JP5649073B2 - Hydrogelator - Google Patents

Description

  The present invention relates to a hydrogelator.

  In general, in the field of paints and resins, gels are added to paints and resins, etc. to adjust fluidity, and waste oil, waste liquid, waste water, etc. are gelled to form solids to prevent water pollution, etc. Widely used in the field of environmental conservation. A gel is a structure in which a fluid such as water or an organic solvent is contained in a three-dimensional network structure formed of a chemical substance. An organogel is used when the fluid is an organic solvent, and a hydrogel when the fluid is water. That's it.

In recent years, the application of gels to technologies such as sensing and screening of biological samples and environmental samples has been studied. In this case, gelation in an aqueous environment, that is, development of hydrogels and hydrogelators is indispensable. It is.
Examples of the technology relating to hydrogels and hydrogelators include hydrogelators composed of specific glycoside amino acid derivatives (see, for example, JP2003-327949A and JP2005-13174A), and specific 2'-deoxyuridine derivatives. Hydrogels produced from (for example, see JP-A-2005-194257) and hydrogelators (for example, see JP-A-2007-217551) containing a specific benzamide derivative as an active ingredient are known.

The hydrogelators described in JP-A-2003-327949, JP-A-2005-13174, and JP-A-2007-217551 are compounds having a long-chain alkyl group, and have molecular symmetry. It has a low structure. Further, the 2′-deoxyuridine derivative described in JP-A-2005-194257 has a structure with low molecular symmetry although it does not have a long-chain alkyl group. It is not clear why the above conventional hydrogelators have long-chain alkyl groups or have a low symmetry structure, and the structures of these conventional hydrogelators have been found based on empirical rules for gelators. It is considered to be a structure.
In other words, the conventional method for developing hydrogelators is a method that relies on the empirical rule of constructing a group (compound library) consisting of a large number of compounds and finding a compound that can be gelled. A clear molecular design guideline for hydrogelators has not yet been established. In addition, a structure having a long-chain alkyl group or a structure with low symmetry has an enormous number of structures that can be selected, and it is difficult to construct a systematic compound library itself.
As described above, it is desired to design a compound having an unprecedented chemical structure, and to develop a hydrogelator or gelation method using the compound, and a use of the compound.

Accordingly, an object of the present invention is to provide a substituted aromatic compound having an unprecedented chemical structure and exhibiting excellent gelling activity with respect to an aqueous sample.
Moreover, the objective of this invention is providing the hydrogelator and hydrogel containing the said substituted aromatic compound.
Moreover, the objective of this invention is providing the gelation method of the aqueous sample which can gelatinize an aqueous sample easily using the said substituted aromatic compound.
Another object of the present invention is to provide a screening method that uses the substituted aromatic compound to select a target compound that interacts with a specific compound by a simple method.

Means for solving the above-mentioned problems are as follows .

< 1 > A substituted aromatic compound represented by the following general formula (II).

In the general formula (II), R represents a hydrogen atom or an alkyl group, Z ⁴ represents an arylene group, and Q ¹ , Q ² , and Q ³ are each independently a divalent or trivalent aromatic hydrocarbon. Represents a group. E represents an ethylene group, and S _g ¹ , S _g ² , and S _g ³ each independently represent a sugar group. m1, m2, and m3 each independently represent 1 or 2, and n1, n2, and n3 each independently represent an integer of 1 to 10.

<2> The substituted aromatic compound according to <1>, wherein R is a hydrogen atom.
<3> The n1, the n2, and the n3 are each independently a substituted aromatic compound according to <1> or <2>, which represents an integer of 1 to 3.
<4> The substituted aromatic compound according to <1>, which is any one of exemplary compounds (1) to (5) described later.
<5> The substituted aromatic compound according to <4>, which is any one of exemplary compounds (1) to (3) described later.
<6> A hydrogelator comprising the substituted aromatic compound according to any one of <1> to <5>.
<7> A hydrogel comprising the substituted aromatic compound according to any one of <1> to <5>.
<8> A method for gelling an aqueous sample, comprising bringing the substituted aromatic compound according to any one of <1> to <5> into contact with the aqueous sample.

< 9 > adding a test compound to an aqueous sample containing a substituted aromatic compound represented by the following general formula (I) and a specific compound that interacts with a hydrophilic group of the substituted aromatic compound;
Detecting the gelling activity of the aqueous sample after the addition;
as well as,
Screening a test compound contained in an aqueous sample in which gelation activity is detected as a target compound that interacts with the specific compound stronger than the hydrophilic group;
A screening method comprising

In general formula (I), R represents a hydrogen atom or an alkyl group, X represents an oxygen atom or a sulfur atom, and Y ¹ , Y ² , and Y ³ are each independently an aryl substituted with a hydrophilic group Represents a group.
L ¹ represents a single bond, an oxygen atom, a methyleneoxy group, an aryleneoxy group, or a — [CH ₂ — (O) _r1 —Z ¹ ] _s1 — group, and L ² represents a single bond, an oxygen atom, methyleneoxy group, arylene group, or a _{- [CH 2 - (O)} r2 -Z 2] s2 - represents a group, ^{L 3} represents a single bond, an oxygen atom, a methylene group, arylene group, or a - [CH ₂ - _{^{(O) r3 -Z 3] s3}} - represents a group.
Z ¹ , Z ² , and Z ³ each independently represent an arylene group, r 1, r 2, and r ³ each independently represent 0 or 1, and s ¹ , s ² , and s ³ are each independently 0 or 1 is represented.

< 10 > The hydrophilic group in the general formula (I) is a hydrophilic group containing a sugar group, the specific compound is a lectin, the test compound is a sugar, and the target compound is a sugar <9 > .
< 11 > The hydrophilic group in the general formula (I) is a hydrophilic group containing an alkyleneoxy group and a sugar group, the specific compound is a lectin, the test compound is a sugar, and the target compound is a sugar. it is a screening method according to <9> is.
<12> the alkylene group is a screening method according to an ethyleneoxy group <11>.

< 13 > An aqueous sample containing a substituted aromatic compound represented by the following general formula (II) and a lectin as a specific compound that interacts with a sugar group of the substituted aromatic compound. Adding,
Detecting the gelling activity of the aqueous sample after the addition,
as well as,
Selecting a saccharide as a test compound contained in an aqueous sample in which gelation activity is detected as a saccharide that interacts with the lectin more strongly than the saccharide group,
Is a screening method comprising the.

In the general formula (II), R represents a hydrogen atom or an alkyl group, Z ⁴ represents an arylene group, and Q ¹ , Q ² , and Q ³ are each independently a divalent or trivalent aromatic hydrocarbon. Represents a group. E represents an ethylene group, and S _g ¹ , S _g ² , and S _g ³ each independently represent a sugar group. m1, m2, and m3 each independently represent 1 or 2, and n1, n2, and n3 each independently represent an integer of 1 to 10.

According to the present invention, it is possible to provide a substituted aromatic compound having an unprecedented chemical structure and having an excellent gelation activity for an aqueous sample.
Moreover, according to this invention, the hydrogelator and hydrogel containing the said substituted aromatic compound can be provided.
Moreover, according to this invention, the gelation method of the aqueous sample which can gelatinize an aqueous sample easily can be provided using the said substituted aromatic compound.
In addition, according to the present invention, it is possible to provide a screening method that uses the substituted aromatic compound to select a target compound that interacts with a specific compound by a simple method.

In this Example 2, it is a photograph when the gelatinization of water by performing ultrasonic irradiation after heating is performed. In this Example 2, it is a photograph when the gelation of water by leaving still is performed. In Example 3, it is a photograph when the gelation of the borate buffer is performed. It is a photograph when water and borate buffer solution are gelled in Example 4. It is a photograph when the experiment of the sol-gel phase transition in the present Example 5 was conducted.

<Substituted aromatic compound>
The substituted aromatic compound of the present invention is a substituted aromatic compound represented by the following general formula (I) (hereinafter also referred to as “compound represented by general formula (I)”).

In general formula (I), R represents a hydrogen atom or an alkyl group, X represents an oxygen atom or a sulfur atom, and Y ¹ , Y ² , and Y ³ are each independently an aryl substituted with a hydrophilic group Represents a group.
L ¹ represents a single bond, an oxygen atom, a methyleneoxy group, an aryleneoxy group, or a — [CH ₂ — (O) _r1 —Z ¹ ] _s1 — group, and L ² represents a single bond, an oxygen atom, methyleneoxy group, arylene group, or a _{- [CH 2 - (O)} r2 -Z 2] s2 - represents a group, ^{L 3} represents a single bond, an oxygen atom, a methylene group, arylene group, or a - [CH ₂ - _{^{(O) r3 -Z 3] s3}} - represents a group.
Z ¹ , Z ² , and Z ³ each independently represent an arylene group, r 1, r 2, and r ³ each independently represent 0 or 1, and s ¹ , s ² , and s ³ are each independently 0 or 1 is represented.

The compound represented by the general formula (I) is composed of a hydrophilic part located on the outer periphery of the compound and a part other than the hydrophilic part (referred to as “hydrophobic part” in the present specification). It is a planar molecule.
The hydrophilic ^portion, Y 1, ^{Y 2,} and composed of hydrophilic groups in ^{Y 3.}
The hydrophobic part has a highly symmetric structure having three urea structures (or thiourea structures).

  The compound represented by the general formula (I) can easily gel an aqueous sample using water as a solvent. That is, the compound represented by the general formula (I) is useful as a hydrogelator exhibiting excellent gelling activity with respect to an aqueous sample.

Hereinafter, although the gelation mechanism estimated about the gelation of the aqueous sample by the compound represented by general formula (I) is demonstrated, this invention is not limited to the following gelation mechanisms.
When the compound represented by the general formula (I) (hereinafter, also simply referred to as “molecule”) comes into contact with water, the main driving force is the interaction between the hydrophobic parts and the hydrogen bond between the urea parts (or thiourea parts). Each molecule self-assembles and overlaps and accumulates in one dimension. As a result, a fibrous supramolecular assembly in which each molecule is one-dimensionally accumulated is formed. At this time, π electrons present in the aryl group in Y ¹ , Y ² , and Y ³ in ^one molecule are π electrons present in the aryl group in Y ¹ , Y ² , and Y ³ in the other molecule. It is thought that the bond (overlap) between molecules is strengthened by interacting with (π stacking).
The fibrous supramolecular assemblies formed as described above are assembled in an aqueous sample to form a three-dimensional network structure. The supramolecular assembly in which the three-dimensional network structure is formed has an affinity for water due to the hydrophilic portion of each molecule, and therefore does not precipitate in an aqueous sample.
Therefore, it is considered that water exists in the gaps of the formed three-dimensional network structure, the fluidity of the aqueous sample is lowered, and gelation occurs.

In the present invention, the gelation activity is detected by visually confirming the gelation of the aqueous sample.
Specifically, 0.1 to 5 mL of an aqueous sample is put into a test tube having an inner diameter of 5 to 20 mm, and the test tube is turned upside down (with the bottom of the test tube facing up and the mouth of the test tube facing down). ), Rest for 60 seconds.
If the sample does not flow down after 60 seconds, it is determined that the sample has gelled (has gelling activity).

Moreover, the compound represented by general formula (I) has a chemical structure with high symmetry which has not existed before. For this reason, it is excellent in terms of ease of synthesis and ease of compound identification.
As described above, as a gelling agent having high molecular symmetry, a urea compound or a thiourea compound described in JP-A-2008-189559 is known as an organogelling agent.
The compound represented by the general formula (I) can be synthesized based on a clear molecular design guideline of introducing a hydrophilic group at the terminal of the organogelator. For this reason, for example, when used in the screening method described below, synthesis with a high degree of freedom (flexibility) that has not been conventionally possible, such as selecting and introducing an appropriate hydrophilic group according to the target compound that is a control target for screening, is possible. It becomes possible.

In the general formula (I), three Rs represent the same group.
R in the general formula (I) is preferably a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, preferably a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, and is a hydrogen atom from the viewpoint of gelation activity. It is particularly preferred.

