JP2016155781A - Colorimetry detection type chiral sensor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a colorimetry detection type chiral sensor capable of identifying chirality of a chiral amine compound by change of color tone and fluorescence.SOLUTION: The present invention relates to a colorimetry detection type chiral sensor consisting of a poly(diphenylacetylene) compound represented by the following formula (I) having a mono-direction helical structure. (I), where each symbol is as described in the application. According to the invention, there can be provided a practical chirality sensing method capable of identifying chirality of the chiral amine compound with good sensitivity by reacting a wide range of chiral amine compounds with the chiral sensor to derivatize it and observing color tone of a solution of the derivative, change of fluorescence intensity or the like.SELECTED DRAWING: None

Description

  The present invention relates to a colorimetric detection type chiral sensor comprising a helical poly (diphenylacetylene) compound capable of distinguishing chirality of a chiral amine compound by a change in color tone and fluorescence.

  Organic compounds have the same physical and chemical properties, such as physical properties such as boiling point, melting point, and solubility, but there are many optical isomers that show differences in physiological activity. In the pharmaceutical technical field, differences in pharmacological activity due to the ease of binding to specific receptors in vivo are well studied, and there are significant differences in optical efficacy and toxicity between optical isomers. It is widely known that there are many cases. For this reason, optical isomer sensing technology (technology for determining the chirality of optical isomers), as well as selective synthesis technology of optical isomers, separation technology of optical isomers from racemates, etc. Has been. That is, when a compound in which an optical isomer exists is synthesized or provided, it is possible to determine which chirality the compound has, or whether it is a racemate, etc., with a simple and accurate chirality. The development of the identification method is an extremely important issue.

  Many studies on chirality identification using circular dichroism (CD) spectra that give spectra that directly reflect molecular asymmetry, chirality identification using NMR shift reagents, chiral HPLC, etc. have been reported so far. However, since it is very expensive as a chirality detection device, it cannot be said that it is a simple sensing method. One of the simplest techniques for identifying chirality is a technique for chirality sensing that uses visible color changes.

  As such a technique, a fluorescent chiral sensor utilizing the characteristics of a host-guest complex formation equilibrium reaction with a fluorescent host compound (or polymer) having an optically active crown ether structure has been reported (Patent Documents 1 and 2). These are chiral sensing methods based on molecular recognition by complex formation between an optically active crown ether structure that is a host compound and a chiral primary amine that is a guest compound (identification target). Problems remain such as being easily affected by conditions such as concentration during measurement, and introducing an expensive optically active functional group into the guest recognition site of the host compound.

Japanese Patent No. 3950117 Japanese Patent No. 4545370

  Against this background, the development of practical chiral sensing methods that can easily and easily identify the chirality of various types of chiral compounds at low cost and without using special equipment. It has been demanded.

  The object of the present invention is to utilize a helical poly (diphenylacetylene) compound, which does not have an expensive optically active functional group in itself, to change the chirality of various kinds of chiral amine compounds to a visible color change. It is to provide a simple and practical technique for chiral sensing that can be used and identified.

  As a result of intensive studies under these circumstances, the present inventors have obtained a wide range of chiral amine compounds represented by the following formula (I) having a unidirectionally wound helical structure:

[Where:
R ¹ , R ¹ ′, R ² , R ² ′, R ³ , R ³ ′ R ⁴ and R ⁴ ′ are each independently a hydrogen atom, a halogen atom, an optionally substituted alkyl group, or a substituted group. Represents an optionally substituted cycloalkyl group, an optionally substituted alkoxy group, an optionally substituted alkylthio group, a trisubstituted silyl group, a trisubstituted siloxy group or an optionally substituted acyloxy group; and n is An integer of 10 or more is shown. ]
A poly (diphenylacetylene) compound represented by the formula (hereinafter also referred to as “compound (I)”) or a salt thereof, or a solvate thereof, reacted with a colorimetric detection-type chiral sensor for derivatization. (Amidation) and by observing changes in the color tone and fluorescence of the solution of the derivative, we found for the first time that it is useful as a practical chirality sensing method that can identify chirality of chiral amine compounds with high sensitivity. The present invention has been completed.

That is, the present invention is as follows.
[1] Formula (I) having a unidirectional spiral structure:

[Where:
R ¹ , R ¹ ′, R ² , R ² ′, R ³ , R ³ ′ R ⁴ and R ⁴ ′ are each independently a hydrogen atom, a halogen atom, an optionally substituted alkyl group, or a substituted group. Represents an optionally substituted cycloalkyl group, an optionally substituted alkoxy group, an optionally substituted alkylthio group, a trisubstituted silyl group, a trisubstituted siloxy group or an optionally substituted acyloxy group; and n is An integer of 10 or more is shown. ]
A colorimetric detection-type chiral sensor comprising a poly (diphenylacetylene) compound represented by the formula:
[2] The chiral sensor according to the above [1], wherein R ¹ and R ¹ ′, R ² and R ² ′, R ³ and R ³ ′, and R ⁴ and R ⁴ ′ are the same group,
[3] A step of condensing the carboxy group of the chiral sensor according to the above [1] or [2] and an amino group of the chiral amine compound to amidate, and a change in the color tone of the solution of the amidated compound, and A method for identifying chirality of a chiral amine compound, comprising a step of determining the chirality of the chiral amine compound by fluorescence measurement,
[4] The method according to [3] above, further comprising the step of determining the optical purity of the chiral amine compound from the measurement data of the ultraviolet / visible absorption spectrum, and [5] the compound in which the chiral amine compound contains a primary amino group The method according to [3] or [4] above.

  The colorimetric detection-type chiral sensor comprising the compound (I) of the present invention exhibits a high-sensitivity chirality discrimination ability for a wide range of chiral amine compounds. Specifically, the carboxy group of the chiral sensor of the present invention and the amino group of the chiral amine compound to be identified are condensed and amidated, and the color tone and fluorescence characteristics of the solution of the amidated compound are determined between optical isomers. Therefore, the chirality can be easily identified using the visible color change. In addition, according to the present invention, since the chiral sensor and the chiral amine compound are strongly bonded by a covalent bond, the measurement is performed in comparison with a conventionally known chiral sensor using molecular recognition (non-covalent interaction). Regardless of conditions (concentration, temperature, etc.), even if a very small amount of sample is used, the chirality can be identified with good reproducibility. Furthermore, according to the chirality identification method of the present invention, the change in the absorption maximum wavelength of the ultraviolet / visible absorption spectrum is particularly remarkable in the low enantiomeric excess (low ee) region. There is also an advantage that a sample having a low ee optical purity, which is difficult to measure, can be accurately identified.

