JP2000300288A - Production of both enantiomers of optically active 4- alkanol compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a safe method for producing highly pure (+) and (-) both enantiomers of an optically active 4-alkanol in high yield. SOLUTION: Both of the objective enantiomers of the optically active 4- alkanol compound are produced by applying a two-step method of selectively esterifying one enantiomer of a racemic 4-alkanol compound with an acylating agent by using a lipase in the presence of an organic solvent, and (i) hydrolyzing the obtained and purified optically active ester compound by using the lipase or (ii) further esterifying the remaining 4-alkanol compound without being esterified by the acylating agent by using the lipase.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to (+) and (-) optically active 4-alkanol compounds having a high enantiomeric purity required in the fields of pharmaceuticals, agricultural chemicals and functional materials utilizing lipase. The present invention relates to a method for producing both enantiomers.

[0002]

2. Description of the Related Art In the production of both (+) and (-) enantiomers of an optically active 4-alkanol compound having high enantiomeric purity, there is no example using a biocatalyst in the known literature. It has also been reported that a synthesis example of a 4-alkanol by a reduction reaction with (No reaction) [J. A
m. Chem. Soc. , 108, 162 (198
6)]. On the other hand, even when referring to the organic chemical method, there are few synthetic examples, and the unsaturated bond of 85% ee [a unit showing enantiomeric purity (enantiomeric excess)] is reduced by a ketone reduction reaction using an organic boron compound. Examples of synthesizing an optically active 4-alkanol compound having a low enantiomeric purity,
It requires an expensive catalyst, has problems in waste liquid treatment, etc., and is not practical [Tetrahedron: Asymme
try, 6, 2683 (1995)]. The present inventors have also reported to date lipase P of the genus Pseudomonas, for example.
It is possible to improve the enantioselectivity of S and AK (manufactured by Amano Pharmaceutical Co., Ltd.) by coexisting an organic solvent (especially acetone is effective) to hydrolyze racemic 2-alkanol or 3-alkanol acetate. Lipase Novozyme 435 of Candida genus (Novo Nordisk) and enantiomerically selective esterification of racemic 2-alkanol or 3-alkanol by using vinyl acetate as an acylating agent, etc. Many methods for producing both (+) and (-) enantiomers of an optically active alkanol compound having purity have been reported. For example, in J. Chem. Soc. , Perkin
Trans. 1, 1996, 961; Liebigs
Ann. Chem. J., 1996, 167; Mol.
Catal. , B: Enzymatic, 4, 53 (1
998); Recent Res. Devel. in A
gricultural & Biological C
hem. , 2, 63 (1998). However, in the case of 4-alkanols, the techniques studied so far have not led to the production of an optically active substance having a satisfactory high enantiomeric purity.

[0003]

The production of the (+) and (-) enantiomers of the optically active 4-alkanol compound having a high enantiomeric purity as described above has been reported by a method which has been reported in a few well-known documents. It has low enantiomeric purity, requires an expensive catalyst, has problems in waste liquid treatment and the like, and is not practical. Therefore, a method for producing both (+) and (-) enantiomers of an optically active 4-alkanol compound having a high yield and a high enantiomeric purity in a safe operation and without producing any waste which adversely affects the environment. Is being developed.

[0004]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, have found that a racemic 4-alkanol compound can be converted into an enantiomer only with an acylating agent in the presence of lipase in an organic solvent. Is selectively esterified, and the optically active ester compound obtained after the purification is hydrolyzed with lipase to further increase the enantiomeric purity, a two-step reaction,
Alternatively, a racemic 4-alkanol compound is selectively esterified with only an enantiomer with an acylating agent in an organic solvent in the presence of lipase to purify and separate the ester compound, and the remaining unesterified 4-alkanol The compound is further esterified with an lipase with an acylating agent (to increase the enantiomeric purity) and the other optically active 4-alkanol compound which is not esterified is isolated by a two-step reaction. The (+) and (-) enantiomers of the optically active 4-alkanol compound having a high yield and high enantiomeric purity in a safe operation and without producing any waste that adversely affects the environment are obtained. And (-) have found a method for producing both enantiomers and have reached the present invention.

