JP2001120297A - Method for producing optically active unsaturated secondary alcohol with enzyme - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing the optically active isomer of a known or new unsaturated secondary alcohol (hereinafter referred to as said substance). SOLUTION: This method for producing optically active said substance of formula (V) comprises reacting racemic said substance of the general formula (I) (R2 is vinyl or ethynyl; R1 is an alkyl, an alkoxy or the like) with an aliphatic vinyl ester of the general formula (II): H2C=CR3-O-CO-R4 (R3 is H or methyl; R4 is a 1 to 4C linear or branched alkyl) in the presence of lipase in the absence of a solvent or in an organic solvent, thereby esterifying only one enantiomer of the racemic substance by an asymmetric interesterification reaction to produce the optically active said substance isomer (R) fatty acid ester of the general formula (III), separating the optically active said substance isomer (R) fatty acid ester of the general formula (III) from the obtained reaction solution, and further hydrolyzing the ester to produce the optically active said substance isomer (R) of the general formula (V).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a process for producing an optically active unsaturated secondary alcohol which involves a step of optically resolving a racemic unsaturated secondary alcohol by a simple and economical enzymatic method. The optically active unsaturated secondary alcohol obtained in the present invention is a known or novel substance that is useful as a raw material for manufacturing pharmaceuticals, agricultural chemicals, liquid crystals, and the like.

[0002]

2. Description of the Related Art Conventionally, an optically active method comprising transesterification between a fatty acid vinyl ester and an alcohol, or a racemic resolution of a racemate of a fatty acid vinyl ester and a secondary alcohol by transesterification in the presence of lipase. As a method for producing a secondary alcohol, for example, various methods described in the following documents are known.

[0003] Vinyl butyrate and ethanol are converted to PPL
(Porcine liver lipase) by subjecting it to a transesterification reaction [“Tetrahedron Lett
ters) ", Vol. 28, pp. 953-954 (1987)]. Vinyl acetate and a racemic secondary alcohol (provided that one of the substituents on the asymmetric carbon of the secondary alcohol may be substituted by halogen (C ₁ to
(C ₁₈ ) alkyl group or (C ₃ -C ₁₀ ) cycloalkyl group) is subjected to a transesterification reaction in the presence of a lipase (Japanese Patent Publication No. 7-2118). A method of subjecting 1-phenyl-2-propen-1-ol and vinyl acetate to a transesterification reaction in the presence of Lipase AK (manufactured by Amano Pharmaceutical Co., Ltd.) [“Journal of American
Chemical Society (Journal of American Chemic
al Society), Volume 113, pp. 6129-6139 (1991
Year)〕.

[0004] 1-phenyl-2-propyn-1-ol,
A method of subjecting vinyl acetate to a transesterification reaction in the presence of a lipase derived from the fungus genus Candida antarctica [Journal of Chemical Society, Chemical
Communications (Journal of Chemical Society,
Chemical Communications), Vol. 21, pp. 2088--2084
P. (1997)]. A method of subjecting a fatty acid vinyl and acetylene alcohol to a transesterification reaction in the presence of a lipase (Japanese Patent Laid-Open No. 5-84
No. 094).

[0005] However, in the above-mentioned method, there is no problem of stereoselectivity because ethanol has no stereoisomerism. In the method of the literature, there is no description about a method of transesterifying a racemic unsaturated secondary alcohol with vinyl acetate according to the present invention.

[0006] In the methods described in the above documents, optically active compounds with high enantioselectivity have not been obtained. In the methods described in the above documents, optically active compounds can be obtained with high enantioselectivity, but no detailed production method is specifically disclosed. In the above-mentioned Japanese Patent Application Laid-Open Publication No. H07-115, there is no disclosure about the production of an optically active unsaturated secondary alcohol other than aliphatic acetylene alcohol.

[0007]

SUMMARY OF THE INVENTION From the racemic form of an unsaturated secondary alcohol having a phenyl group and a vinyl or ethynyl group on the asymmetric carbon atom at the α-position, the optically active isomer of the unsaturated secondary alcohol is obtained. It is desired to develop a new method that can easily and efficiently produce a compound (enantiomer) with high optical purity, and it is an object of the present invention to provide such a new method.