It is CD and absorption spectrum of compound (II-1S) and compound (II-1R) measured in tetrahydrofuran or chloroform. a is the CD and absorption spectrum of compound (II-1S) measured in chloroform, b is the CD and absorption spectrum of compound (II-1R) measured in chloroform, c is compound (II −1S) is the CD and absorption spectrum measured in tetrahydrofuran, and d is the CD and absorption spectrum of compound (II-1R) measured in tetrahydrofuran. The color of the solution of Compound (II-1R) and Compound (II-1S) in chloroform (left diagram) and tetrahydrofuran (right diagram) is shown (concentration: 1.0 × 10 ⁻³ M). Fluorescence spectrum (excitation wavelength: 282 nm) in a mixed solution of compound (II-1S) (a) and compound (II-1R) (b) in dimethylformamide / chloroform (2: 8, v / v) (left figure) And the color of each solution of the compound (II-1S) and the compound (II-1R) in a mixed solution of dimethylformamide / chloroform (2: 8, v / v) (concentration: 1.0 × 10 ⁻⁵ M) (Upper part of the right figure) and the color of each solution under the irradiation of ultraviolet light with a wavelength of 365 nm (lower part of the right figure) are shown. The figure on the left shows the change in the maximum wavelength of the absorption spectrum of compound (II-1) measured in chloroform relative to the enantiomeric excess (% ee) of 1- (1-naphthyl) ethylamine (Δλ = compound (II-1) It is the figure which plotted (absorption maximum wavelength of compound-absorption maximum wavelength of compound (II-1S)). The right figure is an enlarged view of the range surrounded by the dotted line in the left figure. It is CD and the absorption spectrum in 25 degreeC of the chloroform solution of the compound (II-6S) whose sample concentration is 2.5 mM, 0.25 mM, and 0.025 mM. It is CD and the absorption spectrum in 25 degreeC of the chloroform solution of the compound (II-6R) whose sample concentration is 2.5 mM, 0.25 mM, and 0.025 mM.

  Details of the present invention will be described below.

(Definition)

  In the present specification, the “halogen atom” means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.

In the present specification, the term “alkyl (group)” means a linear or branched alkyl group having 1 or more carbon atoms, and particularly when there is no limitation on the carbon number range, an _1-20 alkyl group, among _them, more preferably _{C 1-12} alkyl _{group, C 1-6} alkyl groups are particularly preferred.

In the present specification, “C _1-20 alkyl (group)” means a linear or branched alkyl group having 1 to 20 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl. , Sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-ethylpropyl, hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2-ethylbutyl, heptyl Octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, eicosyl and the like.

In the present specification, “C _1-12 alkyl (group)” means a linear or branched alkyl group having 1 to 12 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl. , Sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-ethylpropyl, hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2-ethylbutyl, heptyl Octyl, nonyl, decyl, undecyl, dodecyl and the like.

In the present specification, “C _1-6 alkyl (group)” means a linear or branched alkyl group having 1 to 6 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl. , Sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-ethylpropyl, hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2-ethylbutyl, etc. Can be mentioned.

In the present specification, the “cycloalkyl (group)” means a cyclic alkyl group, and is preferably a C _3-8 cycloalkyl group, particularly when there is no limitation on the carbon number range.

In the present specification, “C _3-8 cycloalkyl (group)” means a cyclic alkyl group having 3 to 8 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like. Is mentioned. Among these, a C _3-6 cycloalkyl group is preferable.

In the present specification, “alkoxy (group)” means a group in which a linear or branched alkyl group is bonded to an oxygen atom, and the carbon number range is not particularly limited, but preferably a C _1-6 alkoxy. It is a group.

In the present specification, “C _1-6 alkoxy (group)” means a linear or branched alkoxy group having 1 to 6 carbon atoms, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, Examples include isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, isopentyloxy, neopentyloxy, hexyloxy and the like. Among these, a C _1-4 alkoxy group is preferable.

In the present specification, “alkylthio (group)” means a group in which a linear or branched alkyl group is bonded to a sulfur atom, and the carbon number range is not particularly limited, but preferably a C _1-6 alkylthio. It is a group.

In the present specification, “C _1-6 alkylthio (group)” means a linear or branched alkylthio group having 1 to 6 carbon atoms, such as methylthio, ethylthio, propylthio, isopropylthio, butylthio, Examples include isobutylthio, sec-butylthio, tert-butylthio, pentylthio, isopentylthio, neopentylthio, hexylthio and the like. Among these, a C _1-4 alkylthio group is preferable.

In the present specification, “alkylsulfonyl (group)” means a group in which a linear or branched alkyl group is bonded to a sulfonyl group, and the carbon number range is not particularly limited, but preferably C _1-6. An alkylsulfonyl group;

In the present specification, “C _1-6 alkylsulfonyl (group)” means a group in which a linear or branched alkyl group having 1 to 6 carbon atoms is bonded to a sulfonyl group, such as methylsulfonyl, Ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl, pentylsulfonyl, isopentylsulfonyl, neopentylsulfonyl, 1-ethylpropylsulfonyl, hexylsulfonyl, isohexylsulfonyl, 1 , 1-dimethylbutylsulfonyl, 2,2-dimethylbutylsulfonyl, 3,3-dimethylbutylsulfonyl, 2-ethylbutylsulfonyl and the like.

In the present specification, “arylsulfonyl (group)” means a group in which an aryl group is bonded to a sulfonyl group, and the carbon number range is not particularly limited, but is preferably a C _6-10 arylsulfonyl group.

In the present specification, the "C _6-10 arylsulfonyl group" means a group "C _6-10 aryl group" is bonded to a sulfonyl group, e.g., phenylsulfonyl, 1-naphthylsulfonyl, 2-naphthylsulfonyl Etc.

In the present specification, “alkylsulfonyloxy (group)” means a group in which an alkylsulfonyl group is bonded to an oxygen atom, and the carbon number range is not particularly limited, but preferably a C _1-6 alkylsulfonyloxy group. It is.

In the present specification, “C _1-6 alkylsulfonyloxy (group)” means a group in which a C _1-6 alkylsulfonyl group is bonded to an oxygen atom. For example, methylsulfonyloxy, ethylsulfonyloxy, propylsulfonyl Examples include oxy, isopropylsulfonyloxy, butylsulfonyloxy and the like.

In the present specification, “arylsulfonyloxy (group)” means a group in which an arylsulfonyl group is bonded to an oxygen atom, and the carbon number range is not particularly limited, but preferably a C _6-10 arylsulfonyloxy group. It is.

In the present specification, “C _6-10 arylsulfonyloxy (group)” means a group in which a C _6-10 arylsulfonyl group is bonded to an oxygen atom, and examples thereof include phenylsulfonyloxy, 1-naphthylsulfonyloxy, 2-naphthylsulfonyloxy and the like can be mentioned.

In the present specification, “acyl (group)” means alkanoyl or aroyl, and the carbon number range is not particularly limited, but is preferably a C _1-7 alkanoyl group or C _7-11 aroyl.

In the present specification, “C _1-7 alkanoyl (group)” is linear or branched formyl or alkylcarbonyl having 1 to 7 carbon atoms, such as formyl, acetyl, propionyl, butyryl, Examples include isobutyryl, pentanoyl, hexanoyl, heptanoyl and the like.

