JP2010285420A - Method for producing optically active aromatic hydroxycarboxylic acid condensate and optically active compound - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing optically active aromatic hydroxycarboxylic acid condensates highly regulated in optical activity, and the optically active aromatic hydroxycarboxylic acid condensates produced by the production method. <P>SOLUTION: The method for producing the optically active aromatic hydroxycarboxylic acid condensates comprises a condensation process for condensing a derivative (I) of formula (1) in which a carboxy group of the optically active aromatic hydroxycarboxylic acid is protected, with a derivative (II) in which a carboxy group of the optically active aromatic hydroxycarboxylic acid of formula (2) is protected. Optically active compounds produced by the production method are also provided. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a method for producing an optically active aromatic hydroxycarboxylic acid condensate and an optically active compound.

If a high molecular weight optically active aromatic hydroxycarboxylic acid condensate having the desired optical activity is obtained by condensing while maintaining the optical activity of the optically active aromatic hydroxycarboxylic acid, the aromatic rings in the condensate are efficient. It is considered that it is useful as a highly functional material that can interact with each other and is excellent in heat resistance, mechanical properties, orientation properties, optical properties, and the like. The optically active aromatic hydroxycarboxylic acid has a structure similar to that of lactic acid (a compound in which the methyl group of lactic acid is substituted with an aromatic hydrocarbon group). The body may be used as a highly functional material capable of acid / alkali hydrolysis and biodegradation.
As representative examples of optically active aromatic hydroxycarboxylic acids, D-mandelic acid or L-mandelic acid is known.

However, when polycondensation of mandelic acid is attempted, two molecules are condensed and a cyclic compound (mandelide) having a condensation degree of 2 is produced, so that a high molecular weight condensate cannot be obtained (Non-patent Document 1).
Therefore, as a method for obtaining a high molecular weight mandelic acid condensate, a method of performing ring-opening polycondensation of a mandelide, which is a cyclic compound, has been shown (Non-patent Document 2).

J. Whitesell, J. Pojman, Chem. Mater., 2, 248 (1990) T. Liu, T. L. Simmons, D. A. Bohnsack, M. E. Mackay, M. R. Smith, G. L. Baker, Macromolecules, 40, 6040 (2007)

However, in the method described in Non-Patent Document 2, an aromatic hydroxycarboxylic acid condensate that maintains the optical activity of the mandelic acid used is sterically inverted and racemized when the cyclic compound (mandelide) is opened. Can't get.
As described above, according to the conventional method, the aromatic rings can be efficiently interacted with each other, and can be used as a high-functional material excellent in heat resistance, etc. A hydroxycarboxylic acid condensate could not be obtained.

  The present invention relates to a method for producing an optically active aromatic hydroxycarboxylic acid condensate having a highly controlled optical activity, and an optical activity having a highly controlled optical activity having a repeating unit derived from the optically active aromatic hydroxycarboxylic acid. The purpose is to provide compounds.

The present invention employs the following configuration in order to solve the above problems.
[1] Condensation for condensing an optically active aromatic hydroxycarboxylic acid derivative (I) represented by the following formula (1) and an optically active aromatic hydroxycarboxylic acid derivative (II) represented by the following formula (2) The manufacturing method of the optically active aromatic hydroxycarboxylic acid condensate which has a process.

(In Formula (1) and Formula (2), p and q are each independently an integer of 1 or more. R ¹¹ is an aralkyl ether type protecting group, an alkyl ether type protecting group, a silyl type protecting group, or an ester type protecting group. is either group or an oxycarbonyl-type protecting group, R ²¹ is .p number of R ³¹ is either aralkyl ether type protecting group, alkyl ether-type protecting group or a silyl-type protecting groups, the carbon independently It is an aromatic hydrocarbon group having a number of 6 to 14. Each q R ³² is independently an aromatic hydrocarbon group having a carbon number of 6 to 14. The carbon atom indicated by * means an asymmetric carbon atom. To do.)
[2] R ¹¹ and R ²¹ are ortho-protecting groups, and are obtained by condensing the optically active aromatic hydroxycarboxylic acid derivative (I) and the optically active aromatic hydroxycarboxylic acid derivative (II). And a deprotecting step of deprotecting either R ¹¹ or R ²¹ of the optically active aromatic hydroxycarboxylic acid condensate (III) represented by the following formula (3), wherein R ¹¹ or R ²¹ [1], wherein the condensate obtained by deprotecting any one of the above is used as the optically active aromatic hydroxycarboxylic acid derivative (I) and / or the optically active aromatic hydroxycarboxylic acid derivative (II) in the condensation step. The manufacturing method of the optically active aromatic hydroxycarboxylic acid condensate of description.

(In the formula (3), n is an integer of 2 or more, .n number of R ³ is the sum of p and q are each independently an aromatic hydrocarbon group having 6 to 14 carbon atoms.)

[3] An optically active compound represented by the following formula (4).

(In the formula (4), .R ¹ n is an integer of 2 or greater, a hydrogen atom, an aralkyl ether type protecting group, alkyl ether-type protecting group, a silyl-type protecting group, ester type protecting group or an oxycarbonyl-type protecting group R ² is any one of a hydrogen atom, an aralkyl ether protecting group, an alkyl ether protecting group, or a silyl protecting group, and at least one of R ¹ and R ² is any one of the protecting groups described above N R ^{3 s} are each independently an aromatic hydrocarbon group having 6 to 14 carbon atoms.)
[4] The optically active compound according to [3], wherein R ³ is a phenyl group.

According to the production method of the present invention, an optically active aromatic hydroxycarboxylic acid condensate having a highly controlled optical activity can be obtained.
The optically active compound of the present invention has a repeating unit derived from an optically active aromatic hydroxycarboxylic acid, and the optical activity is highly controlled.

2 is a ¹ H-NMR spectrum of Ot-butyl-D-mandelic acid (tBu-MDA) obtained in Synthesis Example 1. 2 is a ¹ H-NMR spectrum of benzyl Ot-butyl-D-mandelate (tBu-MDA-Bn) obtained in Synthesis Example 2. 2 is a ¹ H-NMR spectrum of benzyl D-mandelate (MDA-Bn) obtained in Synthesis Example 3. 1 is a ¹ H-NMR spectrum of Ot-butyl-D-mandelic acid dimer benzyl (tBu-MDA2-Bn) obtained in Example 1. FIG. 2 is a ¹³ C-NMR spectrum of Ot-butyl-D-mandelic acid dimer benzyl (tBu-MDA2-Bn) obtained in Example 1. FIG. 2 is a ¹ H-NMR spectrum of an Ot-butyl-D-mandelic acid dimer (tBu-MDA2) obtained in Example 2. FIG. 2 is a ¹ H-NMR spectrum of D-mandelic acid dimer benzyl (MDA2-Bn) obtained in Example 3. FIG. 4 is an HMBC spectrum of Ot-butyl-D-mandelic acid tetramer benzyl (tBu-MDA4-Bn) obtained in Example 4. It is an enlarged view of H: 4.8-6.2 ppm and C: 165-175 ppm in the HMBC spectrum of FIG. 4 is an HMQC spectrum of Ot-butyl-D-mandelic acid tetramer benzyl (tBu-MDA4-Bn) obtained in Example 4. FIG. 11 is an enlarged view of H: 4.8 to 6.2 ppm and C: 65 to 80 ppm in the HMQC spectrum of FIG. 10. 2 is a ¹ H-NMR spectrum of Ot-butyl-D-mandelic acid tetramer benzyl (tBu-MDA4-Bn) obtained in Example 4. 4 is a ¹³ C-NMR spectrum of Ot-butyl-D-mandelic acid tetramer benzyl (tBu-MDA4-Bn) obtained in Example 4. FIG. 2 is a MALDI-TOF-MS spectrum of Ot-butyl-D-mandelic acid tetramer benzyl (tBu-MDA4-Bn) obtained in Example 4. FIG. 2 is a ¹ H-NMR spectrum of Ot-butyl-D-mandelic acid tetramer (tBu-MDA4) obtained in Example 5. FIG. 2 is a ¹ H-NMR spectrum of D-mandelic acid tetramer benzyl (MDA4-Bn) obtained in Example 6. 4 is an HMBC spectrum of Ot-butyl-D-mandelic acid octamer benzyl (tBu-MDA8-Bn) obtained in Example 7. 4 is an HMQC spectrum of Ot-butyl-D-mandelic acid octamer benzyl (tBu-MDA8-Bn) obtained in Example 7. 2 is a ¹ H-NMR spectrum of Ot-butyl-D-mandelic acid octamer benzyl (tBu-MDA8-Bn) obtained in Example 7. 2 is a ¹³ C-NMR spectrum of Ot-butyl-D-mandelic acid octamer benzyl (tBu-MDA8-Bn) obtained in Example 7. FIG. 2 is a MALDI-TOF-MS spectrum of Ot-butyl-D-mandelic acid octamer benzyl (tBu-MDA8-Bn) obtained in Example 7. FIG. 6 is a ¹ H-NMR spectrum of phenacyl D-mandelate (MDA-Pac) obtained in Synthesis Example 4. 2 is a ¹ H-NMR spectrum of Ot-butyl-D-mandelic acid dimer phenacyl (tBu-MDA2-Pac) obtained in Example 8. 2 is a MALDI-TOF-MS spectrum of Ot-butyl-D-mandelic acid dimer phenacyl (tBu-MDA2-Pac) obtained in Example 8. FIG. 4 is a ¹ H-NMR spectrum of an Ot-butyl-D-mandelic acid dimer (tBu-MDA2) obtained in Example 9. 2 is an HMBC spectrum of Ot-butyl-D-mandelic acid tetramer phenacyl (tBu-MDA4-Pac) obtained in Example 11. It is an enlarged view of H: 5.0-6.6 ppm and C: 150.0-200.0 ppm in the HMBC spectrum of FIG. 2 is an HMBC spectrum of Ot-butyl-D-mandelic acid tetramer phenacyl (tBu-MDA4-Pac) obtained in Example 11. It is an enlarged view of H: 5.0-6.5 ppm and C: 65.0-80.0 ppm in the HMBC spectrum of FIG. 2 is a ¹ H-NMR spectrum of Ot-butyl-D-mandelic acid tetramer phenacyl (tBu-MDA4-Pac) obtained in Example 11. 2 is a ¹³ C-NMR spectrum of Ot-butyl-D-mandelic acid tetramer phenacyl (tBu-MDA4-Pac) obtained in Example 11. FIG. 2 is a MALDI-TOF-MS spectrum of Ot-butyl-D-mandelic acid tetramer phenacyl (tBu-MDA4-Pac) obtained in Example 11. 2 is a ¹ H-NMR spectrum of Ot-butyl-D-mandelic acid dimer nitrobenzyl (tBu-MDA2-NBn) obtained in Synthesis Example 5. FIG.