The methyleneoxy group in L ¹ , L ² , and L ³ may be bonded to the benzene ring on the oxygen atom side or bonded to the benzene ring on the carbon atom side. From the viewpoint, it is preferably bonded to the benzene ring on the carbon atom side.
In addition, the aryleneoxy groups in L ¹ , L ² , and L ³ are preferably bonded to a benzene ring on the carbon atom side from the viewpoint of gelation activity and the like. Examples of the aryleneoxy group include a phenyleneoxy group, a biphenyleneoxy group, and a naphthyleneoxy group.
Moreover, in the ^{L 1,} wherein ^{L 2,} and wherein _{^{L 3, - [CH 2 -}} (O) r1 -Z 1] s1 - _{group, - [CH 2 - (O} ) r2 -Z 2] s2 - groups, _{and, - [CH 2 - (O} ) r3 -Z 3] s3 - group, from the viewpoint of gelation activity, etc., "- CH ₂ -" is preferably bonded to the benzene ring in the side.

In the general formula (I), L ¹ represents a single bond, an oxygen atom, a methyleneoxy group, an aryleneoxy group, or a — [CH ₂ — (O) _r1 —Z ¹ ] _s1 — group. Among these, from the viewpoint of gelation _{activity, - [CH 2 - (O} ) r1 -Z 1] s1 - groups are preferred, '- CH ₂ - "bonds to the benzene ring in the side _{- [CH 2 - (O)} r1 —Z ¹ ] _s1 — group is more preferable.
In the — [CH ₂ — (O) _r1 —Z ¹ ] _s1 — group, Z ¹ represents an arylene group, r1 represents 0 or 1, and s1 represents 0 or 1.
The r1 is preferably 1 from the viewpoint of gelation activity.
From the same viewpoint, the s1 is preferably 1.

In the general formula (I), ^{L 2} represents a single bond, an oxygen atom, a methylene group, arylene group, _{or, - [CH 2 - (O} ) r2 -Z 2] s2 - represents a group, among these from the viewpoint of gelation _{activity, - [CH 2 - (O} ) r2 -Z 2] s2 - groups are preferred, '- CH ₂ - "bonds to the benzene ring in the side _{- [CH 2 - (O)} r2 -Z ^2] _s2 - groups are more preferred.
The _{- [CH 2 - (O)} r2 -Z 2] s2 - In the group, ^{Z 2} represents an arylene group, r2 represents 0 or 1, s2 is 0 or 1.
The r2 is preferably 1 from the viewpoint of gelation activity.
From the same viewpoint, the s2 is preferably 1.

In the general formula (I), ^{L 3} represents a single bond, an oxygen atom, a methylene group, arylene group, _{or, - [CH 2 - (O} ) r3 -Z 3] s3 - represents a group, among these from the viewpoint of gelation _{activity, - [CH 2 - (O} ) r3 -Z 3] s3 - groups are preferred, '- CH ₂ - "bonds to the benzene ring in the side _{- [CH 2 - (O)} r3 -Z ^3] _s3 - group are more preferable.
The _{- [CH 2 - (O)} r3 -Z 3] s3 - in groups, ^{Z 3} represents an arylene group, r3 is 0 or 1, s3 represents 0 or 1.
The r3 is preferably 1 from the viewpoint of gelation activity.
From the same viewpoint, the s3 is preferably 1.

In the general formula (I), the L ¹ , the L ² , and the L ³ may be the same group or different groups, but the compound represented by the general formula (I) From the viewpoint of symmetry, the same group is preferable.

Examples of the arylene group represented by Z ¹ , Z ² , and Z ³ include a phenylene group, a biphenylene group, a naphthylene group, and the like, but the molecular weight of the compound represented by the general formula (I) is reduced. From these viewpoints, a phenylene group is preferable.
Z ¹ , Z ² , and Z ³ may be the same group or different groups, but are the same group from the viewpoint of symmetry of the compound represented by the general formula (I). It is preferable.

Moreover, in general formula (I), X represents an oxygen atom or a sulfur atom.
Three Xs in the general formula (I) are the same group.
X is preferably an oxygen atom from the viewpoint of gelation activity and ease of synthesis.

In the general formula (I), Y ¹ , Y ² , and Y ³ each independently represents an aryl group substituted with a hydrophilic group.
Y ¹ , Y ² , and Y ³ may be the same group or different groups, but are the same group from the viewpoint of symmetry of the compound represented by the general formula (I). It is preferable.
In Y ¹ , Y ² , and Y ³ , the number of hydrophilic groups relative to the aryl group can be appropriately adjusted according to the required degree of hydrophilicity, but from the viewpoint of ease of synthesis and the like, 1 or 2 It is preferable that

In Y ¹ , Y ² , and Y ³ , the substitution position of the hydrophilic group with respect to the aryl group is the outermost contour of the compound represented by the general formula (I) from the viewpoint of gelation activity. It is preferable that the substitution position is located.
Specifically, when the aryl group is a phenyl group substituted with one hydrophilic group, the hydrophilic group is preferably substituted at the 4-position of the phenyl group. Moreover, when the aryl group is a phenyl group substituted by two hydrophilic groups, the hydrophilic group is preferably substituted at the 3-position and 5-position of the phenyl group.

In the general formula (I), examples of the aryl group in Y ¹ , Y ² , and Y ³ include a phenyl group, a naphthyl group, a biphenyl group, and the like. From the viewpoint of increasing the molecular weight, a phenyl group is preferable.

In addition, the hydrophilic group in Y ¹ , Y ² , and Y ³ is not particularly limited, but —OH group, —SO ₃ H group, —SO ₃ M group (M represents an alkali metal element), — OSO ₃ H group, —OSO ₃ M group (M represents an alkali metal element), —COOH group, —COOM group (M represents an alkali metal element), —NR ¹ R ² X group (R ¹ and R ² Each independently represents an alkyl group, and X represents a halogen element, preferably a group containing at least one selected from a —NH ₂ group, an alkyleneoxy group, and a sugar group.

Here, the sugar group represents a monovalent group derived from sugar.
Specifically, it refers to a residue obtained by removing a hydrogen atom from one of the hydroxyl groups of a sugar.
The sugar group may be substituted with a substituent such as an alkyl group (such as a methyl group or an ethyl group) or a sulfo group.
The type of sugar is not particularly limited, but from the viewpoint of gelation activity, monosaccharides or oligosaccharides are preferable, monosaccharides or disaccharides are more preferable, and monosaccharides are particularly preferable.

As the monosaccharide, pentose or hexose is preferable.
Examples of the pentose include ribose, deoxyribose, and fructose.
Examples of the hexose include glucose, mannose, galactose, methyl-α-glucose, methyl-α-mannose, and the like.
Among the above, hexose is preferable, and glucose, mannose, galactose, methyl-α-glucose, and methyl-α-mannose are particularly preferable.

Examples of the disaccharide include maltose, isomaltose, lactose, trehalose, sucrose, and cerobiose.
Among these, maltose is particularly preferable.

In addition, the alkyleneoxy group is preferably an alkyleneoxy group having 1 to 10 carbon atoms, more preferably an alkyleneoxy group having 1 to 4 carbon atoms, and an ethyleneoxy group (that is, 2 carbon atoms) from the viewpoint of maintaining hydrophilicity. Are particularly preferred.
The alkyleneoxy group is preferably bonded to the aryl group on the oxygen atom side. Further, in one hydrophilic group, only one alkyleneoxy group (hereinafter, also referred to as “-AO-group”) may be contained alone, or a plurality of them may be linked in a chain, It may be contained in a state of-(AO) _n -structure (n is an integer of 1 to 10, for example).

The alkyl group represented by R ¹ and R ² is preferably an alkyl group having 1 to 10 carbon atoms and more preferably an alkyl group having 1 to 4 carbon atoms from the viewpoint of maintaining hydrophilicity.
The alkali metal represented by M is preferably K or Na.
The halogen element represented by X is preferably F, Cl, Br, or I.

Among the above, from the viewpoint of gelation activity, the hydrophilic group in Y ¹ , Y ² , and Y ³ includes a sugar group (preferably a sugar group derived from a monosaccharide) and an alkyleneoxy group (preferably A hydrophilic group including a combination of an alkyleneoxy group having 1 to 4 carbon atoms, more preferably an ethyleneoxy group) is preferable.
Among such hydrophilic groups, a hydrophilic group that is a combination of one sugar group (preferably a sugar group derived from a monosaccharide) and 1 to 10 ethyleneoxy groups is particularly preferable. [(OE) _n S _g ] group (where E represents an ethylene group, n represents an integer of 1 to 10 (preferably an integer of 1 to 3), and S _g represents a sugar group (preferably a monosaccharide). Represents a derived sugar group).

The compound represented by the general formula (I) is preferably a low-molecular compound, specifically a compound having a molecular weight of 5000 or less, and a compound having a molecular weight of 3000 or less from the viewpoint of ease of synthesis. Is more preferable. Further, the lower limit of the molecular weight of the compound represented by the general formula (I) is preferably 500 from the viewpoint of gelling activity.
More specifically, the molecular weight of the compound represented by the general formula (I) is preferably 500 to 3000, more preferably 1500 to 2500, from the viewpoints of gelling activity and ease of synthesis.

  As the substituted aromatic compound represented by the general formula (I) described above, from the viewpoint of obtaining the effect of the present invention more effectively, a substituted aromatic compound represented by the following general formula (II) (hereinafter, "Also referred to as" compound represented by formula (II) ") is preferred.

In the general formula (II), R represents a hydrogen atom or an alkyl group, Z ⁴ represents an arylene group, and Q ¹ , Q ² , and Q ³ are each independently a divalent or trivalent aromatic hydrocarbon. Represents a group. E represents an ethylene group, and S _g ¹ , S _g ² , and S _g ³ each independently represent a sugar group. m1, m2, and m3 each independently represent 1 or 2, and n1, n2, and n3 each independently represent an integer of 1 to 10.

Three R in general formula (II) are the same groups. R in general formula (II) is synonymous with R in general formula (I), and its preferable range is also the same.
Three Z ⁴ in the general formula (II) are the same arylene group. Z ⁴ in the general formula (II) has the same meaning as Z ¹ in the general formula (I), and the preferred range is also the same.

In the general formula (II), the divalent or trivalent aromatic hydrocarbon group represented by Q ¹ is substituted with one or two — [(OE) _n1 S _g ¹ ] groups in other words. An aryl group. Examples of the aryl group, in the general formula ^{(I), Y 1, Y} 2, and have the same meaning as the aryl group for Y ^3, the preferred range is also the same.
From the viewpoint of gelation activity, the substitution position of the — [(OE) _n1 S _g ¹ ] group with respect to the aryl group is the substitution position where the hydrophilic group is located at the outermost contour of the compound represented by the general formula (I). It is preferable that
Specifically, when the aryl group is a phenyl group substituted by one — [(OE) _n1 S _g ¹ ] group, the — [(OE) _n1 S _g ¹ ] group is the phenyl group It is preferable to substitute at the 4-position. In the case where the aryl group is a phenyl group substituted by two — [(OE) _n1 S _g ¹ ] groups, the — [(OE) _n1 S _g ¹ ] group is the 3-position of the phenyl group. And preferably substituted at the 5-position.

In general formula (II), the divalent or trivalent aromatic hydrocarbon group represented by Q ² is substituted by one or two — [(OE) _n2 S _g ² ] groups. An aryl group. Examples of the aryl group, in the general formula ^{(I), Y 1, Y} 2, and have the same meaning as the aryl group for Y ^3, the preferred range is also the same.
The preferred substitution position of the-[(OE) _n2 S _g ² ] group for Q ^{2 is the same as} the preferred substitution position of the-[(OE) _n1 S _g ¹ ] group for Q ¹ described above.

In the general formula (II), the divalent or trivalent aromatic hydrocarbon group represented by Q ³ is substituted with one or two — [(OE) _n3 S _g ³ ] groups in other words. An aryl group. Examples of the aryl group, in the general formula ^{(I), Y 1, Y} 2, and have the same meaning as the aryl group for Y ^3, the preferred range is also the same.
The preferred substitution position of the-[(OE) _n3 S _g ³ ] group for Q ^{3 is the same as} the preferred substitution position of the-[(OE) _n1 S _g ¹ ] group for Q ¹ described above.

Q ¹ , Q ² , and Q ³ may be the same group or different groups, but are the same group from the viewpoint of symmetry of the compound represented by the general formula (II). It is preferable.
Moreover, it is preferable that said n1, n2, and n3 are each independently an integer of 1-3.