In the present specification, “C _7-11 aroyl (group)” is arylcarbonyl having 7 to 11 carbon atoms, and examples thereof include benzoyl.

In the present specification, “acyloxy (group)” means a group in which an alkanoyl group or an aroyl group is bonded to an oxygen atom, and the carbon number range is not particularly limited, but preferably a C _1-7 alkanoyloxy group or C _7-11 aroyloxy group.

In the present specification, examples of the “C _1-7 alkanoyloxy (group)” include formyloxy, acetoxy, ethylcarbonyloxy, propylcarbonyloxy, isopropylcarbonyloxy, butylcarbonyloxy, isobutylcarbonyloxy, sec-butylcarbonyl. Examples include oxy, tert-butylcarbonyloxy, pentylcarbonyloxy, isopentylcarbonyloxy, neopentylcarbonyloxy, hexylcarbonyloxy and the like.

In the present specification, examples of the “C _7-11 aroyloxy (group)” include benzoyloxy, 1-naphthoyloxy, 2-naphthoyloxy and the like.

In the present specification, “aryl (group)” means a monocyclic or polycyclic (condensed) hydrocarbon group exhibiting aromaticity, and specifically includes, for example, phenyl, 1-naphthyl, C _6-14 aryl groups such as 2-naphthyl, biphenylyl and 2-anthryl are shown. Of these, a C _6-10 aryl group is preferable.

In the present specification, “C _6-10 aryl (group)” means, for example, phenyl, 1-naphthyl, 2-naphthyl, and phenyl is particularly preferable.

In the present specification, the “aralkyl (group)” means a group in which an aryl group is substituted on an alkyl group, and the carbon number range is not particularly limited, but C _7-14 aralkyl is preferable.

In the present specification, “C _7-14 aralkyl (group)” means a group in which “C _6-10 aryl group” is substituted on “C _1-4 alkyl group”, for example, benzyl, 1-phenyl Ethyl, 2-phenylethyl, (naphthyl-1-yl) methyl, (naphthyl-2-yl) methyl, 1- (naphthyl-1-yl) ethyl, 1- (naphthyl-2-yl) ethyl, 2- ( Naphthyl-1-yl) ethyl, 2- (naphthyl-2-yl) ethyl, biphenylylmethyl and the like.

In the present specification, “tri-substituted silyl (group)” means a silyl group substituted by the same or different three substituents (eg, C _1-6 alkyl group, C _6-10 aryl group, etc.). Examples of the group include trialkylsilyl groups such as trimethylsilyl group, triethylsilyl group, triisopropylsilyl group, and tert-butyldimethylsilyl group (preferably, tri-C _1-6 alkylsilyl group), tert-butyldiphenylsilyl. Group, triphenylsilyl group and the like are preferable.

In the present specification, “tri-substituted siloxy (group)” means a group in which a tri-substituted silyl group is bonded to an oxygen atom. The group is preferably a trialkylsiloxy group (preferably a triC _1-6 alkylsiloxy group) such as a trimethylsiloxy group, a triethylsiloxy group, a triisopropylsiloxy group, or a tert-butyldimethylsiloxy group.

In the present specification, the “protected amino group” means an amino group protected with a “protecting group”. As the “protecting group”, for example, an amino-protecting group described in Protective Groups in Organic Synthesis, published by John Wiley and Sons (1980) can be used. For example, a C _1-6 alkyl group, C _7-14 Protecting groups such as an aralkyl group, a C _6-10 aryl group, a C _1-7 alkanoyl group, a C _7-14 aralkyl-carbonyl group, and a tri C _1-6 alkylsilyl group can be mentioned. The protecting group may be further substituted with a halogen atom, a C _1-6 alkyl group, a C _1-6 alkoxy group or a nitro group. Specific examples of the amino-protecting group include methyl, acetyl, trifluoroacetyl, pivaloyl, tert-butoxycarbonyl, benzyloxycarbonyl and the like.

In the present specification, “optionally substituted” means that one or more substituents may be included, and the “substituent” includes (1) a halogen atom, (2 ) Nitro, (3) cyano, (4) C _1-6 alkyl, (5) C _3-8 cycloalkyl, (6) C _1-6 alkoxy, (7) C _6-10 aryl, (8) C _{7 -14} aralkyl, (9) C _1-7 alkanoyloxy, (10) C _7-11 aroyloxy, (11) C _1-7 alkanoyl, (12) C _7-11 aroyl, (13) azide, (14) C _1-6 alkylthio, (15) C _6-10 arylthio, (16) carbamoyl optionally substituted with a C _1-6 alkyl group, (17) C _1-6 alkylsulfonyloxy group, (18) C _{6- 10} arylsulfonyloxy group, (19 Tri _{C 1-6} alkylsilyl group, and (20) protected amino group. Among them, halogen atom, C _1-6 alkyl, C _1-6 alkoxy, acetyl, formyl, carbamoyl, azide, trimethylsilyl, triethylsilyl, triisopropylsilyl, tert-butyldimethylsilyl, dimethylamino, acetylamino, tert-butoxycarbonyl Amino, benzyloxycarbonylamino and the like are preferable, and a halogen atom is particularly preferable. When a plurality of substituents are present, each substituent may be the same or different.

The above substituent may be further substituted with the above substituent. The number of substituents is not particularly limited as long as it is a substitutable number, but is preferably 1 to 5, more preferably 1 to 3. When a plurality of substituents are present, each substituent may be the same or different. The substituent may further include a C _1-6 alkyl group, a C _3-8 cycloalkyl group, a C _6-10 aryl group, a C _7-14 aralkyl group, a halogen atom, a carboxy group, a protected amino group, a carbamoyl group, It may be substituted with a cyano group, a nitro group, an oxo group or the like. The number of substituents is not particularly limited as long as it is a substitutable number, but is preferably 1 to 5, more preferably 1 to 3. When a plurality of substituents are present, each substituent may be the same or different.

  In the present specification, the “one-way spiral structure” may be a right-handed or left-handed spiral structure, and is preferably a completely right-handed or left-handed spiral structure. A compound having a “unidirectionally wound helical structure” exhibits optical activity only due to a biased helical structure even if it does not have an optically active functional group in the molecule.

  In the present specification, “optical activity” means a state of rotating the plane polarized light of light, that is, a state having an optical rotatory power. Preferably, it is in an optically pure state.

  In the present specification, the “chiral compound” means a compound having central chirality, axial chirality or planar chirality, for example, central chirality (asymmetric center, ie, asymmetric carbon atom). ).

