JP2002065295A - Method of producing optically active 2,6-diaminoheptanoic acid - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing optically active 2,6- diaminoheptanoic acid that is very important as an intermediate for a variety of industrial chemicals, agrochemicals and medicines. SOLUTION: The living cell bodies of a microorganism that has the activity of stereoselectively hydrolyzing amino acid amide or a cell body-treated product of this microorganism are allowed to act on a racemic mixture of 2,6- aminoheptanamide.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing optically active 2,6-diaminoheptanoic acid represented by the general formulas (2) and (3). More specifically, the present invention relates to a method for producing a corresponding optically active 2,6-diaminoheptanoic acid by asymmetrically biochemically hydrolyzing a racemic mixture of 2,6-diaminoheptanamide. BACKGROUND ART Optically active 2,6-diaminoheptanoic acid is an important substance as a production intermediate of various industrial chemicals, agricultural chemicals, and pharmaceuticals.

[0002]

2. Description of the Related Art Optically active 2,6-diaminoheptanoic acid has a carboxyl group and two amino groups in the molecule and is itself an optically active compound. It is an important substance as an intermediate for the production of pharmaceuticals. 2, represented by general formulas (2) and (3)
The preparation of a racemic mixture of 6-diaminoheptanoic acid, wherein X is hydrogen, is described in J. Am. Chem. Soc., 73, p4478, (195
It is described in 1). However, the production method described therein uses 2-methylcyclohexanone oxime as a starting material, and proceeds in four steps including protection and deprotection steps. Because it is used, it is not an industrially advantageous method. Also, the 2,6-diaminoheptanoic acid obtained here is a racemic mixture, and an optically active substance cannot be obtained by the method described herein.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to solve the above-mentioned problems in the prior art, and to provide an optically active 2,6-, which is very important as an intermediate for producing various industrial chemicals, agricultural chemicals, and pharmaceuticals. An object of the present invention is to provide a production method for producing diaminoheptanoic acid in a small number of steps and at low cost.

[0004]

Means for Solving the Problems The present inventors have conducted intensive studies on a production method for producing optically active 2,6-diaminoheptanoic acid in a small number of steps and at low cost, and as a result, a novel compound 2 The present invention has been achieved in which optically active 2,6-diaminoheptanoic acid is produced by biochemical hydrolysis of 2,6-diaminoheptanamide.

That is, the present invention relates to a viable cell of a microorganism having an activity of stereoselectively hydrolyzing an amino acid amide or a viable cell of the racemic mixture of 2,6-diaminoheptanamide represented by the general formula (1). (2S) -2,6-diaminoheptanoic acid represented by formula (2) or (2R) -2,6-diaminoheptanoic acid represented by formula (3) This is a method for producing optically active 2,6-diaminoheptanoic acid, characterized by the following: Further, according to the present invention, a living cell of a microorganism having an activity of stereoselectively hydrolyzing an amino acid amide or a treated product of the cell is acted on 2,6-diaminoheptanamide represented by the general formula (1). And producing optically active 2,6-diaminoheptanoic acid in the method for producing optically active 2,6-diaminoheptanoic acid. Racemizing the amide,
It can be used again as a raw material. Further, according to the present invention, the recovered optically active amino acid amide can be further hydrolyzed to produce optically active 2,6-diaminoheptanoic acid.

[0006]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The details of the present invention will be described below. X of the 2,6-diaminoheptanamide and 2,6-diaminoheptanoic acid represented by the above general formulas (1), (2) and (3) is hydrogen or a lower alkyl group having 1 to 4 carbon atoms. Well, there is no particular limitation, for example, a methyl group,
An ethyl group or the like is preferred, and a methyl group is particularly preferred.

In the present invention, the optically active 2,6-diaminoheptanamide represented by the general formula (1) is (2S)-
And (2R) -2,6-diaminoheptanamide, and the optically active 2,6-diaminoheptanoic acid represented by the general formulas (2) and (3) are (2S)-and (2R) -2,6-diamino, respectively. Although described as heptanoic acid, when X in the general formula representing these compounds is a methyl group, the carbon atom at the 6-position is no longer an asymmetric carbon, and these are hereinafter referred to as (S)-and
(R) -2,6-diaminoheptanamide, (S)-and (R)-
Also described as 2,6-diaminoheptanoic acid.

