JP2001328970A - Method for producing optically active alpha-amino acid and optically active alpha-amino acid amide - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for efficiently producing an optically active alpha-amino acid and an optically active alpha-amino acid amide. SOLUTION: This method for producing the optically active alpha-amino acid and the optically active alpha-amino acid amide, comprising bringing the optically impure α-amino acid amide into contact with microbial cells having an asymmetric hydrolysis ability or their treated products in an aqueous solvent, replacing the water used as the solvent by at least one solvent selected from >=3C linear, branched or cyclic alcohols and further preferentially depositing the optically active alpha-amino acid from the obtained alcohol solution. The optically active alpha-amino acid amide-containing alcohol solution obtained after the separation of the optically active alpha-amino acid is recycled to the racemization reaction process.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing an optically active α-amino acid and an optically active α-amino acid amide. Optically active α-amino acids and optically active α-amino acid amides are used as starting materials for pharmaceuticals and agricultural chemicals.

[0002]

2. Description of the Related Art There are many reports on the production of optically active α-amino acids in both chemical and biological synthesis methods. For example, as a biological synthesis method, a racemic α using a microorganism having an α-amino acid amide asymmetric hydrolytic ability, etc.
-Optical resolution of amino acid amides is known. This method is capable of easily producing an α-amino acid having high optical purity by obtaining a microorganism having high stereoselectivity, easily producing a racemic α-amino acid amide as a raw material, a natural type and a non-amino acid amide. It is useful as a general-purpose production method for optically active α-amino acids because it can be applied to any optically active α-amino acid of the natural type.

[0003] However, in the above-mentioned optical resolution method of racemic or non-optically pure α-amino acid amide using a microorganism having an asymmetric hydrolytic ability of α-amino acid amide, after completion of the reaction, the objective solution is dissolved in a liquid. Since the optically active α-amino acid and the optically active α-amino acid amide are mixed, it is necessary to separate the optically active α-amino acid and the optically active α-amino acid amide.

As a method for separating an α-amino acid and an α-amino acid amide, a method of removing the α-amino acid amide by solvent extraction and then recovering the α-amino acid at an isoelectric point (Japanese Patent Laid-Open No. 58-209989). JP-A-57-1300
No. 0), a method of preferentially crystallizing amino acids by adding ethanol (JP-A-63-87998, JP-A-61-274690, JP-A-60-184392,
JP-A-59-159789, and a method of performing adsorption separation using an ion-exchange resin (JP-A-1-2264)
No. 82) or an α-amino acid amide is adsorbed on a cation exchange resin, and then an enzyme is brought into contact with the ion exchange resin to perform a stereospecific hydrolysis reaction, thereby simultaneously performing the reaction and the separation. Method for producing amino acid
No. 23996).

After the optical resolution reaction, water contained in the obtained aqueous solution of the optically active α-amino acid is removed under reduced pressure, and the residue is washed with a hot organic solvent to selectively remove the α-amino acid amide. A method of recovering the remaining optically active α-amino acid has also been reported (see JP-A-61-293394). In this report, the optically active α-
A strongly basic compound is added to an amino acid amide solution in an organic solvent, and the mixture is heated to racemize the α-amino acid amide. The resulting α-amino acid amide of the mixture of D- and L-forms is subjected to asymmetric hydrolysis reaction. Is also described. Regarding racemization, a method of heating an α-amino acid amide by heating in an organic solvent in the presence of an alkali is described in Japanese Patent Application Laid-Open No. 62-252751. In any report, in order to suppress the hydrolysis reaction of α-amino acid amide that occurs as a side reaction during the racemization reaction, it is essential to keep the water content of the optically active α-amino acid amide solution low, for example, JP-A-62-252751 specifies that the water content in an organic solvent is 10% or less.