[0008]

Means for Solving the Problems The present inventors have made intensive studies to achieve the above object. As a result, unsaturated 2 having a phenyl group (which may be substituted with an alkyl group, an alkoxy group, a halo group, etc.) and a vinyl group or an ethynyl group on the asymmetric carbon atom at the α-position of the alcohol molecule.
When a racemic secondary alcohol and a fatty acid vinyl ester are reacted in the presence of a lipase enzyme, a transesterification reaction can proceed asymmetrically, and one of the secondary alcohols (R)
It was found that only the enantiomer (enantiomer) of the isomer can undergo the transesterification specifically and selectively to produce the fatty acid ester of the (R) -form secondary alcohol. The present invention has been completed based on this finding.

Accordingly, in the present invention, general formula (I) (Wherein R ² is a vinyl group —CH = CH ₂ or an ethynyl group —C≡
It indicates CH, R ¹ is (C ₁ ~C ₄₎ alkyl group, (C ₁ ~
C ₄ ) represents a phenyl group which may be substituted with an alkoxy group, a halogen or a nitro group)
Formula (II) H ₂ C = CR ³ -O-CO-R ⁴ (II) (wherein R ³ is a hydrogen atom or Represents a methyl group, and R ⁴ represents a linear or branched alkyl group having 1 to 18 carbon atoms)
By reacting only one enantiomer of the racemic unsaturated secondary alcohol with the vinyl ester of the general formula (II). Into the following general formula (III) Wherein R ¹ and R ² have the same meanings as defined above, to produce a fatty acid ester of an unsaturated secondary alcohol which is an optically active (R) form, and General formula (IV) Wherein R ¹ and R ² have the same meanings as described above, and the unreacted (S) -form unsaturated secondary alcohol is allowed to remain in the reaction solution without being reacted. From the general formula (I
The optically active unsaturated secondary alcohol fatty acid ester of II) is separated, and the obtained ester of general formula (III) is hydrolyzed to obtain the following general formula (V) Wherein R ¹ and R ² have the same meanings as described above, which is characterized by producing an optically active (R) -form unsaturated secondary alcohol represented by the formula: There is provided a method for producing the optically active unsaturated secondary alcohol represented by the general formula (V).

The lipase used in the method of the present invention includes Pseudomonas genus and Aspergillus (Aspergillus).
gillus), Mucor, Rhizopus
Genus, Alcaligenes, Achromobacter or Candid
a) It is preferably a lipase from the genus. This lipase can also be used as a crude enzyme extracted from the above-mentioned microorganisms or in the form of cell lysates of the microorganisms.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the method of the present invention will be described in more detail. The method of the present invention includes a first reaction step and a second reaction step represented by the following reaction formula.

[0012] However, in the above reaction formula, R ¹ , R ² , R ³ and R ⁴ have the same meaning as defined above.

In the above first reaction step, the fatty acid vinyl ester of the formula (II) is added to the racemic form of the alcohol of the formula (I), and lipase is added to the obtained solution. It is not necessary to add another organic solvent, but it can be added if desired. The asymmetric transesterification proceeds only by stirring and mixing the obtained reaction mixture. This reaction selectively esterifies only one enantiomer of the racemic alcohol of formula (I). The other enantiomer, Formula (I
The compound of V) remains unreacted in the reaction mixture. In this transesterification reaction, the fatty acid vinyl ester of formula (II) is converted to vinyl alcohol, which is immediately rearranged to a ketone or aldehyde of formula (VI). Therefore, the reverse reaction is suppressed, and the asymmetric transesterification reaction proceeds rapidly and with high yield.

In the first reaction step of the method of the present invention, the compound of the formula (I)
The secondary alcohol of formula (II) and the fatty acid vinyl ester of formula (II) are used in an amount of 0.5 to 2.0 moles of the fatty acid vinyl ester of formula (II) with respect to 1 mole of the secondary alcohol of formula (I).
Preferably, 0.5 to 1.0 mol is used. The amount of the enzyme lipase to be used is 0.1 to 500 g, preferably 0.1 to 10 g, per mole of the alcohol of the formula (I).