[Method for producing optically active aromatic hydroxycarboxylic acid condensate]
The method for producing the optically active aromatic hydroxycarboxylic acid condensate of the present invention (hereinafter referred to as “the present condensate”) is an optically active aromatic hydroxycarboxylic acid derivative in which the carboxy group of the optically active aromatic hydroxycarboxylic acid is protected. (I) (hereinafter referred to as “derivative (I)”) and an optically active aromatic hydroxycarboxylic acid derivative (II) in which the hydroxy group of the optically active aromatic hydroxycarboxylic acid is protected (hereinafter referred to as “derivative (II)”) And a condensing step of condensing the gas.

The derivative (I) is a derivative of an optically active aromatic hydroxycarboxylic acid represented by the following formula (1). Derivative (I) the carboxy group of the optically active aromatic hydroxycarboxylic acid is protected by a protecting group R ^21.

In formula (1), the carbon atom indicated by * means an asymmetric carbon atom.
p is an integer of 1 or more. p may be appropriately selected depending on the degree of condensation of the intended condensate, and is preferably 10,000 or less from the viewpoint of the efficiency of the condensation reaction.

R ²¹ is any one of an aralkyl ether protecting group, an alkyl ether protecting group, and a silyl protecting group.
Examples of the aralkyl ether type protecting group include benzyl group, 1-phenylethyl group, 1-phenylpropyl group, 1-phenylbutyl group, 2-methyl-1-phenylpropyl group, 1-phenylpentyl group, and 2-methyl. Examples include -1-phenylbutyl group, 3-methyl-1-phenylbutyl group, diphenylmethyl group, 1,1-diphenylethyl group, naphthylmethyl group, and 1-naphthylethyl group. The protecting group may have a substituent. Examples of the substituent include a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms, a nitro group, an acyl group, and a halogen atom. Can be mentioned. Specific examples of the protecting group having a substituent include a phenacyl group and a nitrobenzyl group.
Among the above-mentioned aralkyl ether type protecting groups, a phenacyl group and a nitrobenzyl group are preferable because the cleavage of the main chain ester bond during the deprotection reaction can be suppressed.
Examples of the alkyl ether type protecting group include a methyl group, a tert-butyl group, a 1-ethoxyethyl group, a 3,4,5,6-tetrahydro-2H-pyran-2-yl group, and a 1-methoxy-1-methyl group. Examples include an ethyl group, a methoxymethyl group, and a 2-methoxyethoxymethyl group. The protecting group may have a substituent. Examples of the substituent include a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms, a nitro group, and a halogen atom.
Examples of the silyl type protecting group include trimethylsilyl group, triethylsilyl group, tripropylsilyl group, triisopropylsilyl group, tributylsilyl group, tert-butyldimethylsilyl group, and tert-butyldiphenylsilyl group.

R ³¹ is an aromatic hydrocarbon group having 6 to 14 carbon atoms. Further, the p R ^{31 s} may all be the same or two or more, but it is preferable that they are all the same.
Specific examples of R ³¹ include phenyl group, benzyl group, xylyl group, toluyl group, cumenyl group, naphthyl group, anthracenyl group, and fluorenyl group.
The aromatic hydrocarbon group for R ³¹ may have a substituent and / or a hetero atom. Examples of the substituent include a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms, a nitro group, and a halogen atom. Examples of the hetero atom include an oxygen atom, a sulfur atom, and a nitrogen atom.
R ³¹ is preferably a phenyl group from the viewpoint of easy availability of raw materials and good solvent solubility of the obtained polymer.

The derivative (II) is a derivative of an optically active aromatic hydroxycarboxylic acid represented by the following formula (2). In the derivative (II), the hydroxy group of the optically active aromatic hydroxycarboxylic acid is protected by the protecting group R ¹¹ .

In formula (2), the carbon atom indicated by * means an asymmetric carbon atom.
q is an integer of 1 or more. q may be appropriately selected depending on the degree of condensation of the target condensate, and is preferably 10,000 or less from the viewpoint of the efficiency of the condensation reaction.

R ¹¹ is a protecting group selected from an aralkyl ether protecting group, an alkyl ether protecting group, a silyl protecting group, an ester protecting group, and an oxycarbonyl protecting group.
Examples of the aralkyl ether-type protecting group, alkyl ether-type protecting group, and silyl-type protecting group include the same protecting groups as those described for R ²¹ .
Examples of ester-type protecting groups include acetyl group, propanoyl group, butanoyl group, isopropanoyl group, pivaloyl group, benzoyl group, 4-nitrobenzoyl group, 4-methoxybenzoyl group, 4-methylbenzoyl group, 4-tert -Butylbenzoyl group, 4-fluorobenzoyl group, 4-chlorobenzoyl group, 4-bromobenzoyl group, 4-phenylbenzoyl group, 4-methoxycarbonylbenzoyl group are mentioned.
Examples of the oxycarbonyl-type protecting group include a tert-butoxycarbonyloxy group and a benzyloxycarbonyl group.

R ³² is an aromatic hydrocarbon group having 6 to 14 carbon atoms. Further, q R ^{32 s} may all be the same or two or more, but are preferably all the same.
Specific examples of R ³² include a phenyl group, a benzyl group, a xylyl group, a toluyl group, a cumenyl group, a naphthyl group, an anthracenyl group, and a fluorenyl group.
The aromatic hydrocarbon group for R ³² may have a substituent and / or a hetero atom. Examples of the substituent include a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms, a nitro group, and a halogen atom. Examples of the hetero atom include an oxygen atom, a sulfur atom, and a nitrogen atom.
R ³² is preferably a phenyl group from the viewpoint of easy availability of raw materials and good solvent solubility of the polymer obtained.
Moreover, it is preferable that all ^R31 and ^R32 are the same aromatic hydrocarbon groups from the point that this condensate excellent in heat resistance, mechanical properties, orientation properties, optical properties and the like is easily obtained.

As a manufacturing method of derivative (I) and derivative (II), the protection method normally used when protecting a hydroxyl group and a carboxy group with a protecting group can be used.
In addition, derivatives (I) and derivatives (II) that are raw materials for the condensation step are various metal salts such as sodium salts, calcium salts, aluminum salts, zinc salts, hydrates, solvates, crystal polymorphs, etc. Can be used in form.

  In the condensation step, the aforementioned derivative (I) and derivative (II) are condensed. The condensation is preferably performed in a solvent from the viewpoint of promoting the condensation reaction. Solvents used in the condensation reaction include water, alcohols such as methanol, primary amines such as N-methylamine, secondary amines such as N, N-dimethylamine, carboxylic acids such as acetic acid, and carboxylic acids such as acetic anhydride. The solvent is not particularly limited as long as an active solvent is not used for the condensation reaction of mineral acids such as acid anhydride and hydrochloric acid. Specific examples of the solvent used in the condensation reaction include, for example, esters such as ethyl acetate, ketones such as acetone, ethers such as diethyl ether and tetrahydrofuran, and tertiary amines such as N, N, N-trimethylamine and pyridine. And aromatic compounds such as toluene, amides such as N, N-dimethylformamide, and sulfoxides such as dimethyl sulfoxide.

The concentration of the derivative (I) in the condensation reaction may be a concentration at which the condensation reaction proceeds sufficiently, and is preferably 0.01 to 10 mol / L. If the concentration of the derivative (I) is 0.01 mol / L or more, the condensation reaction tends to proceed. Moreover, if the density | concentration of derivative (I) is 10 mol / L or less, it will be easy to advance a condensation reaction stably.
The concentration of the derivative (II) in the condensation reaction is preferably the same as that of the derivative (I).

The condensation of the derivative (I) and the derivative (II) may be performed by adding a condensing agent in order to promote the progress of the condensation reaction.
Any condensing agent may be used as long as it generates an active carboxylic acid derivative in the reaction system. For example, N, N′-dicyclohexylcarbodiimide (hereinafter referred to as “DCC”), 1-hydroxybenzotriazole, 1-ethyl BOPs such as -3- (3′-dimethylaminopropyl) carbodiimide (also referred to as water-soluble carbodiimide; hereinafter referred to as “WSCI”), diphenyl phosphate azide, benzotriazol-1-yloxy-trisdimethylaminophosphonium salt, etc. A reagent.

  The addition amount of the condensing agent may be an amount that can promote the condensation reaction, and is preferably equimolar amount to 5 times molar amount with respect to the charged amount of derivative (I) and derivative (II). A molar amount of 1 to 3 is more preferable. When the addition amount of the condensing agent is equal to or more than an equimolar amount, the condensation reaction is easily completed. Moreover, if the said addition amount of a condensing agent is 5 times mole amount or less, a refinement | purification process can be simplified.