That is, the present invention provides 1) a method for producing both enantiomers of an optically active 4-alkanol compound, which comprises optically resolving a racemic 4-alkanol compound using lipase; and 2) a racemic 4-alkanol compound. An alkanol compound is selectively esterified with only one enantiomer with an acylating agent in the presence of lipase in an organic solvent, and the optically active ester compound obtained after purification is hydrolyzed in the presence of lipase. 1) A method for producing both enantiomers of the optically active 4-alkanol compound of 1), and 3) the racemic 4-alkanol compound is selectively esterified with an acylating agent in the presence of lipase in an organic solvent to form only one enantiomer. After separating and purifying the ester compound, the residual compound is further esterified with an acylating agent in the presence of lipase, and the other optically active compound A method for preparing both enantiomers of the optically active 4-alkanol compound 1) comprising a two-step reaction comprising recovering the alkanol compound, and 4) converting the racemic 4-alkanol compound with an acylating agent in an organic solvent in the presence of lipase. Only enantiomers are selectively esterified and after purification (i)
Hydrolyzing the obtained optically active ester compound with lipase, (ii) further esterifying the remaining compound after purification with an acylating agent in the presence of lipase, and recovering the non-esterified optically active alkanol. Method for producing both enantiomers of the optically active 4-alkanol compound of 1) comprising a step reaction, and 5) the 4-alkanol compound is

[0006]

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Wherein the acylating agent is R
₃ COOCH = CH ₂ 1), 2),
3) or 4) the method for producing both enantiomers of the optically active 4-alkanol compound according to the above [wherein R ₁ represents an alkyl group which may have a substituent, and the main chain has 16 or less carbon atoms. ,
R ₂ is an alkyl group having 3 carbon atoms and optionally having a substituent,
R ₃ represents an alkenyl group or an alkynyl group;
The above 18 represents an alkyl group which may have a substituent, a 5- or 6-membered alicyclic hydrocarbon which may have a substituent, and an aromatic hydrocarbon which may have a substituent], 6) The 4-alkanol compound is selected from the group of the following compounds (1) to (7).
For producing both enantiomers of the described optically active 4-alkanol compounds

[0008]

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(1) 4-hexadecanol, (2) 2-
Dodecene-4-ol, (3) 1-dodecene-4-ol, (4) 1-dodecin-4-ol, (5) 11-dodecene-4-ol, (6) 11-methyl-4-dodecanol, (7) 8-phenyl-4-octanol, 7)
Lipases are of the genus Candida, the genus Pseudomonas, the mucor (Mu)
(b) Production of both enantiomers of the optically active 4-alkanol compound according to (1), (2), (3), (4), (5) or (6), which are selected from microbial sources including the genus cor) Method.

The present invention will be described in detail. In the method for producing both enantiomers of the optically active 4-alkanol compound of the present invention, in the first method, as shown in the following reaction formula, (1) a racemic form of the 4-alkanol compound is used in the presence of lipase in an organic solvent. Lower acylating agents such as R ₃ COOCH
= CH ₂ selectively esterifies only one enantiomer,
(2) The optically active ester compound obtained after purification is hydrolyzed in the presence of lipase to further increase the enantiomeric purity, and a two-step reaction is employed. The other enantiomer that has not been esterified first becomes the starting material of the formula (2) of the second method described below. Further, the ester compound having a low enantiomeric purity obtained by the formula (2) is
After hydrolysis with aqueous sodium hydroxide solution, racemic 4-
It can be treated and reused like alkanol compounds.