The unsaturated secondary alcohol of the formula (I) is a known compound and can be obtained by a known method.
For example, an alcohol in the case where R ¹ in the formula (I) is a p-methoxyphenyl group and R ² is a vinyl group can be obtained by reacting p-methoxybenzaldehyde with vinylmagnesium chloride [“Journal of American
Chemical Society (Journal of American Chemic
al Society), Vol. 100, pp. 6407-6413 (1978
Year)〕.

Specific examples of the unsaturated secondary alcohol of the formula (I) include the following. 1-phenyl-2-propen-1-ol, 1- (p-methoxyphenyl) -2
-Propen-1-ol, 1- (p-ethoxyphenyl) -2-propen-1-ol, 1- (pn-propoxyphenyl) -2-propen-1-ol, 1- (p-isopropoxyphenyl) 2-propen-1-ol, 1- (pn-butoxyphenyl) -2-propen-1
-Ol, 1- (p-isobutoxyphenyl) -2-propene-1-
All, 1- (p-sec-butoxyphenyl) -2-propen-1-ol, 1- (p-tert-butoxyphenyl) -2-propen-1-ol, 1- (p-methylphenyl) -2 -Propen-1-ol, 1-
(p-ethylphenyl) -2-propen-1-ol, 1- (pn-propylphenyl) -2-propen-1-ol, 1- (p-isopropylphenyl) -2-propen-1-ol, 1 -(pn-butylphenyl) -2-propen-1-ol, 1- (p-isobutylphenyl) -2-propen-1-ol, 1- (p-sec-butylphenyl)-
2-propen-1-ol, 1- (p-tert-butylphenyl) -2-
Propen-1-ol, 1- (p-fluorophenyl) -2-propen-1-ol, 1- (p-chlorophenyl) -2-propen-1-ol, 1- (p-bromophenyl) -2- Propen-1-ol, 1-
(p-nitrophenyl) -2-propen-1-ol,
Also 1-phenyl-2-propyn-1-ol, 1- (p-methoxyphenyl) -2-propyn-1-ol, 1- (p-ethoxyphenyl) -2-propyn-1-ol, 1- ( pn-propoxyphenyl) -2-propyn-1-ol, 1- (p-isopropoxyphenyl) -2-propyn-1-ol, 1- (pn-butoxyphenyl)-
2-propyn-1-ol, 1- (p-isobutoxyphenyl) -2-
Propin-1-ol, 1- (p-sec-butoxyphenyl) -2-propyn-1-ol, 1- (p-tert-butoxyphenyl) -2-propyn-1-ol, 1- (p-methyl (Phenyl) -2-propyne-1
-Ol, 1- (p-ethylphenyl) -2-propyn-1-ol, 1- (pn-propylphenyl) -2-propyn-1-ol,
1- (p-isopropylphenyl) -2-propyn-1-ol, 1-
(pn-butylphenyl) -2-propyn-1-ol, 1- (p-isobutylphenyl) -2-propyn-1-ol, 1- (p-sec-butylphenyl) -2-propyn-1-ol , 1- (p-tert-butylphenyl) -2-propyn-1-ol, 1- (p-fluorophenyl) -2-propyn-1-ol, 1- (p-chlorophenyl) -2-
Propin-1-ol, 1- (p-bromophenyl) -2-propyne
-1-ol, 1- (p-nitrophenyl) -2-propyn-1-ol, and the above para-substituted phenyl compound is
A phenyl compound substituted by ortho or meta may be used.

The fatty acid vinyl ester of the formula (II) is a known compound, and may be obtained by a known method or a commercially available product may be used. As the fatty acid vinyl ester of the formula (II), specifically, for example, vinyl acetate, vinyl propionate, vinyl butyrate, vinyl octanoate, vinyl laurate, and isopropenyl acetate can be used.

Specific examples of the lipase include Pseudomonas and Aspergillus.
s) genus, Mucor genus, Rhizopus genus, Alcaligenes genus, Achromobacter (Ac)
lipases derived from microorganisms of the genus hromobacter or Candida. Commercial products of these lipases are trade names Lipase PS, Lipase A
K, lipase A, lipase M, lipase F, lipase AY (all, manufactured by Amano Pharmaceutical Co., Ltd.), lipase MY, lipase OF, lipase QL, lipase AL, lipase PL (all, Meito Sangyo Co., Ltd.)
And Novozym 435 (manufactured by Roche Corp.). Lipase PS and Novozym435 are preferred.

