JP4544385B2 - Process for producing optically active 2,6-diaminoheptanoic acid - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a process for producing optically active 2,6-diaminoheptanoic acid represented by 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 biochemically asymmetric hydrolysis of a racemic mixture of 2,6-diaminoheptanamide. Optically active 2,6-diaminoheptanoic acid is an important substance as a production intermediate for various industrial chemicals, agricultural chemicals, and pharmaceuticals.
[0002]
[Prior 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. Therefore, it manufactures various optically active industrial chemicals, agricultural chemicals, and pharmaceuticals. It is an important substance as an intermediate. Production of a racemic mixture of 2,6-diaminoheptanoic acid represented by the general formulas (2) and (3) in which X is hydrogen is described in J. Am. Chem. Soc., 73, p4478, ( 1951). However, since the production method described therein uses 2-methylcyclohexanone oxime as a starting material and proceeds in 4 steps including a protection and deprotection step, it is very labor intensive and an expensive reagent is used. Since it is used, it is not an industrially advantageous method. Further, 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]
[Problems to be solved by the invention]
The object of the present invention is to solve the above-mentioned problems in the prior art and to add optically active 2,6-diaminoheptanoic acid, which is very important as an intermediate for the production of various industrial chemicals, agricultural chemicals, and pharmaceuticals, with a small number of steps. It is to provide a manufacturing method for manufacturing at low cost.
[0004]
[Means for Solving the Problems]
As a result of intensive studies on a production method for producing optically active 2,6-diaminoheptanoic acid at a low cost with a small number of steps, the present inventors have biochemically synthesized 2,6-diaminoheptanamide, which is a novel compound. In the present invention, optically active 2,6-diaminoheptanoic acid is produced by hydrolysis.
[0005]
That is, the present invention relates to a living microbial cell having activity of stereoselectively hydrolyzing an amino acid amide or a treatment of the microbial cell to a racemic mixture of 2,6-diaminoheptanamide represented by the general formula (1). To produce (2S) -2,6-diaminoheptanoic acid represented by the general formula (2) or (2R) -2,6-diaminoheptanoic acid represented by the general formula (3). This is a method for producing an optically active 2,6-diaminoheptanoic acid. Furthermore, according to the present invention, the 2,6-diaminoheptanamide represented by the general formula (1) is subjected to the action of a living microbial cell having an activity of hydrolyzing an amino acid amide in a stereoselective manner or a treated product thereof. In the process for producing optically active 2,6-diaminoheptanoic acid, wherein unreacted optically active amino acid amide is recovered and recovered optically active amino acid It is also possible to racemize the amide and use it again as a raw material. According to the present invention, the optically active amino acid amide recovered can be further hydrolyzed to produce optically active 2,6-diaminoheptanoic acid.
[0006]
DETAILED DESCRIPTION OF THE INVENTION
Details of the present invention will be described below.
If X of 2,6-diaminoheptanamide and 2,6-diaminoheptanoic acid represented by the general formulas (1), (2) and (3) is hydrogen or a lower alkyl group having 1 to 4 carbon atoms, Although there is no particular limitation, for example, a methyl group, an ethyl group, and the like are preferable, and a methyl group is particularly preferable.
[0007]
In the present invention, the optically active form of 2,6-diaminoheptanamide represented by general formula (1) is (2S)-and (2R) -2,6-diaminoheptanamide, general formulas (2) and (3 ) Are represented by (2S)-and (2R) -2,6-diaminoheptanoic acid, respectively. In the general formulas showing these compounds, X is a methyl group. In some cases, the carbon atom at the 6-position is no longer an asymmetric carbon, so these are respectively (S)-and (R) -2,6-diaminoheptanamide, (S)-and (R) -2,6- Also described as diaminoheptanoic acid.