[0011]

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In the formula, R ₁ represents an alkyl group which may have a substituent, wherein the main chain has 16 or less carbon atoms, and R ₂ is an alkyl group having 3 carbon atoms and which may have a substituent. R ₃ represents an alkyl group, an alkenyl group or an alkynyl group which has 1 to 18 carbon atoms and may have a substituent;
And a membered alicyclic hydrocarbon and an aromatic hydrocarbon which may have a substituent. Specifically, the substituent of R ₁ and R ₃ is an alkyl group such as a methyl group or an ethyl group, or a methoxy group;
Examples include an alkoxy group such as an ethoxy group, a halogen group such as chloro and bromo, an aryl group such as phenyl and naphthyl, and an alicyclic hydrocarbon group such as cyclohexyl and cyclopentyl. Examples of the substituent of R ₂ include an alkyl group such as a methyl group and an alkoxy group such as a methoxy group. In the method for producing both enantiomers of the optically active 4-alkanol compound of the present invention, in the second method, as shown in the following reaction formula, (1) the racemic form of the 4-alkanol compound is added to the presence of lipase in an organic solvent. After selectively esterifying only one enantiomer with a lower acylating agent and separating and purifying the ester compound, (2) the residue is further acylated with an acylating agent in the presence of lipase, and The optically active 4-alkanol compound is isolated with high purity. One of the first esterified enantiomers is the first as described above.
[Formula 4] of the method (1). Further, the ester compound having a low enantiomeric purity obtained in (2) in the second method can be treated and reused in the same manner as a racemic 4-alkanol compound after being hydrolyzed with an aqueous solution of caseizoda.

[0013]

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In the formula, R ₁ , R ₂ and R ₃ are the same as described above.

The 4-alkanol compound of the present invention includes any compound having an alcoholic OH group at the 4-position and having optical activity at that position, and specific examples thereof include the following ( Examples include the compounds 1) to (7), but the present invention is not limited to these compounds.

[0016]

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The acylating agent used in the present invention is R ₃ C
OOCH ＝ CH ₂ , wherein R ₃ is an alkyl group, an alkenyl group or an alkynyl group which has 1 to 18 carbon atoms and may have a substituent; A cyclic hydrocarbon and an aromatic hydrocarbon which may have a substituent; specifically, vinyl butyrate, vinyl caproate, vinyl caprylate, vinyl caprate, vinyl laurate, vinyl myristate, palmitic acid Vinyl, vinyl stearate, vinyl pivalate, vinyl octylate, vinyl chloroacetate, vinyl bromoacetate, vinyl cyclohexanecarboxylate, vinyl benzoate, vinyl p-methylbenzoate, vinyl α-naphthoate, vinyl β-naphthoate, And vinyl cinnamate. The acylating agent of the present invention is not limited to these compounds. Although any lipase may be used in the present invention, it is necessary to selectively esterify only one of the (+) and (−) enantiomers, and the candida (Ca)
ndida), Pseudomonas
As) and those derived from various microorganisms such as the genus Mucor are preferably used. Specifically, as the genus Candida, Kirazyme L-2 and Kirazyme L-5
(Manufactured by Roche Diagnostics Co., Ltd.), Novozyme 435 (manufactured by Novo Nordicx Co., Ltd.), and Kirazyme L-1 and Kirazyme L-6 as pseudomonas species
(Above, manufactured by Roche Diagnostics Co., Ltd.), and the genus Mucor include Kirazyme L-9 (manufactured by Roche Diagnostics Co., Ltd.).