The relationship between the above-mentioned lipase commercial products and the types of microorganisms producing the same is summarized in Table 1 below.

[0020]

In the first reaction step, a solvent may not be used, but a solvent may be used if necessary.
Specific examples of solvents that can be used include cyclohexane, n-
Hexane, n-heptane, toluene, tert-butanol,
Examples include ethyl ether, tetrahydrofuran, carbon tetrachloride, and chloroform. Among them, non-polar solvents such as cyclohexane, n-hexane, n-heptane and toluene are preferred. However, when the reaction is performed in the absence of a solvent, it is easier to collect the target substance. The reaction temperature is generally 0 to 70 ° C, preferably 20 to 40 ° C, and the reaction time is generally 1 to 150 hours, preferably 1 to 96 hours.

After the completion of the reaction in the first reaction step, the lipase is removed from the reaction solution by filtration or the like, and the resulting filtrate is distilled to obtain the ester of the formula (III).

After the ester of formula (III) produced in the first reaction step is separated and collected as described above,
In the reaction step, the ester of the formula (III) is hydrolyzed to produce an optically active secondary alcohol of the formula (IV). This hydrolysis can be carried out by ordinary alkaline hydrolysis. For example, it is preferable to carry out hydrolysis in 1 to 10 mol of methanol at a temperature of 0 to 20 ° C. for 7 to 8 hours using 1 to 10 mol of potassium hydroxide per 1 mol of the ester of the formula (III). When the obtained reaction solution is subjected to silica gel chromatography (developing solvent: ethyl acetate-n-hexane or chloroform-methanol), the desired alcohol of the formula (IV) can be obtained in high yield.

[0024]

Next, the present invention will be described in detail with reference to examples. Example 1 (1) Formation of optically active (R) -1-phenyl-2-propen-1-ol propanoate of the following formula (IIIa) 5 g of racemic 1-phenyl-2-propen-1-ol (37 mm
ol) and 20 g (200 mmol) of vinyl propionate were placed in a reaction flask, and stirred using a magnetic stirrer (the solvent was not added). To this mixed solution, 0.1% of lipase PS was added.
g was added and stirred at 25 ° C. The reaction was terminated when the conversion to the ester reached 40% (Ceramosphe as stationary phase).
r Ru-1 column, measured by HPLC using methanol as mobile phase).

The lipase was removed from the obtained reaction solution by suction filtration. Subsequently, the filtrate was concentrated and then subjected to silica gel chromatography (ethyl acetate / n-hexane = 1/1).
[Volume ratio]) to obtain 2.53 g (yield 36.0%) of (R) -form 1-phenyl-2-propen-1-ol propanoate. The enantiomeric excess (ee) of the obtained (R) form of 1-phenyl-2-propen-1-ol propanoate was> 99% from the result of HPLC analysis.

(2) 1-phenyl-2- optically active substance of the following formula (Va)
Formation of propen-1-ol 1.46 g (26 mmol) of potassium hydroxide and 4.17 g of methanol (130
mmol) was placed in a reaction flask and stirred using a magnetic stirrer. The (R) obtained in Example 1 (1) was added to this solution.
1-Phenyl-2-propen-1-ol propanoate
2.53 g (13 mmol) was added dropwise at a temperature of 20 ° C or less.
Stirring was continued for hours. After completion of the reaction, 5 g of toluene and 5 g of water were added to the reaction solution, and the organic layer was washed with 5 ml of saturated saline.

Subsequently, the organic layer was concentrated and then subjected to silica gel chromatography (ethyl acetate / n-hexane = 1/1).
[Volume ratio]) and purified by the 1-form of the (R) form represented by formula (Va).
1.70 g (95% yield) of phenyl-2-propen-1-ol was obtained. The enantiomeric excess (ee) of 1-phenyl-2-propen-1-ol in the obtained (R) form was> 99% from the result of HPLC analysis.