[0008]
Representative examples of 2,6-diaminoheptanamide represented by the general formula (1) of the present invention include 2,6-diamino-6-methylheptanamide. 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, and for example, the corresponding α-amino nitrile easily obtained by the Strecker method, That is, it can be obtained by a method of partially hydrolyzing 2,6-diaminoheptanenitrile. As a method of partially hydrolyzing α-amino nitrile, a method of partially hydrolyzing α-amino nitrile in an aqueous medium in the presence of a basic substance and ketones, for example, a method described in JP-B-58-17741 is preferable. . This method uses a basic substance such as an inorganic base such as sodium hydroxide and potassium hydroxide and an organic base such as an organic quaternary ammonium compound such as tetramethylammonium hydroxide. The amount is set to a ratio of 0.01 mol or less with respect to 1 mol of α-amino nitrile so that the pH of the reaction solution exceeds 14, and this reaction system includes acetone, methyl ethyl ketone, diethyl ketone, methyl isopropyl ketone and cyclohexanone. It is a method characterized in that a hydrolysis reaction is carried out while adding a ketone, keeping the reaction temperature at 40 ° C. or lower, and maintaining the pH of the reaction solution at a pH exceeding 14. The crude 2,6-diaminoheptanamide-containing liquid obtained by concentrating the α-amino nitrile hydrolysis reaction product liquid to remove ketones is used as it is or by means of distillation or recrystallization as necessary. After purification, it can be used as a raw material.
[0009]
In addition, 2,6-diaminoheptanamide is a method for recovering unreacted optically active amino acid amide and heating the recovered optically active amino acid amide in the presence of a strongly basic substance to racemize as described later. Can also be obtained.
[0010]
The microorganism used for the biochemical hydrolysis of 2,6-diaminoheptanamide of the present invention stereoselectively selects 2,6-diaminoheptanamide corresponding to the target optically active 2,6-diaminoheptanoic acid. Any microorganism may be used as long as it has an activity of hydrolyzing. Examples of such microorganisms include microorganisms that hydrolyze (2S) -amino acid amides. Microorganisms belonging to the genus, such as Pseudomonas rosea NCIB 10605, Cryptococcus laurentii ATCC 18803, Cryptococcus neoformans ATCC 32045, Rothdelomyces Lod e 676 Rhodosporidium toluroides (Rh odosporidium toruloides) IFO 0871, Rhodosporidium diobovatum IFO 1828, Mycoplana dimorpha IFO 13291 (ATCC 4279), Mycoplana dimorpha Myfoplana dimorpha NCIB 9439 dimorpha NCIB 9439 13213, Mycoplana bullata IFO 13290 (ATCC 4278), Mycoplana bullata NCIB 9440, Mycoplana bullata IFO 13267, Mycoplana sp (Mycoplana sp) IFO 13240 and Pachisoren tan tannophilus) IFO 1007, but is not limited to these.
[0011]
As microorganisms that hydrolyze (2R) -amino acid amides, microorganisms belonging to the genus Rhodococcus, Pseudomonas and Serratia, specifically Rhodococcus erythropolis NR-23 (FERM P-8937), Rhodococcus・ Erythropolis (Rhodococcus erythropolis) NR-28 (FERM P-8938), Rhodococcus erythropolis (Rhodococcus erythropolis) JCM 3201, Pseudomonas fluorescens IFO 12055, Serratia marcescens (143) Although it is mentioned, it is not limited to these.
[0012]
These microorganisms are usually cultured using a medium containing an assimilable carbon source, a nitrogen source, an inorganic salt essential for each microorganism, nutrients, etc. It is also effective to add an α-amino acid amide. The α-amino acid amide added at this time is preferably 2,6-diaminoheptanamide corresponding to the desired 2,6-diaminoheptanoic acid. , Valine amide and the like may be used without any particular limitation. The pH during the culture is in the range of 4 to 10, and the temperature is 20 to 50 ° C. The culture is performed aerobically for about 1 day to 1 week. The microorganisms cultured in this manner are used in the reaction as viable cells or treated products of the viable cells, such as culture broth, separated cells, disrupted cells, and further purified enzymes. In addition, cells or enzymes can be immobilized and used according to a conventional method.
[0013]
The conditions for the biochemical hydrolysis reaction of 2,6-diaminoheptanamide are as follows: 2,6-diaminoheptanamide concentration is 1 to 40 wt%, and the amount of microorganism used relative to 2,6-diaminoheptanamide is the weight of dry cells. The ratio is 0.005 to 3, the reaction temperature is 20 to 70 ° C., and the pH is 5 to 13.
