JPH07206756A - Process for producing optically active 2-methylbutanoic acid and its derivatives - Google Patents

Abstract

(57) [Summary] [Structure] An optical activity (S) produced by reacting an enzyme that preferentially hydrolyzes 2-methylbutanoic acid alkyl or 2-methylbutanoic acid alkoxyalkyl and / or a microorganism that produces the enzyme. -2-methylbutanoic acid, and optically active (R) -2-methylbutanoic acid alkyl or optically active
The alkoxyalkyl (R) -2-methylbutanoate is recovered. [Effect] Optically active (R) -2-methylbutanoic acid and its derivatives having a high optical purity can be industrially produced.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to an optically active 2-methylbutanoic acid characterized by allowing an enzyme or a microorganism producing the enzyme to act on an alkyl 2-methylbutanoate or an alkoxyalkyl 2-methylbutanoate. The present invention relates to a method for producing the derivative.

[0002]

2. Description of the Related Art It is widely known that optical isomers exist in many compounds exhibiting biological activity, and in general, the desired desired biology is desired. The optical isomers exhibiting biological activity are limited to a part thereof, and the other isomers do not exhibit the desired biological activity or are accompanied by undesirable physiological effects such as toxicity.

Therefore, in the case of a compound having an optical isomer, if there is no suitable means / method for obtaining a biologically active isomer, all the optical isomers in a mixed state are used as pesticides or pesticides. It is often used for pharmaceutical applications, and there have been problems that the original biological activity of the desired optical isomer is significantly reduced and that it is accompanied by undesirable physiological effects such as toxicity.

In order to overcome this problem, various methods for resolving optical isomers have been investigated. For example, an enzyme which prepares various ester derivatives of optical isomers to be resolved and optically selectively hydrolyzes the ester. Has been proposed, and a method for separating optical isomers from each other by utilizing the difference in solubility of the reaction system in a solvent, etc.,
In order to realize this method, research on microorganisms producing esterases having various optical selectivities is under way.

In such a technical background, the optically active 2-
Methylbutanoic acid is a compound useful as an intermediate for liquid crystal compounds, and optically active 2-methylbutanoic acid and its derivatives are known to exist in nature as aromatic components of various foods, and therefore, , Is regarded as important as a compound for use as a fragrance.

As a method for producing the optically active 2-methylbutanoic acid and its derivative, a method utilizing asymmetric hydrogenation of an α, β unsaturated carboxylic acid (JP-A-3-157346), or racemic 2-methylbutane Method by asymmetric esterification of acid with candida lipase or hydrolysis of 2-methylbutanoate KH Engel, Tetrahedoron As
ymmetry, 2, 165 (1991); Erland Holmberg et al., App
lied Microbiologyand Biotechnology, 35, 572 (1991)
Has been proposed, but by any method,
It has been pointed out that there are drawbacks such as low optical purity of the obtained optically active substance.

Optically active 2-methylbutanol, which is one of the above-mentioned optically active 2-methylbutanoic acid derivatives, has conventionally been regarded as important as a physiologically active substance for pharmaceutical or agrochemical use or a synthetic intermediate for liquid crystal materials. Has been done.

As one of the separation / purification means currently adopted for this optically active 2-methylbutanol, there is a method for separating optically active S-isomer 2-methylbutanol from fusel oil. According to this method, , It is necessary to repeat precision distillation for fractionation with other components in fusel oil, and therefore a multi-step purification process must be carried out, and thus, according to this method, the yield is low and The problem is that the manufacturing cost is high. On the other hand, R
2-methylbutanol of the body was synthesized from (+) α, α-dimethylsuccinic acid Chemistry and Industry
(London), p.1093, 1926, but this method is not suitable for industrialization because the raw materials are expensive and the synthesis process is complicated. Furthermore, recently, a method for producing optically active 2-methylbutanol by esterification using an enzyme such as lipase has been proposed (JP-A-2-242700), but this method also produces an optically active 2-methylbutanol. When separating methylbutanol,
It is not a practical means because it requires precision distillation.

[0009]

SUMMARY OF THE INVENTION The present invention has been made in view of the problems of the above-mentioned prior art,
An object of the invention is to provide a method capable of industrially producing optically active 2-methylbutanoic acid and its derivatives having high optical purity.