Further, the condensation of the derivative (I) and the derivative (II) may be performed by adding a catalyst together with a condensing agent in order to further promote the progress of the condensation reaction.
The catalyst may be any catalyst that can promote the condensation reaction, and examples thereof include N, N-dimethyl-4-aminopyridine (hereinafter referred to as “DMAP”).

  The addition amount of the catalyst may be an amount that can accelerate the condensation reaction, and is preferably 0.01 to 0.7 times the molar amount relative to the less charged amount of the derivative (I) and the derivative (II). A molar amount of 0.05 to 0.5 times is more preferable. If the addition amount of the catalyst is 0.01 times the molar amount or more, the condensation reaction is easily completed. Moreover, if the said addition amount of a catalyst is 0.7 times mole amount or less, a refinement | purification process can be simplified.

The atmosphere in the reaction vessel in the condensation reaction of the derivative (I) and the derivative (II) may be an atmosphere inert to the condensation reaction, and an atmosphere of nitrogen or argon is preferable.
Moreover, -100-100 degreeC is preferable and, as for the reaction temperature in a condensation reaction, 0-80 degreeC is more preferable. When the reaction temperature is −100 ° C. or higher, the condensation reaction tends to proceed. Moreover, if reaction temperature is 100 degrees C or less, it will be easy to suppress the thermal deterioration of this condensate obtained. In addition, when the condensing agent is used, when the condensing agent is added, it generates a lot of heat. Therefore, the reaction vessel may be cooled with a refrigerant or the like at the start of the reaction.
The reaction time in the condensation reaction of the derivative (I) and the derivative (II) is preferably 10 minutes to 50 hours, more preferably 2 to 30 hours. If the reaction time is 10 minutes or more, the condensation reaction is likely to proceed sufficiently. Moreover, if reaction time is 50 hours or less, productivity will improve.

In the production method of the present invention, by condensing the derivative (I) and the derivative (II) as described above, the present condensate in which both the hydroxy group and the carboxy group are protected with a protecting group is obtained.
In the production method of the present invention, it is preferable that R ¹¹ and R ²¹ in the derivative (I) and the derivative (II) are ortho-protecting groups. Thus, the optically active aromatic hydroxycarboxylic acid condensate (III) represented by the following formula (3) obtained by condensing the derivative (I) and the derivative (II) (hereinafter referred to as “condensate (III)”) It is possible to perform a deprotection step in which only one of R ^{11 and} R ^{21 in} the above is deprotected. The condensate in which only one of R ^{11 and} R ²¹ is deprotected by the deprotection step can be used again in the condensation step as the aforementioned derivative (I) and / or derivative (II).

N in the condensate (III) is an integer of 2 or more, and is the sum of p and q.
R ³ is an aromatic hydrocarbon group having 6 to 14 carbon atoms, and is determined by R ³¹ and R ^{32 of} the derivative (I) and the derivative (II) to be condensed. The n R ^{3 s} may all be the same or two or more, but are preferably all the same. That is, it is preferable that R ³¹ of the derivative (I) and R ^{32 of the} derivative (II) are all the same aromatic hydrocarbon group.

The combination in which R ¹¹ and R ²¹ are ortho-protecting groups may be a combination in which only one protecting group is deprotected under specific reaction conditions. For example, R ¹¹ is a tert-butyl group, and R ²¹ is Combination of benzyl group, R ¹¹ is tert-butyl group, R ²¹ is triethylsilyl group combination, R ¹¹ is tert-butyl group, R ²¹ is allyl group combination, R ¹¹ is methoxymethyl group, R ²¹ is triethylsilyl group R ¹¹ is a triethylsilyl group, R ²¹ is a tert-butyl group, R ¹¹ is an allyl group, R ²¹ is a tert-butyl group, R ¹¹ is a tert-butyl group, and R ²¹ is a phenacyl group. ^{combination, R 11} is tert- butyl ^{group, R 21} can be mentioned a combination of nitrobenzyl group .

Specific examples of the case where the product subjected to the deprotection step is used again in the condensation step include the following.
As shown in the following formula, a derivative (IA) in which the carboxy group of D-mandelic acid is protected with R ²¹ (p = 1, a derivative (I) in which R ³ is a phenyl group), and hydroxy of D-mandelic acid By condensing a derivative (II-A) (q = 1, R ³ is a phenyl group derivative (II)) wherein the group is protected by R ¹¹ having an ortho relationship with R ²¹ , the degree of condensation is 2 A chain D-mandelic acid condensate (III-A) (n = 2, R ³ is a phenyl group condensate (III)) is obtained.

Then, by deprotecting one of R ²¹ and R ¹¹ in the obtained condensate (III-A), a derivative (IB) represented by the following formula (p = 2, R ³ is a phenyl group) Derivative (I)) and derivative (II-B) (q = 2, R ³ is a phenyl group derivative (II)). These derivatives (IB) and (II-B) are further condensed in a condensation step to give a condensate (III-B) (n = 4) of linear D-mandelic acid having a condensation degree of 4. , R ³ is a phenyl group condensate (III)).
Further, the condensate obtained by deprotecting the condensate (III-B) can be used as the derivative (I) and the derivative (II) in the condensation step. That is, by performing the deprotection step and the condensation step in the same manner as described above, a condensate of D-mandelic acid with n = 8 can be obtained. Thus, by repeating the condensation step and the deprotection step using the orthologous protecting groups R ¹¹ and R ²¹ , the high molecular weight main condensate can be produced with high efficiency.

  Moreover, you may use the condensate after a deprotection process only as either one of derivative | guide_body (I) or derivative | guide_body (II). For example, the derivative (IB) and the derivative (II-A) may be condensed to obtain a condensate of D = mandelic acid with n = 3.

The deprotection of the condensate (III) is preferably performed in a solvent from the viewpoint of promoting the progress of the deprotection reaction.
The solvent used for deprotection may be any solvent inert to the deprotection reaction, such as water, alcohols such as methanol, primary amines such as N-methylamine, N, N-dimethylamine and the like. Secondary amines, carboxylic acids such as acetic acid, carboxylic acid anhydrides such as acetic anhydride, mineral acids such as hydrochloric acid, esters such as ethyl acetate, ketones such as acetone, ethers such as diethyl ether and tetrahydrofuran, N, Examples thereof include tertiary amines such as N, N-trimethylamine and pyridine, aromatic compounds such as toluene, amides such as N, N-dimethylformamide, and sulfoxides such as dimethyl sulfoxide.

The deprotection of the condensate (III) is performed using a deprotecting agent.
Any deprotecting agent may be used as long as it can selectively deprotect either hydroxy group or carboxyl group, that is, R ¹¹ or R ^21. For example, trifluoroacetic acid (hereinafter referred to as “TFA”). ), Organic acids such as acetic acid; metal salts such as zinc and magnesium of the organic acids; mineral acids such as hydrochloric acid; alkalis such as sodium hydroxide and tetrabutylammonium fluoride (hereinafter referred to as “TBAF”); palladium A mixture of carbon and hydrogen; tetrakis (triphenylphosphine) palladium; a Lindlar catalyst.

For example, if the protecting group R ¹¹ for the hydroxy group is a tert-butyl group and the protecting group R ^{21 for} the carboxyl group is a benzyl group, TFA for the deprotection reaction of R ¹¹ and palladium-carbon and hydrogen for the deprotection reaction of R ²¹ Or a combination of Lindlar catalysts can be used. When R ¹¹ is a tert-butyl group and R ²¹ is a triethylsilyl group, a combination of TFA for the deprotection reaction of R ¹¹ and TBAF for the deprotection reaction of R ²¹ can be used. When R ¹¹ is a tert-butyl group and R ²¹ is an allyl group, a combination of TFA for the deprotection reaction of R ¹¹ and tetrakis (triphenylphosphine) palladium for the deprotection reaction of R ²¹ can be used. When R ¹¹ is a methoxymethyl group and R ²¹ is a triethylsilyl group, a combination of TFA for the deprotection reaction of R ¹¹ and TBAF for the deprotection reaction of R ²¹ can be used. When R ¹¹ is a triethylsilyl group and R ²¹ is a tert-butyl group, a combination of TBAF can be used for the deprotection reaction of R ¹¹ and TFA can be used for the deprotection reaction of R ²¹ . When R ¹¹ is an allyl group and R ²¹ is a tert-butyl group, a combination of tetrakis (triphenylphosphine) palladium for the deprotection reaction of R ¹¹ and TFA for the deprotection reaction of R ²¹ can be used. When R ¹¹ is a tert-butyl group and R ²¹ is a phenacyl group, a combination of TFA can be used for the deprotection reaction of R ¹¹ and TBAF can be used for the deprotection reaction of R ²¹ . When R ¹¹ is a tert-butyl group and R ²¹ is a nitrobenzyl group, a combination of TFA for the deprotection reaction of R ¹¹ and TBAF, zinc acetate, or magnesium acetate for the deprotection reaction of R ²¹ can be used.
The deprotecting agent may be used as a reaction solvent, or may be used in combination with the solvent.

  The addition amount of the deprotecting agent may be an amount that allows the deprotection reaction to proceed sufficiently, and is preferably 0.01 to 30 times the molar amount relative to the total mass of the condensate (III), and 0.05 to 20 A double molar amount is more preferred. When the addition amount of the deprotecting agent is 0.01 times the molar amount or more, the deprotection reaction is easily completed. Moreover, if the said addition amount of a deprotecting agent is 30 times mole amount or less, a refinement | purification process can be simplified.

  The concentration of the condensate (III) in the deprotection reaction may be a concentration at which the deprotection reaction proceeds sufficiently, and is preferably 0.01 to 10 mol / L. When the concentration of the condensate (III) is 0.01 mol / L or more, the productivity of the condensate is improved. Moreover, if the density | concentration of condensate (III) is 10 mol / L or less, a deprotection reaction will advance easily.