The obtained compound exhibited the following physical properties. [α] _D ²⁵ + 3.0 ° (c = 5.17, CHCl ₃ ) ¹ H-NMR (CDCl ₃ ) peak value: δ: 7.15 to 7.50 (m, 5H), 6.0 (m, 1H), 5.9 (m, 1H), 5.3
(d, 1H), 5.2 (m, 1H), 2.4 (s, 1H)

Examples 2 to 18 (1) Example 1 was repeated except that the types of the reactants and enzymes used in Example 1 (1) and the conditions of the asymmetric transesterification were changed as shown in Table 2. A transesterification reaction was performed in the same manner as in (1). That is, all the transesterification reactions were performed at a reaction temperature of 25 ° C., and the reaction was stopped when the conversion to the ester was 40%.

[0030] (2) The optical purity of the obtained optically active ester of the formula (III) was measured. The optical purity of the ester is indicated by an E value. The results are shown in Table 3. In addition, E value was calculated by the following formula.

[0031] Where C: conversion rate = 0.4 eeester: optical purity of the produced ester (III) (90%
→ 0.9)

[0032]

From the results shown in Table 3 above, it is recognized that the obtained optically active ester (III) has high optical purity.

The ester of the formula (III) shown in Table 3 can be hydrolyzed in the same manner as in Examples 1 and (2).

Among the racemic unsaturated secondary alcohols of the general formula (I) used as raw materials in the method of the present invention, the following general formula (Ia) Wherein R ² is a vinyl group —CH = CH ₂ or an ethynyl group —C≡CH
And the tert-butoxy group on the phenyl group shown in the formula is at the para-position or the meta-position of the phenyl group].
(p-tert-butoxyphenyl) -2-propen-1-ol, 1-
(m-tert-butoxyphenyl) -2-propen-1-ol, 1-
(p-tert-butoxyphenyl) -2-propyn-1-ol or 1- (m-tert-butoxyphenyl) -2-propyn-1-ol is a novel compound.

The unsaturated secondary alcohol of the general formula (Ia) is
Vinyl or ethynyl represented by the general formula (A) R ² -MgX (A) wherein R ² is a vinyl group or an ethynyl group, and X is a halogen atom, preferably a chlorine, bromine or iodine atom・ Magnesium halide and general formula (B) Reacting with p- or m-tert-butoxybenzaldehyde represented by the following formula by a Grignard reaction and then hydrolyzing: Wherein R ² is a vinyl group —CH = CH ₂ or an ethynyl group —C≡CH
And the tert-butoxy group on the phenyl group shown in the formula is at the para-position or meta-position of the phenyl group.]

Some examples of the production of the unsaturated secondary alcohol (racemic) represented by the above general formula (Ia) are shown below as Reference Examples.

Reference Example 1 1- (p-tert-butoxyphenyl)-
Synthesis of 2-propen-1-ol 9.7 g (0.4 mol) of metal magnesium and anhydrous tetrahydrofuran
30 ml was added, and about 2 ml of ethyl bromide was further added and stirred, and the reaction due to foaming was confirmed. Then, after adding 300 ml of anhydrous tetrahydrofuran, 8960 ml of vinyl chloride (0.4 m
ol) was blown at 30 to 40 ° C. over 5 hours (magnesium disappeared) to prepare a solution of vinyl magnesium chloride (0.4 mol).

To this solution, 71.3 g (0.4 mol) of p-tert-butoxybenzaldehyde was added dropwise at 30 to 40 ° C. over 2 hours, and stirring was continued at the same temperature for 1 hour. After the reaction,
The reaction solution was cooled to room temperature, and 60 ml of water was added at 30 ° C. or lower to hydrolyze. Then, after the usual post-treatment (that is, after washing the reaction mixture with a saline solution, separating into an aqueous layer and an organic layer, and distilling off the solvent from the obtained organic layer), the obtained crude was obtained. Tertiary butyl catechol was added as a polymerization inhibitor to the product, and distillation was performed under reduced pressure to obtain 72.5 g of 1- (p-tert-butoxyphenyl) -2-propen-1-ol (gas chromatograph). 99.0 purity by graphy
%, Yield 88.0%). Physical properties of the obtained compound were as follows. Boiling point: 133 ° C./8 mmHg ¹ H-NMR (CDCl ₃ ) peak value δ: 1.35 (s, 9H), 2.40 (s, 1H), 5.20-5.75 (m, 3H), 5.
90-6.15 (m, 1H), 6.93 (d, 2H), 7.60 (d, 2H)