[0014]
The optically active 2,6-diaminoheptanoic acid produced by the biochemical hydrolysis reaction of 2,6-diaminoheptanamide is removed from the reaction-finished solution by a conventional solid-liquid separation means such as centrifugation or filtration membrane. After removing the body and concentrating under reduced pressure, an organic solvent is added to precipitate optically active 2,6-diaminoheptanoic acid, and the precipitated optically active 2,6-diaminoheptanoic acid is collected by filtration, or microbial cells are removed. Then, water is removed under reduced pressure, an organic solvent is added to the residual solid to dissolve unreacted optically active 2,6-diaminoheptanamide, and insoluble optically active 2,6-diaminoheptanoic acid is collected by filtration. It can be easily separated by such a method. At this time, the organic solvent added to precipitate optically active 2,6-diaminoheptanoic acid or dissolve unreacted optically active 2,6-diaminoheptanamide is the solubility of optically active 2,6-diaminoheptanoic acid. The solvent is not particularly limited as long as the solvent is low and the solubility of unreacted optically active 2,6-diaminoheptanamide is high, but ethanol, 2-propanol, 2-methyl-1-propanol, 1-butanol and 2 -Alcohols such as butanol are preferably used. In addition, after removing the unreacted optically active 2,6-diaminoheptanamide from the reaction-finished solution from which the microbial cells have been separated by a method such as solvent extraction, the optically active 2,6 by a method such as crystallization from the residual solution. -Diaminoheptanoic acid can also be separated. At this time, examples of the solvent for extracting optically active 2,6-diaminoheptanamide include nonpolar solvents such as hexane, benzene, toluene and xylene. In addition, a method of selectively separating and recovering only optically active 2,6-diaminoheptanoic acid by ion-exchange electrodialysis after removing microbial cells from the reaction completion solution is also effective.
[0015]
Unreacted optically active 2,6-diaminoheptanamide is obtained by concentrating the liquid after separating optically active 2,6-diaminoheptanoic acid from the biochemical hydrolysis reaction completion liquid of 2,6-diaminoheptanamide. Alternatively, it can be easily recovered by a method such as solvent extraction from the reaction-finished solution after microbial cell separation. The recovered optically active 2,6-diaminoheptanamide is hydrolyzed by the action of, for example, a living cell of a microorganism having acid or hydrolytic activity or a processed product of the living cell, thereby producing a corresponding optically active 2, Can be converted to 6-diaminoheptanoic acid. The recovered optically active 2,6-diaminoheptanamide can be easily racemized by heating in the presence of a strongly basic substance to give a racemic 2,6-diaminoheptanamide. The optically active 2,6-diaminoheptanamide used in the racemization reaction of the optically active 2,6-diaminoheptanamide was recovered from the solution obtained after the biochemical hydrolysis reaction of 2,6-diaminoheptanamide. The optically active 2,6-diaminoheptanamide can be used as it is or after being purified by an operation such as recrystallization as necessary.
[0016]
The strongly basic substance used in the racemization reaction of optically active 2,6-diaminoheptanamide may be an organic or inorganic strong basic substance. Typical examples are tetramethylammonium hydroxide and tetraethylammonium hydroxide. Organic quaternary ammonium 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, a substance that can be changed into the above-mentioned strongly basic substance, for example, an alkali metal simple substance such as sodium and potassium, and an alkaline earth metal simple substance such as barium can be added. The amount of these strongly basic substances used is 0.001 to 0.5 mol, preferably 0.01 to 0.1 mol, per mol of optically active 2,6-diaminoheptanamide. It is.
[0017]
The racemization reaction of optically active 2,6-diaminoheptanamide can be carried out without the use of a solvent. However, when a solvent is used, the reaction temperature can be lowered, so that a by-product may be generated. Therefore, it is possible to lower the property. The solvent used in this case may be inert to each of the optically active 2,6-diaminoheptanamide and the strongly basic substance, such as hexane, heptane, cyclohexane, benzene, toluene and xylene. There are hydrocarbons, alcohols such as 2-propanol, 2-methyl-1-propanol, 2-butanol, 1-butanol and 1-pentanol, ethers and isobutyronitrile. Although there is no restriction | limiting in particular in the usage-amount of a solvent, Practically, it is not necessary to make more than 100 times with respect to the weight of optically active 2, 6- diamino heptane amide, and about 1 to 20 times is preferable.
[0018]
Less water is preferable in the racemization reaction solution, but there is almost no problem if it is about 1 wt% or less. The temperature of the racemization reaction is 20 to 200 ° C, preferably 50 to 150 ° C. The racemization reaction is usually performed under normal pressure, but does not prevent the reaction from being performed under reduced pressure or under pressure.