In the case of esterification, the solvent used in the production method of the present invention is, for example, pentane, hexane, heptane,
Hydrocarbons such as octane, diethyl ether, methyl
Any of ethers such as t-butyl ether, di-n-butyl ether and tetrahydrofuran, aromatics such as toluene, xylene and benzene, and halogens such as dichloromethane and chloroform may be mixed or mixed. In the case of hydrolysis, water is basically used, and examples thereof include hydrocarbons such as pentane, hexane, heptane and octane; ethers such as diethyl ether, methyl-t-butyl ether, di-n-butyl ether and tetrahydrofuran; and toluene. , Xylene, aromatics in the benzene building, halogens such as dichloromethane, chloroform, etc., alcohols such as methanol, ethanol, propanol, isopropanol, acetone, methyl ethyl ketone,
Any of ketones such as methyl isobutyl ketone or a mixture with a plurality of solvents can be used. In the case of esterification, the amount of these solvents used must be at least an amount that completely dissolves the racemic 4-alkanol compound as a raw material, and is, for example, 3 to 50 times by weight, preferably 5 to 5 times the weight of the racemic 4-alkanol compound. ３０30 times the weight.
In the case of hydrolysis, the amount of water required for the reaction is racemic 4
-1 to 50 times the weight of the alkanol compound and the total amount of the solvent is 1 to 100 times that of the racemic 4-alkanol compound.
It is by weight, preferably 5 to 30 times by weight. In the case of esterification, lipase is suspended in a mixed solvent system of a racemic 4-alkanol compound and an acylating agent, and the suspension is gently shaken or stirred. At this time, only one of the enantiomers (+) and (-) is selectively esterified. At this time, the conversion of esterification is kept at 45 to 50% in order to increase the enantiomeric purity.
Which of (+) and (-) is selected depends on the used 4-
Depends on the structure of the alkanol compound. The esterified product is separated by fractional extraction, fractional distillation, column chromatography and the like, and the product is further hydrolyzed with lipase. In the case of this hydrolysis, lipase is suspended in a mixed solvent system of an optically active 4-alkanol ester compound and water, and the suspension is gently shaken or stirred. 100% enantiomeric purity
The conversion of the hydrolysis to be close to ee is 65-70.
%. The hydrolyzed 4-alkanol compound is separated as described above. Thereby, one enantiomer of the optically active 4-alkanol compound is obtained with high purity.

In the second method of the present invention, the other enantiomer, 4-alkanol, which has not been esterified during the esterification in the above-mentioned first method, is separated and then further acylated. The lipase is suspended in a mixed solvent system with an agent and subjected to an esterification reaction treatment by gentle shaking or stirring. At this time, the conversion of esterification is
50-60 to make the enantiomeric purity close to 100% ee
%. The unesterified 4-alkanol compound is separated as described above. The obtained non-esterified compound is an optically active 4-alkanol compound which is the other enantiomer and is obtained with high purity. The temperature at the time of the optical resolution may be any temperature as long as the lipase acts, but is preferably 15 to 40 ° C. The progress of the reaction
A part of the reaction solution can be tracked by performing analysis by gas chromatography or high performance liquid chromatography. After completion of the reaction, the optically active 4-alkanol and the optically active 4-alkanol ester are separated from the reaction solution by any of fractional extraction, fractional distillation, column chromatography, or a combination thereof. The enantiomeric purity of both (+) and (-) optically active 4-alkanols prepared can be determined by high performance liquid chromatography after derivation to the corresponding 3,5-dinitrophenyl urethane using 3,5-dinitrophenyl isocyanate. Performed by analysis.

[0020]

BEST MODE FOR CARRYING OUT THE INVENTION (1) Racemic 4-hexadecanol, acylating agent (R ₃ COOCH ＝ CH ₂ , for example, vinyl halide, vinyl caproate, etc.) and lipase (for example, Cirazyme L- 2, Novonozyme 435, Kirazyme L as Pseudomonas
1, Kirazyme L-9 as Mucor is added to an organic solvent (hydrocarbon, ether, aromatic, etc.), and the mixture is stirred by gas chromatography while confirming the conversion. After suction filtration, the organic solvent was distilled off from the filtrate under reduced pressure,
A crude product is obtained. For example, an acylated product of 4-hexadecanol and 4-hexadecanol are obtained by column chromatography on silica gel (n-hexane). The obtained acylated product of 4-hexadecanol and lipase are added to a phosphate buffer (pH 7.4), and the mixture is stirred while confirming the conversion rate by gas chromatography. After suction filtration, the filtrate is evaporated under reduced pressure to remove the organic solvent (hydrocarbon, ether or aromatic) to obtain a crude product. For example, column chromatography on silica gel (n-hexane)
To obtain highly pure acylated (−)-4-hexadecanol and 4-hexadecanol.

(2) (+) 4-hexadecanol not esterified in the above (1), an acylating agent (R ₃ CO
OCH ＝ CH ₂ , halogenated vinyl acetate, vinyl caproate, etc.) and lipase (for example, Kirazyme L-2 as Candida and Kirazyme L as Pseudomonas)
1, Kirazyme L-9) as a genus of mucor is added to an organic solvent (e.g., hydrocarbon type, ether type, aromatic type), and the mixture is stirred while confirming the conversion rate by gas chromatography. After suction filtration, the filtrate is evaporated under reduced pressure to remove the organic solvent to obtain a crude product. (+)-4-Hexadecanol and 4-hexadecanol chloroacetate were separated by column chromatography on silica gel (n-hexane). (+)-4-Hexadecanol obtained by purification is of high purity.