In general formula (II), the sugar groups represented by S _g ¹ , S _g ² , and S _g ³ are synonymous with the sugar groups described in the description of general formula (I), and the preferred ranges are also the same. is there.
The sugar groups represented by S _g ¹ , S _g ² , and S _g ³ may be the same group or different groups, but from the viewpoint of symmetry of the compound represented by the general formula (II) Are preferably the same group.
Moreover, said m1, m2, and m3 are 1 or 2, and can be suitably selected according to the required degree of hydrophilicity.

The substituted aromatic compound of the present invention (compound represented by formula (I) or formula (II)) can be synthesized, for example, in the following three steps using a benzene derivative as a raw material.
A trisnitro compound is synthesized by reacting a halogenated benzene derivative such as 1,3,5-tris (bromomethyl) -2,4,6-triethylbenzene with nitrophenol (first stage).
The obtained trisnitro compound is reduced to obtain a trisamine compound (second stage).
For the obtained trisamine compound, a hydrophilic group (for example, the “— [(OE) _n1 S _g ¹ ] group”, the “— [(OE) _n2 S _g ² ] group”, the “— [(OE ) _{n3 S} g ^_3] group ", etc.) and an isocyanate group (-NCO group), or by reacting an aromatic compound having a thioisocyanate group (-NCS group), a substituted aromatic of the present invention is a Torisuurea compound or Torisuchiourea compound Group 3 compounds are obtained (stage 3).

Such a synthesis is described in detail in paragraphs [0020] to [0023] of JP-A-2008-189559, except that a hydrophilic group is introduced into the aromatic compound having an isocyanate group in the third stage. It can be performed by a method similar to the synthesis method of the organogelator.
As described above, the substituted aromatic compound of the present invention is based on an unprecedented logical molecular design in which a hydrophilic group is introduced into the aromatic compound used in the third stage in a known organogelator synthesis method. It can be synthesized.

  Hereinafter, exemplary compounds (Exemplary Compounds (1) to (5)) of the substituted aromatic compound represented by General Formula (I) or General Formula (II) are shown. However, the present invention is not limited to these exemplary compounds.

  In the above exemplary compound group, the group represented by “1βGlu” represents a monovalent group obtained by removing a hydrogen atom from the hydroxyl group at the 1-position of β-glucose, and the group represented by “1βMal” is represented by β This is a monovalent group obtained by removing a hydrogen atom from the hydroxyl group at the 1-position of maltose.

<Hydrogelling agent>
The hydrogelator of the present invention contains a compound represented by the aforementioned general formula (I) (including a compound represented by the general formula (II), the same applies hereinafter).
That is, as the form of the hydrogelator of the present invention, the compound represented by the above general formula (I) and other components may be used, even if the form is only the compound represented by the above general formula (I). (A form of a mixture or a form other than a mixture may be used).
When a hydrogelator in a form other than the mixture is added to water, the compound represented by the general formula (I) and other components may be added simultaneously or separately.
Examples of the other component include a binder component and a component that further promotes hydrogelation (for example, a buffer solution solute described later).

<Hydrogel>
The hydrogel of the present invention contains a compound represented by the aforementioned general formula (I).
As a specific form of the hydrogel of the present invention, at least water (and, if necessary, other components) in the gap portion of the three-dimensional network structure formed by self-assembly of the compound represented by the general formula (I) The form which exists is mentioned.
Here, as described above, the three-dimensional network structure is a structure formed by further assembling a fibrous supramolecular assembly formed by self-assembly of the compounds represented by the general formula (I). .
Examples of other components that can be contained together with water in the gaps of the three-dimensional network structure include proteins such as lectins described later, solutes in buffer solutions, sugars, and surfactants such as sodium dodecyl sulfate (SDS).

The hydrogel of the present invention is suitably produced by, for example, a water-based sample gelation method described later.
Hereinafter, the reaction in which the aqueous sample gels is also referred to as “phase transition reaction from sol to gel”.
Using this sol-to-gel phase transition reaction, screening can be performed by selecting target compounds having specific properties (properties that strongly interact with specific compounds) from a group of unknown test compounds. . The specific method will be described in detail in the section <Screening Method> described later.

In addition, the hydrogel of the present invention is in a gel state at room temperature (15 ° C. to 25 ° C.) as in the case of general hydrogels, but external stimuli (stimulation by heating, physical stimulation such as stirring, addition of chemical substances) Etc.), the self-assembly of the compounds represented by the general formula (I) is eliminated and the sol is formed.
As an example of the solubilization of the hydrogel by the addition of a chemical substance, there is a reaction in which an anion is added to eliminate the self-assembly of the compounds represented by the general formula (I) to form a sol. The anion can be added in the form of a metal salt such as a sodium salt.
The anion added here is a urea group (or thiourea group) of the compound represented by the general formula (I) from the viewpoint of more effectively eliminating the self-assembly of the compounds represented by the general formula (I). An anion that interacts with is preferred. Specific examples of such anions include halogen ions such as fluorine ions (F ⁻ ), chlorine ions (Cl ⁻ ), bromine ions (Br ⁻ ), and iodine ions (I ⁻ ), and acetate ions (CH ₃ COO). ^- ), Etc.
As another example of the solubilization of the hydrogel by adding a chemical substance, by adding a lectin that strongly interacts with the hydrophilic group at the terminal of the compound represented by the general formula (I), the hydrogel is represented by the general formula (I). The reaction which eliminates the self-assembly of the compounds to be made and sols.
Hereinafter, the reaction in which the hydrogel forms a sol is also referred to as “phase transition reaction from gel to sol”.

The hydrogel of the present invention can be used as an electrophoresis gel by containing sodium dodecyl sulfate (SDS) as required.
That is, the target substance (protein, nucleic acid, etc.) can be developed on the hydrogel of the present invention by electrophoresis. In this case, the target substance can be efficiently recovered by making the hydrogel in which the target substance is developed into a sol by a phase transition reaction from the gel to the sol.
For example, when the hydrogel of the present invention is used as a gel for protein electrophoresis, analysis such as MALDI / TOFMS (matrix-assisted laser desorption / ionization time-of-flight mass spectrometer) is performed from each spot after electrophoresis. A possible amount of protein sample can be recovered.

<Gelification method of aqueous sample>
The method for gelling an aqueous sample of the present invention includes bringing the compound represented by the above general formula (I) into contact with an aqueous sample.
The contact can be performed by adding and mixing the compound represented by the general formula (I) to the aqueous sample.
After mixing, the aqueous sample can be gelled as described above by allowing it to stand for 1 hour or longer as necessary.
Therefore, the method for gelling an aqueous sample of the present invention is preferably used for sensing an aqueous environmental sample or an aqueous biological sample containing protein, sugar, etc. (for example, the screening method of the present invention described later). it can.

Here, the aqueous sample may be water, or an aqueous solution or dispersion using water as a solvent.
The aqueous solution is preferably a buffer solution from the viewpoint of gelation activity.
Examples of the buffer include sodium phosphate buffer, Tris-HCl buffer, 4- (2-hydroxyethyl) -1-piperazineethanesulfonic acid-sodium hydroxide (HEPES- NaOH) buffer, sodium acetate (NaOAc) buffer, borate buffer (borate), borate-sodium hydroxide (borate NaOH) buffer, tris-glycine-sodium dodecyl sulfate (Tris-glycine-SDS) buffer Various buffer solutions such as can be used.
The pH of the aqueous sample (for example, buffer) is preferably 3 to 11 and more preferably 4 to 10 from the viewpoint of gelation activity.

In the gelation method of the aqueous sample of the present invention, the aqueous sample after contact with the compound represented by the general formula (I) is subjected to heat treatment and ultrasonic treatment in order to further increase the gelation activity as necessary. You may give at least one of these.
Here, the heat treatment and the ultrasonic treatment may be used in combination.
As a combination method, heat treatment and ultrasonic treatment may be sequentially performed (any treatment may be performed first), or heat treatment and ultrasonic treatment may be simultaneously performed.

The heat treatment is performed, for example, under conditions of 70 ° C. or higher (preferably 80 ° C. or higher).
The heating time is, for example, 30 minutes or more (preferably 60 minutes or more).
After the heat treatment, for example, the gelation can be further advanced by cooling to room temperature (15 ° C. to 25 ° C.).
In addition, the ultrasonic treatment is performed, for example, using a commercially available ultrasonic treatment apparatus for 5 minutes or more (preferably 15 minutes or more).

  As mentioned above, although heat processing and ultrasonic treatment were demonstrated, in the gelation method of the aqueous sample of this invention, these processes are not essential. From the viewpoint of suppressing denaturation of biological samples including proteins and sugars, it is preferable not to perform heat treatment or ultrasonic treatment.

<Screening method>
The screening method of the present invention comprises an aqueous sample containing a compound represented by the aforementioned general formula (I) and a specific compound that interacts with the hydrophilic group of the compound represented by the general formula (I). Adding the test compound, detecting the gelation activity of the aqueous sample after the addition, and causing the test compound contained in the aqueous sample in which the gelling activity is detected to be stronger than the hydrophilic group Screening as a target compound that interacts with a specific compound.
Hereinafter, although the mechanism estimated about the mechanism which selects the target compound which interacts with a specific compound stronger than a hydrophilic group with the screening method of this invention is demonstrated, this invention is not limited to the following mechanisms. .

In the screening method of the present invention, an aqueous sample containing a compound represented by the general formula (I) and a specific compound that interacts with the hydrophilic group of the compound represented by the general formula (I) is used.
As described above, when the compound represented by the general formula (I) is brought into contact with the aqueous sample, the aqueous sample gels.
However, when the aqueous sample further contains a specific compound that interacts with the hydrophilic group, the aqueous sample does not gel. The reason for not gelling is presumed as follows.
That is, in an aqueous sample containing the compound represented by the general formula (I) and the specific compound, an aggregate (hereinafter referred to as “aggregate”) in which the compound represented by the general formula (I) and the specific compound are associated. (Also referred to as “A”) (in the aggregate A, the hydrophilic group of the compound represented by the general formula (I) interacts with the specific compound). In such a state of the aggregate A, it is considered that the self-assembly of the compounds represented by the general formula (I) is inhibited due to the influence of steric hindrance by the specific compound.
Therefore, when the aqueous sample contains the specific compound, it is considered that the aqueous sample does not gel and maintains the state of an aqueous dispersion (sol) in which the aggregate A is dispersed.

Next, a test compound is added to the aqueous sample in the state of the aqueous dispersion (sol). Here, the test compound refers to an unspecified compound to be tested.
After the addition, the strength of the interaction between the hydrophilic group and the specific compound (hereinafter also referred to as “interaction A”) and the interaction between the specific compound and the test compound (hereinafter also referred to as “interaction B”). ), The result is divided into two results: whether the aqueous sample gels or keeps the sol state.

(1) When interaction B is stronger than interaction A In this case, gelation of the aqueous dispersion occurs (that is, gelation activity appears).
The reason is considered as follows.
That is, when a test compound is added to the aqueous sample, the test compound extracts the specific compound from the aggregate A, and an aggregate of the specific compound and the test compound (hereinafter also referred to as “aggregate B”) is formed. Is done. With the formation of the aggregate B, the association in the aggregate A is canceled, and the compound represented by the general formula (I) exists alone. As a result, since the compound represented by the general formula (I) self-assembles, it is considered that gelation of the aqueous dispersion occurs.

(2) When interaction B is weaker than interaction A In this case, gelation of the aqueous dispersion does not occur (that is, gelation activity does not appear).
The reason is considered as follows.
That is, even when a test compound is added to the aqueous sample, the test compound does not extract the specific compound from the aggregate A, and the aggregate A is maintained as it is.
Therefore, even when the test compound is added to the aqueous sample, the self-assembly of the compounds represented by the general formula (I) is maintained while being inhibited, and thus the gelation of the aqueous dispersion does not occur. It is done.

  As described above, when a test compound is added to the aqueous sample and gelation activity is detected (the aqueous sample gels), the test compound interacts with the specific compound stronger than the hydrophilic group As a target compound (that is, as a target compound satisfying a stronger relationship between the specific compound-target compound interaction (interaction B) than the hydrophilic group-specific compound interaction (interaction A)) Can be sorted. This selection can be performed by a simple method of visually confirming gelation.

According to the screening method of the present invention, from the hydrophilic group-specific compound, information on the interaction between the already-known hydrophilic group and the specific compound is used. It is possible to select a target compound that strongly interacts with a specific compound.
Since the compound represented by the general formula (I) can be synthesized by introducing a hydrophilic group at the end of a known organogelator as described above, a hydrophilic group can be freely selected according to the target compound. Can be synthesized.
As described above, the screening method of the present invention is a screening method with a high degree of flexibility (flexibility) in that the structure of a compound that becomes a hydrogelator can be determined according to the target compound.