That is, the gist of the present invention is that
Referring to FIG. 1, an enzyme that preferentially hydrolyze an ester of its S-form and / or a microorganism that produces the enzyme is allowed to act on alkyl 2-methylbutanoate or alkoxyalkyl 2-methylbutanoate to obtain an optical activity ( S) -2-methylbutanoic acid and (R) -2-methylbutanoic acid alkyl or (R) -2-methylbutanoic acid alkoxyalkyl, characterized in that it is characterized by a method for producing optically active 2-methylbutanoic acid and its derivatives is there.

Further, in another embodiment of the present invention, the optically active (R) -2-methylbutanoic acid alkyl or alkoxyalkyl is further chemically reduced to give (R) -2.
-Optical activity characterized by obtaining methylbutanol
This is a method for producing (R) -2-methylbutanol.

Further, there is provided a method for producing optically active (R) -2-methylbutanoic acid, characterized in that the optically active (R) -2-methylbutanoic acid alkyl or alkoxyalkyl is hydrolyzed.

That is, the present invention has a high optical selectivity with respect to alkyl (R) -2-methylbutanoate or alkoxyalkyl (R) -2-methylbutanoate, that is, by hydrolyzing alkyl 2-methylbutanoate, (R) -2-methylbutanoic acid alkyl or (R) -2-methylbutanoic acid alkoxyalkyl having the ability to remain in the reaction solution, the genus Aspergillus, Bacillus
It has been completed based on the knowledge of a protease or ester-degrading enzyme derived from a microorganism belonging to the genus Serratia.

The racemic alkyl or alkoxyalkyl 2-methylbutanoate, which is a substrate for the enzymatic reaction in the present invention, is not particularly limited, but it can be easily synthesized and obtained by a known esterification method.
Ester derivatives such as methyl, ethyl and methoxyethyl are preferred.

Further, examples of the enzyme usable in the method of the present invention include Bacillus (Aspergillus).
us), microorganisms belonging to the Serratia genus, in particular,
Aspergillus melleus, Aspergillus oryzae, Bacillus subtilis, Bacillus amyloliquefaciens, or Serratia marcescens (Serratia marcescens)
s) is a protease or ester-degrading enzyme produced by a microorganism belonging to, and is not particularly limited as long as it can optically and selectively hydrolyze alkyl or alkoxyalkyl 2-methylbutanoate, for example,
A microbial cell containing the enzyme, a microbial cell culture, a microbial cell-treated product, or the like is also applicable.

Examples of the microorganism-derived enzyme described above include XP-488 (derived from Aspergillus melleus, manufactured by Nagase Seikagaku), Denazyme AP-15 (derived from Aspergillus oryzae,
Nagase Seikagaku Corporation), Sumiteam MP (Aspergillus me)
lleus origin, manufactured by Shin Nippon Chemical Co., Ltd., bioprase SP-10 (Bac
illus subtilis derived from Nagase Seikagaku), crystalline protease Nagase (Bacillus subtilis derived from Nagase Seikagaku), heat-resistant alkaline protease (Bacill
derived from us sp., manufactured by Kurita Water Industries, SM enzyme (Serratiamarcesce)
ns origin, Nagase Seikagaku Co., Ltd.) and other enzymes.

In the present specification, the method of the present invention is performed through the following steps unless otherwise specified.

First, in the enzymatic reaction, the above-mentioned protease or ester-degrading enzyme is added to water or a buffer solution containing racemic 2-methylbutanoic acid alkyl or alkoxyalkyl and stirred. The pH of the reaction solution at this time is
Considering the activity of the enzyme (reaction characteristics), it is set to 4 to 10, preferably 6 to 8, and the reaction temperature is 5 ° C to 60 ° C for the same reason.
The temperature is preferably 10 ° C to 45 ° C. The amount of the enzyme used is not particularly limited, but about 1 to 100 g / mol of substrate is preferable range for promoting a smooth enzymatic reaction with respect to the substrate of alkyl or alkoxyalkyl 2-methylbutanoate. Further, the reaction time varies depending on the amount of enzyme added, the reaction temperature, the reaction pH, etc., but is usually set to be completed in about 1 to 24 hours.