[0022]

According to the present invention, a racemic 4-alkanol compound is selectively esterified with only one enantiomer with an acylating agent in the presence of an organic solvent using a lipase, and then (i)
By hydrolyzing the purified optical ester compound in the presence of lipase, or (ii) applying a two-step method in which the 4-alkanol compound remaining without esterification is further esterified with an acylating agent in the presence of lipase. It is capable of producing both (+) and (-) enantiomers of an optically active 4-alkanol with high yield and high enantiomeric purity in a safe operation and without producing any waste that adversely affects the environment. .

[0023]

EXAMPLES Example 1 [(-)-4-hexadecanol Production of Formula (1)] 20 g of 4-hexadecanol and 30 g of vinyl chloroacetate
And 8 g of Kirazyme L-2 (manufactured by Roche Diagnostics Co., Ltd.) with t-butyl methyl ether 400
The mixture was stirred for 60 minutes at 30 ° C while confirming the conversion rate by gas chromatography at 30 ° C (120 rotations per minute).
did. After suction filtration, t-butyl methyl ether was distilled off from the filtrate under reduced pressure to obtain 23 g of a crude product. The conversion was 48% from gas chromatography. Silica gel 1
Column chromatography (n-hexane) was performed with 15 g to obtain 11.8 g of 4-hexadecanol chloroacetate (yield: 4).
4.9%) and 10.1 g (yield 50.5%) of 4-hexadecanol. A very small amount of the obtained 4-hexadecanol chloroacetate was hydrolyzed with an aqueous potassium hydroxide solution in order to examine the enantiomeric purity and optical rotation. The enantiomeric purity was determined by treating 4-hexadecanol and 3,5-dinitrophenylisocyanate in toluene at room temperature in the presence of pyridine to give the corresponding 3,5-dinitrophenylurethane derivative by high performance liquid chromatography (Smichiral O
A2100I; n-hexane: 1,2-dichloroethane: ethanol = 100: 5: 0.2), and 88
% Ee. Optical rotation: [α] ²⁰ −1.18 ° (C =
3.5, pentane) Next, 11 g of 88% ee of 4-hexadecanol chloroacetate and 4.4 g of Kirazyme L-2 (manufactured by Roche Diagnostics Co., Ltd.) were added to a phosphate buffer (p).
H7.4) and stirred at 30 ° C. for 60 minutes (120 rotations per minute) at 30 ° C. while checking the conversion by gas chromatography. After suction filtration, the filtrate was extracted with t-butyl methyl ether, and the extraction solvent was distilled off under reduced pressure to obtain 10 g of a crude product. The conversion was 65% from gas chromatography. Column chromatography (n-hexane) is performed on 50 g of silica gel, 5.3 g of (-)-4-hexadecanol (63.4% yield), and 3.8 g of 4-hexadecanol chloroacetate (yield 34. 5%)
Obtained. The enantiomeric purity of the obtained (−)-4-hexadecanol is determined by converting the corresponding 3,5-dinitrophenyl urethane derivative to high performance liquid chromatography (Smichiral O).
A 2100I; n-hexane: 1,2-dichloroethane: ethanol = 100: 5: 0.2),
It was 0% ee. Optical rotation: [α] ²⁰ -2.31 ° (C
= 4.1, pentane).