[0019]
After completion of the racemization reaction, the produced 2,6-diaminoheptanamide is separated and recovered by, for example, distilling off the solvent under reduced pressure, cooling to precipitate crystals, and filtering or centrifuging. Separating and recovering by solid-liquid separation operation, or adding water to the racemization reaction completed solution, and eluting 2,6-diaminoheptanamide into the aqueous phase, either as it is or after circulation to the biochemical hydrolysis step However, the latter is more reasonable industrially.
[0020]
In this way, the optically active 2,6-diaminoheptanamide is racemized to form 2,6-diaminoheptanamide, which is circulated to the biochemical hydrolysis reaction system to achieve the total amount of 2,6-diaminoheptanamide. To optically active 2,6-diaminoheptanoic acid. Specifically, according to the method of the present invention, 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]
【Example】
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 40 g of distilled water and 40 g of acetone were placed in a 300 m four-necked flask equipped with a stirrer, thermometer and pH electrode, and cooled to 5 ° C. 2,5.7-diamino-6-methylheptanenitrile (35.7 g, 0.23 mol) was added, and 40% aqueous sodium hydroxide solution (2.5 g, 1.0 g, 0.025 mol as sodium hydroxide) was added with stirring under ice cooling. did. After the addition of 40% aqueous sodium hydroxide solution, the temperature of the reaction solution rose to 15 ° C. After stirring the reaction mixture for 10 hours, 18 g of hydrochloric acid 5.0 g (0.9 g as hydrochloric acid, 0.025 mol) was added, 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 with an evaporator and cooled to 5 ° C., and the precipitated white crystals of 2,6-diamino-6-methylheptanamide were collected by filtration. The weight of the obtained crystals after drying was 32.9 g (0.19 mol), and the yield based on 2,6-diamino-6-methylheptanenitrile was 83 mol%.
[0022]
Example 2
(A) Production of (S) -2,6-diamino-6-methylheptanoic acid A medium having the following composition was prepared, 200 ml of this medium was placed in a 1 L Erlenmeyer flask, sterilized, and then Mycoplana bullata NCIB 9440 And shaking culture was performed at 30 ° C. for 48 hours.
Medium composition (pH7.0)
Glucose 10 g
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 in the culture was 5 g / kg. From 100 g of this culture solution, live cells corresponding to 0.5 g of dry cells were obtained by centrifugation. Suspend the viable cells in 100 ml of distilled water, put them in a 1 L Erlenmeyer flask, add 5.0 g (29 mmol) of a racemic mixture of 2,6-diamino-6-methylheptanamide, and shake at 40 ° C for 5 hours. Thus, a hydrolysis reaction was performed. After the reaction, the reaction solution is sterilized by centrifugation, water is removed under reduced pressure with an evaporator, and 100 ml of 2-propanol is added to remove unreacted (R) -2,6-diamino-6-methylheptanamide. Dissolved and insoluble (S) -2,6-diamino-6-methylheptanoic acid was filtered off 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. The yield based on 91 mol%. The produced (S) -2,6-diamino-6-methylheptanoic acid was analyzed by liquid chromatography using a chiral column for optical resolution. As a result, the optical purity was 99% ee or higher.
[0023]
(B) Recovery of (R) -2,6-diamino-6-methylheptanamide
The solvent of the filtrate after filtering the solid of (S) -2,6-diamino-6-methylheptanoic acid was distilled off under reduced pressure with an evaporator, and 50 ml of diisopropyl ether was added, and the insoluble solid was collected by filtration. Unreacted (R) -2,6-diamino-6-methylheptanamide was recovered as a white solid. The weight after drying was 2.2 g (13 mmol), the recovery rate for 2,6-diamino-6-methylheptanamide was 44 mol%, and the recovery rate for (R) -2,6-diamino-6-methylheptanamide was 88%. Mol%. The recovered (R) -2,6-diamino-6-methylheptanamide was analyzed by liquid chromatography using a chiral column for optical resolution. As a result, the optical purity was 99% ee or higher.