  In the present specification, the “optically active chiral compound” is a low-molecular compound having the property of rotating the plane polarized light of light, that is, an optical rotatory power, and has central chirality, axial chirality or planar chirality. Examples include organic compounds having a molecular weight of 500 or less, but are not particularly limited. Preferred are compounds having one optically pure asymmetric carbon atom. For example, both optically pure enantiomers are commercially available 1-phenylethylamine, 1-cyclohexylethylamine, 1- (1 -Naphthyl) ethylamine, 1- (2-naphthyl) ethylamine, sec-butylamine, 1-phenyl-2- (p-tolyl) ethylamine, 1- (p-tolyl) ethylamine, 1- (4-methoxyphenyl) ethylamine, β-methylphenethylamine, 2-amino-1-butanol, 2-amino-1,2-diphenylethanol, 1-amino-2-indanol, 2-amino-1-phenyl-1, 3-propanediol, 2-amino -1-propanol, leucinol, phenylalaninol, 2-phenylglycinol, valino , Norephedrine, methioninol, 1-benzyl-3-aminopyrrolidine, 2- (methoxymethyl) pyrrolidine, 1-methyl-2- (1-piperidinomethyl) pyrrolidine, 1- (2-pyrrolidinomethyl) pyrrolidine, 1-phenyl Ethyl alcohol, 1-phenyl-2-propanol, 1,2,3,4-tetrahydro-1-naphthol, 1-acetyl-3-pyrrolidinol, 1-benzyl-3-pyrrolidinol, 1-acetyl-3-pyrrolidinol, 2 -Butanol, α-hydroxy-γ-butyrolactone, 3-hydroxytetrahydrofuran, 1-methyl-3-pyrrolidinol, 2-octanol, 2-pentanol, 1- (2-naphthyl) ethanol, menthol, borneol, quinidine, quinine, Quincoline, quincollidine, cinco Jin, cinchonine, optically active form thereof include a chiral compound such as an amino acid with a protected carboxyl group. Among them, (R)-(−)-2-phenylglycinol or (S)-(+)-2-phenylglycinol is particularly preferable. As the optically active chiral compound, it is preferable to use an optically pure compound. However, even when a compound with low optical purity is used, a helical structure in which the poly (diphenylacetylene) main chain is offset in one direction is induced. It is possible to prepare compound (I). Accordingly, the “optically active chiral compound” includes not only an optically pure compound but also a compound having a low optical purity. The low molecular weight compound may be liquid or solid, and is preferably liquid.

  In this specification, “ee” is an abbreviation for enantiomeric excess and represents the optical purity of a chiral compound. “Ee” is calculated by subtracting the amount of material of the smaller enantiomer from the amount of material of the larger enantiomer and dividing by 100 and multiplying by the total amount of material, and expressed as “% ee”.

  In this specification, “optically pure” represents a state showing an optical purity of 99% ee or more.

  In the present specification, the “enantiomer” means an optical enantiomer in which the configuration of all asymmetric carbon atoms in the optically active low molecular compound is different, and the optically active low molecular compound and It constitutes a pair of optical isomers that are in the relationship between the right hand and the left hand. Specifically, for example, when the optically active low molecular compound is (R)-(−)-2-phenylglycinol, the enantiomer is (S)-(+)-2-phenylglycinol. .

  In the present specification, the “racemate” means a compound in a state in which it does not show optical rotation due to the presence of two equivalent enantiomers (enantiomers) of a chiral compound.

  In the present specification, the “chiral sensor” means a substance (compound etc.) capable of measuring and discriminating the chirality of an optically active chiral compound with high sensitivity. In the present specification, performing and measuring using a “chiral sensor” is called “chiral sensing”.

  In the present specification, “colorimetric detection” is a method in which a measurement substance or reaction product is changed to a color developing substance, and the degree of color development is colorimetrically determined by absorbance using visible light of an appropriate wavelength. . The “colorimetric detection” in the present invention includes a detection method using a visible color change, a fluorescence detection method using a fluorescence intensity change, and a detection method using an ultraviolet / visible absorption spectrum.

(Colorimetric detection type chiral sensor of the present invention)
The colorimetric detection type chiral sensor of the present invention is compound (I), that is, the following formula (I) having a unidirectionally wound helical structure in the polymer main chain:

[Where:
R ¹ , R ¹ ′, R ² , R ² ′, R ³ , R ³ ′ R ⁴ and R ⁴ ′ are each independently a hydrogen atom, a halogen atom, an optionally substituted alkyl group, or a substituted group. Represents an optionally substituted cycloalkyl group, an optionally substituted alkoxy group, an optionally substituted alkylthio group, a trisubstituted silyl group, a trisubstituted siloxy group or an optionally substituted acyloxy group; and n is An integer of 10 or more is shown. ]
A colorimetric detection-type chiral sensor comprising a poly (diphenylacetylene) compound represented by the formula (1) or a salt thereof, or a solvate thereof.

  Examples of the salt of compound (I) include a salt with an inorganic base, a salt with an organic base, and a salt with an amino acid.

Examples of the salt with an inorganic base include sodium salt, potassium salt, calcium salt, magnesium salt, ammonium salt and the like.
As a salt with an organic base, for example, methylamine, diethylamine, trimethylamine, triethylamine, ethanolamine, diethanolamine, triethanolamine, ethylenediamine, tris (hydroxymethyl) methylamine, dicyclohexylamine, N, N′-dibenzylethylenediamine, guanidine , Salts with pyridine, picoline, choline, cinchonine, meglumine and the like.
Examples of the salt with amino acid include salts with lysine, arginine, aspartic acid, glutamic acid and the like.

  The solvate of compound (I) or a salt thereof is a compound in which a solvent molecule is coordinated to compound (I) or a salt thereof, and includes a hydrate. Examples thereof include hydrates of compound (I) or a salt thereof, ethanol solvates, dimethyl sulfoxide solvates and the like.

  Hereinafter, each group of compound (I) will be described.

R ¹ , R ¹ ′, R ² , R ² ′, R ³ , R ³ ′ R ⁴ and R ⁴ ′ are each independently a hydrogen atom, a halogen atom, an optionally substituted alkyl group, or a substituted group. It represents an optionally substituted cycloalkyl group, an optionally substituted alkoxy group, an optionally substituted alkylthio group, a trisubstituted silyl group, a trisubstituted siloxy group, or an optionally substituted acyloxy group.

R ¹ , R ¹ ′, R ² , R ² ′, R ³ , R ³ ′ R ⁴ and R ⁴ ′ are preferably each independently a hydrogen atom, a halogen atom, an optionally substituted alkyl group, An optionally substituted alkoxy group, a trialkylsilyl group or a trialkylsiloxy group, more preferably a C _1-6 alkyl group which may independently be independently substituted with a hydrogen atom, a halogen atom or a halogen atom. And a C _1-6 alkoxy group, a tri C _1-6 alkylsilyl group or a tri C _1-6 alkylsiloxy group which may be substituted by a halogen atom, among which a hydrogen atom or a halogen atom is particularly preferable.

R ¹ , R ¹ ′, R ² , R ² ′, R ³ , R ³ ′ R ⁴ and R ⁴ ′ are preferably R ¹ and R ¹ ′, R ² and R ² ′, R ³ and R ^3. 'And R ⁴ and R ⁴ ' are the same group. R ¹ , R ¹ ′, R ² , R ² ′, R ³ , R ³ ′ R ⁴ and R ⁴ ′ may all be the same group.

  n is an integer of 10 or more, preferably an integer of 30 or more and 10,000 or less.