The atmosphere in the reaction vessel in the deprotection reaction of the condensate (III) may be an atmosphere inert to the deprotection reaction, and is preferably an atmosphere of nitrogen or argon. In addition, since it is necessary to use hydrogen in order to supply an element necessary for the deprotection reaction, a hydrogen atmosphere is preferably used without using nitrogen or argon.
The reaction temperature in the deprotection reaction of the condensate (III) is preferably -100 to 100 ° C, more preferably 0 to 80 ° C. When the reaction temperature is −100 ° C. or higher, the deprotection reaction easily proceeds. Moreover, if reaction temperature is 100 degrees C or less, it will be easy to suppress the thermal deterioration of this condensate obtained.
The reaction time in the deprotection reaction of the condensate (III) is preferably 10 minutes to 50 hours, more preferably 2 to 30 hours. If the reaction time is 10 minutes or more, the condensation reaction is likely to proceed sufficiently. Moreover, if reaction time is 50 hours or less, productivity will improve.

  Moreover, it is preferable to perform a refinement | purification process after a condensation process and a deprotection process. By performing the purification step, the reaction efficiency of each step is improved when the condensation step and the deprotection step are repeated. The purification method is not particularly limited as long as it can purify the target product in each step of the condensation step and the deprotection step, and examples thereof include a recrystallization method.

The production method of the present invention repeats the condensation step and the deprotection step by using an ortho-protecting group as described above from the point that a high molecular weight main condensate having a highly controlled optical activity can be obtained with a small number of steps. Thus, a method of producing the condensate (III) such that n is 2, 4, 8, 16, etc., and the structural units are sequentially increased (hereinafter referred to as “method (X)”) is preferable.
In the method (X), the derivative (IB) and the derivative (II-A) are condensed to form a condensate (III) having a degree of condensation of 3 (n = 3). Alternatively, the condensate (III) may be produced so that the structural units become longer sequentially such that n is 6, 12, 24, or the like.
However, the production method of the present invention is not limited to the method (X), and for example, the derivative (II-A) is added to the derivative (II-A) and condensed, and then R ²¹ is deprotected. May be used to condense the derivatives (IA) one by one.

  In the conventional polycondensation method of mandelic acid, even when trying to polycondense D-mandelic acid or L-mandelic acid, mandelide which is a cyclic compound having a condensation degree of 2 is produced, so that a high molecular weight condensate is obtained. I couldn't. Further, as described in Non-Patent Document 2, it is possible to obtain a high molecular weight condensate by ring-opening polycondensation of mandelide, but since it is racemized by steric inversion, the optical activity is highly controlled. I couldn't get a body.

On the other hand, in the production method of the present invention, the derivative (I) and the derivative (II) can be condensed while maintaining their optical activity. Therefore, the optically pure present condensate having a highly controlled optical activity. Is obtained.
For example, using the derivative (I) in which the carboxy group of D-mandelic acid is protected and the derivative (II) in which the hydroxy group of D-mandelic acid is protected, the condensation step and the deprotection step are repeated by the method (X). As a result, a high molecular weight condensate (III) having an enantiomeric excess of 100% ee in which the optical activity of D-mandelic acid is maintained in all the structural units can be obtained.
Moreover, D-mandelic acid and L-mandelic acid are condensed in the desired order by appropriately using derivatives (I) and derivatives (II) in which the carboxy group or hydroxy group of D-mandelic acid and L-mandelic acid are protected. The condensed product (III) can also be obtained.

[Optically active compound]
The optically active compound of the present invention (hereinafter referred to as “the present compound”) is a compound represented by the following formula (4).

N in Formula (4) is an integer of 2 or more. n is not particularly limited, but is preferably 10,000 or less from the viewpoint that the present compound can be obtained efficiently.
R ¹ is any ^one of a hydrogen atom, an aralkyl ether protecting group, an alkyl ether protecting group, a silyl protecting group, an ester protecting group, or an oxycarbonyl protecting group.
R ² is any one of a hydrogen atom, an aralkyl ether protecting group, an alkyl ether protecting group, or a silyl protecting group.
At least one of R ¹ and R ² is any one of the above protecting groups. Examples of the respective protecting groups for R ¹ and R ² include the same protecting groups as those described above for R ¹¹ and R ²¹ . When both R ¹ and R ² are not hydrogen atoms, R ¹ and R ² are preferably ortho-protecting groups from the viewpoint of chemical stability. The combination of ortho-protecting groups is the same as in R ¹¹ and R ²¹ .

R ³ is each independently an aromatic hydrocarbon group having 6 to 14 carbon atoms. The n R ^{3 s} may all be the same or two or more, but are preferably all the same.
R ³ is particularly preferably a phenyl group. That is, the present condensate represented by the following formula (5) is preferable.

  The enantiomeric excess of this compound is preferably 70 to 100% ee, more preferably 80 to 100% ee, and more preferably 90 to 100% from the viewpoint of excellent heat resistance, mechanical properties, orientation properties, optical properties, and the like. ee is more preferable.

  Further, the form of the present compound is not particularly limited, and various forms such as metal salts such as sodium salts, calcium salts, aluminum salts, zinc salts, hydrates, solvates, and crystal polymorphs may be used. it can.

As a method for producing this compound, the above-described production method is preferably used. By using the above-described production method, the present compound with highly controlled optical activity can be obtained. That is, this compound is a condensate obtained by condensing the derivative (I) and the derivative (II) by the above-described production method, in which both the hydroxy group and the carboxy group are protected, or ortho-protecting groups R ¹¹ and R ^21. It is preferably a compound selected from the group consisting of condensates obtained by deprotecting either R ¹¹ or R ²¹ of the condensate (III) protected with. In this case, in this compound, R ¹ is a hydrogen atom or R ¹¹ , R ² is a hydrogen atom or R ²¹ , and ^one of R ¹ and R ² is a protecting group.
As a manufacturing method of this compound represented by said Formula (5), the derivative | guide_body (IA) and the derivative | guide_body (II-A) which protected the hydroxy group or carboxy group of D-mandelic acid and L-mandelic acid are condensed. A method or a method of deprotecting either R ¹¹ or R ²¹ in the condensate (III-A) obtained by the method is preferred.

Hereinafter, the present invention will be described in detail with reference to Examples and Comparative Examples. However, the present invention is not limited by the following description.
[NMR analysis]
The chemical structures of the condensates and derivatives obtained in this example were confirmed by ¹ H-NMR and ¹³ C-NMR (manufactured by JEOL Ltd., JNM-ECX400). The measurement conditions were deuterated chloroform as the measurement solvent, sample concentration of 2 mass / volume%, and measurement temperature at room temperature. The number of integrations was 16 times when the observation nucleus was ¹ H and 5000 times when the observation nucleus was ¹³ C.

[Mass spectrometry]
The mass of the condensate was confirmed by a matrix-assisted laser desorption / ionization time-of-flight mass spectrometer (hereinafter referred to as “MALDI-TOF-MS”) equipped with a nitrogen laser (manufactured by Shimadzu Corporation, AXIMA-CFRplus). .
A MALDI-TOF-MS measurement sample was prepared by the following procedure.
First, a solution in which 1 mg of sodium iodide as a cationizing agent was dissolved in 1 mL of tetrahydrofuran (hereinafter referred to as “THF”) was prepared, and 1 μL of the solution was dropped on a sample plate and allowed to dry naturally. Next, 1 μL of a solution prepared by dissolving 1 mg of the condensate synthesized in the Examples in 1 mL of methylene chloride was dropped on the portion of the sample plate where sodium iodide had been deposited, and was naturally dried. Then, a solution in which 10 mg of trans-2- [3- (4-t-butylphenyl) -2-methyl-2-propenylindene] malononitrile as a matrix agent was dissolved in 1 mL of THF was mixed with sodium iodide of the sample plate. 1 μL was dropped on the portion where the compound was deposited and allowed to dry naturally.
The mass calibration was performed by an external standard method using Triton X-100 (trade name, manufactured by Wako Pure Chemical Industries, Ltd.). The masses of Triton X-100 used for calibration were a 10-mer 6699.4172, an 11-mer 7133.4433, and a 12-mer 7577.4694 (both are sodium ion adducts).

[Specific rotation]
The specific rotation of the condensate and the derivative was measured at room temperature using a polarimeter (manufactured by JASCO Corporation, DIP-360) for a solution obtained by dissolving 0.1 g of a sample in 10 mL of chloroform.

[Melting point]
The melting points of the condensate and the derivative were measured using a trace melting point measuring device (manufactured by Yanaco Corporation, MP-S2).

[Synthesis Example 1] Synthesis of benzyl D-mandelate (MDA-Bn) 30.4 g (200 mmol) of D-mandelic acid represented by the following formula (6), carbonic acid was added to a 500 mL eggplant flask containing a stirrer in advance. 15.2 g (110 mmol) of potassium, 100 mL of N, N-dimethylformamide, and 34.2 g (200 mmol) of benzyl bromide were added to dissolve the contents, and the mixture was stirred at room temperature with a stirrer for 2 hours to protect the carboxy group. Reaction was performed. After completion of the reaction, the reaction solution was transferred to a separatory funnel. The flask containing the reaction solution was washed with 200 mL of ethyl acetate, and the washing solution was also transferred to a separatory funnel. The solution transferred to the separatory funnel was washed three times with 300 mL of distilled water.
The washed organic phase was transferred to a 500 mL eggplant flask, concentrated with an evaporator, dried under reduced pressure with a vacuum pump, and a white solid crude benzyl D-mandelate (crude MDA-Bn) represented by the following formula (7): 42.2 g (87% yield) was obtained.