After completion of the reaction, the produced 2-methylbutanoic acid and unreacted alkyl or alkoxyalkyl 2-methylbutanoate are separated by a commonly used separation means such as a solvent extraction method, a crystal precipitation method or a column chromatography method. In connection with this separation means, according to the solvent extraction method, when the reaction solution is adjusted to around pH 9 with sodium carbonate or the like and then extracted with a solvent such as ethyl acetate, isopropyl ether, toluene, heptane, or dichloromethane. It was revealed from the examples described later that the unreacted optically active (R) -2-methylbutanoic acid alkyl or alkoxyalkyl can be recovered from the reaction solution at a recovery rate of 90% or more.

Then, the separated alkyl or alkoxyalkyl (R) -2-methylbutanoate is reduced by a method using lithium aluminum hydride or the like to obtain optically active (R) -2-methylbutanol.

Further, the separated alkyl or alkoxyalkyl (R) -2-methylbutanoate is further hydrolyzed by a known method using an alkali or the like to obtain optically active (R) -2-methylbutanoic acid. It is possible.

[0022]

EXAMPLES Preferred examples of the method of the present invention will be specifically described below, but the following examples are for illustrative purposes and should not be construed as limiting the present invention.

Example 1: Alkyl (R) -2-methylbutanoate
Preparation (Part 1 ) To a vial containing 5 ml of 300 mM phosphate buffer (pH 8.0), methyl 2-methylbutanoate was added to a concentration of 300 mM, and the enzyme XP-488 (from Aspergillus melleus; (Manufactured by Kagaku Kogyo Co., Ltd.), and the mixture was stirred at 25 ° C for 24 hours. After completion of the reaction, add 5% sodium carbonate aqueous solution to the reaction solution.
Add 1.5 ml and adjust to pH around 9, then 10 ml of ethyl acetate
Was added to extract methyl (R) -2-methylbutanoate.
When the extract was analyzed by gas chromatography under the following conditions, methyl (R) -2-methylbutanoate with an optical purity of 100% (yield 39%) was obtained.

== Gas chromatographic analysis conditions == Column: CDX-B, 30 m (manufactured by J & W) Temperature: Column initial temperature ...... 45 ° C (20 minutes), heating rate ......
27.5 ° C / min, final temperature: 100 ° C (20 minutes), injector temperature: 250 ° C, detector temperature: 250 ° C Carrier gas: helium, 1 ml / min Detector: FID Example 2: (R) Preparation of alkyl-2-methylbutanoate (part
2 ) To a vial containing 5 ml of 300 mM phosphate buffer (pH 7.0), add methyl 2-methylbutanoate to a concentration of 300 mM, and add the enzyme agent Denazyme AP-15 (Aspergillus oryza).
from e; Nagase Seikagaku Co., Ltd.) at 100 mg,
It was stirred for 24 hours. After completion of the reaction, 1.5 ml of 5% aqueous sodium carbonate solution was added to the reaction solution to adjust the pH to around 9, and then 10 ml of ethyl acetate was added to extract methyl (R) -2-methylbutanoate. When the extract was analyzed by gas chromatography under the analysis conditions shown in Example 1, methyl (R) -2-methylbutanoate (yield 44%) having an optical purity of 94% was obtained.

Example 3: Alkyl (R) -2-methylbutanoate
Preparation (Part 3 ) Add methyl 2-methylbutanoate to a concentration of 300 mM in a vial containing 5 ml of 300 mM phosphate buffer (pH 7.0), and add Sumiteam MP (from Aspergillus melleus; manufactured by Shin Nippon Kagaku). 50 mg was added, and the mixture was stirred at 35 ° C. for 24 hours. After completion of the reaction, add 5% sodium carbonate aqueous solution to the reaction solution.
After 1.5 ml was added to adjust the pH to around 9, 10 ml of isopropyl ether was added to extract methyl (R) -2-methylbutanoate. When the extract was analyzed by gas chromatography according to the analysis conditions shown in Example 1, methyl (R) -2-methylbutanoate (yield 44%) having an optical purity of 90% was obtained.

Example 4: Alkyl (R) -2-methylbutanoate
Preparation (Part 4 ) To a vial bottle containing 5 ml of 300 mM phosphate buffer (pH 8.0), methyl 2-methylbutanoate was added to a concentration of 300 mM, and the enzyme biopulase SP-10 (Bacillus subtilis) was added.
Origin: Nagase Seikagaku Co., Ltd.) (50 mg) was added, and the mixture was stirred at 35 ° C. for 24 hours.