However, the above-mentioned methods for producing optically active α-amino acids have disadvantages, and are not industrially efficient. In the method in which the α-amino acid amide is removed by solvent extraction and then the α-amino acid is recovered at the isoelectric point, a large amount of solvent is required for the extraction. Therefore, it is disadvantageous in terms of equipment and cost. In addition, the method of performing adsorption separation using an ion-exchange resin requires adsorption, desorption, and recovery, and requires many steps, which leads to problems such as an increase in capital investment, a reduction in recovery efficiency, and an increase in opportunities for impurity contamination. Is industrially undesirable.

[0007] On the other hand, ethanol is added to the reaction concentrate to add α-
The method of preferentially crystallizing an amino acid has a feature that, compared to other methods, concentration and crystallization can be performed in the same tank, so that the operation is simple and the equipment investment on the apparatus is small.
However, in this method, it is necessary to add several times or more of ethanol to the volume of the concentrated solution, which causes an increase in cost. In addition, the reported example of this technique has only a limited number of natural amino acids, and it is only valine that describes the purity of the obtained amino acid. It is unknown at all. Therefore, this method cannot be said to be a versatile technique.

Further, when it is assumed that the separated optically active α-amino acid amide is racemized and reused in the optical resolution reaction, ethanol has a low boiling point and is not a suitable solvent for the racemization reaction. Is obvious. For example, Japanese Patent Application Laid-Open No. 62-252751 discloses an example of a racemization reaction using an ethanol solution.
The reaction is carried out by heating the vessel to 0 to 120 ° C. The method requires special equipment on an industrial scale. Therefore, when ethanol is used, it is difficult to carry out the reaction at normal pressure without equipment investment on the apparatus.

Further, considering that the separated and recovered ethanol solution containing the optically active α-amino acid amide has a high water content, the racemization reaction of the optically active α-amino acid amide requires additional solution. Operations such as dehydration and solvent substitution, or operations for isolating and drying the optically active α-amino acid amide crystal are required, and the operation steps become complicated.

The method of removing the water, washing the residue with a hot organic solvent, and selectively washing away the α-amino acid amide is a method of isolating the optically active α-amino acid amide from the solution without isolating the α-amino acid amide from the solution. It has the characteristic that it can react,
It is technically difficult to completely remove water from a solution and concentrate it to dryness in industrial-scale production, and this method is not a practical production method in view of operability and equipment investment on equipment. .

For the above reasons, the method for producing an optically active α-amino acid by a known method has a problem in terms of efficiency and the like in the method for recovering the optically active α-amino acid after the reaction, and is an industrially superior method. I didn't get it.

[0012]

SUMMARY OF THE INVENTION The present invention provides an efficient method for producing an optically active α-amino acid and an optically active α-amino acid amide which solves the above problems.

[0013]

Means for Solving the Problems The inventors of the present invention have made intensive studies to solve the above-mentioned problems, and as a result, have found that the optically active α-
By replacing the solvent of the aqueous solution containing an amino acid and an optically active α-amino acid amide from water with an alcohol solvent having 3 or more carbon atoms, and obtaining the optically active α-amino acid preferentially from the alcohol solution, a very high yield It has been found that optically active α-amino acids can be produced.

Furthermore, in order to produce an optically active α-amino acid more efficiently, an asymmetric hydrolysis reaction, an optically active α-amino acid,
After the crystallization / separation operation of the amino acid, the optically active α-amino acid amide can be obtained without isolating the optically active α-amino acid amide from the optically active α-amino acid amide-containing alcohol solution obtained as the separated mother liquor. A racemization reaction can be performed. In addition, by performing a water removal operation such as azeotropic dehydration after the addition of the basic compound, the water generated by the reaction with the basic compound can be removed, so that the racemization reaction of the optically active α-amino acid amide can be more efficiently performed. It has been found that the mixture of D-form and L-form α-amino acid amide recovered after the racemization reaction can be recycled as a raw material for the asymmetric hydrolysis reaction of α-amino acid amide.