[0024]
(C) Racemization of (R) -2,6-diamino-6-methylheptanamide
1.0 g (5.8 mmol) of (R) -2,6-diamino-6-methylheptanamide was dissolved in 10 ml of 2-methyl-1-propanol, and 0.02 g (0.5 mmol) of sodium hydroxide was added thereto to add 110 Stir at 30 ° 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 to obtain 2,6-diamino-6-methylheptanamide. The weight of the solid after drying was 0.91 g (5.3 mmol), and the recovery rate was 91 mol%. As a result of analyzing this solid by liquid chromatography using a chiral column for optical resolution, the racemization rate of (R) -2,6-diamino-6-methylheptanamide was 98%. In this case, the racemization rate was calculated as follows.
Racemization rate (%) = (S) -amide / ((S) -amide + (R) -amide) × 2 × 100
A racemization rate of 100% indicates that (S) -amide and (R) -amide are equivalent to each other.
[0025]
(D) Production of (R) -2,6-diamino-6-methylheptanoic acid Rhodococcus erythropolis NR-28 (FERM P-8938) was cultured in the same medium and method as in (a). The culture solution was centrifuged to obtain viable cells corresponding to 0.1 g of dry cells. A 50 ml Erlenmeyer flask was charged with 1.0 g (5.8 mmol) of (R) -2,6-diamino-6-methylheptanamide, 20 ml of water and viable cells and heated at 40 ° C. for 5 hours. As a result of liquid chromatography analysis of the reaction solution after completion of the reaction, (R) -2,6-diamino-6-methylheptanoic acid was obtained with a yield of 89% and an optical purity of 99% ee or higher.
[0026]
Example 3
Viable cells corresponding to 0.1 g of dried cells obtained by centrifugation from 20 g of the culture solution of Mycoplana bullata NCIB 9440 of Example 2 were suspended in 20 ml of distilled water, placed in a 100 ml Erlenmeyer flask, Add 0.5 g (2.9 mmol) of 2,6-diamino-6-methylheptanamide racemized and recovered in Example 2 and 0.5 g (2.9 mmol) of a new racemic mixture of 2,6-diamino-6-methylheptanamide. Then, the hydrolysis reaction was carried out by shaking at 40 ° C. for 5 hours. After the reaction, post-treatment was performed 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 the yield based on newly added 2,6-diamino-6-methylheptanamide was 89 mol%. The produced (S) -2,6-diamino-6-methylheptanoic acid was analyzed by liquid chromatography using a chiral column for optical resolution. As a result, the optical purity was 99% ee or higher.
[0027]
Example 4
(A) Production of (R) -2,6-diamino-6-methylheptanoic acid Rhodococcus erythropolis NR-28 (FERM P-8938) was cultured in the same manner as in Example 2, and the culture solution was centrifuged. After separation, live cells corresponding to 0.5 g of dry cells were obtained. Suspend the viable cells in 100 ml of distilled water, put them in a 1 L Erlenmeyer flask, add 5.0 g (29 mmol) of a racemic mixture of 2,6-diamino-6-methylheptanamide, and shake at 40 ° C for 5 hours. Thus, a hydrolysis reaction was performed. 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 as a white solid by filtration. The weight of the obtained solid after drying was 2.2 g (13 mmol), the yield based on 2,6-diamino-6-methylheptanamide was 44 mol%, (R) -2,6-diamino-6-methylheptanamide The yield based on 87 mol%. The produced (R) -2,6-diamino-6-methylheptanoic acid was analyzed by liquid chromatography using a chiral column for optical resolution. As a result, the optical purity was 99% ee or higher.
[0028]
(B) Recovery of (S) -2,6-diamino-6-methylheptanamide
The solvent of the filtrate after filtering the solid of (R) -2,6-diamino-6-methylheptanoic acid was treated in the same manner as in Example 2 to give unreacted (S) -2,6-diamino. -6-methylheptanamide was recovered as a white solid. The weight after drying was 2.0 g (11 mmol), the recovery rate for 2,6-diamino-6-methylheptanamide was 40 mol%, and the recovery rate for (S) -2,6-diamino-6-methylheptanamide was 80%. Mol%. The recovered (S) -2,6-diamino-6-methylheptanamide was analyzed by liquid chromatography using a chiral column for optical resolution. As a result, the optical purity was 99% ee or higher.