Example 2 [(+)-4-Hexadecanol Preparation of Formula (1)] (+)-4-Hexadecanol was prepared from 4-hexadecanol which was not esterified in Example 1. . The enantiomeric purity of this was converted to the corresponding 3,5-dinitrophenyl urethane derivative and analyzed by high performance liquid chromatography (Sumichiral OA2100I; n-hexane: 1,2-dichloroethane: ethanol = 100: 5: 0.2). It was 79% ee. Optical rotation: [α] ² +1.1
5% (C = 5.8, pentane) 10 g of (+) 4-hexadecanol with 79% ee, 15 g of vinyl chloroacetate and Kirazyme L-2 (Roche
4 g of Diagnostics Co., Ltd.) was added to 200 ml of t-butyl methyl ether, and the mixture was stirred at 30 ° C. for 5 hours while confirming the conversion by gas chromatography (1).
120 revolutions per minute). After suction filtration, t-butyl methyl ether was distilled off from the filtrate under reduced pressure to obtain 13 g of a crude product. The conversion was 55% from gas chromatography. Perform column chromatography (n-hexane) on 65 g of silica gel and 4.3 g of (+)-4-hexadecanol.
(Yield: 43.0%), 7.1 g (yield: 54.0%) of 4-hexadecanol chloroacetate was obtained. The enantiomeric purity of the (+)-4-hexadecanol obtained is determined by converting the corresponding 3,5-dinitrophenylurethane derivative to high performance liquid chromatography (Smichiral OA 2100I;
n-hexane: 1,2-dichloroethane: ethanol =
100: 5: 0.2) and found to be 100% ee. Optical rotation: [α] ²⁰ + 2.23 ° (C = 5.1, pe
ntane).

Example 3 [(-)-11-dodecene-4-
All Production of Formula (5)] 11-dodecene-4-ol 20 g, vinyl butyrate 37 g
And 8 g of Kirazyme L-2 (manufactured by Roche Diagnostics Co., Ltd.) with t-butyl methyl ether 400
The mixture was stirred for 50 minutes at 30 ° C while confirming the conversion rate by gas chromatography (120 rotations per minute) at 30 ° C.
did. After suction filtration, t-butyl methyl ether was distilled off from the filtrate under reduced pressure to obtain 25 g of a crude product. The conversion was 46% from gas chromatography. Silica gel 1
Perform column chromatography (n-hexane) with 25 g and perform 11-
12.5 g of dodecene-4-ol butyrate (yield 4
5.3%), 10.6 g of 11-dodecene-4-ol.
(53.0% yield). 11-dodecene-4 obtained
-A very small amount of allbutyrate was hydrolyzed with aqueous potassium hydroxide solution to determine enantiomeric purity and optical rotation.
The enantiomeric purity was converted to the corresponding 3,5-dinitrophenyl urethane derivative and analyzed by high performance liquid chromatography (Sumichiral OA 2100I; n-hexane: 1,2-dichloroethane: ethanol = 100: 5: 0.2).
It was 92% ee. Optical rotation: [α] ²⁰ −1.02 ° (C = 4.7, pentane) Next, 12 g of 92% ee of 11-dodecene-4-olbutyrate and Kirazyme L-2 (Roche Diagnostics ( 4.8 g) in a phosphate buffer (p
H7.4) and stirred at 30 ° C. for 60 minutes (120 rotations per minute) at 30 ° C. while checking the conversion by gas chromatography. After suction filtration, the filtrate was extracted with t-butyl methyl ether, and the extraction solvent was distilled off under reduced pressure to obtain 10 g of a crude product. The conversion was 68% from gas chromatography. Column chromatography (n-hexane) is performed on 50 g of silica gel to give (-)-11-dodecene-4-ol (5.8 g, yield 66.7%) and 11-dodecene-4-ol butyrate (3.7 g). Yield 30.
8%). The enantiomeric purity of the resulting (-)-11-dodecene-4-ol was determined by converting it into the corresponding 3,5-dinitrophenylurethane derivative by high performance liquid chromatography (Smichiral OA 2100I; n-hexane: 1,2-dichloroethane: (Ethanol = 100: 5: 0.2), it was 100% ee. Optical rotation: [α] ²⁰ -1.
71 ° (C = 6.2, pentane).