The screening method of the present invention can be, for example, a screening method using sugar-lectin interaction.
In this screening method, the hydrophilic group in the general formula (I) is a hydrophilic group containing a sugar group (more preferably, a hydrophilic group containing a sugar group and an alkyleneoxy group), and the specific compound is a lectin. There is preferred a form in which the test compound is a sugar and the target compound is a sugar.
More preferably, an aqueous sample containing a compound represented by the above general formula (II) and a lectin as a specific compound that interacts with a sugar group of the compound represented by the general formula (II), Adding a sugar as a test compound, detecting the gelation activity of the aqueous sample after the addition, and converting the sugar as the test compound contained in the aqueous sample in which the gelation activity is detected into the sugar Screening as a sugar that interacts with the lectin more strongly than the group.
Examples of the combination of [sugar corresponding to sugar group, lectin] in the screening method of the present invention include a combination of [β-glucose, concanavalin A].
Other combinations include [methyl-α-glucose, concanavalin A], [methyl-α-mannose, concanavalin A], [mannose trimer, concanavalin A], [galactose, galectin-1 (P-type). ], [Galactose, galectin-3 (C-type)], [galactose, galectin-9 (T-type)] and the like can be used.

The screening method using the sugar-lectin interaction is useful as a simple evaluation system for elucidation of sugar function.
A simple evaluation system for sugar-lectin interaction is still in high demand in the basic research field for the purpose of elucidating vital functions, but in the future, establishment of medical technology for individuals such as tailor-made medicine and sugar chain medicine The industrial and social demands for the practical application of this technology are increasing.

The screening method of the present invention can also be applied to combinations in which the hydrophilic group is a group derived from an antigen and the specific compound is an antibody. This system is a screening method using the antigen-antibody interaction. In this case, it is possible to select an antigen having a stronger interaction with the antibody than the group derived from the antigen.
The screening method of the present invention can also be applied to a combination in which the hydrophilic group is a group derived from DNA and the specific compound is a DNA-binding protein. This system is a screening method utilizing the interaction of DNA-DNA binding proteins. In this case, it is possible to select a DNA having a stronger interaction with a DNA binding protein than a group derived from the DNA.

As a modification of the screening method of the present invention, a screening method in which the relationship between the specific compound and the test compound is exchanged is also suitable.
The screening method according to the modification includes a compound represented by the above general formula (I) and a test compound that interacts with the hydrophilic group of the compound represented by the general formula (I) (unspecified compound) ), And a test compound contained in the aqueous sample in which the gelation activity is detected, adding a specific compound to the aqueous sample containing, detecting the gelation activity of the aqueous sample after the addition, Screening as a target compound that has a stronger interaction with a specific compound than an interaction with the hydrophilic group.

  Examples of the present invention will be described below, but the present invention is not limited to these examples. In the examples, “%” and “wt%” represent “mass%” unless otherwise specified. Moreover, "room temperature" in an Example represents 15 to 25 degreeC.

[Example 1]
As Example 1, an exemplary compound of the substituted aromatic compound of the present invention was synthesized.
<Synthesis of Exemplary Compound (1)>
Exemplified compound (1) was synthesized according to the following reaction schemes 1-1 to 1-6.
Hereinafter, the synthesis example of exemplary compound (1) is demonstrated in detail.

  First, compound (1-c) was synthesized according to the following reaction scheme 1-1.

Hereinafter, details of the reaction scheme 1-1 will be described.
Under an argon atmosphere, a solution of 4.00 g (10.3 mmol) of the starting material (1-a), which is ice-cooled on ice, in a solution of acetic acid (30.7 mL), 2.65 mL (35.8 mmol) of acetyl bromide, 0.55 mL (13.6) of methanol (MeOH) mmol) was added sequentially. After stirring at room temperature for 18 hours, the low boiling point compound was distilled off under reduced pressure while heating at 80 ° C. to obtain a crude product of compound (1-b). The obtained crude product was used in the next reaction without further purification.
Under an argon atmosphere, 14.6 g (103 mmol) of sodium sulfate and 10.0 mL (105 mmol) of sodium disulfate were sequentially added to a methylene chloride (400 mL) solution of the above crude product cooled on ice, and the mixture was stirred at room temperature for 15 minutes. The obtained solution was ice-cooled again, 5.89 g (21.4 mmol) of silver carbonate was added, and the mixture was stirred at room temperature for 20 hours. From the obtained solution, components insoluble in methylene chloride were removed by suction filtration. The filtrate was washed successively with water and saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure from the resulting solution to obtain a crude product.
The resulting crude product was purified by silica gel column chromatography (AcOEt / Hexane = 2/1 → AcOEt) to obtain 2.83 g (yield 63%) of the target compound (1-c) as a white solid. .

-NMR data of compound (1-c)-
¹ H NMR (600 MHz, CDCl ₃ )
δ = 2.01 (s, 3H), 2.03 (s, 3H), 2.06 (s, 3H), 2.09 (s, 3H), 2.21 (t, J = 6.2 Hz, 1H), 3.56-3.61 (m, 2H) , 3.66 (t, J = 4.5 Hz, 2H), 3.70-3.76 (m, 4H), 3.97 (dt, J = 5.5, 8.9 Hz, 2H), 4.15 (dd, J = 2.1, 12.4 Hz, 1H), 4,26 (dd, J = 4.8, 13.4 Hz, 1H), 4.61 (d, J = 7.6 Hz, 1H), 5.00 (dd, J = 7.6, 9.6 Hz, 1H), 5.10 (t, J = 9.6 Hz , 1H), 5.22 (t, J = 9.6 Hz, 1H).

  Next, compound (1-d) was synthesized according to the following reaction scheme 1-2.

Hereinafter, details of the reaction scheme 1-2 will be described.
Synthesized above as starting material in methylene chloride (12.5 mL) solution of 1.22 g (6.39 mmol) tosyl chloride and 24.6 mg (0.201 mmol) N, N-dimethyl-4-aminopyridine (DMAP) under argon atmosphere 2.78 g (6.36 mmol) of compound (1-c) was added, and 2.65 mL (19.0 mmol) of triethylamine was further added, followed by stirring at room temperature for 16 hours. A saturated ammonium chloride aqueous solution was added to the reaction solution after stirring, and water and methylene chloride were further added to dilute, and the mixture was separated into an aqueous layer and an organic layer. The aqueous layer was extracted twice using methylene chloride, and the organic layer was recovered.
Next, the organic layer separated above and the organic layer collected above were combined and washed with saturated saline. The organic layer after washing was dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure to obtain a crude product.
The obtained crude product was purified by silica gel column chromatography (AcOEt / Hexane = 1/1 → 2/1) to give 3.54 g (yield 95%) of the target compound (1-d) as a white solid. )Obtained.

-NMR data of compound (1-d)-
¹ H NMR (600 MHz, CDCl ₃ )
δ = 2.00 (s, 3H), 2.02 (s, 3H), 2.03 (s, 3H), 2.08 (s, 3H), 2.45 (s, 3H), 3.57-3.59 (m, 2H), 3.66 (dt, J = 1.4, 4.8 Hz, 2H), 3.68-3.71 (m, 2H), 3.89 (dt, J = 5.5, 9.4 Hz, 1H), 4.13-4.15 (m, 3H), 4.26 (dd, J = 4.8, 12.4 Hz, 1H), 4.58 (d, J = 8.3 Hz, 1H), 4.97 (dd, J = 8.2, 9.6 Hz, 1H), 5.08 (t, J = 9.6 Hz, 1H), 5.21 (t, J = 9.6 Hz, 1H), 7.36 (d, J = 8.3 Hz, 2H), 7.80 (d, J = 8.3 Hz, 2H).
¹³ C NMR (150 MHz, CDCl ₃ )
δ = 170.75, 170.32, 169.53, 169.49, 144.98, 133.10, 129.97, 128.08, 100.91, 72.91, 71.90, 71.38, 70.51, 69.30, 69.09, 68.90, 68.49, 62.03, 21.74, 20.84, 20.75, 20.72, 20.70.

  Next, compound (1-e) was synthesized according to the following reaction scheme 1-3.

Hereinafter, details of Reaction Scheme 1-3 will be described.
In an argon atmosphere, 154 mg (1.02 mmol) of 5-Azideresorcinol and 841 mg (6.10 mmol) of potassium carbonate in a suspension of dimethylformamide (DMF) (10.0 mL), the above compound as a starting material (1-d) A solution of 1.50 g (2.54 mmol) in DMF (13.0 mL) was added. The resulting reaction solution was heated at 100 ° C. for 5.5 hours. The heated reaction solution was cooled to room temperature, and insoluble components were removed by suction filtration. The filtrate was diluted with water and methylene chloride and separated into an aqueous layer and an organic layer. The aqueous layer was extracted three times with methylene chloride, and the organic layer was recovered.
Next, the organic layer separated above and the organic layer collected above were combined and washed with saturated saline. The organic layer after washing was dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure to obtain a crude product.
The resulting crude product was purified by silica gel column chromatography (AcOEt / Hexane = 2/3) to obtain 903 mg (90% yield) of the target compound (1-e) as a yellow oil.

-NMR data of compound (1-e)-
¹ H NMR (600 MHz, CDCl ₃ )
δ = 2.00 (s, 6H), 2.02 (s, 6H), 2.03 (s, 6H), 2.08 (s, 6H), 3.70-3.72 (m, 6H), 3.74-3.78 (m, 2H), 3.80- 3.82 (m, 4H), 3.97 (dt, J = 4.1, 11.0 Hz, 2H), 4.06 (t, J = 4.5 Hz, 4H), 4.13 (dd, J = 2.4, 12.0 Hz), 4.25 (dd, J = 4.8, 12.4 Hz, 2H), 4.60 (d, J = 8.3 Hz), 5.00 (dd, J = 8.9, 9.6 Hz, 2H), 5.09 (t, J = 9.8 Hz, 2H), 5.20 (t, J = 9.6 Hz, 2H), 6.21 (s, 2H), 6.27 (s, 1H).

  Next, compound (1-f) was synthesized according to the following reaction scheme 1-4.

Hereinafter, details of Reaction Scheme 1-4 will be described.
Under a hydrogen atmosphere, a suspension of the above compound (1-e) 874 mg (0.885 mmol) as a starting material and a catalyst (10% palladium on activated carbon) 87.5 mg in ethyl acetate (13.0 mL) at room temperature was 3.5. Stir for hours. The catalyst was removed from the stirred solution by filtration, and the solvent of the filtrate was distilled off under reduced pressure to obtain a crude product.
The resulting crude product was purified by silica gel column chromatography (AcOEt / Hexane = 2/1 → 4/1) to obtain the target compound (1-f) as a white solid, 806 mg (yield 95%) Obtained.

-NMR data of compound (1-f)-
¹ H NMR (600 MHz, CDCl ₃ )
δ = 2.00 (s, 6H), 2.02 (s, 6H), 2.03 (s, 6H), 2.08 (s, 6H), 3.68-3.71 (m, 6H), 3.78-3.79 (m, 6H), 3.95 ( dt, J = 4.1, 11.7 Hz, 2H), 4.04 (t, J = 4.8 Hz, 4H), 4.13 (dd, J = 2.7, 12.4 Hz, 2H), 4.25 (dd, J = 4.9, 12.4 Hz, 2H) ), 4.65 (d, J = 8.2 Hz, 2H), 5.00 (dd, J = 7.6, 9.6 Hz, 2H), 5.09 (t, J = 9.6 Hz, 2H), 5.22 (t, J = 9.2 Hz, 2H) ), 5.91 (s, 3H).
¹³ C NMR (150 MHz, CDCl ₃ )
δ = 20.96, 21.00, 21.02, 21.11, 55.98, 62.31, 67.59, 68.79, 69.31, 70.18, 71.00, 71.67, 72.10, 73.24, 95.13, 101.19, 148.94, 161.13, 169.79, 169.82, 170.69, 171.06.

  Next, the compound (1-g) was synthesized according to the following reaction scheme 1-5.