That is, the present invention provides (1) an optically active α-
Optically active α-amino acid and optically active α, wherein the solvent of the solution containing the amino acid and the optically active α-amino acid amide is substituted from water to an alcoholic solvent, and the optically active α-amino acid is preferentially precipitated from the alcohol solution. -A method for producing an amino acid amide. (2) After obtaining an optically active α-amino acid, a basic compound is added to an optically active α-amino acid amide-containing alcohol solution obtained as a separated mother liquor, and a racemicization reaction of the optically active α-amino acid amide is carried out to obtain an asymmetric amino acid amide. A method for producing an optically active α-amino acid and an optically active α-amino acid amide, which is characterized by being recycled for use in a hydrolysis reaction.

[0016]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The general embodiments of the present invention will be described below.

The type of the α-amino acid amide used in the present invention is not limited, but those represented by the following general formula (III) are preferred.

[0018]

Embedded image (Wherein R1 and R2 are the same or different and each represent a hydrogen atom, a lower alkyl group, a substituted lower alkyl group, a lower alkenyl group, a substituted lower alkenyl group, a cycloalkyl group,
A phenyl group, a substituted phenyl group, a heterocyclic group and a substituted heterocyclic group are shown. Examples of the compound represented by the general formula (III) include alaninamide, valinamide, leucinamide, isoleucinamide, methioninamide, tryptophanamide, phenylalaninamide, serinamide, cysteinamide, tyrosineamide, lysineamide, histidineamide and 2-amino. Butyric acid amide, cyclohexylalanine amide, norvaline amide, norleucinamide, 6
-Hydroxynorleucinamide, neopentylglycinamide, penicillamine, tert-leucinamide, phenylglycinamide, 2-chlorophenylglycinamide, 3-chlorophenylglycinamide, 4
-Chlorophenylglycinamide and the like.

In the present invention, the type of α-amino acid is not limited, but those represented by the following general formula (IV) are preferred.

[0020]

Embedded image (Wherein R1 and R2 are the same or different and each represent a hydrogen atom, a lower alkyl group, a substituted lower alkyl group, a lower alkenyl group, a substituted lower alkenyl group, a cycloalkyl group,
A phenyl group, a substituted phenyl group, a heterocyclic group and a substituted heterocyclic group are shown. ) As those represented by the general formula (IV), for example, alanine, valine, leucine, isoleucine, methionine, tryptophan, phenylalanine, serine, cysteine, tyrosine, lysine, histidine, 2-aminobutyric acid,
Cyclohexylalanine, norvaline, norleucine,
6-hydroxynorleucine, neopentylglycine,
Penicillamine, tert-leucine, phenylglycine, 2-chlorophenylglycine, 3-chlorophenylglycine, 4-chlorophenylglycine and the like can be mentioned.

The optical resolution reaction of the α-amino acid amide acts stereospecifically on the racemic or optically pure α-amino acid amide in an aqueous medium, and the α-amino acid amide has an optical property corresponding to that of the optically active α-amino acid. -It can be carried out by the action of a microorganism giving the amino acid amide. The microorganism is not particularly limited as long as it catalyzes the above reaction. For example, the microorganism may be Enterobacter cloassay N
-7901 (FERMBP-873); coli
JM109 / pLA205 (FERM BP-713
2) and the like. These microorganisms are used as they are or as processed cells (washed cells, dried cells, crushed cells, cell extracts, crude or purified enzymes, and immobilized products thereof).

The optical resolution reaction is carried out in an aqueous medium using α
-It is carried out by contacting the amino acid amide with the above-mentioned cells or the treated cells. Usually, the concentration of α-amino acid amide is 0.1 to 60% by mass, preferably 1 to 40% by mass,
The concentration of the cells or the processed cells varies depending on the amount of activity, but 1/10000 to 1% by mass relative to the amino acid amide mass,
Preferably 1/1000 to 1/10 mass, pH of reaction solution
Is 4-11, preferably 6-10, and the reaction temperature is 10
-60 ° C, preferably 20-50 ° C.

After completion of the reaction, the method for removing the cells or the treated cells from the reaction solution is not particularly limited.
It can be performed using a method such as filtration. The reaction solution from which the cells or the treated product has been removed may be subjected to vacuum concentration if necessary.

