 g, yield: 35 .0%).
FT-IR (ATR): 2921 cm ⁻¹ (ν, —CH ₃ ), 2365 cm ⁻¹ (ν, —C≡C—), 1468 cm ⁻¹ (ν, —CH ₂ —CH ₂ —CH ₂ —)

[Synthesis Example 12]
・4,4′-((1E,1′E)-(((2,5-bis(dodecyloxy)-1,4-phenylene)bis(ethyne-2,1-diyl)bis(2,5-bis) Synthesis of (dodecyloxy)-4,1-phenylene))bis(ethene-2,1-diyl))dipyridine (17)

Tris(2-methylphenyl)phosphine was added to a toluene solution (7 mL) of compound 16 (0.14 g, 8.56×10 ⁻⁵ mol) and 4-vinylpyridine (0.022 mL, 2.05×10 ⁻⁴ mol). (0.78 mg, 2.57×10 ⁻⁶ mol) was added and stirred for 30 minutes under a nitrogen stream. After that, palladium acetate (0.58 mg, 2.57×10 ⁻⁶ mol) and 7 mL of TEA were added to the reaction solution, and the mixture was stirred and refluxed at 100° C. overnight. After completion of the reaction, the solvent was distilled off under reduced pressure, and purification was performed twice by silica gel column chromatography (CH ₂ Cl ₂ : methanol = 19:1) to obtain compound 17 as a yellow solid (yield: 0.03 g, yield: 22.1%).
FT-IR (ATR): 2919 cm ^-1 (ν, -CH ₃ ), 2360 cm ^-1 (ν, -C≡C-), 1594 cm ^-1 (ν, pyridine)

[Synthesis Example 13]
・4,4′-((1E,1′E)-(((2,5-bis(dodecyloxy)-1,4-phenylene)bis(ethyne-2,1-diyl)bis(2,5-bis) Synthesis of (dodecyloxy)-4,1-phenylene))bis(ethene-2,1-diyl))bis(1-(4-boronobenzyl)pyridin-1-ium)bromide (4)

A toluene solution (9 mL) of compound 17 (0.03 g, 1.89×10 ⁻⁵ mol) and p-(bromomethyl)phenylboronic acid (9.7 mg, 4.53×10 ⁻⁵ mol) was heated at 120° C. Stir overnight. After completion of the reaction, the solvent was distilled off under reduced pressure, acetone was added for purification, and a solid was obtained by filtration. After recovering this solid with ethanol, the solvent was distilled off under reduced pressure to obtain compound 4 as a red solid (yield: 0.026 g, yield: 68.4%).
FT-IR (KBr): 3347 cm ⁻¹ (ν, —OH), 2923 cm ⁻¹ (ν, —CH ₃ ), 2354 cm ⁻¹ (ν, —C≡C—)
¹ H-NMR (DMSO-d ₆ , 300.13 MHz): δ = 6.23-7.97 (s, 18H, Ar- H , Py- H , -C H =C H -), 5.36- 5.38 (s, Py- H ), 3.66-4.12 (s, 16H, -OC H ₂ -, -O H ), 2.19-2.20 (m, 4H, -C H ₂ -), 1.78-1.94 (m, 12H, -OCH ₂ CH ₂ -), 1.40-1.64 (m, 12H, -OCH ₂ CH ₂ CH ₂ -), 1.26 −1.40 (m, 96H, −C H ₂ −), 0.88−0.95 (t, J=3.00 Hz, 18H, −C H ₃ )

[Addition test of sugar compound to compound 1]
A methanol solution of compound 1 (1.72×10 ⁻⁵ mol/L) was prepared. This solution is called Solution 1A (“A” lchol solution of Compound 1). Next, a solution was prepared by mixing solution 1A with water or a 0.1 M sodium hydroxide aqueous solution at a volume ratio of 1:1. The solutions are referred to as Solution 1N (“N” eutral solution of Compound 1) and Solution 1B (“B” asic solution of Compound 1), respectively. Furthermore, solutions were prepared by adding a sugar compound to solution 1N or 1B, and these were called solution 1N+S (“S” ugar”) and solution 1B+S, respectively. The sugar compound used was glucose or fructose. For solution 1N+S, sugar compounds were added at 0.1, 1, 3, 5, and 10 times the molar concentration of compound 1, and for solution 1B+S. added the saccharide compound at a molar concentration of 1 times the molar concentration of Compound 1.

Fluorescence spectra were measured for each of solutions 1A, 1N, 1B, 1N+S and 1B+S when glucose was used as the sugar compound. The measurement results are shown in FIG. The excitation wavelength in fluorescence spectrum measurement was 390 nm, which is the absorption maximum of compound 1.

In FIG. 1, the solid curves are for neutral solutions (1A, 1N and 1N+S) and the dashed curves are for basic solutions (1B and 1B+S). As shown in FIG. 1, compound 1 showed a red-shift of the fluorescence peak with the addition of glucose under neutral conditions (1N→1N+S), and showed a tendency for fluorescence to become stronger as the amount added increased. . This is considered to be due to the formation of a dimer of compound 1 through the sugar compound and the energy transfer, as described below. It should be noted that this red shift already appears markedly with the addition of 0.1-fold molar glucose (order of 10 ⁻⁶ M), indicating that the compound of the present invention has a high ability to recognize sugar compounds. be done. In addition, under basic conditions, no red shift in fluorescence was observed as in the case of glucose, and a decrease in fluorescence intensity (66% decrease) was observed (1B→1B+S).