Hereinafter, details of Reaction Scheme 1-5 will be described.
Under an argon atmosphere, 208 mg (208 μmol) of the starting material compound (1-f) in 1,2-dichloroethane (0.4 mL) was added to 62.8 mg (212 μmol) of triphosgene. A 2-dichloroethane (0.4 mL) solution and triethylamine were sequentially added, and the mixture was stirred at room temperature for 1 hour, and then the low boiling point compound was distilled off under reduced pressure to obtain a white solid mainly composed of isocyanate. This white solid was dissolved in 1,2-dichloroethane (1.0 mL), 32.0 mg (72.5 μmol) of trisamine was added, and the mixture was heated to reflux for 17 hours. After the refluxed reaction liquid was cooled to room temperature, a saturated aqueous ammonium chloride solution was added, water and methylene chloride were further added for dilution, and the aqueous layer and the organic layer were separated. The aqueous layer was extracted three times with methylene chloride, and the organic layer was recovered.
Next, the organic layer separated above and the organic layer collected above were combined and washed with saturated saline. The organic layer after washing was dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure to obtain a crude product.
The resulting crude product was purified by silica gel column chromatography (AcOEt / Hexane = 7/1 → 1/0) to obtain 175 mg (yield 71%) of the target compound (1-g).

-NMR data of compound (1-g)-
¹ H NMR (600 MHz, Acetone-d ₆ )
δ = 1.94 (s, 18 H), 1.98 (s, 18H), 1.99 (s, 18H), 2.01 (s, 18H), 3.66-3.70 (m, 18H), 3.75-3.78 (m, 6H), 3.80 (t, J = 4.5 Hz, 12H), 3,90-3.92 (m, 18H), 4.09-4.12 (m, 18 H), 4.25 (dd, J = 4.8, 12.4 Hz, 6H), 4.82 (d, J = 7.6 Hz, 6H), 4.91 (t, J = 8.9 Hz, 6H), 5.02 (t, J = 9.6 Hz, 6H), 5.17 (s, 6H), 5.24 (t, J = 9.3 Hz, 6H) , 6.21 (t, J = 2.1 Hz, 3H), 6.67 (dd, J = 2.1, 8.2 Hz, 3H), 6.82 (d, J = 2.1 Hz, 6H), 7.07 (d, J = 8.2 Hz, 3H) , 7.17 (t, J = 7.9 Hz, 3H), 7.36 (s, 3H), 7.58 (s, 3H), 8.15 (s, 3H), 8.16 (s, 3H).
¹³ C NMR (150 MHz, Acetone-d ₆ )
δ = 20.69, 20.72, 20.78, 20.81, 62.83, 68.39, 69.52, 69.88, 70.26, 70.43, 71.07, 72.26, 72.43, 73.66, 96.44, 98.78, 101.48, 106.62, 109.66, 112.36, 126.97, 130.55, 139.04, 141.93, 142.45, 153.44, 160.31, 161.35.

  Next, Exemplified Compound (1) was synthesized as a final product according to the following Reaction Scheme 1-6.

Hereinafter, details of Reaction Scheme 1-6 will be described.
To a solution of 159 mg (46.8 μmol) of the starting compound (1-g) in ethanol (1.1 mL) was added 20.0 mg (294 μmol) of NaOEt, and the mixture was stirred at room temperature for 18 hours. The reaction mixture after stirring was purified using a dialysis membrane. Due to this purification, the product obtained by concentration contained an intermediate with insufficient reaction, so the product was dissolved again in ethanol (1.1 mL) and 30.6 mg (450 μmol) of NaOEt was added. And stirred at room temperature for 22 hours. The solution after stirring was purified using a dialysis membrane, and the solvent was distilled off under reduced pressure to obtain 96.1 mg (yield 86%) of Illustrative Compound (1) as the target compound as an ocherous solid.
It was confirmed by electron spray ionization mass spectrometry (JEOL JMS-T100LC AccTOF) that the obtained target compound (Exemplary Compound (1)) had a molecular weight of 2395.

-NMR data of exemplary compound (1)-
1H NMR (600 MHz, DMSO-d ₆ )
δ = 2.93-2.97 (m, 6H), 3.01-3.05 (m, 6H), 3.06-3.09 (m, 6H), 3.10-3.14 (m, 6H), 2.40-3.44 (m, 6H), 3.59-3.66 (m, 24H), 4.02 (s, 12H), 3.88-3.90 (m, 6H), 4.15 (d, J = 7.6 Hz, 6H), 4.50 (t, J = 5.8 Hz, 6H), 4.89 (d, J = 4.8 Hz, 6H), 4.95 (s, 6H), 5.02 (d, J = 4.1 Hz, 6H), 5.11 (s, 6H), 6.13 (s, 3H), 6.62 (d, J = 7.7 Hz, 3H), 6.70 (s, 6H), 7.06 (s, 3H), 7.15 (t, J = 7.9 Hz, 3H), 7.18 (s, 3H), 7.50 (s, 3H), 8.98 (s, 3H).

<Synthesis of Exemplary Compound (2)>
Exemplified compound (2) was synthesized according to the following reaction schemes 2-1 to 2-6.
Hereinafter, the synthesis example of exemplary compound (2) is demonstrated in detail.

  First, compound (2-c) was synthesized according to the following reaction scheme 2-1.

Hereinafter, details of the reaction scheme 2-1 will be described.
In a solution of 4.01 g (10.3 mmol) of the starting compound (2-a) in acetic acid (37.0 mL) under ice-cooled ice-cooling under an argon atmosphere, add 2.65 mL (35.8 mmol) of acetyl bromide and 0.55 mL (13.6 mmol) of MeOH. Added sequentially. After stirring the obtained solution at room temperature for 19 hours, the low boiling point compound was distilled off under reduced pressure while heating to 80 ° C. to obtain a crude product of compound (2-b).
The obtained crude product was used in the next reaction without further purification.
Under an argon atmosphere, 14.6 g (103 mmol) of sodium sulfate and 6.00 mL (105 mmol) of ethyleneglycol were sequentially added to a methylene chloride (400 mL) solution of the above crude product cooled on ice, and stirred at room temperature for 15 minutes. The obtained solution was ice-cooled again, 5.94 g (21.5 mmol) of silver carbonate was added, and the mixture was stirred at room temperature for 36 hours. From the obtained solution, components insoluble in methylene chloride were removed by suction filtration. The filtrate was washed successively with water and saturated brine, and then dried over anhydrous sodium sulfate. From the obtained solution, the solvent was distilled off under reduced pressure to obtain a crude product.
The resulting crude product was purified by silica gel column chromatography (AcOEt / Hexane = 2/1 → AcOEt) to obtain 2.24 g (yield 56%) of the target compound (2-c) as a white solid. .

-NMR data of compound (2-c)-
¹ H NMR (600 MHz, CDCl ₃ )
δ = 2.01 (s, 3H), 2.03 (s, 3H), 2.06 (s, 3H), 2.11 (s, 3H), 2.41 (t, J = 6.5 Hz, 1H), 3.69 -3.77 (m, 2H) , 3.84-3.85 (m, 2H), 4.20 (d, J = 4.1 Hz, 2H), 4.55 (d, J = 8.2 Hz, 1H), 5.01 (t, J = 8.9 Hz, 1H), 2.06 (t, J = 9.6 Hz, 1H), 5.22 (t, J = 9.3 Hz, 1H).

  Next, compound (2-d) was synthesized according to the following reaction scheme 2-2.

Hereinafter, details of the reaction scheme 2-2 will be described.
Under an argon atmosphere, to a solution of 0.74 g (3.87 mmol) tosyl chloride and 14.5 mg (0.119 mmol) DMAP in methylene chloride (7.8 mL) was added 1.50 g (3.82 mmol) triethylamine 1.50 mL (3.82 mmol) starting compound (2-c). 10.8 mmol) was added and stirred at room temperature for 16 hours. A saturated ammonium chloride aqueous solution was added to the reaction solution after stirring, and water and methylene chloride were further added to dilute, and the mixture was separated into an aqueous layer and an organic layer. The aqueous layer was extracted twice using methylene chloride, and the organic layer was recovered.
Next, the organic layer separated above and the organic layer collected above were combined and washed with saturated saline. The organic layer after washing was dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure to obtain a crude product.
The obtained crude product was purified by silica gel column chromatography (AcOEt / Hexane = 1/2 → 1/1) to obtain 1.64 g (yield 79%) of the target compound (2-d) as a white solid. Obtained.

-NMR data of compound (2-d)-
¹ H NMR (600 MHz, CDCl ₃ )
δ = 2.00 (s, 3H), 2.02 (s, 3H), 2.05 (s, 3H), 2.08 (s, 3H), 2.46 (s, 3H), 3.65-3.68 (m, 1H), 3.78-3.82 ( m, 1H), 3.97-4.00 (m, 1H), 4.10-4.18 (m, 3H), 4.23 (dd, J = 4.8, 12.4 Hz, 1H), 4.51 (d, J = 7.6 Hz, 1H), 4.92 (dd, J = 8.2, 9.8 Hz, 1H), 5.05 (t, J = 9.6 Hz, 1H), 5.18 (t, J = 9.6 Hz, 1H), 7.36 (d, J = 8.3 Hz, 2H), 7.78 (d, J = 8.2 Hz, 2H).

  Next, compound (2-e) was synthesized according to the following reaction scheme 2-3.

Hereinafter, details of the reaction scheme 2-3 will be described.
Under an argon atmosphere, to a suspension of 5-Azideresorcinol 57.6 mg (0.381 mmol) and potassium carbonate 316 mg (2.29 mmol) in DMF (4.2 mL) was added tosyl compound (2-d) 499 mg (0.913 mmol). DMF (4.6 mL) solution was added. The reaction was heated at 90 ° C. for 8 hours. The heated reaction solution was cooled to room temperature, and insoluble components were removed by suction filtration. The filtrate was diluted with water and methylene chloride, and separated into an aqueous layer and an organic layer. The aqueous layer was extracted three times with methylene chloride, and the organic layer was recovered.
Next, the organic layer separated above and the organic layer collected above were combined and washed with saturated saline. The organic layer after washing was dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure to obtain a crude product.
The obtained crude product was purified by silica gel column chromatography (AcOEt / Hexane = 2/3) to obtain 287 mg (yield 84%) of the target compound (2-e) as a yellow oil.

-NMR data of compound (2-e)-
¹ H NMR (600 MHz, CDCl ₃ )
δ = 1.94 (s, 6H), 1.98 (s, 6H), 2.01 (s, 6H), 2.06 (s, 6H), 3.70-3.72 (m, 2H), 3.88-3.92 (m, 2H), 4.05- 4.14 (m, 8H), 4.25 (dd, J = 4.8, 12.4 Hz, 2H), 4.63 (d, J = 7.6 Hz, 2H), 4.99 (t, J = 8.6 Hz, 2H), 5.08 (t, J = 9.6 Hz, 2H), 5.20 (t, J = 9.3 Hz, 2H), 6.16 (d, J = 2.1 Hz, 2H), 6.21 (s, 1H).

  Next, compound (2-f) was synthesized according to the following reaction scheme 2-4.

Hereinafter, details of the reaction scheme 2-4 will be described.
In a hydrogen atmosphere, a suspension of 269 mg (0.299 mmol) of the starting compound (2-e) and 27.8 mg of catalyst (10% palladium on activated carbon) in ethyl acetate (3.0 mL) was added at room temperature to 7.5. Stir for hours. The catalyst was removed from the stirred solution by filtration, and the solvent of the filtrate was distilled off under reduced pressure to obtain a crude product.
The resulting crude product was purified by silica gel column chromatography (AcOEt / Hexane = 2/1 → 3/1) to obtain 199 mg (yield 77%) of the compound (2-f) as a white solid as the target product. It was.

-NMR data of compound (2-f)-
¹ H NMR (600 MHz, CDCl ₃ )
δ = 1.95 (s, 6H), 2.00 (s, 6H), 2.03 (s, 6H), 2.08 (s, 6H), 3.70-3.73 (m, 4H), 3.88-3.92 (m, 2H), 4.04 ( t, J = 4.8 Hz, 4H), 4.08-4.18 (m, 4H), 4.26 (dd, J = 4.5, 12.0 Hz, 2H), 4.65 (d, J = 7.6 Hz, 2H), 5.02 (dd, J = 8.2, 9.6 Hz, 2H), 5.09 (t, J = 9.6 Hz, 2H), 5.22 (t, J = 9.6 Hz, 2H), 5.86 (s, 3H).
¹³ C NMR (150 MHz, CDCl ₃ )
δ = 20.92, 20.97, 21.09, 62.25, 67.55, 68.72, 71.55, 72.24, 73.14, 92.66, 95.13, 101.47, 148.89, 161.08, 169.76, 169.85, 170.62, 171.04.