[0008] As a typical example of the 2,6-diaminoheptanamide represented by the general formula (1) of the present invention, 2,6-diamino-6-
And methylheptaneamide. The 2,6-diaminoheptanamide represented by the general formula (1), which is a raw material of the present invention, is not particularly limited in its production method and quality, for example, the corresponding α-aminonitrile easily obtained by the Strecker method, That is, it can be obtained by a method of partially hydrolyzing 2,6-diaminoheptanenitrile or the like. α-
As a method for partially hydrolyzing aminonitrile, a method for partially hydrolyzing α-aminonitrile in an aqueous medium in the presence of a basic substance and a ketone, for example, Japanese Patent Publication No.
The method described in 17741 is preferred. This method
For example, an inorganic base such as sodium hydroxide and potassium hydroxide, and a basic substance such as an organic base such as an organic quaternary ammonium compound such as tetramethylammonium hydroxide are used. −
The ratio is 0.01 mol or less with respect to 1 mol of aminonitrile, the pH of the reaction solution is higher than 14, and acetone, methyl ethyl ketone, diethyl ketone,
A method comprising adding ketones such as methyl isopropyl ketone and cyclohexanone, and performing the hydrolysis reaction while maintaining the reaction temperature at 40 ° C. or lower and maintaining the pH of the reaction solution at a pH exceeding 14. It is. The crude 2,6-diaminoheptanamide-containing liquid obtained by concentrating the α-aminonitrile hydrolysis reaction liquid to remove ketones is used as it is, or by means of distillation or recrystallization if necessary. After purification, it can be used as a raw material.

In addition, 2,6-diaminoheptanamide is obtained by recovering unreacted optically active amino acid amide and heating the recovered optically active amino acid amide in the presence of a strongly basic substance, as described below. It can also be obtained by a method of forming

[0010] The microorganism used for the biochemical hydrolysis of 2,6-diaminoheptanamide of the present invention is a microorganism having 2,3-diaminoheptanamide corresponding to the desired optically active 2,6-diaminoheptanoic acid. Any microorganism having an activity of selectively hydrolyzing may be used.
(2S)-As a microorganism that hydrolyzes amino acid amides, microorganisms belonging to the genus Pseudomonas, Cryptococcus, Rotuderomyces, Rhodosporium, Mycoplana, and Patissolen, specifically, Pseudomonas sp.
Rosea (Pseudomonas rosea) NCIB 10605, Cryptococcus laurentii ATCC
18803, Cryptococcus neoformans
ccus neoformans) ATCC 32045, Lodderomyces elogisporus IFO 1676,
Rhodosporidium toruodes
loides) IFO 0871, Rhodosporidium Geobodam
(Rhodosporidium diobovatum) IFO 1828, Mycoplana dimorpha IFO 13291 (ATCC
4279), Mycoplana dimorp
ha) NCIB 9439, Mycoplana dimorpha (Mycoplan
a dimorpha) IFO 13213, Mycoplana Brata
ana bullata) IFO 13290 (ATCC 4278), Mycoplana bullata NCIB 9440, Mycoplana bullata (Mycoplana bullata) IFO 13267, Micoplana sp
(Mycoplana sp) IFO 13240 and Pachysolen tannophilus IFO 1007, but are not limited thereto.

As microorganisms that hydrolyze (2R) -amino acid amides, microorganisms belonging to the genera Rhodococcus, Pseudomonas and Serratia, specifically Rhodococcus erythropolis NR-2
3 (FERM P-8937), Rhodococcus erythropolis (Rh
odococcus erythropolis) NR-28 (FERM P-8938), Rhodococcus erythropolis
s) JCM 3201, Pseudomonas floretensens (Pse
udomonas fluorescens) IFO 12055, Serratia marcescens IAM 12143, but is not limited thereto.