Ethyl acetate was added to a 500 mL eggplant flask containing crude MDA-Bn at room temperature until the crude MDA-Bn was completely dissolved, and then kept in a cool dark place at −30 ° C. for 24 hours, and purified by recrystallization.
The obtained crystals were filtered off using 5C filter paper, dried under reduced pressure with a vacuum pump, and 35.4 g (yield 73%) of purified white solid benzyl D-mandelate (MDA-Bn, derivative (I)). Obtained.
The chemical structure of the obtained MDA-Bn was confirmed by ¹ H-NMR. ^{The 1} H-NMR spectrum is shown in FIG. Moreover, the specific rotation [α] _D of MDA-Bn was −56 °, and the melting point was 106.0 to 106.5 ° C.

[Synthesis Example 2] Synthesis of benzyl ot-butyl-D-mandelate (tBu-MDA-Bn) The above formula obtained in the same manner as in Synthesis Example 1 in a 500 mL eggplant flask containing a stir bar in advance. 48.5 g (200 mmol) of MDA-Bn represented by (7) and 300 mL of methylene chloride were added to dissolve the contents, and then the solution was cooled to −78 ° C. in a dry ice / methanol bath.
On the other hand, bomb-filled isobutene (boiling point -6.9 ° C.) was introduced into a sealed 200 mL eggplant flask equipped with a Dewar cooler that had been cooled beforehand in a dry ice / methanol bath, and 100 mL of liquefied isobutene was collected.
After transferring 100 mL of liquefied isobutene to the flask containing the MDA-Bn / methylene chloride solution cooled to −78 ° C., 9.2 g of concentrated sulfuric acid was added. With this flask attached with a three-way cock and sealed, the mixture was stirred with a stirrer at −78 ° C. for 3 hours, and further stirred in an ice-water bath (0 ° C.) for 21 hours to carry out a hydroxy group protection reaction.
After completion of the reaction, the reaction solution was transferred to a separatory funnel. The flask containing the reaction solution was washed with 200 mL of methylene chloride, and the washing solution was also transferred to a separatory funnel. The solution transferred to the separatory funnel was washed once with 100 mL of a saturated aqueous solution of sodium bicarbonate, twice with 300 mL of distilled water, and once with 100 mL of a 10 mass% sodium chloride aqueous solution.
The organic phase after washing was transferred to a 500 mL eggplant flask, concentrated with an evaporator, dried under reduced pressure with a vacuum pump, and a cream-colored liquid D-mandelic acid t-butyl ether-benzyl ester represented by the following formula (8) ( 56.7 g (yield 95%) of tBu-MDA-Bn) was obtained.
The chemical structure of the obtained tBu-MDA-Bn was confirmed by ¹ H-NMR. A ¹ H-NMR spectrum of tBu-MDA-Bn is shown in FIG.

[Synthesis Example 3] Synthesis of Ot-Butyl-D-mandelic acid (tBu-MDA) In a 500 mL eggplant flask containing a stirrer in advance, tBu-MDA of the above formula (8) obtained in Synthesis Example 2 was used. -56.7 g (190 mmol) of -Bn, 5.0 g of a palladium / carbon mixture wet with about 55% water (palladium content 5 mass%) was added, and a three-way cock was attached. Then, after reducing the pressure in the flask with a vacuum pump, a nitrogen replacement operation for introducing dry nitrogen and returning to normal pressure was repeated a total of three times. Thereafter, the inside of the flask was further depressurized with a vacuum pump, and the hydrogen replacement operation for returning to normal pressure by introducing hydrogen gas was repeated a total of three times.
While maintaining the inside of the flask in a hydrogen atmosphere, 200 mL of stabilizer-free THF was added to the flask to dissolve the contents, followed by stirring with a stirrer at room temperature for 24 hours to perform a deprotection reaction.
In order to desorb hydrogen adsorbed on palladium, the inside of the flask was depressurized with a vacuum pump, and then dry nitrogen was introduced to return to normal pressure. The reaction liquid in the flask was stirred with a stirrer for 30 minutes, and then solids in the reaction liquid were filtered off with 5C filter paper. Further, the flask and the solid were washed with 100 mL of THF without addition of a stabilizer.
The filtrate was transferred to a 500 mL eggplant flask, concentrated with an evaporator, and then dried under reduced pressure with a vacuum pump, and a pale yellow to white solid Ot-butyl-D-mandelic acid (tBu-MDA) represented by the formula (9) Derivative (II)) was obtained 39.2 g (99% yield).
The chemical structure of the obtained MDA-Bn was confirmed by ¹ H-NMR. The ¹ H-NMR spectrum of MDA-Bn is shown in FIG. Moreover, the specific rotation [α] _D of MDA-Bn was −112 °, and the melting point was 87.5 to 88.5 ° C.

[Example 1] Synthesis of Ot-butyl-D-mandelic acid dimer benzyl (tBu-MDA2-Bn) The above formula (1) obtained in Synthesis Example 1 was added to a 100 mL eggplant flask with a stir bar in advance. 7) MDA-Bn of 2.4 g (10 mmol), tBu-MDA of the formula (9) obtained in Synthesis Example 3 was 2.1 g (10 mmol), DCC was 2.5 g (12 mmol) as a condensing agent, 0.24 g (2 mmol) of DMAP was added as a catalyst, and a three-way cock was attached. Thereafter, the pressure inside the flask was reduced with a vacuum pump, and the nitrogen substitution operation for returning to normal pressure by introducing dry nitrogen was repeated a total of three times.
While keeping the inside of the flask in a nitrogen atmosphere, 20 mL of dehydrated methylene chloride was added to the flask to dissolve the contents, followed by stirring with a stirrer at room temperature for 24 hours to perform a condensation reaction.

After completion of the reaction, the solid matter in the reaction solution was filtered off with 5C filter paper. The flask and solids were washed with 80 mL of methylene chloride. The filtrate was transferred to a separatory funnel and washed twice with 100 mL of a saturated aqueous solution of sodium bicarbonate and once with 100 mL of a 10 mass% aqueous sodium chloride solution.
After the organic phase after washing was transferred to a 200 mL beaker, 10 g of sodium sulfate was added and retained for 12 hours for dehydration, and the sodium sulfate was filtered off with 5C filter paper. The filtrate was transferred to a 200 mL eggplant flask, concentrated with an evaporator, dried under reduced pressure with a vacuum pump, and a colorless to white solid Ot-butyl-D-mandelic acid dimer benzyl represented by the following formula (10). Of 3.7g (crude tBu-MDA2-Bn) was obtained (98% yield).
Transfer the entire amount of crude tBu-MDA2-Bn to a 500 mL eggplant flask, add 10 mL of methanol, add diethyl ether until the crude tBu-MDA2-Bn is completely dissolved, then hold in a cool dark place at −30 ° C. for 24 hours. Purified with crystals.
The obtained crystals were filtered off with 5C filter paper, dried under reduced pressure with a vacuum pump, and 2.8 g of purified colorless to white solid Ot-butyl-D-mandelic acid dimer benzyl (tBu-MDA2-Bn). (Yield 75%).
The chemical structure of the obtained tBu-MDA2-Bn was confirmed by ¹ H-NMR and ¹³ C-NMR. The ¹ H-NMR spectrum of tBu-MDA2-Bn is shown in FIG. 4, and the ¹³ C-NMR spectrum is shown in FIG. The specific rotation [α] _D of tBu-MDA2-Bn was −57 °, and the melting point was 92.0 to 93.0 ° C.

[Example 2] Synthesis of Ot-butyl-D-mandelic acid dimer (tBu-MDA2) In a 100 mL eggplant flask containing a stirrer in advance, the above formula (10) obtained in Example 1 was obtained. 5.2 g (12 mmol) of tBu-MDA2-Bn, 0.5 g of a palladium / carbon mixture (palladium content 5 mass%) wetted with about 55% water was added, and a three-way cock was attached. Thereafter, the pressure inside the flask was reduced with a vacuum pump, and the nitrogen substitution operation for returning to normal pressure by introducing dry nitrogen was repeated a total of three times. Further, the pressure inside the flask was reduced with a vacuum pump, and then the hydrogen replacement operation for returning to normal pressure by introducing hydrogen gas was repeated a total of three times.
While keeping the inside of the flask in a hydrogen atmosphere, 20 mL of THF without addition of a stabilizer was added to the flask to dissolve the contents, followed by stirring with a stirrer at room temperature for 1 hour to perform a deprotection reaction.

After developing the reaction solution by thin layer chromatography and confirming the disappearance of the raw material spots, the flask was depressurized with a vacuum pump to desorb the hydrogen adsorbed on the palladium, and then dry nitrogen was introduced to normal pressure. Returned. The developing solution used was n-hexane / ethyl acetate = 1/4 (volume ratio). The Rf value of the raw material represented by the following formula (10) was 0.34, and the Rf value of the product represented by the following formula (11) was 0.11.
The reaction liquid in the flask was stirred with a stirrer for 30 minutes, and then solids in the reaction liquid were filtered off with 5C filter paper. Further, the flask and the solid were washed with 80 mL of THF without addition of a stabilizer.
The filtrate was transferred to a 200 mL eggplant flask, concentrated with an evaporator, dried under reduced pressure with a vacuum pump, and a colorless to white solid Ot-butyl-D-mandelic acid dimer represented by the following formula (11). 4.1 g (yield 99%) of a crude product (crude tBu-MDA2) was obtained.
Transfer the entire amount of crude tBu-MDA2 to a 500 mL eggplant flask, add 10 mL of n-hexane, add diethyl ether until the crude tBu-MDA2 is completely dissolved, and then keep in a cool dark place at −30 ° C. for 24 hours. Purified.
The obtained crystals were filtered off with 5C filter paper, dried under reduced pressure with a vacuum pump, and purified needle-like colorless to white solid Ot-butyl-D-mandelic acid dimer (tBu-MDA2) 3.3 g. (Yield 80%).
The chemical structure of the obtained tBu-MDA2 was confirmed by ¹ H-NMR. The ¹ H-NMR spectrum of tBu-MDA2 is shown in FIG. Moreover, the specific rotation [α] _D of tBu-MDA2 was −94 °, and the melting point was 145.5 to 146.5 ° C.