The water in the obtained reaction solution or concentrated solution has 3 or more carbon atoms, preferably 3 to 6, more preferably 4 to 6 carbon atoms.
At least one solvent selected from among linear, branched or cyclic alcohols. The solvent is replaced by an operation such as azeotropic distillation, and the water contained in the aqueous solution containing the optically active α-amino acid and the optically active α-amino acid amide obtained after the asymmetric hydrolysis reaction of the α-amino acid amide is preferably 90 mass%. The operation is continued until the substitution with the alcohol solvent to at least%.

After substitution with an alcohol solvent, the optically active α
-The method for obtaining an amino acid is not particularly limited, and examples thereof include an obtaining method by precipitation. Concentration of optically active α-amino acid when precipitating optically active α-amino acid,
The temperature is not particularly limited as long as the optically active α-amino acid can be recovered in a high yield, but the concentration is 1 to 50% by mass, preferably 5 to 30% by mass in consideration of operation efficiency and the like. The reaction is performed at -20 to 60C, preferably 0 to 40C. After heating and stirring the solution at a higher temperature than during the precipitation operation, the optically active α-amino acid can be precipitated at the above-mentioned temperature to obtain a highly pure optically active α-amino acid. Further precipitated optically active α-
The operation of recovering amino acids can be performed by any of continuous and batch methods.

By the above operation, the optically active α-amino acid precipitated as crystals is recovered by a method such as centrifugation or filtration. As a result, the optically active α-amino acid dissolved in the solution is removed. Can be separated from amide.

If necessary, the optically active α-amino acid amide in the separated mother liquor can be recovered in a solid form by substitution with a solvent having low solubility for the optically active α-amino acid amide or by removing the solvent.

The racemization reaction of the optically active α-amino acid amide is carried out by adding a basic compound to an optically active α-amino acid amide-containing alcohol solution obtained as a separated mother liquor.
As the basic compound, at least one of an alkali metal hydroxide and an alkali metal alcoholate is selected. Examples of the alkali metal hydroxide include sodium hydroxide and potassium hydroxide, and examples of the alkali metal alcoholate include sodium methylate, sodium ethylate, potassium methylate, and potassium-tert.
-Butyrate and the like. The amount of the basic compound to be added is 0.01 to 1.0 molar equivalent, preferably 0.05 to 0.5 molar equivalent, based on the amino acid amide. α
-When α-amino acids are mixed in the amino acid amide-containing alcohol solution, a basic compound of 1.0 molar equivalent or more of α-amino acids can be added to the above-mentioned amount. In addition, by performing a water removal operation such as azeotropic dehydration after the addition of the basic compound, the water generated by the reaction with the basic compound can be removed, so that the racemization reaction of the optically active α-amino acid amide can be more efficiently performed. It is possible to do. The optically active α-amino acid amide thus recovered as an alcohol solution can be subjected to a racemization reaction only by a simple operation without going through complicated steps while being dissolved in an alcohol solvent.

The conditions for the racemization reaction of the optically active α-amino acid amide are as follows: α-amino acid amide, type of basic compound,
Although it depends on various factors such as concentration and is not particularly limited, the reaction temperature is generally 80 to 200 ° C., preferably 1 to 200 ° C.
Perform at 00 to 150 ° C. for 10 minutes to 24 hours. After the reaction, D
The -isomer and L-isomer α-amino acid amide mixture can be recovered by a known method and recycled to an asymmetric amino acid amide hydrolysis reaction.

[0030]

Next, the present invention will be described in detail with reference to examples.

Reference Example 1 Preparation of an Aqueous Solution Containing Optically Active α-Amino Acid and Optically Active α-Amino Acid Amide According to the method described in JP-A-62-55097, Enterobacter Cloassay N-7901 (FERM)
P-873). 1 L of the culture solution is centrifuged, and then the wet cells are suspended in distilled water to form a cell suspension solution 8.
00 g was prepared. After 200 g of D, L-tert-leucinamide was dissolved in this suspension,
Allowed to react for hours. After the reaction, the cells were removed by centrifugation to obtain 970 g of an aqueous solution containing 10% by mass of each of L-tert-leucine and D-tert-leucinoamide.
The concentrations of tert-leucine and tert-leucinamide were analyzed under high performance liquid chromatography (HPLC) analysis condition 1, and the optical purity of each was analyzed under HPLC analysis condition 2. The water content of the solution was measured using a Karl Fischer moisture meter (Mitsubishi Moisture Meter CA-60: manufactured by Mitsubishi Kasei Corporation).