After completion of the reaction, 1.5 ml of 5% aqueous sodium carbonate solution was added to the reaction solution to adjust the pH to around 9, and then 10 ml of isopropyl ether was added to extract methyl (R) -2-methylbutanoate. When the extract was analyzed by gas chromatography according to the analysis conditions shown in Example 1,
Methyl (R) -2-methylbutanoate with 100% optical purity (yield 39
%)was gotten.

Example 5: Alkyl (R) -2-methylbutanoate
Preparation (Part 5 ) To a vial containing 5 ml of 300 mM phosphate buffer (pH 7.0), methyl 2-methylbutanoate was added to a concentration of 300 mM, and the crystalline alkaline protease nagase (Baci
5 mg of llus subtilis derived from Nagase Seikagaku Corporation was added, and the mixture was stirred at 35 ° C. for 24 hours. After completion of the reaction, 1.5 ml of 5% aqueous sodium carbonate solution was added to the reaction solution to adjust the pH to around 9, and then 10 ml of heptane was added to extract methyl (R) -2-methylbutanoate. When the extract was analyzed by gas chromatography according to the analysis conditions shown in Example 1, methyl (R) -2-methylbutanoate having an optical purity of 100% (yield 38%) was obtained.

Example 6: Alkyl (R) -2-methylbutanoate
Preparation (Part 6 ) To a vial containing 5 ml of 300 mM phosphate buffer (pH 8.0), methyl 2-methylbutanoate was added to a concentration of 300 mM, and a heat-resistant alkaline protease (Bacillus sp.
Origin: manufactured by Kurita Water Industries Ltd.) was added, and the mixture was stirred at 40 ° C. for 24 hours. After completion of the reaction, add 5% sodium carbonate aqueous solution to the reaction solution.
Add 1.5 ml and adjust the pH to around 9, then add dichloromethane.
Methyl (R) -2-methylbutanoate was extracted by adding 10 ml.

The extract was analyzed by gas chromatography according to the analysis conditions shown in Example 1. As a result, methyl (R) -2-methylbutanoate having an optical purity of 100% (yield 40%) was obtained.
was gotten.

Example 7: Alkyl (R) -2-methylbutanoate
Preparation (Part 7 ) To a vial containing 5 ml of 300 mM phosphate buffer (pH 7.0), methyl 2-methylbutanoate was added to a concentration of 300 mM, and SM enzyme (derived from Serratia marcescens; manufactured by Nagase Biochemical Industry) ) Was added and the mixture was stirred at 35 ° C for 24 hours.
After the reaction was completed, the reaction solution was added with a 5% sodium carbonate aqueous solution 1.5.
After adding 10 ml and adjusting the pH to around 9, 10 ml of toluene was added to extract methyl (R) -2-methylbutanoate. When the extract was analyzed by gas chromatography under the analysis conditions shown in Example 1, (R) -2- having an optical purity of 100% was obtained.
Methyl methylbutanoate (40% yield) was obtained.

Example 8: Alkyl (R) -2-methylbutanoate
Preparation (Part 8 ) To a vial containing 5 ml of 300 mM phosphate buffer (pH 8.0), ethyl 2-methylbutanoate was added to a concentration of 300 mM, and XP-488 (from Aspergillus melleus; Nagase Biochemical Industry) was added. (Manufactured by K.K.) was added, and the mixture was stirred at 25 ° C. for 24 hours.
After the reaction was completed, the reaction solution was added with a 5% sodium carbonate aqueous solution 1.5.
After adjusting the pH to around 9 by adding ml, 10 ml of ethyl acetate was added to extract ethyl (R) -2-methylbutanoate. The extract was analyzed by gas chromatography according to the analysis conditions shown in Example 1. As a result, (R)-having an optical purity of 100% was obtained.
Ethyl 2-methylbutanoate (yield 40%) was obtained.

Example 9: (R) -2-Methylbutanoic acid Alkoxy
Preparation of Sialyl To a vial containing 5 ml of 300 mM phosphate buffer (pH 8.0), methoxyethyl 2-methylbutanoate was added to a concentration of 300 mM, and XP-488 (from Aspergillus melleus; manufactured by Nagase Seikagaku Corporation) was added. 50 mg was added, and the mixture was stirred at 25 ° C for 24 hours. After completion of the reaction, add 1.5 ml of 5% sodium carbonate aqueous solution to the reaction mixture to adjust the pH to around 9, then add ethyl acetate.
10 ml was added to extract methoxyethyl (R) -2-methylbutanoate. When the extract was analyzed by gas chromatography under the analysis conditions shown in Example 1, methoxyethyl (R) -2-methylbutanoate (yield 37.7%) having an optical purity of 100% was obtained.