[Example 3] Synthesis of D-mandelic acid dimer benzyl (MDA2-Bn) In a 100 mL eggplant flask with a stirrer placed in advance, tBu-MDA2-Bn of the above formula (10) obtained in Example 1 was used. 6.5 g (15 mmol) and 62 mL of TFA were added to dissolve the contents, and the mixture was stirred at room temperature with a stirrer for 3 hours to carry out a deprotection reaction.
After concentrating the reaction liquid in the flask with an evaporator, 20 mL of diethyl ether was added to dissolve the residue, and then transferred to a separatory funnel. The flask was washed with 80 mL of diethyl ether and transferred to the separatory funnel. The solution in the separatory funnel was washed three times with 100 mL of a saturated aqueous solution of sodium bicarbonate and once with 100 mL of a 10 mass% sodium chloride solution.
After the washed organic phase was transferred to a 200 mL beaker, 10 g of sodium sulfate was added and the mixture was dehydrated by holding for 12 hours, and then sodium sulfate was filtered off with 5C filter paper. The filtrate was transferred to a 200 mL eggplant flask, concentrated with an evaporator, and then dried under reduced pressure with a vacuum pump. A colorless to white solid D-mandelic acid dimer benzyl crude product (crude MDA2) represented by the following formula (12) -Bn) was obtained 5.5g (yield 98%).
Transfer the entire amount of crude MDA2-Bn to a 500 mL eggplant flask, add 10 mL of n-hexane, add diethyl ether until the crude MDA2-Bn is completely dissolved, then hold in a cool dark place at −30 ° C. for 24 hours, and recrystallize. Purified.
The obtained crystals were filtered off with 5C filter paper and dried under reduced pressure with a vacuum pump to obtain 4.6 g (yield 82%) of purified colorless to white solid D-mandelic acid dimer benzyl (MDA2-Bn). .
The chemical structure of the obtained MDA2-Bn was confirmed by ¹ H-NMR. The ¹ H-NMR spectrum of MDA2-Bn is shown in FIG. Moreover, the specific rotation [α] _D of MDA2-Bn was −79 °, and the melting point was 82.5 to 83.0 ° C.

[Example 4] Synthesis of Ot-butyl-D-mandelic acid tetramer benzyl (tBu-MDA4-Bn) The above formula (2) obtained in Example 2 was added to a 100 mL eggplant flask containing a stir bar in advance. 11) tBu-MDA2 of 0.58 g (1.7 mmol), MDA2-Bn of the formula (12) obtained in Example 3 was 0.64 g (1.7 mmol), and WSCI as a condensing agent was 0.31 g. (2.0 mmol), 0.05 g (0.4 mmol) of DMAP was added as a catalyst, and a three-way cock was attached. Thereafter, the pressure inside the flask was reduced with a vacuum pump, and the nitrogen substitution operation for returning to normal pressure by introducing dry nitrogen was repeated a total of three times.
While maintaining the inside of the flask in a nitrogen atmosphere, 10 mL of dehydrated methylene chloride was added to the flask to dissolve the contents, followed by stirring with a stirrer at room temperature for 24 hours to perform a condensation reaction.
After completion of the reaction, the solid matter in the reaction solution was filtered off with 5C filter paper. The flask and solids were washed with 140 mL of methylene chloride. The filtrate was transferred to a separatory funnel and washed twice with 150 mL of a saturated aqueous solution of sodium bicarbonate and once with 100 mL of a 10 mass% aqueous sodium chloride solution.
After the washed organic phase was transferred to a 200 mL beaker, 10 g of sodium sulfate was added and the mixture was dehydrated by holding for 12 hours, and then sodium sulfate was filtered off with 5C filter paper. The filtrate was transferred to a 200 mL eggplant flask, concentrated with an evaporator, dried under reduced pressure with a vacuum pump, and a light tan solid Ot-butyl-D-mandelic acid tetramer benzyl represented by the following formula (13). 2.3 g (yield 95%) of a crude product (crude tBu-MDA4-Bn) was obtained.
Transfer the entire amount of crude tBu-MDA4-Bn to a 500 mL eggplant flask, add 10 mL of methanol, add diethyl ether until the crude tBu-MDA4-Bn is completely dissolved, and then keep it in a cool dark place at -30 ° C for 24 hours. Purified by crystals.
The obtained crystals were filtered off with 5C filter paper, dried under reduced pressure with a vacuum pump, and purified white solid Ot-butyl-D-mandelic acid tetramer benzyl (tBu-MDA4-Bn, this condensate) 2 0.1 g (yield 87%) was obtained.

The chemical structure of the obtained tBu-MDA4-Bn was confirmed by ¹ H-NMR, ¹³ C-NMR, and MALDI-TOF-MS. FIGS. 8 and 9 show the HMBC spectrum of tBu-MDA4-Bn, FIGS. 10 and 11 show the HMQC spectrum, FIG. 12 shows the ¹ H-NMR spectrum, FIG. ¹³ shows the ¹³ C-NMR spectrum, and FIG. 13 shows the MALDI-TOF-MS spectrum. 14 shows.
After assigning protons in the HMBC spectrum, carbon was assigned in the HMQC spectrum. As shown in FIG. 9, in the obtained tBu-MDA4-Bn, no correlation peak is observed in the region α in the HMBC spectrum. This is because the obtained tBu-MDA4-Bn is condensed while maintaining the optical activity of D-mandelic acid, the molecular chain is elongated, and the bond angle is fixed. In the case of racemic tBu-MDA4-Bn, a correlation peak should be observed in the region α, and from this result, an n = 4 condensate (tetramer) maintaining the optical activity of D-mandelic acid is obtained. I was able to confirm.
Moreover, the specific rotation [α] _D of tBu-MDA4-Bn was −84 °, and the melting point was 109.0 to 110.0 ° C.

[Example 5] Synthesis of Ot-butyl-D-mandelic acid tetramer (tBu-MDA4) In a 100 mL eggplant flask with a stirrer previously added, the compound of the above formula (13) obtained in Example 4 was used. 1.00 g (1.4 mmol) of tBu-MDA4-Bn and 0.1 g of Lindlar catalyst were added, and a three-way cock was attached. Thereafter, the pressure inside the flask was reduced with a vacuum pump, and the nitrogen substitution operation for returning to normal pressure by introducing dry nitrogen was repeated a total of three times. Further, the pressure inside the flask was reduced with a vacuum pump, and then the hydrogen replacement operation for returning to normal pressure by introducing hydrogen gas was repeated a total of three times.
While keeping the inside of the flask in a hydrogen atmosphere, 20 mL of THF without addition of a stabilizer was added to the flask to dissolve the contents, followed by stirring with a stirrer at room temperature for 2 hours to perform a deprotection reaction.

After developing the reaction solution by thin layer chromatography and confirming the disappearance of the raw material spot, the inside of the flask was decompressed with a vacuum pump to desorb the hydrogen adsorbed on the Lindlar catalyst, and then dry nitrogen was introduced to constantly The nitrogen replacement operation for returning to the pressure was repeated a total of 3 times. The developing solution used was n-hexane / ethyl acetate = 1/4 (volume ratio). The Rf value of the raw material represented by the following formula (13) was 0.278, and the Rf value of the product represented by the following formula (14) was 0.00.
The reaction liquid in the flask was stirred with a stirrer for 30 minutes, and then solids in the reaction liquid were filtered off with 5C filter paper. Further, the flask and the solid were washed with 80 mL of THF without addition of a stabilizer.
The filtrate was transferred to a 200 mL eggplant flask, concentrated with an evaporator, dried under reduced pressure with a vacuum pump, and a colorless to white solid Ot-butyl-D-mandelic acid tetramer represented by the following formula (14). 0.90 g (99% yield) of a crude product (crude tBu-MDA4) was obtained.
The chemical structure of the obtained crude tBu-MDA4 was confirmed by ¹ H-NMR. The ¹ H-NMR spectrum of tBu-MDA4 is shown in FIG.

[Example 6] Synthesis of D-mandelic acid tetramer benzyl (MDA4-Bn) In a 100 mL eggplant-shaped flask containing a stirrer in advance, tBu-MDA4-Bn of the formula (13) obtained in Example 4 was used. 1.00 g (1.4 mmol) and 5 mL of TFA were added to dissolve the contents, followed by stirring with a stirrer at room temperature for 3 hours to carry out a deprotection reaction.
After concentrating the reaction liquid in the flask with an evaporator, 20 mL of methylene chloride was added to dissolve the residue, and then transferred to a separatory funnel. The flask was washed with 60 mL of methylene chloride and transferred to the separatory funnel. The solution in the separatory funnel was washed three times with 100 mL of a saturated aqueous solution of sodium bicarbonate and once with 100 mL of a 10 mass% sodium chloride solution.
After the washed organic phase was transferred to a 200 mL beaker, 10 g of sodium sulfate was added and the mixture was dehydrated by holding for 12 hours, and then sodium sulfate was filtered off with 5C filter paper. The filtrate was transferred to a 200 mL eggplant flask, concentrated with an evaporator, and then dried under reduced pressure with a vacuum pump. A colorless to white solid D-mandelic acid tetramer benzyl crude product (crude MDA4 represented by the following formula (15): 0.88 g (yield 96%) of -Bn) was obtained.
The chemical structure of the obtained crude MDA4-Bn was confirmed by ¹ H-NMR. The ¹ H-NMR spectrum of MDA4-Bn is shown in FIG.