  Next, compound (2-g) was synthesized according to the following reaction scheme 2-5.

Hereinafter, details of Reaction Scheme 2-5 will be described.
Under argon atmosphere, add 1,2-dichloroethane solution of triphosgene and triethylamine to 1,2-dichloroethane solution of 177 mg (202 μmol) of starting compound (2-f), and stir at room temperature for 1 hour. The low boiling point compound was distilled off under reduced pressure to obtain a white solid mainly composed of isocyanate. This white solid was dissolved in 1,2-dichloroethane, trisamine was added, and the mixture was heated to reflux for 24 hours. After the refluxed reaction liquid was cooled to room temperature, a saturated aqueous ammonium chloride solution was added, water and methylene chloride were further added for dilution, and the aqueous layer and the organic layer were separated. The aqueous layer was extracted three times with methylene chloride, and the organic layer was recovered.
Next, the organic layer separated above and the organic layer collected above were combined and washed with saturated saline. The organic layer after washing was dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure to obtain a crude product.
The obtained crude product was purified by silica gel column chromatography (AcOEt / Hexane = 2/1 → 15/1) to obtain 110 mg (yield 52%) of the compound (2-g) as the target product.

-NMR data of compound (2-g)-
¹ H NMR (600 MHz, Acetone-d ₆ )
δ = 1.93 (s, 18H), 1.93 (s, 18H), 1.98 (s, 18H), 2.02 (s, 18H), 3.91-3.96 (m, 12H), 4.05-4.12 (m, 24H), 4.27 ( dd, J = 4.8, 12.4 Hz, 6H), 4.85 (d, J = 8.2 Hz, 6H), 4.93 (dd, J = 8.2, 9.6 Hz, 6H), 5.03 (t, J = 9.6 Hz, 6H), 5.12 (s, 6H), 5.26 (t, J = 9.6 Hz, 6H), 6.20 (s, 3H), 6.68 (dd, J = 2.1, 8.2 Hz, 3H), 6.79 (d, J = 8.2 Hz, 6H ), 7.06 (d, J = 8.2 Hz, 3H), 7.18 (t, J = 8.2 Hz, 3H), 7.34 (s, 3H), 7.53 (s, 3H), 8.10 (s, 3H), 8.13 (s , 3H).
¹³ C NMR (150 MHz, Acetone-d ₆ )
δ = 20.54, 20.60, 20.64, 20.67, 62.72, 67.93, 68.95, 69.39, 70.14, 72.07, 72.40, 73.47, 96.44, 98.70, 101.54, 106.52, 109.55, 112.26, 126.88, 130.43,138.93, 141.81, 142.39, 153.32, 160.19, 161.13, 169.78, 170.01, 170.30, 170.78.

  Next, Exemplified Compound (2) was synthesized according to the following Reaction Scheme 2-6.

Hereinafter, details of Reaction Scheme 2-6 will be described.
To a solution of 107 mg (34.2 μmol) of the starting compound (2-g) in ethanol (0.8 mL) was added 29.8 mg (438 μmol) of NaOEt, and the mixture was stirred at room temperature for 36 hours. The reaction mixture after stirring was purified using a dialysis membrane. As a result of this purification, the product obtained by concentration contained an insufficiently reactive intermediate. Therefore, the product was dissolved again in ethanol (0.8 mL), and 13.2 mg (194 μmol) of NaOEt was added. And stirred at room temperature for 24 hours. The solution after stirring was purified using a dialysis membrane, and the solvent was distilled off under reduced pressure to obtain 60.2 mg (yield 83%) of Example Compound (2) as a target compound as a yellow solid.
It was confirmed by electron spray ionization mass spectrometry (JEOL JMS-T100LC AccTOF) that the obtained target compound (Exemplary Compound (2)) had a molecular weight of 2131.

-NMR data of Exemplified Compound (2)-
¹ H NMR (600 MHz, DMSO-d ₆ )
δ = 2.98-3.02 (m, 6H), 3.05-3.09 (m, 6H), 3.11-3.18 (m, 12H), 3.45-3.48 (m, 6H), 3.68 (dd, J = 4.5, 10.7 Hz, 6H ), 3.79-3.82 (m, 6H), 4.03-4.10 (m, 18H), 4.23 (d, J = 4.2 Hz, 6H), 4.37 (t, J = 5.8 Hz, 6H), 4.77 (dd, J = 4.5, 12.0 Hz, 12H), 4.87 (d, J = 4.8 Hz, 6H), 5.11 (s, 6H), 5.71 (s, 3H), 6.65 (dd, J = 2.1, 8.3 Hz, 3H), 6.68 ( d, J = 2.1 Hz, 6H), 7.01 (d, J = 7.8 Hz, 3H), 7.17 (t, J = 8.2 Hz, 3H), 7.19 (s, 3H), 7.51 (s, 3H), 8.62 ( s, 3H), 8.64 (s, 3H).

<Synthesis of Exemplary Compound (3)>
Exemplified compound (3) was synthesized according to the following reaction schemes 3-1 to 3-5.
Hereinafter, the synthesis example of exemplary compound (3) is demonstrated in detail.

  First, compound (3-b) was synthesized according to the following reaction scheme 3-1.

Hereinafter, details of the reaction scheme 3-1 will be described.
Compound (3-a) (1.06 g 1.80) which is a glucose derivative in a suspension of 4-nitrophenol (325 mg, 2.34 mmol), K ₂ CO ₃ (745 mg, 5.39 mmol) in DMF (26.0 mL) under an argon atmosphere. mmol) in DMF (9.0 mL) was added and heated at 100 ° C. for 1.5 hours. Insoluble components were removed from the heated solution by suction filtration, water and methylene chloride were added to the filtrate, and the mixture was separated into an aqueous layer and an organic layer. The aqueous layer was extracted three times with methylene chloride, and the organic layer was recovered.
Next, the organic layer separated above and the organic layer collected above were combined and washed with saturated saline. The organic layer after washing was dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure to obtain a crude product.
The resulting crude product was purified by silica gel column chromatography (AcOEt / Hexane = 1/1 → 2/1), and 956 mg (yield) of the desired product, compound (3-b), as a colorless transparent syrup. Rate 95%).

-NMR data of compound (3-b)-
¹ H NMR (600 MHz, CDCl ₃ )
δ = 2.01 (s, 3H), 2.02 (s, 6H), 2.08 (s, 3H), 3.68 (ddd, J = 2.4, 4.5, 10.0 Hz, 1H), 3.71-3.77 (m, 3H), 3.87 ( t, J = 4.8 Hz, 2H), 3.98 (dt, J = 4.0, 10.7 Hz, 1H), 4.14 (dd, J = 2.7, 12.4 Hz, 1H), 4.19-4.21 (m, 2H), 4.25 (dd , J = 4.8, 12.4 Hz, 1H), 4.59 (d, J = 7.6 Hz, 1H), 5.00 (dd, J = 7.6, 9.6 Hz, 1H), 5.08 (t, J = 10.0 Hz, 1H), 5.19 (t, J = 9.3 Hz, 1H), 6.99 (d, J = 8.9 Hz, 2H), 8.21 (d, J = 8.9 Hz, 2H).
¹³ C NMR (150 MHz, CDCl ₃ )
δ = 170.56, 170.20, 169.37, 169.27, 163.76, 141.66, 125.89, 114.55, 100.81, 72.71, 71.80, 71.26, 70.60, 69.47, 69.05, 68.37, 68.15, 61.93, 20.69, 20.62, 20.58, 20.56

  Next, compound (3-c) was synthesized according to the following reaction scheme 3-2.

Hereinafter, details of the reaction scheme 3-2 will be described.
Under hydrogen atmosphere, an ethyl acetate suspension of 650 mg (1.17 mmol) of the starting material compound (3-b) and 65.0 mg of a catalyst (10% palladium on activated carbon) was stirred at room temperature for 1.5 hours. The catalyst was removed from the stirred solution by filtration, and the solvent of the filtrate was distilled off under reduced pressure to obtain a crude product.
The resulting crude product was purified by silica gel column chromatography (AcOEt / Hexane = 1/1 → 2/1), and the target compound (3-c) was 532 mg (yield 87%) as an orange syrup. Obtained.

-NMR data of compound (3-c)-
¹ H NMR (600 MHz, CDCl ₃ )
δ = 2.01 (s, 3H), 2.02 (s, 3H), 2.03 (s, 3H), 2.08 (s, 3H), 3.43 (s, 2H), 3.67-3.73 (m, 3H), 3.76-3.79 ( m, 3H), 3.96 (dt, J = 4.3, 11.2 Hz, 1H), 4.03 (t, J = 4.8 Hz, 2H), 4.13 (dd, J = 2.1, 12.4 Hz, 1H), 4.25 (dd, J1 = 4.8, 12.4 Hz, 1H), 4.62 (d, J = 8.2 Hz, 1H), 5.00 (dd, J = 8.2, 9.6 Hz, 1H), 5.08 (t, J = 9.6 Hz, 1H), 5.20 (t , J = 9.3 Hz, 1H), 6.63 (d, J = 8.9 Hz, 2H), 6.76 (d, J = 8.9 Hz, 2H).
¹³ C NMR (150 MHz, CDCl ₃ )
δ = 170.77, 170.35, 169.51, 151.90, 140.38, 116.41, 115.92, 100.89, 72.90, 71.80, 71.33, 70.57, 70.13, 69.17, 68.47, 68.22, 61.99, 20.82, 20.74, 20.70, 20.68

  Next, compound (3-d) was synthesized according to the following reaction scheme 3-3.

Hereinafter, details of the reaction scheme 3-3 will be described.
Under a argon atmosphere, 562 mg (1.07 mmol) of the starting compound (3-c) in 1,2-dichloroethane (2.0 mL) was added to 317 mg (1.07 mmol) of 1,2-dichloroethane (2.2 mL) of triphosgene. The solution and 0.30 mL (2.15 mmol) of triethylamine were sequentially added and stirred at room temperature for 30 minutes, and then the low boiling point compound was distilled off under reduced pressure to obtain a white solid mainly composed of isocyanate. This white solid was dissolved in 1,2-dichloroethane (4.2 mL), trisamine 157 mg (0.355 mmol) was added, and the mixture was heated to reflux for 36 hours. After the refluxed reaction liquid was cooled to room temperature, a saturated aqueous ammonium chloride solution was added, water and methylene chloride were further added for dilution, and the aqueous layer and the organic layer were separated. The aqueous layer was extracted three times with methylene chloride, and the organic layer was recovered.
Next, the organic layer separated above and the organic layer collected above were combined and washed with saturated saline. The organic layer after washing was dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure to obtain a crude product.
The obtained crude product was purified by reprecipitation of AcOEt / Hexane to obtain 624 mg (84% yield) of the target compound (3-d) as a white solid.

-NMR data of compound (3-d)-
¹ H NMR (600 MHz, DMSO-d ₆ )
δ = 1.92 (s, 9H), 1.96 (s, 18H), 2.00 (s, 9H), 3.53-3.61 (m, 6H), 3.62-3.66 (m, 3H), 3.69 (t, J = 4.8 Hz, 6H), 3.81 (ddd, J = 3.8, 5.5, 11.3 Hz, 3H), 3.95 (ddd, J1 = 2.4, 4.8, 10.0 Hz, 3H), 3.99-4.01 (m, 9H), 4.16 (dd, J = 4.8, 12.4 Hz, 3H), 4.75 (dd, J = 8.2, 9.6 Hz, 3H), 4.83 (d, J = 8.3 Hz, 3H), 4.89 (t, J = 9.6 Hz, 3H), 5.10 (s, 6H), 5.24 (t, J = 9.6 Hz, 3H), 6.62 (dd, J = 2.1, 8.2 Hz, 3H), 6.84 (d, J = 8.9 Hz, 6H), 6.95 (d, J = 8.2 Hz, 3H), 7.15 (t, J = 8.2 Hz, 3H), 7.24 (s, 3H), 7.32 (d, J = 8.9 Hz, 6H), 7.51 (s, 3H), 8.50 (s, 3H), 8.63 ( s, 3H).
¹³ C NMR (150 MHz, DMSO-d ₆ )
δ = 20.28, 20.36, 20.38, 20.50, 61.71, 67.28, 68.19, 68.62, 68.94, 69.06, 69.47, 70.57, 70.89, 72.07, 99.51, 104.77, 107.85, 110.75, 114.62, 120.00, 126.32, 129.57, 132.77, 137.66, 141.15, 152.63, 153.63, 158.77, 169.09, 169.29, 169.56, 170.05

  Next, Exemplified Compound (3) was synthesized according to the following Reaction Scheme 3-4.