Culture of these microorganisms is usually performed using a medium containing assimilable carbon sources and nitrogen sources, inorganic salts essential for each microorganism, nutrients, and the like. It is also effective to add α-amino acid amide to the medium in advance. The α-amino acid amide added at this time is 2,2 corresponding to the target 2,6-diaminoheptanoic acid.
It is preferred to use 6-diaminoheptanamide,
General α-amino acid amides, such as alanine amide,
Valinamide may be used, and there is no particular limitation. PH during culture
Ranges from 4 to 10 and the temperature is from 20 to 50C. Culture is performed aerobically for about one day to one week. The microorganism cultured in this manner is used in the reaction as a viable cell or a processed product of the viable cell, for example, a culture solution, a separated cell, a crushed cell, or a purified enzyme. In addition, according to a conventional method, cells or enzymes can be immobilized and used.

The conditions for the biochemical hydrolysis of 2,6-diaminoheptanamide are as follows: 2,6-diaminoheptanamide concentration: 1 to 40% by weight; 0.005 to weight ratio as body
3. The reaction temperature is in the range of 20-70 ° C and pH 5-13.

The optically active 2,6-diaminoheptanoic acid produced by the biochemical hydrolysis of 2,6-diaminoheptanamide is separated from the reaction solution by a conventional solid-liquid separation means such as centrifugation or a filtration membrane. After removing the microbial cells by filtration, concentrating under reduced pressure, adding an organic solvent to precipitate optically active 2,6-diaminoheptanoic acid, and collecting the precipitated optically active 2,6-diaminoheptanoic acid by filtration, After removing the body, water was removed under reduced pressure, an organic solvent was added to the residual solid to dissolve unreacted optically active 2,6-diaminoheptanamide, and insoluble optically active 2,6-diaminoheptanoic acid was removed. It can be easily separated by a method such as filtration.
At this time, the organic solvent added for precipitating optically active 2,6-diaminoheptanoic acid or dissolving unreacted optically active 2,6-diaminoheptanamide is optically active.
Any solvent having a low solubility of 2,6-diaminoheptanoic acid and a high solubility of unreacted optically active 2,6-diaminoheptanamide may be used without any particular limitation, and ethanol, 2-propanol, 2-methyl- Alcohols such as 1-propanol, 1-butanol and 2-butanol are preferably used.
Further, from the reaction solution obtained by separating the microbial cells, unreacted optically active 2,6-diaminoheptanamide is removed by a method such as solvent extraction, and then the optically active 2,6 is obtained by a method such as crystallization from the remaining liquid. -Diaminoheptanoic acid can also be separated. At this time, examples of the solvent for extracting the optically active 2,6-diaminoheptaneamide include non-polar solvents such as hexane, benzene, toluene and xylene. In addition, it is also effective to selectively separate and recover only optically active 2,6-diaminoheptanoic acid by ion-exchange electrodialysis after removing the microbial cells from the reaction completed solution.

The unreacted optically active 2,6-diaminoheptanamide is obtained by separating the optically active 2,6-diaminoheptanoic acid from the above-mentioned solution after the completion of the biochemical hydrolysis of 2,6-diaminoheptanamide. The solution is easily recovered by a method such as concentration of the liquid or solvent extraction from the reaction completed liquid after the separation of the microorganism cells. The recovered optically active 2,6-diaminoheptanamide is hydrolyzed by the action of, for example, a living cell of a microorganism having an acid or a hydrolyzing activity or a treated product of the living cell, whereby the corresponding optically active 2,6-diaminoheptanamide is obtained. It can be converted to 6-diaminoheptanoic acid. The recovered optical activity
2,6-Diaminoheptanamide can be easily racemized by heating in the presence of a strongly basic substance,
It can be 2,6-diaminoheptanamide. The optically active 2,6-diaminoheptanamide used in the racemization reaction of the optically active 2,6-diaminoheptanamide is as described above.
To use the optically active 2,6-diaminoheptanamide recovered from the liquid after the completion of the biochemical hydrolysis reaction of 2,6-diaminoheptanamide as it is or after performing purification by an operation such as recrystallization if necessary. Can be.