[Example 7] Synthesis of Ot-butyl-D-mandelic acid octamer benzyl (tBu-MDA8-Bn) The above formula (5) obtained in Example 5 was added to a 100 mL eggplant flask containing a stir bar in advance. 14) 0.88 g of crude tBu-MDA4, 0.95 g of crude MDA4-Bn of the formula (15) obtained in Example 6, 0.33 g (1.73 mmol) of EDC as a condensing agent, and catalyst 0.035 g (0.288 mmol) of DMAP was added, and a three-way cock was attached. Thereafter, the pressure inside the flask was reduced with a vacuum pump, and the nitrogen substitution operation for returning to normal pressure by introducing dry nitrogen was repeated a total of three times.
The flask was immersed in an ice bath at 0 ° C. while maintaining the inside of the flask in a nitrogen atmosphere. Thereafter, 10 mL of dehydrated methylene chloride was added to the flask to dissolve the contents, and the mixture was stirred at 0 ° C. with a stirrer for 2 hours. Thereafter, the flask was moved to room temperature and further stirred for 22 hours to conduct a condensation reaction.
After completion of the reaction, the solid matter in the reaction solution was filtered off with 5C filter paper. The flask and solids were washed with 80 mL of methylene chloride. The filtrate was transferred to a separatory funnel and washed twice with 100 mL of a saturated aqueous solution of sodium bicarbonate and once with 100 mL of a 10 mass% aqueous sodium chloride solution.
After the washed organic phase was transferred to a 200 mL beaker, 10 g of sodium sulfate was added and the mixture was dehydrated by holding for 12 hours, and then sodium sulfate was filtered off with 5C filter paper. The filtrate was transferred to a 200 mL eggplant flask, concentrated with an evaporator, dried under reduced pressure with a vacuum pump, and a light tan solid Ot-butyl-D-mandelic acid octamer benzyl represented by the following formula (16). 1.67 g (yield 94%) of a crude product (crude tBu-MDA8-Bn) was obtained.

The chemical structure of the obtained crude tBu-MDA8-Bn was confirmed by ¹ H-NMR, ¹³ C-NMR, and MALDI-TOF-MS. FIG. 17 shows the HMBC spectrum of tBu-MDA8-Bn, FIG. 18 shows the HMQC spectrum, FIG. 19 shows the ¹ H-NMR spectrum, FIG. 20 shows the ¹³ C-NMR spectrum, and FIG. 21 shows the MALDI-TOF-MS spectrum.
In the MALDI-TOF-MS spectrum, a signal having a mass / charge ratio (m / z) = 1259.54 was observed most strongly. This m / z agreed with the monoisotope mass (1259.40 Da) of the sodium ion adduct of tBu-MDA8-Bn within an error range.
Further, as in Example 4, it was confirmed from the HMBC spectrum and HMQC spectrum that an n = 8 condensate (octamer) maintaining the optical activity of D-mandelic acid was obtained.

[Synthesis Example 4] Synthesis of phenacyl D-mandelate (MDA-Pac) In a 300 mL eggplant flask containing a stirrer in advance, 16.74 g (110 mmol) of D-mandelic acid represented by the following formula (6), carbonic acid 8.36 g (60 mmol) of potassium, 55 mL of N, N-dimethylformamide, and 21.89 g (110 mmol) of 2-bromoacetophenone were added to dissolve the contents, and the mixture was stirred at room temperature with a stirrer for 2 hours. A protective reaction was performed. The protection reaction was performed in a dark place. After completion of the reaction, the reaction solution was transferred to a separatory funnel. The flask containing the reaction solution was washed with 200 mL of ethyl acetate, and the washing solution was also transferred to a separatory funnel. The solution transferred to the separatory funnel was washed three times with 300 mL of distilled water.
The washed organic phase was transferred to a 500 mL eggplant flask, concentrated with an evaporator, dried under reduced pressure with a vacuum pump, and a white solid crude phenacyl D-mandelate represented by the following formula (17) (crude MDA-Pac ) Was obtained 25.75 g (99% yield).

Ethyl acetate was added to a 500 mL eggplant flask containing the crude MDA-Pac at 40 ° C. until the crude MDA-Pac was completely dissolved, then kept in a cool dark place at 5 ° C. for 48 hours, and purified by recrystallization.
The obtained crystals were filtered off using 5C filter paper, dried under reduced pressure with a vacuum pump, and purified white solid phenacyl D-mandelate (MDA-Pac, derivative (I)) 25.8 g (yield 87%). Obtained.
The chemical structure of the obtained MDA-Pac was confirmed by ¹ H-NMR. ^{The 1} H-NMR spectrum is shown in FIG. Further, the specific rotation [α] _D of MDA-Pac was 110 °, and the melting point was 97.0 to 99.0 ° C.

Example 8 Synthesis of Ot-butyl-D-mandelic acid dimer phenacyl (tBu-MDA2-Pac) First, 31.6 g (153 mmol) of DCC as a condensing agent and 3.7 g of a catalyst. (30.6 mmol) of DMAP was dissolved in 100 mL of dehydrated methylene chloride and this solution was transferred to a 200 mL addition funnel.
In a 1000 mL three-necked flask with a stir bar in advance and connected to the dropping funnel, 33.1 g (122.5 mmol) of MDA-Pac of the formula (17) obtained in Synthesis Example 4 was obtained in Synthesis Example 3. Further, 27.5 g (122.5 mmol) of tBu-MDA of the formula (9) was added, and a three-way cock was attached. Thereafter, the pressure inside the flask was reduced with a vacuum pump, and the nitrogen substitution operation for returning to normal pressure by introducing dry nitrogen was repeated a total of three times.
While keeping the inside of the flask in a nitrogen atmosphere, 300 mL of dehydrated methylene chloride was added to the flask to dissolve the contents.
After immersing the three-necked flask in an ice bath at 0 ° C., the solution in the dropping funnel was dropped into the three-necked flask over 1 hour, and further stirred with a stirrer at 0 ° C. for 2 hours, and then the three-necked flask was moved to room temperature. The mixture was stirred for 22 hours to conduct a condensation reaction.

After completion of the reaction, the solid matter in the reaction solution was filtered off with 5C filter paper. The flask and solids were washed with 150 mL of methylene chloride. The filtrate was transferred to a separatory funnel and washed twice with 200 mL of a saturated aqueous solution of sodium bicarbonate and once with 200 mL of a 10% by mass aqueous sodium chloride solution.
After the washed organic phase was transferred to a 200 mL beaker, 20 g of sodium sulfate was added and the mixture was dehydrated by holding for 12 hours, and the sodium sulfate was filtered off with 5C filter paper. The filtrate was transferred to a 1000 mL eggplant flask, concentrated with an evaporator, dried under reduced pressure with a vacuum pump, and a colorless to white solid Ot-butyl-D-mandelic acid dimer phenacyl represented by the following formula (18). 70.6 g (yield 125%) of the crude product (crude tBu-MDA2-Pac) was obtained.
70.6 g of crude tBu-MDA2-Pac was purified by column chromatography using a developing solvent of ethyl acetate / n-hexane = 2/3 (volume ratio).
The obtained solution was transferred to a 500 mL eggplant flask, concentrated with an evaporator, and then dried under reduced pressure with a vacuum pump to obtain 56.6 g (yield 94%) of purified white solid tBu-MDA2-Bn.
The chemical structure of the obtained tBu-MDA2-Pac was confirmed by ¹ H-NMR and MALDI-TOF-MS. FIG. 23 shows a ¹ H-NMR spectrum of tBu-MDA2-Pac, and FIG. 24 shows a MALDI-TOF-MS spectrum.
In the MALDI-TOF-MS spectrum, a signal having a mass / charge ratio (m / z) = 483.15 was observed most strongly. This m / z agreed with the monoisotope mass (483.19 Da) of the sodium ion adduct of tBu-MDA2-Pac within an error range.
The specific rotation [α] _D of tBu-MDA2-Pac was 58.9 °, and the melting point was 100.0-101.0 ° C.

[Example 9] Synthesis of Ot-butyl-D-mandelic acid dimer (tBu-MDA2) by phenacyl group deprotection of tBu-MDA2-Pac In a 100 mL eggplant flask containing a stir bar in advance, Example 0.10 g (0.217 mmol) of tBu-MDA2-Pac of the formula (18) obtained in 8 above, 1.00 mL of 1 mol / L tetrabutylammonium fluoride / THF solution, 0.06 g of distilled water, After adding 2 mL of THF to dissolve the contents, the mixture was stirred at room temperature with a stirrer for 30 minutes to perform a deprotection reaction.

After concentrating the reaction liquid in the flask with an evaporator, 20 mL of methylene chloride was added to dissolve the residue, and then transferred to a separatory funnel. The flask was washed with 60 mL of methylene chloride and transferred to the separatory funnel. The solution in the separatory funnel was washed three times with 100 mL of saturated aqueous sodium hydroxide solution and once with 100 mL of saturated aqueous citric acid solution.
After the washed organic phase was transferred to a 200 mL beaker, 10 g of sodium sulfate was added and the mixture was dehydrated by holding for 12 hours, and then sodium sulfate was filtered off with 5C filter paper. The filtrate was transferred to a 200 mL eggplant flask, concentrated with an evaporator, dried under reduced pressure with a vacuum pump, and a crude yellow solid Ot-butyl-D-mandelic acid dimer represented by the following formula (11). A body (crude tBu-MDA2) was obtained.
The chemical structure of the obtained crude tBu-MDA2 was confirmed by ¹ H-NMR. The ¹ H-NMR spectrum of tBu-MDA2 is shown in FIG.