[HPLC analysis conditions 1] Column: Inertosyl ODS-3V (4.6φ × 25)
0 mm) Moving layer: 0.1% phosphoric acid aqueous solution Flow rate: 1 mL / min Detection: RI [HPLC analysis condition 2] Column: SUMICHIRAL OA-5000 (4.
6φ × 250mm) Moving layer: water-methanol (85:15) Flow rate: 1 mL / min Detection: UV 254 nm

Example 1 L-te obtained in Reference Example 1
After 200 g of an aqueous solution containing rt-leucine and D-tert-leucinamide was concentrated under reduced pressure to 72 g, 300 g of isopropyl alcohol was added to the solution. The solution was further concentrated under reduced pressure to finally obtain 140 g of a concentrated solution. At this time, the water concentration of the concentrated liquid was 6.5% by mass. After stirring this concentrated liquid at 50 ° C. for 1 hour, the solution was cooled and then cooled to 15 ° C.
And further stirred for 4 hours. The precipitated crystals were collected by suction filtration to obtain L-tert-leucine having a dry mass of 18.4 g (yield 92%). At this time, the amount of D-tert-leucinamide contained in the L-tert-leucine crystal was 0.01% by mass or less.

Example 2 L-te obtained in Reference Example 1
After 400 g of an aqueous solution containing rt-leucine and D-tert-leucinamide was concentrated under reduced pressure to 140 g, 300 g of 1-butanol was added to the solution. Further, the solution was concentrated under reduced pressure to finally obtain 265 g of a concentrated liquid. At this time, the water concentration of the concentrated liquid was 0.9% by mass. After a solution obtained by adding 10 g of 1-butanol to the concentrated solution was stirred at 60 ° C. for 1 hour, the solution was cooled and further stirred at 20 ° C. for 3 hours. The precipitated crystals were collected by centrifugal filtration and had a dry mass of 3
9.2 g of L-tert-leucine was obtained (yield 98).
%). At this time, the amount of D-tert-leucinamide contained in the L-tert-leucine crystal was 0.05% by mass.
Met.

Example 3 L-te obtained in Reference Example 1
After 500 g of an aqueous solution containing rt-leucine and D-tert-leucinamide was concentrated under reduced pressure to 250 g, 250 g of 1-butanol was added to the solution. The solution was further concentrated under reduced pressure, and when the amount of the distillate reached 240 g, 1-
250 g of butanol was added. After the addition, the mixture was again concentrated under reduced pressure to finally obtain 350 g of a concentrated liquid. At this time, the water concentration of the concentrated liquid was 0.6% by mass. 6
After stirring at 0 ° C. for 2 hours, the solution was cooled and further stirred at 20 ° C. for 2 hours. The precipitated crystals were collected by centrifugal filtration to obtain 48.9 g of dry mass of L-tert-leucine (yield 98%). At this time, the amount of D-tert-leucinamide contained in the L-tert-leucine crystal was less than 0.01% by mass. Separated mother liquor 29 collected
5 g contained 49.0 g of D-tert-leucinamide.

Example 4 D-te obtained in Example 3
3.0 g of sodium hydroxide was added to 295 g of a 1-butanol solution of rt-leucinamide (separated mother liquor), and the mixture was refluxed for 4 hours. After the reaction solution was concentrated under reduced pressure to 80 g,
100 g of n-heptane was added to the concentrated solution, and the mixture was stirred at 5 ° C for 10 hours. The precipitated crystals were collected by suction filtration, and tert-type mixture of D-form and L-form having a dry mass of 38.7 g was obtained.
-Leucinamide was obtained (yield from separated mother liquor 79
%). At this time, D- of the tert-leucinamide crystal
The abundance ratio of body: L-form was 50.2: 49.8.