[0029]
(C) Racemization of (S) -2,6-diamino-6-methylheptanamide
1.0 g (5.8 mmol) of (S) -2,6-diamino-6-methylheptanamide was dissolved in 10 ml of 2-methyl-1-propanol, and 0.02 g (0.5 mmol) of sodium hydroxide was added thereto to add 110 Stir at 30 ° C. for 30 minutes. After completion of the reaction, the same treatment as in Example 2 was performed to obtain 2,6-diamino-6-methylheptanamide. The weight of the solid after drying was 0.88 g (4.7 mmol), and the recovery rate was 88 mol%. As a result of analyzing the solid by liquid chromatography using a chiral column for optical resolution, the racemization ratio of (S) -2,6-diamino-6-methylheptanamide was 95%.
[0030]
(D) Production of (S) -2,6-diamino-6-methylheptanoic acid
In a 50 ml Erlenmeyer flask, put (S) -2,6-diamino-6-methylheptanamide 1.0 g (5.8 mmol), 20 ml of water, and live mycoplana bullata (Mycoplana bullata) equivalent to 0.1 g of dry cells And stirred at 40 ° C. for 5 hours. As a result of analysis by liquid chromatography of the reaction solution after completion of the reaction, (S) -2,6-diamino-6-methylheptanoic acid was obtained with a yield of 89% and an optical purity of 99% ee or higher.
[0031]
Example 5
Viable cells corresponding to 0.1 g of dried cells obtained by centrifugation from the culture solution of Rhodococcus erythropolis NR-28 (FERM P-8938) of Example 4 were suspended in 20 ml of distilled water. Into an Erlenmeyer flask, 0.5 g (2.9 mmol) of 2,6-diamino-6-methylheptanamide recovered in racemic form in Example 4 and a new racemic mixture of 2,6-diamino-6-methylheptanamide 0.5 g (2.9 mmol) was added, and the hydrolysis reaction was carried out by shaking at 40 ° C. for 5 hours. After the reaction, post-treatment was performed in the same manner as in Example 4 to obtain (R) -2,6-diamino-6-methylheptanoic acid 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 produced (R) -2,6-diamino-6-methylheptanoic acid was analyzed by liquid chromatography using a chiral column for optical resolution. As a result, the optical purity was 99% ee or higher.
[0032]
【The invention's effect】
Optically active 2,6-diaminoheptanoic acid that is very useful as an intermediate for the production of various optically active industrial chemicals, agricultural chemicals, and pharmaceuticals can be produced at a low cost with a small number of steps.

Claims (9)

A live cell of a microorganism derived from the genus Mycoplana having the activity of stereoselectively hydrolyzing (2S) -amino acid amide, or a live cell of the racemic mixture of 2,6-diaminoheptanamide represented by the general formula (1) To produce (2S) -2,6-diaminoheptanoic acid represented by the general formula (2), leaving (2R) -2,6-diaminoheptanamide unreacted. A process for producing optically active (2S) -2,6-diaminoheptanoic acid characterized by

 The method according to claim 1, wherein unreacted (2R) -2,6-diaminoheptanamide is racemized by heating in the presence of a strongly basic substance and used again as a raw material.  The method according to claim 1, wherein unreacted (2R) -2,6-diaminoheptanamide is hydrolyzed to produce (2R) -2,6-diaminoheptanoic acid.  The method according to claim 1, 2 or 3, wherein X in the general formula (1) and the general formula (2) is a methyl group. A living cell of a microorganism derived from the genus Rhodococcus having the activity of stereoselectively hydrolyzing (2R) -amino acid amide in a racemic mixture of 2,6-diaminoheptanamide represented by the general formula (1) To produce (2R) -2,6-diaminoheptanoic acid represented by the general formula (3), leaving (2S) -2,6-diaminoheptanamide unreacted. A process for producing optically active (2R) -2,6-diaminoheptanoic acid characterized by

 6. The method according to claim 5, wherein unreacted (2S) -2,6-diaminoheptanamide is racemized by heating in the presence of a strongly basic substance and used again as a raw material.  The method according to claim 5, wherein unreacted (2S) -2,6-diaminoheptanamide is hydrolyzed to produce (2S) -2,6-diaminoheptanoic acid.  The method according to claim 5, 6 or 7, wherein X in the general formula (1) and the general formula (3) is a methyl group.  2,6-diaminoheptanamide represented by the general formula (1).