As the compound (I), the following compounds are suitable.
[Compound (IA)]
R ¹ , R ¹ ′, R ² , R ² ′, R ³ , R ³ ′ R ⁴ and R ⁴ ′ are each independently a hydrogen atom, a halogen atom, an optionally substituted alkyl group, or a substituted group. And may be an alkoxy group, a trialkylsilyl group or a trialkylsiloxy group, and R ¹ and R ¹ ′, R ² and R ² ′, R ³ and R ³ ′, and R ⁴ and R ⁴ ′ are the same. Compound (I) wherein n is an integer of 10 or more.

More preferred compound (I) is the following compound.
[Compound (IB)]
R ¹ , R ¹ ′, R ² , R ² ′, R ³ , R ³ ′ R ⁴ and R ⁴ ′ each independently represent a hydrogen atom, a halogen atom or a halogen atom which may be substituted with a C _{1- A 6} alkyl group, a C _1-6 alkoxy group optionally substituted by a halogen atom, a tri C _1-6 alkylsilyl group, or a tri C _1-6 alkylsiloxy group, and R ¹ and R ¹ ′, R ² And R ² ′, R ³ and R ³ ′ and R ⁴ and R ⁴ ′ are the same group; and n is an integer of 30 or more and 10,000 or less.

Further preferred compounds (I) are the following compounds.
[Compound (IC)]
R ¹ , R ¹ ′, R ² , R ² ′, R ³ , R ³ ′ R ⁴ and R ⁴ ′ are each independently a hydrogen atom or a halogen atom, and R ¹ and R ¹ ′, R ² And R ² ′, R ³ and R ³ ′ and R ⁴ and R ⁴ ′ are the same group; and n is an integer of 30 or more and 10,000 or less.

  The number average degree of polymerization (average number of diphenylethylene units contained in one molecule) of the compound (I) is 10 or more, preferably 30 or more, and there is no particular upper limit. This is desirable.

In addition, compound (I) may be labeled with an isotope (eg, ³ H, ² H (D), ¹⁴ C, ³⁵ S, etc.).

(Synthesis of Compound (I))
Although it does not specifically limit as a manufacturing method of compound (I), For example, it can synthesize | combine through the following reactions.

  The raw material compounds can be easily obtained as commercial products unless otherwise stated, or according to methods known per se (eg, International Publication No. 2014/125667, International Publication No. 2014/1226028, etc.) or a method analogous thereto. Can be manufactured.

  In addition, the compound obtained at each process in the following reaction formula can also be used for next reaction as a reaction liquid or a crude product. Alternatively, the compound can be isolated from the reaction mixture according to a conventional method, and can be easily purified by usual separation means such as recrystallization, distillation, chromatography and the like.

  Compound (I) can be produced, for example, by the following steps.

[Wherein, R ⁵ and R ⁵ ′ represent an optionally substituted alkyl group, an optionally substituted aryl group, an optionally substituted aralkyl group, and other symbols are as defined above. is there. ]

Process 1
The said process is a process of converting into the compound 2 by polymerizing the compound 1.
The reaction is performed using a metal catalyst in a nitrogen atmosphere in a solvent that does not affect the reaction.

As the metal catalyst, for example, a mixed catalyst of tungsten chloride (VI) and tetraphenyltin (IV) is preferable.
The amount of the metal catalyst to be used is generally 0.001-1 mol, preferably 0.05-0.5 mol, relative to compound 1 (1 mol).

  Examples of the solvent include aromatic hydrocarbons such as toluene and xylene; ethers such as diethyl ether, tetrahydrofuran and dioxane, and mixtures thereof, among which toluene and the like are preferable.

  The amount of the solvent used in this step is preferably an amount such that Compound 1 has a concentration of about 0.01 to 4M. An amount that gives a concentration of about 0.1 to 1M is particularly preferable.

The reaction temperature is usually −10 ° C. to 200 ° C., preferably 10 ° C. to 120 ° C.
The reaction time is usually 0.5 to 30 hours.

Process 2
This step is a step in which the ester of compound 2 is hydrolyzed and converted to compound (I ′), that is, optically inactive compound (I).
The reaction is performed using a base in a solvent that does not affect the reaction.

Examples of the base include inorganic bases such as potassium hydroxide and sodium hydroxide, among which potassium hydroxide is preferable.
The amount of the base to be used is generally 1 to 100 mol with respect to compound 2 (1 mol).

  Examples of the solvent include a mixed solvent of an ether solvent such as tetrahydrofuran (THF), diethyl ether, tert-butyl methyl ether, diisopropyl ether, ethylene glycol-dimethyl ether (DME), diethylene glycol dimethyl ether (diglyme), and water. Among them, a mixed solvent of tetrahydrofuran and water is preferable.

The reaction temperature is usually 0 ° C to 100 ° C, preferably 50 ° C to 90 ° C.
The reaction time is usually 0.5 to 30 hours.

Process 3
This step is a step of inducing a one-way spiral chirality by adding an optically active low molecular compound to the compound (I ′) (step 3-1), followed by removal of the optically active low molecular compound. This is a step of converting the optically active compound (I) by a step (step 3-2) of memorizing the directionally wound spiral chirality.

  Step 3-1 is performed by mixing compound (I ′) and an optically active low-molecular compound in a solvent that does not affect the reaction.

Examples of the optically active low-molecular compound include the compounds exemplified above, among which (R)-(−)-2-phenylglycinol, (S)-(+)-2-phenylglycinol, (R) -(-)-1-phenylethylamine, (S)-(+)-1-phenylethylamine and the like are preferably used. As the optically active low molecular weight compound, an optically pure compound (99% ee or more) is preferably used. The low molecular compound may be liquid or solid, and is preferably liquid.
The usage-amount of an optically active low molecular weight compound is 1-50 mol normally with respect to compound (I ') (1 mol).

  Examples of the solvent include water, dimethyl sulfoxide (DMSO), N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMA), and water is particularly preferable.

The reaction temperature is generally 0 ° C to 120 ° C, preferably room temperature to 100 ° C, more preferably 80 ° C to 100 ° C.
The reaction time is usually 0.5 to 30 hours.

  Step 3-2 removes the optically active low-molecular-weight compound from the mixed solution containing the compound (I) in which the unidirectional spiral chirality is induced, thereby storing the compound in which the unidirectional spiral structure is stored ( This is a step of obtaining I). Specifically, in this step, an acid is added to the reaction solution in Step 3-1, and the resulting precipitate is washed with water to obtain Compound (I).

  Examples of the acid include hydrochloric acid, phosphoric acid, sulfuric acid and the like, and among them, hydrochloric acid is preferable.

  Whether or not the unidirectionally wound spiral chirality is induced in the compound (I) can be confirmed by measuring CD and ultraviolet / visible absorption spectra.