Next, fluorescence spectra were measured for each of solutions 1A, 1N, 1B, 1N+S and 1B+S when fructose was used as the sugar compound. The measurement results are shown in FIG. The excitation wavelength in fluorescence spectrum measurement was 390 nm, which is the absorption maximum of compound 1A.

In FIG. 2, the solid curves are for neutral solutions (1A, 1N and 1N+S) and the dashed curves are for basic solutions (1B and 1B+S). As shown in FIG. 2, compound 1 showed a red shift in fluorescence peak even when fructose was added under neutral conditions (1N→1N+S), but not as significant as glucose. rice field. On the other hand, under basic conditions, a decrease in fluorescence intensity (79% decrease) was observed with the addition of fructose, and the amount of decrease was greater than that with glucose (1B→1B+S). At this time, it is presumed that a 1:1 compound of sugar compound and fructose is formed as described below.

From the above, it can be seen that compound 1 is excellent in detecting glucose under neutral conditions and excellent in detecting fructose under basic conditions.

[Addition test of sugar compound to compound 2]
A methanol solution (9.24×10 ⁻⁶ mol/L) of compound 2 was prepared, and the same operation as for compound 1 was performed to prepare solutions 2A, 2N, 2B, 2N+S and 2B+S. The sugar compound used here is glucose, fructose or γ-cyclodextrin, and as before, for solution 2N+S, 0.1, 1, 3, 5, and 10 times the molar concentration of compound 2 concentration of sugar compound was added, and for solution 2B+S, sugar compound was added at a molar concentration of 1 times the molar concentration of compound 2.

Fluorescence spectra were measured for each of the solutions 2A, 2N, 2B, 2N+S and 2B+S when glucose was used as the sugar compound. The measurement results are shown in FIG. The excitation wavelength in the fluorescence spectrum measurement was 467 nm, which is the maximum absorption of compound 2.

In FIG. 3, the solid curves are for neutral solutions (2A, 2N and 2N+S) and the dashed curves are for basic solutions (2B and 2B+S). As shown in FIG. 3, compound 2 was observed to show a decrease in fluorescence intensity with an increase in glucose concentration under neutral conditions. This is probably because Compound 2, which has two phenylboronic acid moieties, captures one molecule of glucose with two phenylboronic acid moieties, forming a 1:1 type large cyclic complex as shown below. , energy transfer from compound 2 to glucose and collapse of the conjugated system, resulting in fluorescence quenching. Also, under basic conditions, a decrease in fluorescence intensity (98% decrease) was observed, and the amount of decrease was greater than that for Compound 1.

Next, fluorescence spectra were measured for each of solutions 2A, 2N, 2B, 2N+S and 2B+S when fructose or γ-cyclodextrin was used as the sugar compound. The measurement results are shown in FIG. 4 (fructose) and FIG. 5 (γ-cyclodextrin). The excitation wavelength in the fluorescence spectrum measurement was 467 nm, which is the maximum absorption of compound 2.

As shown in FIGS. 4 and 5, when the sugar compound was fructose or cyclodextrin, unlike the case of glucose, an increase in fluorescence intensity was observed as the concentration of the sugar compound increased. This is probably because fructose and cyclodextrin are less likely to form macrocyclic complexes, and energy transfer is more likely to occur due to 1:2 type dimer formation, as in the case of compound 1 above. Under basic conditions, a decrease in fluorescence intensity (98% decrease) was observed with the addition of fructose, and the amount of decrease was greater than in the case of Compound 1.

[Addition test of sugar compound to compound 4]
A methanol solution (4.95×10 ⁻⁶ mol/L) of compound 4 was prepared, and the same operation as for compound 1 was performed to prepare solutions 4A, 4N, 4B, 4N+S and 4B+S. The sugar compound used here is glucose, and as before, for the solution 4N+S, the sugar compound is added at 0.1, 1, 3, 5, and 10 times the molar concentration of compound 4, For solution 4B+S, the sugar compound was added at 1× molar concentration relative to the molar concentration of compound 4.

Fluorescence spectra were measured for each of the solutions 4A, 4N, 4B, 4N+S and 4B+S when glucose was used as the sugar compound. The measurement results are shown in FIG. The excitation wavelength in the fluorescence spectrum measurement was 467 nm, which is the absorption maximum of Compound 4.

In FIG. 6, the solid curves are for neutral solutions (4A, 4N and 4N+S) and the dashed curves are for basic solutions (4B and 4B+S). As shown in FIG. 6, in compound 4, no proportional relationship was confirmed between the increase in glucose concentration and the increase in fluorescence under neutral conditions, but similar to compounds 1 and 2, sugar under basic conditions A significant decrease in fluorescence intensity with compound addition was observed.

Claims (3)

A compound represented by the following general formula (A4) or (B4).

(In the above general formula (A4), each R is independently an alkyloxy group having 12 to 20 carbon atoms , X ^- is a counter ion of a pyridinium cation, R ¹ is a hydrogen atom, or and each m is independently an integer of 0 to 4 when R ¹ is an alkyloxy group having 12 to 20 carbon atoms, and an integer of 1 to 4 in other cases. and n is an integer of 1 to 5. In the general formula (B4), each R is independently an alkyloxy group having 12 to 20 carbon atoms , X ^- is a counterion of a pyridinium cation, and each m is each independently an integer of 1 to 4, and n is an integer of 1 to 5.) Claim 1 A material for detecting sugar compounds comprising the compounds described. Claim 1 A sugar compound detection characterized by adding a sample to be measured to a solution containing the described compound, and detecting the presence of the sugar compound contained in the sample to be measured by examining a change in fluorescence emission caused by the compound. Method.

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