The strongly basic substance used in the racemization reaction of the optically active 2,6-diaminoheptanamide may be any organic or inorganic strong basic substance, and typical examples include tetramethylammonium hydroxide and water. Organic quaternary ammonium compounds such as tetraethylammonium oxide and alkali metal compounds such as sodium hydroxide, potassium hydroxide, sodium methylate, sodium ethylate, sodium amide and sodium hydride;
And alkaline earth metal compounds such as barium hydroxide. In the reaction system, it is also possible to add a substance which can be converted into the above-mentioned strong basic substance, for example, an alkali metal simple substance such as sodium and potassium, and an alkaline earth metal simple substance such as barium. The amount of these strongly basic substances used is
0.001 to 1 mol of diaminoheptanamide
The ratio is 0.5 mol, preferably 0.01 to 0.1 mol.

The racemization reaction of optically active 2,6-diaminoheptanamide can be carried out without using a solvent. However, when a solvent is used, the reaction temperature can be lowered, and as a result, by-products The risk of generation can be reduced, which is more preferable. As the solvent used at this time, it is sufficient that the solvent is inert to each of the optically active 2,6-diaminoheptaneamide and the strongly basic substance, and for example, hexane, heptane, cyclohexane, benzene,
Examples include hydrocarbons such as toluene and xylene, alcohols such as 2-propanol, 2-methyl-1-propanol, 2-butanol, 1-butanol and 1-pentanol, ethers, and isobutyronitrile. Although there is no particular limitation on the amount of the solvent used, in practice, it is not necessary to make the weight of the optically active 2,6-diaminoheptanamide more than 100 times, and preferably about 1 to 20 times.

It is preferable that the amount of water in the racemization reaction solution is as small as possible, but there is almost no problem if the water content is about 1% by weight or less. The temperature of the racemization reaction is from 20 to 200 ° C, preferably from 50 to 15 ° C.
0 ° C. The racemization reaction is usually performed under normal pressure, but does not prevent it from being performed under reduced pressure or under increased pressure.

After the racemization reaction is completed, the produced 2,6-diaminoheptanamide is separated and recovered, for example, by distilling off the solvent under reduced pressure, cooling to precipitate crystals, and collecting by filtration or centrifugation. Separation and recovery by the usual solid-liquid separation procedure described above, or water is added to the solution after the racemization reaction to elute 2,6-diaminoheptanamide into the aqueous phase and biochemical hydrolysis is performed as it is or after pH adjustment There is a method of circulating to the process, but the latter is more rational industrially.

In this way, the optically active 2,6-diaminoheptanamide is racemized into 2,6-diaminoheptanamide, which is circulated to the biochemical hydrolysis reaction system,
The entire amount of 2,6-diaminoheptanamide can be converted to the desired optically active 2,6-diaminoheptanoic acid. According to the method of the present invention, specifically, for example, (2S) -2,6-diaminoheptanoic acid derivatives such as (S) -2,6-diamino-6-methylheptanoic acid and (R) -2,6- It is possible to produce (2R) -2,6-diaminoheptanoic acid derivatives such as diamino-6-methylheptanoic acid.

[0021]

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples. Example 1 Production of 2,6-diamino-6-methylheptanamide A 300-m four-necked flask equipped with a stirrer, a thermometer and a pH electrode was charged with 40 g of distilled water and 40 g of acetone, and cooled to 5 ° C. , 6-Diamino-6-methylheptanenitrile 35.7g
(0.23 mol), and a 40% aqueous sodium hydroxide solution
2.5 g (1.0 g as sodium hydroxide, 0.025 mol) was added with stirring under ice cooling. After the addition of the 40% aqueous sodium hydroxide solution, the temperature of the reaction solution rose to 15 ° C. After stirring the reaction mixture for 10 hours, 5.0 g of 18% hydrochloric acid (0.9% as hydrochloric acid)
g, 0.025 mol), and water and acetone were distilled off with an evaporator. The residue was dissolved by adding 100 ml of dimethyl carbonate, and the insoluble solid was removed by filtration. The solvent of the filtrate was concentrated by an evaporator, cooled to 5 ° C., and the precipitated white crystals of 2,6-diamino-6-methylheptaneamide were collected by filtration. The weight of the obtained crystals after drying was 32.9 g (0.19 mol
), The yield based on 2,6-diamino-6-methylheptanenitrile was 83 mol%.