Hereinafter, details of Reaction Scheme 3-4 will be described.
To a solution of 300.1 mg (143 μmol) of the starting compound (3-d) in ethanol (3.4 mL) was added 29.1 mg (428 μmol) of NaOEt, and the mixture was stirred at room temperature for 18 hours. The reaction mixture after stirring was purified using a dialysis membrane, and the solvent was distilled off under reduced pressure to obtain 221 mg (yield 97%) of Example Compound (3) as the target compound as an ocherous solid.
It was confirmed by electron spray ionization mass spectrometry (JEOL JMS-T100LC AccTOF) that the obtained target compound (Exemplary Compound (3)) had a molecular weight of 1597.

-NMR data of Exemplified Compound (3)-
¹ H NMR (600 MHz, DMSO-d ₆ )
δ = 2.93-2.96 (m, 3H), 3.01-3.05 (m, 3H), 3.06-3.10 (m, 3H), 3.10-3.13 (m, 3H), 3.40-3.44 (m, 3H), 3.60-3.66 (m, 12H), 3.72 (t, J = 5.2 Hz, 6H), 3.89 (t, J = 6.2 Hz, 3H), 4.01 (t, J = 4.5 Hz, 6H), 4.15 (d, J = 8.2 Hz , 3H), 4.49 (t, J = 5.8 Hz, 3H), 4.89 (d, J = 5.5 Hz, 3H), 4.93 (d, J = 4.8 Hz, 3H), 4.99 (d, J = 4.8 Hz, 3H ), 5.10 (s, 6H), 6.63 (dd, J = 2.1, 8.2 Hz, 3H), 6.84 (d, J = 8.9 Hz, 6H), 7.00 (d, J = 7.6 Hz, 3H), 7.14 (t , J = 8.2 Hz, 3H), 7.25 (s, 3H), 7.35 (d, J = 8.9 Hz, 6H), 7.51 (s, 3H), 8.98 (s, 3H), 9.10 (s, 3H).
¹³ C NMR (150 MHz, DMSO-d ₆ )
δ = 61.09, 67.29, 67.87, 68.94, 69.04, 69.84, 70.05, 73.41, 76.75, 76.91, 103.01, 104.79, 107.80, 110.78, 114.62, 120.01, 126.33, 129.56, 132.83, 137.67, 141.22, 152.69, 153.62, 158.76.

  As mentioned above, although the synthesis example of exemplary compound (1)-exemplary compound (3) was demonstrated, the compound represented with other general formula (I) is compoundable by the method similar to these synthesis examples.

[Example 2]
<Gelification of aqueous sample 1>
The exemplary compound (1) synthesized above was used as a gelling agent to gel an aqueous sample.
~ Gel formation by ultrasonic irradiation after heating ~
An aqueous sample was prepared by adding 2.0 mg of the above gelling agent to a 2.2 mL test tube (inner diameter 5 mm), adding 100 μL of water (gelling agent concentration 2.0 wt%) and mixing.
The prepared aqueous sample was subjected to ultrasonic irradiation for 30 minutes using an ultrasonic cleaner (B25SON made by BRANSON), then heated at 90 ° C for 60 minutes and allowed to stand at room temperature. A gel was formed.
Determination of gelation was carried out by allowing the test tube to turn upside down so that the bottom was up and the mouth down, and let it pass for 60 seconds after standing at room temperature (in the following examples and reference examples) The determination method of gelation is also the same).
As shown in the center photograph in FIG. 1, the water sample did not flow down even after 60 seconds had passed after the test tube was turned upside down, and it was confirmed that the water sample was gelled. .
In addition, the determination of gelation in the following examples and reference examples was also performed by the same method as described above.
Hereinafter, the gel formed under the condition of the gelling agent concentration of 2.0 wt% may be referred to as “2.0 wt% gel” (other concentrations may be similarly referred to).

  Moreover, although illustration is abbreviate | omitted, formation of the gel was able to be confirmed even if the borate buffer solution (pH 8.6) was used on the conditions similar to the gelatinization of the said water.

Next, in the gel formation of water, the amount of the gelling agent is 1.0 mg (gelling agent concentration 1.0 wt%), 1.5 mg (gelling agent concentration 1.5 wt%), 3.0 mg (gelling agent concentration 3.0 wt%). %) Except that each was changed to an aqueous sample by the same method as described above, subjected to ultrasonic treatment and heat treatment, and allowed to stand at room temperature. A photograph when the test tube is turned upside down after standing at room temperature is shown in FIG.
As shown in the photograph on the left side in FIG. 1, the aqueous sample did not flow down under the condition of the gelling agent concentration of 1.5 wt%, and gelation was confirmed. Further, as shown in the photograph on the right side in FIG. 1, the aqueous sample did not flow down even under the condition of the gelling agent concentration of 3.0 wt%, and gelation was confirmed.
On the other hand, although not shown, the aqueous sample did not gel under the condition where the gelling agent concentration was 1.0 wt%.
Based on the above, the minimum gelation concentration for water was determined to be 1.5 wt%.

Moreover, as shown in FIG. 1, when the gelling agent concentration was increased, the transparency of the gel was reduced, and the gel having a gelling agent concentration of 3.0 wt% was white and opaque.
These gels kept their gel state even after several months at room temperature.

~ Formation of gel by standing ~
Moreover, the gel was formed only by mixing a gelatinizer (Exemplary Compound (1)) and water and allowing to stand at room temperature.
Specifically, 100 μL of water (gelling agent concentration: 2.0 wt%) was added to 2.0 mg of the gelling agent and allowed to stand at room temperature for 2-3 hours. FIG. 2 shows a photograph when the test tube is turned upside down after standing at room temperature for 2 to 3 hours.
As shown in FIG. 2, the aqueous sample did not flow down, and gelation was confirmed. The color of the gel was almost colorless and transparent.
The gel became clouded after several days at room temperature, formed a gel, and changed to a white suspension after about 4 days.

Example 3
<Gelification of aqueous sample 2>
The exemplary compound (2) synthesized above was used as a gelling agent to gel an aqueous sample.
~ Gelation of water ~
When 100 μL of water (gelling agent concentration: 2.0 wt%) was added to the gelling agent and allowed to stand at room temperature for 2 to 3 hours, a white and cloudy partial gel was obtained (not shown).

~ Borate buffer gelation ~
When a borate buffer (pH 8.6) 100 μL (gelator concentration 1.0 wt%) was added to the gelling agent and allowed to stand at room temperature for 2 to 3 hours, an almost colorless and transparent gel was obtained. FIG. 3 shows a photograph when the test tube is turned upside down after the standing.
As shown in FIG. 3, the aqueous sample (borate buffer) did not flow down, and gelation was confirmed. The color of the gel was almost colorless and transparent.
The borate buffer gel retained its gel state after standing at room temperature for several days.

Example 4
<Gelification of aqueous sample 3>
The exemplary compound (3) synthesized above was used as a gelling agent to gel an aqueous sample.
~ Gelation of water ~
The gelling agent and water were mixed (gelling agent concentration: 1.0 wt%), heated in a 90 ° C. oil bath with shaking, and slowly cooled after dissolution. A photograph when the test tube is turned upside down after the cooling is shown on the left side in FIG.
As shown in the photograph on the left side of FIG. 4, the aqueous sample (water having a gelling agent concentration of 1.0 wt%) did not flow down, and gelation was confirmed. The gel formed was white and translucent.

~ Borate buffer gelation ~
Next, the borate buffer solution was gelated under the same conditions as the water gelation except that the water was changed to borate buffer and the gelling agent concentration was 2.0 wt%. It was. After cooling, the photograph when the mouth of the test tube is tilted so as to be below the bottom is shown on the right side in FIG.
As shown in the photograph on the right side of FIG. 4, the aqueous sample (borate buffer solution having a gelling agent concentration of 1.0 wt%) did not flow down, and gelation was confirmed. The color of the gel was white and translucent.

~ Gelation of other buffers ~
Next, the above-described borate buffer solution was mixed with each buffer solution (trisodium phosphate buffer solution, tris-HCl buffer solution, 4- (2- Hydroxyethyl) -1-piperazineethanesulfonic acid-sodium hydroxide (HEPES-NaOH) buffer, sodium acetate (NaOAc) buffer, boric acid-borate NaOH buffer), Tris (25 mM) -glycine Each buffer solution was gelled under the same conditions as the gelation of the borate buffer solution, except that it was changed to (192 mM) -0.1% sodium dodecyl sulfate (Tris-Glycine-SDS) buffer solution).
The evaluation results are shown in Table 1 below. In addition, the determination method of gelation is the same as the determination method of gelation in Example 2.

  As shown in Table 1, gelation was confirmed in various buffers having various pHs.

Example 5
<Sol-gel phase transition by addition of concanavalin A (ConA)>
Using the exemplified compound (1) synthesized above as a gelling agent, an experiment was conducted on the sol-gel phase transition of an aqueous dispersion containing the gelling agent and concanavalin A (ConA).
Hereinafter, experimental results will be described with reference to FIG.

100 μL of water (gelling agent concentration: 2.0 wt%) was added to 2.0 mg of the above gelling agent and allowed to stand at room temperature for 2 to 3 hours. The photograph when the test tube is turned upside down after standing is shown on the left side in FIG.
As shown in the photograph on the left side of FIG. 5, the aqueous sample did not flow down, and gelation of the aqueous sample was confirmed. The formed gel was almost colorless and transparent.

Further, 100 μL of water (gelling agent concentration: 2.0 wt%) was added to 2.0 mg of a gelling agent and 1.0 mg of concanavalin A (ConA), and the mixture was allowed to stand at room temperature for 2 to 3 hours. After standing, the photograph when the test tube is leveled (the bottom and mouth are at the same height) is shown in the center of FIG.
As shown in the middle photograph in FIG. 5, the aqueous sample was a white suspension (sol) having fluidity. That is, gelation did not occur.
As a result, the 1βGlu group derived from β-glucose, which is the hydrophilic group of the gelling agent, and ConA interact to form an association between the gelling agent and ConA, and the gelling agent molecules This is thought to be a result of the inhibition of self-assembly.
It is already known that glucose and ConA exhibit an interaction (association constant 8.0 × 10 ² ) (egBiochemistry 33, 1149-1156, 1994).

In addition, 100 μL of water (gelling agent concentration 2.0 wt%) was added to a mixture of 2.0 mg of gelling agent, 1.0 mg of ConA and 0.15 mg of methyl-α-mannose (Me-α-Man), and 2 to 2 at room temperature. It was left for 3 hours. The photograph when the test tube is turned upside down after standing is shown in the upper right in FIG.
As shown in the upper right photograph in FIG. 5, the aqueous sample did not flow down, and gelation of the aqueous sample was confirmed. The formed gel was slightly white.
This result shows that the interaction between Me-α-Man and ConA is stronger than the interaction between ConA and the group derived from β-glucose which is the hydrophilic group of the gelling agent molecule. This is considered to be a result of the formation of an association between Man and ConA, the presence of the gelling agent alone, and the self-assembly of the gelling agents.
The interaction between Me-α-Man and ConA (association constant 1.1 × 10 ⁴ ) is already stronger than the interaction between glucose and ConA (association constant 8.0 × 10 ² ). Known (egBiochemistry 33, 1149-1156, 1994).

Further, 100 μL of water (gelator concentration: 2.0 wt%) was added to a mixture of 2.0 mg of a gelling agent, 1.0 mg of ConA and 0.15 mg of galactose (Gal), and allowed to stand at room temperature for 2 to 3 hours. After standing, a photograph when the test tube is leveled (the bottom and the mouth are at the same height) is shown in the lower right in FIG.
As shown in the lower right photograph in FIG. 5, the aqueous sample was a white suspension (sol) having fluidity. That is, gelation did not occur.
This result indicates that the interaction between galactose and ConA is weaker than the interaction between ConA and the group derived from β-glucose, which is the hydrophilic group of the gelling agent molecule. This is considered to be a result of the formation of the gelling agent molecule and ConA in association with each other and the self-assembly of the gelling agent molecules being inhibited.
It is already known that the interaction between galactose and ConA is weaker than the interaction between β-glucose and ConA.