  It can be confirmed by measuring the peak intensity (Δε) of the CD spectrum whether or not the optical purity of the compound (I) induces unidirectionally wound helical chirality. That is, the higher the peak intensity, the more the spiral winding direction is offset in one direction.

  The optically active low molecular weight compound removed by the water washing can be recovered and reused any number of times.

(Method for discriminating chirality of optically active chiral compound by colorimetric detection-type chiral sensor of the present invention comprising compound (I))

  When compound (I) is derivatized (especially amidated) by condensation with an optically active chiral compound to be tested (identified), depending on the absolute configuration and optical purity of the test object, Changes in the color of the solution and / or fluorescence intensity are observed. Then, by observing the change in the color tone and / or the fluorescence intensity and the change in the ultraviolet / visible absorption spectrum, it is possible to identify the absolute configuration and optical purity of the identification target with high sensitivity.

  As the optically active chiral compound to be identified, an optically active chiral amine is preferable.

  The optically active chiral amine capable of identifying chirality is not particularly limited, but is preferably a primary amine (eg, 1- (1-naphthyl) ethylamine, 1-phenylethylamine, 2-butylamine, 1-cyclohexyl). Such as ethylamine), amino alcohols (eg, 2-phenylglycinol, phenylalaninol, 2-aminopropanol, etc.), amino acids derivatives (eg, t-butyl esters of amino acids such as alanine, phenylalanine, leucine, etc.) Examples thereof include an active form, and among them, a compound having a primary amino group is particularly suitable.

Synthesis of compound (II) by derivatization (amidation) by condensation between compound (I) and an optically active chiral compound (optically active chiral amine) to be identified is carried out in the presence of a condensing agent according to a method known per se. It is carried out by a method of reacting I) with an optically active chiral amine (preferably the compound exemplified above).
The reaction is performed using a condensing agent in the presence of a condensing additive in a solvent that does not affect the reaction, if necessary.

Condensation additives include 1-hydroxybenzotriazole (HOBt), 1-hydroxy-1H-1,2,3-triazole-5-carboxylic acid ethyl ester (HOCt), 1-hydroxy-7-azabenzotriazole (HOAt) ) And the like.
The amount of the condensation additive to be used is preferably 0.05 to 1.5 mol with respect to 1 mol of compound (I).

As the condensing agent, 4- (4,6-dimethoxy-1,3,5-triazin-2-yl) -4-methylmorpholinium chloride (DMT-MM), dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC) ), N-ethyl-N′-3-dimethylaminopropylcarbodiimide and its hydrochloride (EDC · HCl), hexafluorophosphoric acid (benzotriazol-1-yloxy) tripyrrolidinophosphonium (PyBop), O- (benzotriazole) -1-yl) -N, N, N ′, N′-tetramethyluronium tetrafluoroborate (TBTU), 1- [bis (dimethylamino) methylene] -5-chloro-1H-benzotriazolium 3- Oxide hexafluorophosphate (HCTU), O-benzotriazole-N , N, N ′, N′-tetramethyluronium hexafluoroborate (HBTU) and the like, DMT-MM that can be used even in an aqueous solvent is particularly suitable.
The amount of the condensing agent to be used can be 1 to 10 mol, preferably 1 to 5 mol, per 1 mol of compound (I).
Examples of the solvent include water; dimethyl sulfoxide (DMSO); aromatic hydrocarbons such as toluene and xylene; ethers such as diethyl ether, tetrahydrofuran and dioxane; halogenated hydrocarbons such as chloroform and dichloromethane; Among them, a mixed solvent of water and DMSO is preferable.
The reaction temperature is usually 0 to 40 ° C., preferably 0 ° C. to room temperature, and the reaction time is usually 0.1 to 30 hours.

  An amide compound (compound (II)) formed by condensation of compound (I) with an optically active chiral amine to be identified is a low polar solvent (eg, tetrahydrofuran, chloroform, etc.), or a small amount of polar solvent (dimethylformamide, dimethyl sulfoxide) Etc.), a change in the color tone and / or fluorescence intensity of the solution is observed due to the difference in absolute configuration and optical purity of the optically active chiral amine. Then, by observing the color tone and / or the change in fluorescence intensity, it is possible to identify the absolute steric configuration to be identified simply and with high sensitivity. Further, as described in the examples described later, by creating a calibration curve, it is possible to accurately measure the optical purity of the identification target.

In the chirality identification method of the present invention, since compound (I) (chiral sensor) and chiral amine (identification target) are firmly bonded by a covalent bond, conventionally known molecular recognition (non-covalent interaction) is performed. Compared to the chiral sensor used, it is not necessary to consider the influence of chemical equilibrium, etc., so the chirality of the identification target can be identified with good reproducibility without depending on the measurement conditions (concentration, temperature, etc.). . In addition, when the compound (I) is used as a fluorescent sensor, it can be accurately identified even with a very small amount of sample of about 10 ⁻⁷ to 10 ⁻⁵ M, which cannot be sufficiently analyzed by other analytical instruments. Has the advantage of being able to.

  Further, according to the chirality identification method of the present invention, the change in the absorption maximum wavelength of the ultraviolet / visible absorption spectrum of compound (II) is particularly low in the low enantiomeric excess (low ee) region (less than about 20% ee). ), The sample having a low ee optical purity, which is difficult to measure accurately in chiral HPLC or the like, can be distinguished with high accuracy.

  As described above, the chiral sensor of the present invention does not need to introduce any expensive optically active functional group into the compound (I), and introduces a unidirectional spiral chirality into the main chain simply and inexpensively. Has the advantage of being able to. In addition, the method for identifying chirality of an optically active chiral compound using the chiral sensor of the present invention is a solution of a derivative (compound (II)) formed by condensation of an optically active chiral compound to be identified and compound (I). It is expensive and special in that the absolute configuration and optical purity of the identification target can be accurately determined simply by observing changes in color tone and / or fluorescence intensity and ultraviolet / visible absorption spectrum. This is a practical chiral sensing technique that does not require a measuring device.

  EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, this invention is not limited at all from these.

¹ H NMR spectrum was measured using JEOL ECA500 using deuterated chloroform, deuterated dimethyl sulfoxide and deuterated water as solvents. Data for ¹ H-NMR are chemical shift (δ ppm), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, quint = quintet, m = multiplet, dd = double doublet, dt = Report as double triplet, brs = broad singlet), coupling constant (Hz), integration and assignment.
The average molecular weight is converted to polystyrene by gel permeation chromatography (JASCO high performance liquid chromatography pump PU-2080, JASCO UV-visible detector UV-970, JASCO column oven CO-1560, Shodex column KF-805L). Calculated with
Circular dichroism (CD) measurement is JASCO's circular dichroism dispersometer J-725, UV-visible absorption measurement is JASCO's UV-visible spectrophotometer V-570, and fluorescence measurement is JASCO spectrofluorometer This was performed using FP-6300.
“Room temperature” in the following examples usually indicates about 10 ° C. to about 25 ° C. The ratio shown in the mixed solvent is a volume ratio unless otherwise specified. Unless otherwise indicated, “%” indicates “% by weight”.
Further, bis [(4-heptyloxycarbonyl) phenyl)] acetylene (compound (1a)) as a raw material compound was synthesized by the method described in International Publication Nos. 2014/125667 and 2014/1226028. I used something.