Example 2 (a) Production of (S) -2,6-diamino-6-methylheptanoic acid A medium having the following composition was prepared, and 200 ml of this medium was placed in a 1-L Erlenmeyer flask, sterilized, and treated with Mycoplana brata. (Mycoplana
bullata) NCIB 9440 was inoculated and cultured with shaking at 30 ° C. for 48 hours. Medium composition (pH 7.0) Glucose 10 g of polypeptone 5 g yeast extract, _{5 g KH 2 PO 4 2 g} MgSO 4 · 7H 2 O 0.4 g FeSO 4 · 7H 2 O 0.01g MnCl 2 · 4H 2 O 0.01g D, L -Valinamide 5 g Distilled water 1 L At the end of the culture, the cell concentration of the culture solution was 5 g / kg. From 100 g of the culture, viable cells equivalent to 0.5 g of dried cells were obtained by centrifugation. The viable cells were suspended in 100 ml of distilled water, placed in a 1-L Erlenmeyer flask, added with 5.0 g (29 mmol) of a racemic mixture of 2,6-diamino-6-methylheptaneamide, and shaken at 40 ° C. for 5 hours. Thus, a hydrolysis reaction was performed.
After the reaction, the bacteria were removed from the reaction solution by centrifugation, and water was removed under reduced pressure using an evaporator.
l was added to dissolve unreacted (R) -2,6-diamino-6-methylheptanamide, and the insoluble (S) -2,6-diamino-6-methylheptanoic acid was collected by filtration as a white solid. . The weight of the obtained solid after drying was 2.3 g (13 mmol), the yield based on 2,6-diamino-6-methylheptanamide was 46 mol%, and (S) -2,6-diamino-6-methylheptanamide was obtained. 91 mol based on
% Met. Further, the resulting (S) -2,6-diamino-6-methylheptanoic acid was analyzed by liquid chromatography using a chiral column for optical resolution, and the optical purity was 99%.
It was more than ee.

(B) Recovery of (R) -2,6-diamino-6-methylheptanamide The solvent of the filtrate obtained after filtering the solid of (S) -2,6-diamino-6-methylheptanoic acid, , Evaporate under reduced pressure with an evaporator,
50 ml of diisopropyl ether was added and the insoluble solid was collected by filtration, and unreacted (R) -2,6-diamino-6-methylheptaneamide was recovered as a white solid. Weight after drying 2.2g (13
mmol), the recovery for 2,6-diamino-6-methylheptanamide was 44 mol%, and the recovery for (R) -2,6-diamino-6-methylheptanamide was 88 mol%. Also,
The recovered (R) -2,6-diamino-6-methylheptanamide was analyzed by liquid chromatography using a chiral column for optical resolution, and as a result, the optical purity was 99% ee or more.

(C) Racemization of (R) -2,6-diamino-6-methylheptanamide 1.0 g (5.8 m) of (R) -2,6-diamino-6-methylheptanamide
mol) was dissolved in 10 ml of 2-methyl-1-propanol, and 0.02 g (0.5 mmol) of sodium hydroxide was added thereto, and
Stirred at C for 30 minutes. After completion of the reaction, the reaction solution was cooled, diisopropyl ether was added, and the precipitated solid was collected by filtration.
2,6-Diamino-6-methylheptanamide was obtained. The weight of the solid after drying was 0.91 g (5.3 mmol), and the recovery was 91%.
Mol%. As a result of analyzing this solid by liquid chromatography using a chiral column for optical resolution,
The racemization ratio of (R) -2,6-diamino-6-methylheptanamide was 98%. In this case, the racemization ratio was calculated as follows. Racemization rate (%) = (S) -amide / ((S) -amide + (R) -amide)
× 2 × 100 A racemization ratio of 100% indicates that (S) -amide and (R) -amide are equivalent to each other.