Example 10: Preparation of (R) -2-methylbutanol 50 ml of dry THF (tetrahydrofuran), 1.90 g (0.05 mol) of lithium aluminum hydride were placed in a 100 ml three-necked flask and cooled to 5 ° C. or lower. And 11.6g
5 (0.1 mol) of methyl (R) -2-methylbutanoate (methyl (R) -2-methylbutanoate prepared in Example 1)
The ml THF solution was added dropwise over 30 minutes while maintaining this cooling temperature. Then, after returning to room temperature and stirring for 3 hours, it is carefully poured into hydrochloric acid / ice water, extracted with ethyl acetate, washed with water, dried and concentrated to give 6.2 g of the following analytical value.
(R) -2-methylbutanol (yield 70.3%) was obtained.

[Analysis data] Boiling point: 124 to 127 ° C. (760 mmHg) Optical rotation (α D ²⁰ ): +4.44 (neat) Infrared absorption analysis value (cm ⁻¹ ): ν3329 (br), 2961, 1461 ,13
80, 1231, 1191, 1048. NMR analysis value: ¹ H NMR (CDCl ₃ ); δ 0.90 (m, 6H), 1.13.
(m, 1H), 1.49 (m, 2H), 1.65 (br, 1H), 3.43 (ddd, 2H, J = 10.
8, 6.4, 5.6Hz) ¹³ C NMR (CDCl ₃ ); δ11.4, 16.2, 25.9, 37.5, 68.1 Infrared absorption analysis is performed by Perkin Elmer FT1600 (KBr tablet method) In addition, the NMR analysis was performed using UNITY400 (400 MHz) manufactured by Varian.

Example 11: Preparation of (R) -2-methylbutanol 50 ml of dry THF (tetrahydrofuran) and 1.90 g (0.05 mol) of lithium aluminum hydride were placed in a 100 ml three-necked flask and cooled to 5 ° C. or lower, A solution of 13.0 g (0.1 mol) of ethyl (R) -2-methylbutyrate (ethyl (R) -2-methylbutanoate prepared in Example 8) in 5 ml of THF was added over 30 minutes while maintaining this cooling temperature. Was dropped. Then return to room temperature,
After stirring for 3 hours, carefully poured into hydrochloric acid / ice water, extracted with ethyl acetate, washed with water, dried and concentrated, and 6.5 g of (R) -2-methylbutanol having the following analytical value (yield 73.7%) Got

[Analysis Data] Boiling point: 124 to 127 ° C. (760 mmHg) Optical rotation (α D ²⁰ ): +4.80 (neat) Infrared absorption analysis value (cm ⁻¹ ): ν3329 (br), 2961, 1461 ,13
80, 1231, 1191, 1048. NMR analysis value: ¹ H NMR (CDCl ₃ ); δ 0.90 (m, 6H), 1.13.
(m, 1H), 1.49 (m, 2H), 1.65 (br, 1H), 3.43 (ddd, 2H, J = 10.
8, 6.4, 5.6Hz) ¹³ C NMR (CDCl ₃ ); δ11.4, 16.2, 25.9, 37.5, 68.1 Infrared absorption analysis is performed by Perkin Elmer FT1600 (KBr tablet method) In addition, the NMR analysis was performed using UNITY400 (400 MHz) manufactured by Varian.

Example 12: Preparation of (R) -2-methylbutanoic acid In a 100 ml three-necked flask, 1.2 g (0.010 mol) of (R) -2-methylbutanoic acid methyl ester ((R) prepared in Example 1) -2-
Methyl methylbutanoate) was stirred in 0.82 g (0.019 mol) of sodium hydroxide and 20 ml of methanol at room temperature for 24 hours, neutralized with 5% hydrochloric acid, extracted with ether, washed with water and washed with magnesium sulfate. After drying, it was concentrated. Then, by purification by distillation, 0.92 having the following analytical value
g (R) -2-methylbutanoic acid (yield 87%) was obtained.