Example 4 [(+)-11-dodecene-4-
All Production of Formula (5)] 11-dodecene-4 not esterified in Example 3
(+)-11-dodecene-4-ol is produced from -ol. The enantiomeric purity of this compound was determined by converting it into the corresponding 3,5-dinitrophenyl urethane derivative by high performance liquid chromatography (Sumichiral OA 2100I; n-hexane: 1,2-dichloroethane: ethanol = 100:
5: 0.2), which was 76% ee. Optical rotation:
[Α] ²⁰ + 0.95 ° (C = 3.2, pentane) 76% ee (+)-11-dodecene-4-ol 10
g, 18.6 g of vinyl butyrate and 4 g of Kirazyme L-2 (manufactured by Roche Diagnostics Co., Ltd.) in 200 ml of t-butyl methyl ether, at 30 ° C. for 4 hours while confirming the conversion by gas chromatography in the middle. Stirring (120 rotations per minute). After suction filtration, t-butyl methyl ether was distilled off from the filtrate under reduced pressure to obtain crude product 13.
g was obtained. The conversion was 52% from gas chromatography.
%Met. Column chromatography (n-
Hexane), and 4.5 g (yield 45.0%) of (+)-11-dodecene-4-ol, 11-dodecene-4-ol
7.0 g (yield 50.0%) of all butyrate was obtained.
The enantiomeric purity of the obtained (+)-11-dodecene-4-ol was determined by converting the corresponding 3,5-dinitrophenylurethane derivative to high performance liquid chromatography (Smichiral O).
A 2100I; n-hexane: 1,2-dichloroethane: ethanol = 100: 5: 0.2),
It was 0% ee. Optical rotation: [α] ²⁰ + 1.61 ° (C
= 5.5, pentane).

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Claims (7)

[Claims] An optical activity of a racemic 4-alkanol compound using lipase.
-A method for producing both enantiomers of an alkanol compound. 2. An optically active ester compound obtained by purifying a racemic 4-alkanol compound in an organic solvent by selectively acylating only one enantiomer with an acylating agent in the presence of lipase in the presence of lipase. 2. The method for producing both enantiomers of an optically active 4-alkanol compound according to claim 1, which comprises a two-step reaction of hydrolyzing the compound. 3. A racemic 4-alkanol compound is selectively esterified with only one enantiomer with an acylating agent in an organic solvent in the presence of a lipase, and the ester compound is separated and purified. 2. The process for producing both enantiomers of an optically active 4-alkanol compound according to claim 1, comprising a two-step reaction in which the other optically active 4-alkanol compound which is not esterified is further esterified with an acylating agent. 4. A racemic 4-alkanol compound is selectively esterified with only an enantiomer with an acylating agent in an organic solvent in the presence of a lipase, and after purification (i) the obtained optically active ester compound is subjected to lipase 2. The optical method according to claim 1, wherein (ii) the residual compound after the purification is further esterified with an acylating agent in the presence of a lipase, and the unesterified optically active alkanol is recovered. A method for producing both enantiomers of an active 4-alkanol compound. 5. The method of claim 4, wherein the 4-alkanol compound is Wherein the acylating agent is R ₃ COOCH
= Is represented by the CH ₂ claim 1, 2, 3 or 4
A process for producing both enantiomers of the described optically active 4-alkanol compound. [Wherein, R ₁ represents an alkyl group which may have a substituent, the main chain has 16 or less carbon atoms, and R ₂ is an alkyl group having 3 carbon atoms and which may have a substituent, R ₃ represents an alkyl group having 1 to 18 carbon atoms which may have a substituent, a 5- or 6-membered alicyclic hydrocarbon which may have a substituent, and a substituent; Represents an aromatic hydrocarbon which may be present) 6. The optically active 4-alkanol compound according to claim 1, wherein the 4-alkanol compound is selected from the group of the following compounds (1) to (7): Production method of both enantiomers. (1) 4-hexadecanol (2) 2-dodecene-4-ol (3) 1-dodecene-4-ol (4) 1-dodecin-4-ol (5) 11-dodecene-4-ol (6 ) 11-Methyl-4-dodecanol (7) 8-phenyl-4-octanol 7. The method of claim 1, wherein the lipase is Candida.
The genus is selected from microbial sources including the genus Pseudomonas and the genus Mucor.
7. A process for producing both enantiomers of the optically active 4-alkanol compound according to 5 or 6.