(D) Production of (R) -2,6-diamino-6-methylheptanoic acid Rhodococcus erythropolis NR-28 (FERM) using the same medium and method as in (a).
P-8938), centrifuge the culture, and dry the cells.
A viable cell equivalent to 1 g was obtained. In a 50ml Erlenmeyer flask,
1.0 g of (R) -2,6-diamino-6-methylheptanamide (5.8 m
mol), 20 ml of water and viable cells were added and heated at 40 ° C. for 5 hours. From the result of analysis of the reaction solution by liquid chromatography after the reaction was completed, the yield was 89% and the optical purity was 99% ee or more.
(R) -2,6-Diamino-6-methylheptanoic acid was obtained.

Example 3 Mycoplana bullata of Example 2
Viable cells equivalent to 0.1 g of dry cells obtained by centrifugation from 20 g of the culture solution of NCIB 9440 were suspended in 20 ml of distilled water, and
0 ml Erlenmeyer flask, 0.5 g of 2,6-diamino-6-methylheptanamide (2.9 g)
mmol) and 0.5 g (2.9 mmol) of a new racemic mixture of 2,6-diamino-6-methylheptanamide at 40 ° C.
The hydrolysis reaction was performed by shaking for a time. After the reaction, post-treatment was carried out in the same manner as in Example 2 to obtain (S) -2,6-diamino-6-methylheptanoic acid as a white solid. The weight of the obtained solid after drying was 0.45 g (2.6 mmol), and 2,6-diamino was newly added.
The yield based on -6-methylheptanamide was 89 mol%. Further, the produced (S) -2,6-diamino-6-methylheptanoic acid was analyzed by liquid chromatography using a chiral column for optical resolution, and as a result, the optical purity was 99% ee or more.

Example 4 (a) Production of (R) -2,6-diamino-6-methylheptanoic acid Rhodococcus erythropolis (Rhod)
ococcus erythropolis) NR-28 (FERM P-8938) was cultured, and the culture was centrifuged to obtain viable cells equivalent to 0.5 g of dried cells. Suspend the viable cells in 100 ml of distilled water and add 1 L
Place in an Erlenmeyer flask, add 5.0 g (29 mmol) of a racemic mixture of 2,6-diamino-6-methylheptanamide,
The hydrolysis reaction was performed by shaking at 40 ° C. for 5 hours. After the reaction, the mixture was treated in the same manner as in Example 2 and (R) -2,6-diamino-6-methylheptanoic acid was collected by filtration as a white solid. The weight of the obtained solid after drying was 2.2 g (13 mmol) and 2,6-diamino-6-
The yield based on methylheptaneamide was 44 mol%, (R) -2,
The yield based on 6-diamino-6-methylheptanamide is 87.
Mol%. In addition, the generated (R) -2,6-diamino-6-
As a result of analyzing methylheptanoic acid by liquid chromatography using a chiral column for optical resolution, the optical purity was
It was 99% ee or more.

(B) Recovery of (S) -2,6-diamino-6-methylheptanamide The solid of (R) -2,6-diamino-6-methylheptanoic acid was collected by filtration, and the solvent of the filtrate was removed. Untreated (S) -2,6-diamino-6-methylheptaneamide was recovered as a white solid by treating in the same manner as in Example 2. The weight after drying is 2.0 g (11 mmol),
The recovery for 2,6-diamino-6-methylheptanamide was 40 mol%, and the recovery for (S) -2,6-diamino-6-methylheptanamide was 80 mol%. Also collected
As a result of analyzing (S) -2,6-diamino-6-methylheptanamide by liquid chromatography using a chiral column for optical resolution, the optical purity was 99% ee or more.

(C) Racemization of (S) -2,6-diamino-6-methylheptanamide 1.0 g (5.8 m) of (S) -2,6-diamino-6-methylheptanamide
mol) was dissolved in 10 ml of 2-methyl-1-propanol, and 0.02 g (0.5 mmol) of sodium hydroxide was added thereto, and
Stirred at C for 30 minutes. After completion of the reaction, the reaction was carried out in the same manner as in Example 2 to obtain 2,6-diamino-6-methylheptanamide.
The weight of the solid after drying was 0.88 g (4.7 mmol), and the recovery was 88 mol%. The solid was analyzed by liquid chromatography using a chiral column for optical resolution. As a result, the racemization ratio of (S) -2,6-diamino-6-methylheptaneamide was 95%.