[Example 10] Synthesis of D-mandelic acid dimer phenacyl (MDA2-Pac) In a 300 mL eggplant flask containing a stirrer in advance, tBu-MDA2-Pac of the above formula (18) obtained in Example 8 was used. 21.9 g (47.6 mmol) and 48 mL of TFA were added to dissolve the contents, and the mixture was stirred at room temperature with a stirrer for 3 hours to carry out a deprotection reaction.
After concentrating the reaction liquid in the flask with an evaporator, 50 mL of methylene chloride was added to dissolve the residue, and then transferred to a separatory funnel. The flask was washed with 100 mL of methylene chloride and transferred to the separatory funnel. The solution in the separatory funnel was washed twice with 200 mL of a saturated aqueous solution of sodium bicarbonate and once with 200 mL of a 10% by mass aqueous sodium chloride solution.
After the washed organic phase was transferred to a 200 mL beaker, 20 g of sodium sulfate was added, and the mixture was dehydrated by holding for 12 hours. Thereafter, sodium sulfate was filtered off with 5C filter paper. The filtrate was transferred to a 500 mL eggplant flask, concentrated with an evaporator, dried under reduced pressure with a vacuum pump, and a pale yellow solid D-mandelic acid dimer phenacyl represented by the following formula (19) (crude MDA2- 19.5 g (98% yield) of Pac) was obtained.

Example 11 Synthesis of Ot-butyl-D-mandelic acid tetramer phenacyl (tBu-MDA4-Pac) First, 12.8 g (60 mmol) of DCC as a condensing agent and 1.5 g as a catalyst. (12 mmol) of DMAP was dissolved in 100 mL of dehydrated methylene chloride and the solution was transferred to a 200 mL addition funnel.
In a 1000 mL three-necked flask containing a stirrer in advance, 16.6 g of tBu-MDA2 of the formula (11) obtained in Example 9 and crude MDA2-Pac of the formula (19) obtained in Example 10 were used. 19.5g was added and a three-way cock was attached. Thereafter, the pressure inside the flask was reduced with a vacuum pump, and the nitrogen substitution operation for returning to normal pressure by introducing dry nitrogen was repeated a total of three times.
While keeping the inside of the flask in a nitrogen atmosphere, 150 mL of dehydrated methylene chloride was added to the flask to dissolve the contents.
After immersing the three-necked flask in an ice bath at 0 ° C., the solution in the dropping funnel was dropped into the three-necked flask over 1 hour, and further stirred with a stirrer at 0 ° C. for 2 hours, and then the three-necked flask was moved to room temperature. The mixture was stirred for 22 hours to conduct a condensation reaction.

After completion of the reaction, the solid matter in the reaction solution was filtered off with 5C filter paper. The flask and solids were washed with 100 mL of methylene chloride. The filtrate was transferred to a separatory funnel and washed twice with 200 mL of a saturated aqueous solution of sodium bicarbonate and once with 200 mL of a 10% by mass aqueous sodium chloride solution.
After the organic phase after washing was transferred to a 500 mL beaker, 10 g of sodium sulfate was added and the mixture was dehydrated by holding for 12 hours, and then sodium sulfate was filtered off with 5C filter paper. The filtrate was transferred to a 500 mL eggplant flask, concentrated with an evaporator, dried under reduced pressure with a vacuum pump, and a light tan solid Ot-butyl-D-mandelic acid tetramer phenacyl represented by the following formula (20). 37.3 g (yield 106%) of a crude product (crude tBu-MDA4-Pac) was obtained.
37.3 g of crude tBu-MDA4-Pac was purified by column chromatography using a developing solvent of ethyl acetate / n-hexane = 1/2 (volume ratio).
The obtained solution was transferred to a 500 mL eggplant flask, concentrated with an evaporator, and then dried under reduced pressure with a vacuum pump to obtain 34.0 g (yield 97%) of purified light tan solid tBu-MDA4-Pac.

The chemical structure of the obtained crude tBu-MDA4-Pac was confirmed by ¹ H-NMR, ¹³ C-NMR, and MALDI-TOF-MS. FIGS. 26 and 27 show the HMBC spectrum of tBu-MDA4-Pac, FIGS. 28 and 29 show the HMQC spectrum, FIG. 30 shows the ¹ H-NMR spectrum, FIG. 31 shows the ¹³ C-NMR spectrum, and FIG. 31 shows the MALDI-TOF-MS spectrum. 32.
In the MALDI-TOF-MS spectrum, a signal having a mass / charge ratio (m / z) = 751.30 was observed most strongly. This m / z agreed with the monoisotope mass (751.25 Da) of the sodium ion adduct of tBu-MDA4-Pac within an error range.
Further, as in Example 4, it was confirmed from the HMBC spectrum and HMQC spectrum that an n = 4 condensate (tetramer) maintaining the optical activity of D-mandelic acid was obtained.

[Synthesis Example 5] Synthesis of Ot-butyl-D-mandelic acid dimer nitrobenzyl (tBu-MDA2-NBn) The above formula obtained in Example 2 was added to a 100 mL eggplant flask containing a stir bar in advance. 1.00 g (2.9 mmol) of tBu-MDA2 of (11), 0.24 g (1.74 mmol) of potassium carbonate, 7 mL of N, N-dimethylformamide, and 0.94 g of 2-nitrobenzyl bromide (2 0.9 mmol), and the contents were dissolved, and then stirred for 2 hours at room temperature with a stirrer to carry out a carboxy group protection reaction. After completion of the reaction, the reaction solution was transferred to a separatory funnel. The flask containing the reaction solution was washed with 80 mL of ethyl acetate, and the washing solution was also transferred to a separatory funnel. The solution transferred to the separatory funnel was washed three times with 120 mL of distilled water.

After the organic phase after washing was transferred to a 200 mL beaker, 5 g of sodium sulfate was added and retained for 12 hours for dehydration, and then the sodium sulfate was filtered off with 5C filter paper. The filtrate was transferred to a 200 mL eggplant flask, concentrated with an evaporator, dried under reduced pressure with a vacuum pump, and a white solid of Ot-butyl-D-mandelic acid dimer nitrobenzyl represented by the following formula (21). 1.33 g (yield 96%) of a crude product (crude tBu-MDA2-NBn) was obtained.
1.33 g of crude tBu-MDA2-NBn was purified by column chromatography using a developing solvent of ethyl acetate / n-hexane = 1/2 (volume ratio).
The obtained solution was transferred to a 500 mL eggplant flask, concentrated with an evaporator, and then dried under reduced pressure with a vacuum pump to obtain 1.03 g (yield 74%) of purified white solid tBu-MDA2-NBn.
The chemical structure of the obtained tBu-MDA2-NBn was confirmed by ¹ H-NMR. A ¹ H-NMR spectrum of tBu-MDA2-Pac is shown in FIG.

By repeating the condensation step and the deprotection step using derivatives (I) and derivatives (II) in which the hydroxy group or carboxy group of D-mandelic acid is protected with an ortho-protective group as in Examples 1 to 11 Thus, condensates having condensation degrees of 2, 4, and 8 maintaining the optical activity of D-mandelic acid were obtained. Furthermore, it is considered that a higher molecular weight condensate can be obtained by repeating the same deprotection step and condensation step.
Also, as in the Synthesis Example 5, the protecting group of R ²¹ were obtained compound represented by the formula is a nitrobenzyl group (21). From this compound, if the tert-butyl group is deprotected, a derivative (I) in which the protecting group for R ²¹ is a nitrobenzyl group can be obtained, and a high molecular weight condensate can also be obtained from the derivative (I). It is considered possible.

  The production method of the present invention is extremely useful because an optically active aromatic hydroxycarboxylic acid condensate having highly controlled optical activity can be obtained. Further, since the optical activity of the optically active compound of the present invention is highly controlled, as a highly functional material excellent in heat resistance, mechanical properties, orientation properties, optical properties, etc., a display orientation film, an environmentally friendly material, It is considered that it can be suitably used for structures / building materials and the like.

Claims (4)

A condensation step of condensing an optically active aromatic hydroxycarboxylic acid derivative (I) represented by the following formula (1) and an optically active aromatic hydroxycarboxylic acid derivative (II) represented by the following formula (2): A method for producing an optically active aromatic hydroxycarboxylic acid condensate.

(In Formula (1) and Formula (2), p and q are each independently an integer of 1 or more. R ¹¹ is an aralkyl ether type protecting group, an alkyl ether type protecting group, a silyl type protecting group, or an ester type protecting group. is either group or an oxycarbonyl-type protecting group, R ²¹ is .p number of R ³¹ is either aralkyl ether type protecting group, alkyl ether-type protecting group or a silyl-type protecting groups, the carbon independently It is an aromatic hydrocarbon group having a number of 6 to 14. Each q R ³² is independently an aromatic hydrocarbon group having a carbon number of 6 to 14. The carbon atom indicated by * means an asymmetric carbon atom. To do.) R ¹¹ and R ²¹ are orthogonal protecting groups,
Optically active aromatic hydroxycarboxylic acid condensation represented by the following formula (3) obtained by condensing the optically active aromatic hydroxycarboxylic acid derivative (I) and the optically active aromatic hydroxycarboxylic acid derivative (II) A deprotection step of deprotecting either R ¹¹ or R ²¹ of the body (III);
The condensate obtained by deprotecting either R ¹¹ or R ^{21 is used as} the optically active aromatic hydroxycarboxylic acid derivative (I) and / or the optically active aromatic hydroxycarboxylic acid derivative (II) in the condensation step. The manufacturing method of the optically active aromatic hydroxycarboxylic acid condensate of Claim 1 to be used.

(In the formula (3), n is an integer of 2 or more, .n number of R ³ is the sum of p and q are each independently an aromatic hydrocarbon group having 6 to 14 carbon atoms.) An optically active compound represented by the following formula (4).

(In the formula (4), .R ¹ n is an integer of 2 or greater, a hydrogen atom, an aralkyl ether type protecting group, alkyl ether-type protecting group, a silyl-type protecting group, ester type protecting group or an oxycarbonyl-type protecting group R ² is any one of a hydrogen atom, an aralkyl ether protecting group, an alkyl ether protecting group, or a silyl protecting group, and at least one of R ¹ and R ² is any one of the protecting groups described above N R ^{3 s} are each independently an aromatic hydrocarbon group having 6 to 14 carbon atoms.) The optically active compound according to claim 3, wherein R ³ is a phenyl group.

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