Example 5 Tert-leucinamide crystal 20 of the mixture of D-form and L-form obtained in Example 4
g and 80 g of the cell suspension prepared in Reference Example 1,
A cell reaction was performed in the same manner as in Reference Example 1. After 52 hours, the reaction solution contained L-tert-leucine and D-tert-
Leucinoamide was present in each 10% by weight.

Example 6 D-te obtained in Example 3
After adding 3.0 g of potassium hydroxide to 295 g of a 1-butanol solution of rt-leucinamide (separated mother liquor), the solution was concentrated under reduced pressure to 206 g. The water concentration of the concentrated liquid was 0.06% by mass. After the concentrated solution was heated under reflux for 6 hours, the reaction solution was concentrated under reduced pressure to 81 g, and 100 g of n-heptane was added to the concentrated solution, followed by stirring at 5 ° C. for 3 hours. The precipitated crystals were collected by suction filtration and had a dry mass of 4
0.2 g of tert-leucinamide as a mixture of D-form and L-form was obtained (82% yield from separated mother liquor). At this time, the abundance ratio of the D-form: L-form of the tert-leucinamide crystal was 50.0: 50.0.

Example 7 Instead of 1-butanol,
The same operation as in Example 2 was performed using each of the alcohol solvents shown in Table 1, and the aqueous solution 4 containing L-tert-leucine and D-tert-leucinamide obtained in Reference Example 1 was obtained.
L-tert-leucine crystals were recovered from 00 g. Table 1 shows the water content, the crystallization temperature, and the L-tert-leucine acquisition yield of each alcohol solution after the solvent replacement operation.

[Table 1]

Reference Example 2 Preparation of Aqueous Solution Containing Optically Active α-Amino Acid and Optically Active α-Amino Acid Amide According to the method described in JP-A-62-55097, Enterobacter Cloassay strain N-7901 (FER)
MBP-873). 500 mL of culture solution
Was centrifuged, and the wet cells were suspended in distilled water to prepare a cell suspension solution (1140 g). D, L-
After dissolving 60g of phenylalanine amide,
For 24 hours. After the reaction, the cells were removed by centrifugation to obtain 1150 g of an aqueous solution containing 2.5% by mass of each of L-phenylalanine and D-phenylalaninamide. The concentrations of phenylalanine and phenylalanine amide were determined under HPLC analysis condition 3, and the optical purity of each was HP
The analysis was performed under LC analysis condition 4.

[HPLC analysis condition 3] Column: Inertosyl ODS-3V (4.6φ × 25)
0 mm) Moving layer: 0.1% phosphoric acid aqueous solution-methanol (80:
20) Flow rate: 1 mL / min Detection: UV 254 nm [HPLC analysis condition 4] Column: SUMICHIRAL OA-5000 (4.
6φ × 250mm) Moving layer: water-methanol (70:30) Flow rate: 1 mL / min Detection: UV 254 nm

Example 8 1100 g of the aqueous solution containing L-phenylalanine and D-phenylalaninamide obtained in Reference Example 2 was concentrated under reduced pressure to 310 g.
770 g of butanol were added. Further, the solution was concentrated under reduced pressure to finally obtain 335 g of a concentrated solution. At this time, the water concentration of the concentrated liquid was 0.2% by mass. After the concentrated solution was stirred at 70 ° C. for 1 hour, the solution was cooled, and further stirred at 40 ° C. for 1 hour.
Stirred for hours. The precipitated crystals are collected by centrifugal filtration,
L-phenylalanine having a dry mass of 28.2 g was obtained (yield 94%). At this time, the amount of D-phenylalanine amide contained in the L-phenylalanine crystal was 0.07% by mass.