[Analysis data] Boiling point: 77-80 ° C. (15 mmHg) Optical rotation (α D ²⁰ ): -18.5 (neat) Infrared absorption analysis value (cm ^-1 ): ν3300-2500 (br), 1716, 14
64, 1418, 1230, 944, 781, 537. NMR analysis value: ¹ H NMR (CDCl ₃ ); δ 0.94 (t, 3H, J = 4.9H)
z), 1.18 (d, 3H, J = 6.8Hz), 1.51 (m, 1H), 1.71 (m, 1H)
, 2.39 (m, 1H), 11.5 (br, 1H) ¹³ C NMR (CDCl ₃ ); δ 11.6, 16.4, 26.6, 41.0, 183.5 Infrared absorption analysis is performed by Perkin Elmer infrared spectrophotometry. The measurement was carried out with a total of FT1600 (KBr tablet method), and the NMR analysis was carried out using UNITY400 (400 MHz) manufactured by Varian.

[0040]

INDUSTRIAL APPLICABILITY According to the method of the present invention, optically active 2-methylbutanol, optically active 2-methylbutanoic acid and its derivatives, which are expected to be applied in various fields, are compared with conventional chemical synthetic methods. An excellent method suitable for industrial mass production is provided, such as being simply produced with high optical purity.

[Brief description of drawings]

FIG. 1 is a schematic view showing a manufacturing process of the present invention.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display part (C12P 41/00 C12R 1:69) (C12P 41/00 C12R 1: 125) (C12P 41/00 C12R 1:07) (C12P 41/00 C12R 1:43) (72) Inventor Chie Miura 2-3-2 Muroya, Nishi-ku, Kobe-shi, Hyogo Nagase & Co., Ltd. Research and Development Center

Claims (8)

[Claims] 1. A method for producing optically active 2-methylbutanoic acid and its derivatives, which comprises the following steps: alkyl 2-methylbutanoate or alkoxyalkyl 2-methylbutanoate and alkyl 2-methylbutanoate or 2-methylbutanoic acid. An optically active (S) -2-methylbutanoic acid, and an optically active (R) -2-methylbutanoic acid alkyl or optical Activity
A method for producing optically active 2-methylbutanoic acid and its derivatives, comprising the step of dividing into (R) -2-methylbutanoic acid alkoxyalkyl. 2. The enzyme is Aspergill.
The method for producing an optically active 2-methylbutanoic acid and its derivative according to claim 1, which is a protease or ester degrading enzyme produced by a microorganism belonging to the genus us), the genus Bacillus or the genus Serratia. 3. The enzyme is Aspergillus meleus.
(Aspergillus melleus), Aspergillus oryzae (Aspergillus melleus)
gillus oryzae), Bacillus subtlis
ilis), Bacillus amyloliquefaciens
samyloliquefaciens), and a protease or ester-degrading enzyme produced by at least one microorganism selected from the group consisting of Serratia marcescens. Production method. 4. The method for producing an optically active 2-methylbutanoic acid and a derivative thereof according to claim 1, wherein the alkyl 2-methylbutanoate is methyl 2-methylbutanoate or ethyl 2-methylbutanoate. 5. The alkoxyalkyl 2-methylbutanoate is methoxyethyl 2-methylbutanoate.
5. A method for producing the optically active 2-methylbutanoic acid and its derivatives according to any one of 4 to 4. 6. The method for producing the optically active 2-methylbutanoic acid and its derivative comprises the following steps, namely, the optically active alkyl 2-methylbutanoate or the optically active compound.
The method for producing an optically active 2-methylbutanoic acid or a derivative thereof according to claim 1, further comprising a step of chemically reducing the alkoxyalkyl 2-methylbutanoate. 7. The step of chemically reducing the optically active alkyl 2-methylbutanoate or the alkoxyalkyl optically active 2-methylbutanoate comprises converting the optically active alkyl (R) -2-methylbutanoate in the presence of lithium aluminum hydride. The method for producing optically active 2-methylbutanoic acid and its derivative according to claim 6, which comprises a step of reducing. 8. The method of producing the optically active 2-methylbutanoic acid and the optically active alkyl 2-methylbutanoate comprises the following steps, that is, the optically active alkyl 2-methylbutanoate or the optically active compound.
The method for producing an optically active 2-methylbutanoic acid or a derivative thereof according to claim 1, further comprising a step of hydrolyzing an alkoxyalkyl 2-methylbutanoate.