Example 1
Synthesis of compound (I-1)

(1) Synthesis of compound (2a) by polymerization of compound (1a)

Under a nitrogen atmosphere, a Schlenk tube was charged with bis [(4-heptyloxycarbonyl) phenyl]] acetylene (1a) (1.85 g, 4.00 mmol), tungsten chloride (VI) (161 mg, 0.41 mmol), tetraphenyltin. (IV) (185 mg, 0.43 mmol) was added, and vacuum distilled dehydrated toluene (8.0 mL) was added. Then, it stirred at 110 degreeC for 24 hours. After cooling to room temperature, it was reprecipitated in a large amount of methanol, and an ocherous solid was obtained by centrifugation. Subsequently, it is dissolved in a small amount of toluene, re-precipitated in a large amount of tetrahydrofuran / methanol (1: 3, v / v) mixed solvent, and centrifuged to poly (diphenylacetylene) heptyl ester (compound (2a)) (1 .19 g, 64% yield) was recovered as an ocher solid. The number average molecular weight _{Mn in} terms of polystyrene of the compound (2a) determined by gel permeation chromatography measurement was 1.25 × 10 ⁴ and the dispersity M _w / M _n was 1.85.
IR (KBr, cm ⁻¹ ): 1721 (C═O);
¹ H NMR (500 MHz, CDCl ₃ , 50 ° C.): δ 7.16-7.28 (br, 4H, Ar—H), 6.41-6.71 (br, 2H, Ar—H), 5.92 _{-6.15 (br, 2H, Ar-} H), 4.03-4.48 (br, 4H, 2OCH 2 CH 2), 1.60-1.93 (br, 4H, 2OCH 2 CH 2), _{1.25-1.47 (br, 16H, 8CH 2} ), 0.79-1.04 (br, 6H, 2CH 3);
Elemental _{analysis: Calcd for C 30 H 38 O} 4: C, 77.89; H, 8.28. Found: C, 77.40; H, 8.42.

(2) Synthesis of Compound (I′-1) by Hydrolysis of Compound (2a)

Compound (2a) (1.10 g) was dissolved in tetrahydrofuran (50 mL), 4N aqueous potassium hydroxide solution (120 mL) was added, and the mixture was stirred at 85 ° C. for 2 hr. Then, tetrahydrofuran was distilled off and stirred at 85 ° C. for 24 hours. Distilled water was added to the reaction solution, followed by washing with diethyl ether and chloroform. The aqueous layer is acidified with 1N hydrochloric acid, and the precipitated solid is collected by centrifugation, and then washed with distilled water to obtain poly (diphenylacetylene) carboxylic acid (compound (I′-1)) (600 mg, yield). 94%) was obtained as a brown solid.
IR (KBr, cm ⁻¹ ): 1701 (C═O);
¹ H NMR (500 MHz, d ₆ -DMSO / D ₂ O (1: 1, v / v), 80 ° C.): δ 7.19-6.88 (br, 4H, Ar—H), 6.53-6 .31 (br, 2H, Ar-H), 6.12-5.82 (br, 2H, Ar-H)
Elemental _{analysis: Calcd for (C 16 H 10} O 4 · 2.1H 2 O) n: C, 63.20; H, 4.71. Found: C, 63.04; H, 4.55.

(3) Synthesis of Compound (I-1) by Inducing Chirality in Compound (I′-1) and Memory

  Compound (I′-1) (297 mg, 1.12 mmol) was dissolved in water (113 mL), (S)-(+)-phenylglycinol (1.24 g, 9.05 mmol) was added, and 95 ° C. After stirring for a period of time, the mixture was allowed to stand at 25 ° C. for 24 hours. The solid precipitated by adding 1N hydrochloric acid to acidity was collected by centrifugation, and washed with distilled water to give compound (I-1) (290 mg, 98% yield) having a one-way spiral structure as a brown solid Got as.

Experimental example 1
Identification of chirality of optically active chiral amine by colorimetric detection type chiral sensor (compound (I)) of the present invention (1) Synthesis of compound (II) by condensation of compound (I) and optically active chiral amine

(I) Synthesis of Compound (II-1S) by Condensation of Compound (I-1) with (S)-(−)-1- (1-naphthyl) ethylamine

  Compound (I-1) (49.9 mg, 0.19 mmol) was dissolved in dimethyl sulfoxide / water (5: 1, v / v) (10 mL), and (S)-(−)-1- (1-naphthyl) was dissolved. ) Ethylamine (121 [mu] L, 0.75 mmol), 4- (4,6-dimethoxy-1,3,5-triazin-2-yl) -4-methylmorpholinium chloride (DMT-MM) (209 mg, 0.76 mmol) ) And stirred at room temperature for 12 hours. The precipitated solid was recovered by centrifugation, washed with a mixed solvent of water / methanol (1: 1, v / v) and water, and dried to give compound (II-1S) (89.5 mg, yield 84%). ) Was obtained as a yellow solid.

(Ii) Synthesis of Compound (II-1R) by Condensation of Compound (I-1) with (R)-(+)-1- (1-naphthyl) ethylamine

  Compound (I-1) (49.9 mg, 0.19 mmol) was dissolved in dimethyl sulfoxide / water (5: 1, v / v) (10 mL), and (R)-(+)-1- (1-naphthyl) was dissolved. ) Ethylamine (121 μL, 0.75 mmol) and DMT-MM (209 mg, 0.76 mmol) were added, and the mixture was stirred at room temperature for 12 hours. The precipitated solid was collected by centrifugation, washed with a water / methanol (1: 1, v / v) mixed solvent and water, and dried to give compound (II-1R) (90.1 mg, yield 84%). ) As an orange-red solid.

(Iii) Compound (I-1) and 2-phenylglycinol in the (R) or (S) configuration, 1-cyclohexylethylamine, phenylalaninol, alanine t-butyl ester, 1-phenylethylamine, phenylalanine t-butyl ester Or compounds (II-2R), (II-2S), (II-3R), (II-3S), (II-4R), (II-4S), (II) by condensation with leucine t-butyl ester -5R), (II-5S), (II-6R), (II-6S), (II-7R), (II-7S), (II-8R) and the synthesis of compound (II-8S)

  Corresponding compounds by condensation with 2-phenylglycine, 1-cyclohexylethylamine, phenylalaninol or 1-phenylethylamine in the (R) or (S) configuration according to the method of (1) (i) or (ii) above (II-2R), (II-2S), (II-3R), (II-3S), (II-4R), (II-4S), (II-6R) and compound (II-6S) Synthesized. On the other hand, when an optically active chiral amine is used, an alanine t-butyl ester hydrochloride, a phenylalanine t-butyl ester hydrochloride or a leucine t-butyl ester hydrochloride having the (R) or (S) configuration is used as described above. (1) By performing the reaction of (i) or (ii) in the presence of triethylamine, compounds (II-5R), (II-5S), (II-7R), (II-7S), (II-8R) ) And compound (II-8S) could be synthesized similarly.