[0043]

EFFECT OF THE INVENTION After contacting racemic α-amino acid amide with a cell or an enzyme having a stereospecific α-amino acid amide hydrolytic ability in an aqueous medium, water as a solvent is converted into a linear C 3 -amino acid amide. By substituting at least one solvent selected from the group consisting of branched or cyclic alcohols, and by preferentially precipitating the optically active α-amino acid from the obtained alcohol solution, the optically active α-amino acid can be obtained in a very high yield. −
Amino acids can be produced. In addition, the optical activity α-
Since the optically active α-amino acid amide-containing alcohol solution obtained after separating the amino acid can be easily subjected to the racemization reaction step, the production efficiency of the optically active α-amino acid can be improved.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) C07C 237/06 C07C 237/06 237/20 237/20 C12P 13/02 C12P 13/02 13/04 13 / 04 41/00 41/00 A // C07B 57/00 365 C07B 57/00 365 370 370 61/00 300 61/00 300 (C12P 13/02 (C12P 13/02 C12R 1:01) C12R 1:01) (C12P 13/04 (C12P 13/04 C12R 1:01) C12R 1:01) (C12P 41/00 (C12P 41/00 A C12R 1:01) C12R 1:01) C07M 7:00 C07M 7: 00F Term (reference) 4B064 AE02 AE03 CA02 CB05 DA16 4H006 AA02 AC82 AC83 AD15 BB14 BC50 BD42 BD52 BE10 BU32 BU36 BV21 BV52 4H039 CA99 CJ20

Claims (9)

[Claims] 1. An optically active α-amino acid and an optically active α-amino acid.
A method for producing an optically active α-amino acid and an optically active α-amino acid amide, wherein the solvent of the amino acid amide-containing aqueous solution is replaced with an alcohol solvent from water, and the optically active α-amino acid is precipitated from the alcohol solution. 2. An optically active α-amino acid and an optically active α-amino acid.
The amino acid amide-containing aqueous solution is not optically pure α-
The method for producing an optically active α-amino acid and an optically active α-amino acid amide according to claim 1, which is obtained by contacting a cell having the asymmetric hydrolysis ability or the treated product with the amino acid amide. 3. The optically active α-amino acid and optically active α according to claim 1 or 2, wherein the alcohol solvent is at least one alcohol selected from the group consisting of linear, branched or cyclic alcohols having 3 or more carbon atoms. -A method for producing an amino acid amide and an optically active α-amino acid amide. 4. The water content of the separated mother liquor after precipitation of the optically active α-amino acid is 10% by mass or less.
3. The method for producing an optically active α-amino acid and an optically active α-amino acid amide according to any one of 3. 5. The optically active α according to claim 1, wherein a basic compound is added to the separated mother liquor after the optically active α-amino acid is precipitated, and a racemization reaction is carried out. -Methods for producing amino acids and optically active α-amino acid amides. 6. The method according to claim 1, wherein the basic compound is at least one of alkali metal hydroxides and alkali metal alcoholates.
The method for producing an optically active α-amino acid and an optically active α-amino acid amide according to claim 5, which is a seed. 7. An optically active α-amino acid and an optically active α-amino acid amide, wherein the α-amino acid amide obtained by the method according to claim 5 or 6 is recycled as a raw material for an asymmetric hydrolysis reaction. Manufacturing method. 8. The optically active α according to any one of claims 1 to 7, wherein the α-amino acid is represented by the general formula (I).
-Methods for producing amino acids and optically active α-amino acid amides. Embedded image (Wherein R1 and R2 are the same or different and each represent a hydrogen atom, a lower alkyl group, a substituted lower alkyl group, a lower alkenyl group, a substituted lower alkenyl group, a cycloalkyl group,
A phenyl group, a substituted phenyl group, a heterocyclic group and a substituted heterocyclic group are shown. ) 9. The method for producing an optically active α-amino acid and an optically active α-amino acid amide according to any one of claims 1 to 7, wherein the α-amino acid amide is represented by the general formula (II). Embedded image (Wherein R1 and R2 are the same or different and each represent a hydrogen atom, a lower alkyl group, a substituted lower alkyl group, a lower alkenyl group, a substituted lower alkenyl group, a cycloalkyl group,
A phenyl group, a substituted phenyl group, a heterocyclic group and a substituted heterocyclic group are shown. )