(D) Preparation of (S) -2,6-diamino-6-methylheptanoic acid In a 50 ml Erlenmeyer flask, 1.0 g (5.8 mmol) of (S) -2,6-diamino-6-methylheptanamide was added. , Water 20ml and dried cells
0.1g Mycoplana bullata
Was stirred at 40 ° C. for 5 hours. Analysis of the reaction solution after completion of the reaction by liquid chromatography showed that the yield was 89%, the optical purity was 99% ee or more, and (S) -2,6-diamino-6-
Methylheptanoic acid was obtained.

EXAMPLE 5 Rhodococcus erythropolis of Example 4
erythropolis) 20 viable cells equivalent to 0.1 g of dry cells obtained by centrifugation from a culture of NR-28 (FERM P-8938).
suspended in 100 ml of distilled water, and placed in a 100 ml Erlenmeyer flask, where 0.5 g (2.9 mmol) of 2,6-diamino-6-methylheptanamide racemized and recovered in Example 4 and fresh 2,6-diamino- 0.5 g (2.9 mm) of a racemic mixture of 6-methylheptanamide
ol), and the mixture was shaken at 40 ° C. for 5 hours to carry out a hydrolysis reaction. After the reaction, post-treatment was carried out in the same manner as in Example 4, and (R)-
2,6-Diamino-6-methylheptanoic acid was obtained as a white solid. The weight of the obtained solid after drying was 0.44 g (2.5 mmol), and the yield based on newly added 2,6-diamino-6-methylheptanamide was 87 mol%. The generated (R) -2,6-
As a result of analyzing diamino-6-methylheptanoic acid by liquid chromatography using a chiral column for optical resolution, the optical purity was 99% ee or more.

[0032]

According to the present invention, optically active 2,6-diaminoheptanoic acid, which is very useful as an intermediate for the production of various optically active industrial chemicals, agricultural chemicals, and pharmaceuticals, can be produced in a small number of steps and at low cost.

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Claims (10)

[Claims] 1. A live microbial cell of a microorganism having an activity of stereoselectively hydrolyzing a (2S) -amino acid amide, or a racemic mixture of a 2,6-diaminoheptanamide represented by the general formula (1). The treated cells are allowed to act to produce (2S) -2,6-diaminoheptanoic acid represented by the general formula (2),
A process for producing optically active (2S) -2,6-diaminoheptanoic acid, wherein (2R) -2,6-diaminoheptanamide is left unreacted. Embedded image 2. The method according to claim 1, wherein the unreacted (2R) -2,6-diaminoheptanamide is racemized by heating in the presence of a strongly basic substance, and reused as a raw material. 3. The process according to claim 1, wherein unreacted (2R) -2,6-diaminoheptanamide is hydrolyzed to produce (2R) -2,6-diaminoheptanoic acid. 4. The method according to claim 1, wherein X in the general formulas (1) and (2) is a methyl group. 5. A live microbial cell of a microorganism having an activity of stereoselectively hydrolyzing a (2R) -amino acid amide or a racemic mixture of the racemic mixture of 2,6-diaminoheptanamide represented by the general formula (1), (2R) -2,6-diaminoheptanoic acid represented by the general formula (3)
A process for producing optically active (2R) -2,6-diaminoheptanoic acid, wherein (2S) -2,6-diaminoheptanamide is left unreacted. 6. The method according to claim 5, wherein the unreacted (2S) -2,6-diaminoheptanamide is racemized by heating in the presence of a strongly basic substance and is used again as a raw material. 7. The method according to claim 5, wherein unreacted (2S) -2,6-diaminoheptanamide is hydrolyzed to produce (2S) -2,6-diaminoheptanoic acid. 8. The method according to claim 5, wherein X in the general formulas (1) and (3) is a methyl group. 9. A 2,6-diaminoheptanamide represented by the general formula (1). 10. A 2,6-diaminoheptanenitrile partially hydrolyzed in an aqueous medium in the presence of a basic substance and a ketone, wherein the 2,6-diaminoheptanenitrile is represented by the general formula (1):
A method for producing diaminoheptanamide.