  Compounds (II-2R), (II-2S), (II-3R), (II-3S), (II-4R), (II-4S), (II-5R), (II-5S), ( The chemical formulas of II-6R), (II-6S), (II-7R), (II-7S), (II-8R) and compound (II-8S) are shown below.

(2) Identification of chirality by changing the color tone of the solution of compound (II)

FIG. 1 shows CDs and absorption spectra of compound (II-1S) and compound (II-1R) obtained in the above (1) (i) and (ii), measured in tetrahydrofuran or chloroform. According to FIG. 1, a remarkable long wavelength shift was observed in the compound (II-1R) compared to the compound (II-1S) in any solvent.
In FIG. 2, the photograph of each tetrahydrofuran solution and chloroform solution of compound (II-1R) and compound (II-1S) was shown. As a result, it was found that the chirality of 1- (1-naphthyl) ethylamine, which is an identification target, can be visually identified as a difference in solution color.

  Table 1 below summarizes the difference in color tone of solutions of the compounds (II-1S / 1R) to (II-8S / 8R) obtained by condensation of the compound (I-1) of the present invention with other optically active chiral amines. Showed.

  According to Table 1, it was found that the absolute configuration of the optically active chiral amine can be easily identified visually by using any compound (II) in tetrahydrofuran, chloroform, or a mixed solvent thereof.

(3) Identification of chirality by change of fluorescence intensity of solution of compound (II)

Regarding the compounds (II-1S) and (II-1R) obtained in the above (1) (i) and (ii), the fluorescence spectrum was measured in a dimethylformamide / chloroform (2: 8, v / v) mixed solution. Measurement (excitation wavelength: 282 nm) was performed. The results are shown in FIG. According to FIG. 3, the compound (II-1R) was observed to have a significantly lower fluorescence intensity than the compound (II-1S). The right side of FIG. 3 shows a solution of a compound (II-1S) and a compound (II-1R) in a dimethylformamide / chloroform (2: 8, v / v) mixed solution (concentration: 1.0 × 10 ⁻⁵ M). The color (upper) and the color of the solution (lower) under ultraviolet light irradiation of 365 nm are shown. Under extremely dilute measurement sample concentration (1.0 × 10 ⁻⁵ M), it was difficult to identify with the difference in the solution color (upper right) (both colorless or light yellow), but the ultraviolet of 365 nm Under light irradiation, the chirality of 1- (1-naphthyl) ethylamine can be clearly identified as a difference in fluorescence intensity of the solution even under extremely dilute concentration conditions (1.0 × 10 ⁻⁵ M). Was confirmed.

(4) Determination of enantiomeric excess (ee) of identification target (optically active chiral amine)

  S-form 100% ee to R-form 100% ee 1- (1-naphthyl) ethylamine is condensed with the compound (I-1) of the present invention, and ultraviolet / visible absorption spectrum measurement is carried out in chloroform. 450-550 nm FIG. 4 shows the result of plotting the change of the absorption maximum wavelength in γ against the enantiomeric excess (ee%) of 1- (1-naphthyl) ethylamine. FIG. 4 shows the difference in λ (nm) on the vertical axis with the absorption maximum wavelength for S-form 100% ee as a reference, and the% ee of 1- (1-naphthyl) ethylamine determined by HPLC on the horizontal axis. It is a plot.

  According to FIG. 4, it was found that the absorption maximum wavelength suddenly red-shifted in the vicinity of S-form 20% ee to R-form 20% ee of 1- (1-naphthyl) ethylamine. The figure on the right is an enlarged view of the vicinity of S body 20% ee to R body 20% ee.

  This result shows that the optical purity in the low ee region of 20% ee or less can be determined by the change in the ultraviolet / visible absorption spectrum, which is very difficult to accurately identify by other instrumental analysis methods.

(5) Sample concentration dependence of the chirality identification method of the present invention

  By measuring CD and ultraviolet / visible absorption spectra of the compound (II-6S) and the compound (II-6R) in chloroform at sample concentrations of 2.5 mM, 0.25 mM and 0.025 mM, respectively, The concentration dependence of the colorimetric chiral sensor was investigated. The results are shown in FIGS. 5-1 and 5-2. Concentration dependence was not observed at all in either compound (II-6S) or compound (II-6R).

  From this result, it was inferred that the difference in color of the compound (II) in the solvent was not caused by the association but was caused by the conformational change of the main chain of the compound (II).

  The colorimetric detection-type chiral sensor comprising the compound (I) of the present invention exhibits a high-sensitivity chirality discrimination ability for a wide range of chiral amine compounds. The chiral sensor of the present invention does not require any expensive optically active functional group to be introduced into the compound (I), and can easily and inexpensively introduce unidirectional spiral chirality into the main chain. Have advantages. In addition, the method for identifying chirality of an optically active chiral compound using the chiral sensor of the present invention is a solution of a derivative (compound (II)) formed by condensation of an optically active chiral compound to be identified and compound (I). By observing the color tone and / or changes in fluorescence intensity, it is possible to determine the absolute configuration and optical purity of the identification target with high accuracy, and it does not require an expensive and special measurement device. Provide a new chirality sensing method. Further, according to the chirality identification method of the present invention, since the change in the absorption maximum wavelength of the ultraviolet / visible absorption spectrum is particularly remarkable in the low enantiomeric excess (low ee) region, other instrumental analysis methods are used. In some cases, it is possible to accurately identify a sample exhibiting low ee optical purity, which is difficult to measure accurately.

Claims (3)

Formula (I) having a unidirectionally wound helical structure:
[Where:
R ¹ , R ¹ ′, R ² , R ² ′, R ³ , R ³ ′ R ⁴ and R ⁴ ′ are each independently a hydrogen atom, a halogen atom, an optionally substituted alkyl group, or a substituted group. Represents an optionally substituted cycloalkyl group, an optionally substituted alkoxy group, an optionally substituted alkylthio group, a trisubstituted silyl group, a trisubstituted siloxy group or an optionally substituted acyloxy group; and n is An integer of 10 or more is shown. ]
A colorimetric detection-type chiral sensor comprising a poly (diphenylacetylene) compound represented by the formula (1) or a salt thereof, or a solvate thereof. A chirality of the chiral amine compound is obtained by condensing the carboxy group of the chiral sensor according to claim 1 with an amino group of the chiral amine compound, amidating, changing the color tone of the solution of the amidated compound, and measuring fluorescence. A method for identifying chirality of a chiral amine compound, comprising a step of determining tea.   The method according to claim 2, further comprising the step of determining the optical purity of the chiral amine compound from the ultraviolet / visible absorption spectrum data.