The above experimental results regarding the sol-gel phase transition suggest that screening using the known information such as the interaction between ConA and glucose and the interaction between ConA and Me-α-Man is possible. Is.
For example, by preparing an aqueous sample containing a gelling agent having 1βGlu group and ConA, and adding non-specific sugar to the aqueous sample to confirm gelation, the interaction between ConA and βglucose It is possible to select sugars that interact with ConA more strongly (for example, Me-α-Man).
Moreover, as a modification, by preparing an aqueous sample containing a gelling agent having a 1βGlu group and an unspecified lectin, adding Me-α-Man to the aqueous sample to confirm gelation, It is also possible to select a lectin (for example, ConA) that has a stronger interaction with Me-α-Man than with β-glucose.

Example 6
<Experiment on lectin-sugar interaction>
In Example 5 above, 100 μL of water (gelling agent concentration) was added to a mixture of 2.0 mg of gelling agent (Exemplary Compound (1)), 1.0 mg of ConA and 0.15 mg of methyl-α-mannose (Me-α-Man). 2.0 wt%) was added, and an example in which a slightly white hydrogel was formed when allowed to stand at room temperature for 2 to 3 hours was shown. In Example 5 above, this result indicates that the interaction between Me-α-Man and ConA is stronger than the interaction between 1βGlu group of the gelator molecule and ConA, and thus Me-α-Man and It was explained that this was a result of the formation of an aggregate with ConA, the presence of the gelling agent molecule alone, and the self-assembling of the gelling agent molecules.
In addition, the quantity (0.15 mg) of the saccharide | sugar (Me- (alpha) -Man) in the said Example 5 is equivalent to 1 equivalent with respect to lectin (ConA) 1.0 mg.

  Next, the lectin-sugar interaction was performed under the same conditions as in Example 5 above, except that the type and amount of added sugar (“Me-α-Man 0.15 mg” in Example 5) were variously changed. Experiments were conducted. The results of the experiment are shown in Table 2 below.

~ Explanation of Table 2 ~
“S” indicates a sol state, “OG” indicates a turbid gel state, and “G” indicates a transparent gel state.
“Me-α-Man” is methyl-α-mannose, “Me-α-Glu” is methyl-α-glucose, “Man” is mannose, “Isomal” is isomaltose, “Gal” is galactose, “Ara” "Represents arabinose," L-Glu "represents L-glucose," Mal "represents maltose, and" Me-β-Glu "represents methyl-β-glucose.

As shown in Table 2, sugars (Me-α-Man, Me-α-Glu, Man, Isomal, Mal, Me-) which interact with ConA more strongly than the interaction between 1βGlu group of the gelator molecule and ConA. It was confirmed that gelation occurred when β-Glu) was added. It was also confirmed that the amount required for gelation differs depending on the type of sugar. This difference in the amount added is considered to result from the difference in the strength of interaction between the sugar and ConA.
From the above results, by preparing an aqueous sample containing a gelling agent having 1βGlu group and ConA, adding unspecified sugar to the aqueous sample and confirming gelation, ConA and 1βGlu group It was confirmed that screening for selecting sugars that interact with ConA more strongly than the above interaction can be performed.

[Reference Example 1]
<Experiment on correlation between sol-gel phase transition and ConA amount>
In Example 5 above, 100 μL of water (gelling agent concentration: 2.0 wt%) was added to 2.0 mg of gelling agent (exemplary compound (1)) and 1.0 mg of concanavalin A (ConA), and allowed to stand at room temperature for 2 to 3 hours. In this example, gelation did not occur and a white suspension (sol) having fluidity was generated. The amount of ConA in this example corresponds to 4.6 × 10 ⁻² equivalents relative to the gelling agent.
In the above example, when the amount of ConA is changed from 1.0 mg (4.6 × 10 ⁻² equivalent to the gelling agent) to 0.5 mg (2.3 × 10 ⁻² equivalent to the gelling agent), the amount of ConA is 1.0 As in the case of mg, gelation did not occur, and a white suspension (sol) having fluidity was formed.
On the other hand, when the amount of ConA was changed from 1.0 mg (4.6 × 10 ⁻² equivalents to the gelling agent) to 0.2 mg (9.2 × 10 ⁻³ equivalents to the gelling agent), gelation occurred. (Produced a cloudy gel).
As described above, in a combination system of a gelling agent containing 1βGlu group as the hydrophilic group (Exemplary Compound (1)) and ConA, the amount of ConA is 2.3 × 10 ⁻² equivalent or more with respect to the gelling agent. It was found that inhibition of self-assembly between gelling agents (ie, solification) occurred.

  From the results of Reference Example 1, a specific amount of gelling agent is added to an aqueous sample containing an unknown amount of a specific lectin, and the presence or absence of gelation is confirmed (that is, gelation activity is detected). It was found that the amount of lectin in the aqueous sample can be titrated.

[Reference Example 2]
<Gelation in the presence of anion>
In Example 2 above, 100 μL of water (gelling agent concentration: 2.0 wt%) was added to 2.0 mg of the gelling agent (Exemplary Compound (1)), and the mixture was allowed to stand at room temperature for 2 to 3 hours. An example was given where a hydrogel was formed.
Here, various types and amounts of anions were added to the above aqueous sample (gelling agent (exemplary compound (1) 2.0 mg and water 100 μL)) (wherein the anions were added in the form of a salt) Conducted the same operation as in the above example, and conducted an experiment to confirm the presence or absence of gelation in the presence of an anion.
The experimental results are shown in Table 3 below.

~ Explanation of Table 3 ~
“S” indicates a sol state, “V” indicates a viscous liquid (a form of sol), “OG” indicates a turbid gel state, and “G” indicates a transparent gel state.

As shown in Table 3, gelation did not occur when a certain amount or more of anions was added to the aqueous sample.
The above results are considered to be a result of self-assembly of the gelling agents being inhibited by the interaction between the urea group in the gelling agent molecule and the anion. It was also confirmed that the amount of anion added for maintaining the sol differs depending on the type of anion. This difference in the amount of added anion is considered to be due to the difference in the strength of interaction between the anion and the urea group in the gelling agent.
From the above results, it was also suggested that by adding an anion to the hydrogel, the self-assembly of the gelling agents was eliminated and a phase transition from gel to sol occurred.

[Reference Example 3]
<Experiment on gelation of mineral water>
As an experiment on gelation in the presence of anions, an experiment on gelation of commercially available mineral water was performed.
Specifically, for mineral water (Sample 1 to Sample 4) shown in Table 4 below, 2.0 mg of a gelling agent (Exemplary Compound (1)) is added to 100 μL of each sample and allowed to stand at room temperature for 2 to 3 hours. The presence or absence of gelation was confirmed.
The experimental results are shown in Table 4 below.

~ Explanation of Table 4 ~
“OS” indicates a turbid sol state (one form of sol), “OG” indicates a turbid gel state, and “G” indicates a transparent gel state.
-Although the amount of cations is shown as the amount of ions, each material contains anions as counter ions for these cations.

As shown in Table 4, gelation occurred in Sample 1 and Sample 2 with a small amount of anion.
On the other hand, Sample 3 and Sample 4 with a large amount of anion did not cause gelation and maintained the sol state.

  From the results of Reference Example 2 and Reference Example 3, a specific amount of gelling agent is added to an aqueous sample containing an unknown amount of anion, and the presence or absence of gelation is confirmed (that is, gelation activity is detected). It was found that the amount of anion in the aqueous sample can be titrated.

The disclosure of Japanese application 2009-049660 is incorporated herein by reference in its entirety.
All documents, patent applications, and technical standards mentioned in this specification are to the same extent as if each individual document, patent application, and technical standard were specifically and individually described to be incorporated by reference, Incorporated herein by reference.

Claims (13)

A substituted aromatic compound represented by the following general formula (II).

[In General Formula (II), R represents a hydrogen atom or an alkyl group, Z ⁴ represents an arylene group, and Q ¹ , Q ² , and Q ³ are each independently a divalent or trivalent aromatic carbonization. Represents a hydrogen group. E represents an ethylene group, and S _g ¹ , S _g ² , and S _g ³ each independently represent a sugar group. m1, m2, and m3 each independently represent 1 or 2, and n1, n2, and n3 each independently represent an integer of 1 to 10. ] The substituted aromatic compound according to claim 1, wherein R is a hydrogen atom. The substituted aromatic compound according to claim 1 or 2, wherein n1, n2, and n3 each independently represents an integer of 1 to 3. The substituted aromatic compound according to claim 1, which is any one of the following exemplified compounds (1) to (5).

[In the exemplary compounds (1) to (5), 1βGlu represents a monovalent group obtained by removing a hydrogen atom from the hydroxyl group at the 1-position of β-glucose, and 1βMal represents a hydrogen atom removed from the hydroxyl group at the 1-position of β-maltose. Represents a monovalent group. ] The substituted aromatic compound according to claim 4, which is any one of the exemplified compounds (1) to (3). A hydrogelator comprising the substituted aromatic compound according to any one of claims 1 to 5 . The hydrogel containing the substituted aromatic compound of any one of Claims 1-5 . A method for gelling an aqueous sample, comprising bringing the substituted aromatic compound according to any one of claims 1 to 5 into contact with an aqueous sample. Adding a test compound to an aqueous sample containing a substituted aromatic compound represented by the following general formula (I) and a specific compound that interacts with a hydrophilic group of the substituted aromatic compound;
Detecting the gelling activity of the aqueous sample after the addition,
as well as,
Screening a test compound contained in an aqueous sample in which gelation activity is detected as a target compound that interacts with the specific compound stronger than the hydrophilic group;
A screening method comprising:

[In General Formula (I), R represents a hydrogen atom or an alkyl group, X represents an oxygen atom or a sulfur atom, and Y ¹ , Y ² , and Y ³ are each independently substituted with a hydrophilic group. Represents an aryl group.
L ¹ represents a single bond, an oxygen atom, a methyleneoxy group, an aryleneoxy group, or a — [CH ₂ — (O) _r1 —Z ¹ ] _s1 — group, and L ² represents a single bond, an oxygen atom, methyleneoxy group, arylene group, or a _{- [CH 2 - (O)} r2 -Z 2] s2 - represents a group, ^{L 3} represents a single bond, an oxygen atom, a methylene group, arylene group, or a - [CH ₂ - _{^{(O) r3 -Z 3] s3}} - represents a group.
Z ¹ , Z ² , and Z ³ each independently represent an arylene group, r 1, r 2, and r ³ each independently represent 0 or 1, and s ¹ , s ² , and s ³ are each independently 0 or 1 is represented. ] Hydrophilic group in the general formula (I) is a hydrophilic group containing the sugar group, the specific compound is a lectin, the test compound is a sugar, according to claim 9 wherein the target compound is a sugar Screening method. The hydrophilic group in the general formula (I) is a hydrophilic group containing an alkyleneoxy group and a sugar group, the specific compound is a lectin, the test compound is a sugar, and the target compound is a sugar. Item 10. The screening method according to Item 9 . The screening method according to claim 11, wherein the alkyleneoxy group is an ethyleneoxy group. A sugar as a test compound is added to an aqueous sample containing a substituted aromatic compound represented by the following general formula (II) and a lectin as a specific compound that interacts with a sugar group of the substituted aromatic compound. about,
Detecting the gelling activity of the aqueous sample after the addition,
as well as,
Selecting a saccharide as a test compound contained in an aqueous sample in which gelation activity is detected as a saccharide that interacts with the lectin more strongly than the saccharide group,
A screening method comprising:

[In General Formula (II), R represents a hydrogen atom or an alkyl group, Z ⁴ represents an arylene group, and Q ¹ , Q ² , and Q ³ are each independently a divalent or trivalent aromatic carbonization. Represents a hydrogen group. E represents an ethylene group, and S _g ¹ , S _g ² , and S _g ³ each independently represent a sugar group. m1, m2, and m3 each independently represent 1 or 2, and n1, n2, and n3 each independently represent an integer of 1 to 10. ]