Reference Example 2 1- (m-tert-butoxyphenyl)-
Synthesis of 2-propen-1-ol The procedure of Example 1 was repeated, except that m-tert-butoxybenzaldehyde was used instead of p-tert-butoxybenzaldehyde, to obtain 1- (m- 70.9 g of tert-butoxyphenyl) -2-propen-1-ol (purity 99.0% by gas chromatography, yield 86.0%) was obtained.
Physical properties of the obtained compound were as follows. Boiling point: 135 ° C./9 mmHg ¹ H-NMR (CDCl ₃ ) peak value δ: 1.34 (s, 9H), 2.60 (s, 1H), 5.20-5.75 (m, 3H), 5.
90-6.10 (m, 1H), 7.05-7.40 (m, 4H)

Reference Example 3 1- (p-tert-butoxyphenyl)-
Synthesis of 2-propyn-1-ol In a 1-liter four-necked flask purged with nitrogen, 9.7 g (0.4 mol) of metal magnesium and anhydrous tetrahydrofuran
30 ml was added, and about 2 ml of ethyl bromide was further added and stirred, and the reaction due to foaming was confirmed. Then, after adding 300 ml of anhydrous tetrahydrofuran, 8960 ml of methyl chloride (0.4 m
ol) was blown in at 30 to 40 ° C. over 5 hours (magnesium disappeared) to prepare a solution (0.4 mol) of methylmagnesium chloride. The solution was further cooled to 20 ° C. or lower, and 8960 ml (0.4 mol) of acetylene was blown at 10 to 20 ° C. over 5 hours to prepare a solution (0.4 mol) of ethynylmagnesium chloride.

To this solution, 71.3 g (0.4 mol) of p-tert-butoxybenzaldehyde was added dropwise at 30 ° C. to 40 ° C. over 2 hours, and stirring was continued at the same temperature for 1 hour. After the completion of the reaction, the reaction solution was cooled to room temperature, and 60 ml of water was added at 30 ° C. or lower to hydrolyze. Then, after the usual post-treatment (that is, after washing the reaction mixture with a saline solution, separating into an aqueous layer and an organic layer, and distilling off the solvent from the obtained organic layer), the obtained crude was obtained. By adding tertiary butyl catechol as a polymerization inhibitor to the product and performing distillation under reduced pressure, 1- (p-tert-butoxyphenyl) -2-propyne-1
-74.2 g of all (purity 9 by gas chromatography)
9.8%, yield 91.0%). Physical properties of the obtained compound were as follows. Boiling point: 135 ° C./5 mmHg ¹ H-NMR (CDCl ₃ ) peak value δ: 1.15 (s, 9H), 2.55 (s, 1H), 2.80 (d, 1H), 5.25
(d, 1H), 6.85 (d, 2H), 7.35 (d, 2H)

[0043]

According to the method of the present invention, compared with the conventional synthesis method,
By a simple and economical method, an optically active unsaturated secondary alcohol useful as a raw material for medicines, agricultural chemicals, liquid crystals and the like can be obtained with high optical purity and high yield.

Continued on the front page (51) Int.Cl. ⁷ Identification code FI Theme coat II (reference) C07M 7:00 C07M 7:00 F term (reference) 4B064 AC17 AD64 BH01 BH04 CA21 CB26 CC03 CD05 CD06 CD27 DA01 DA11 4H006 AA02 AC13 AC46 AC83 AD17 BA06 BB14 BC10 BC19

Claims (4)

[Claims] 1. Formula (I) (Wherein R ² is a vinyl group —CH = CH ₂ or an ethynyl group —C≡
It indicates CH, R ¹ is (C ₁ ~C ₄₎ alkyl group, (C ₁ ~
C ₄ ) represents a phenyl group which may be substituted with an alkoxy group, a halogen or a nitro group)
Formula (II) H ₂ C = CR ³ -O-CO-R ⁴ (II) (wherein R ³ is a hydrogen atom or Represents a methyl group, and R ⁴ represents a linear or branched alkyl group having 1 to 18 carbon atoms)
And thereby reacting only one of the racemates of the unsaturated secondary alcohol with the vinyl ester of the general formula (II) by an asymmetric transesterification reaction. Into the following general formula (III) Wherein R ¹ and R ² have the same meanings as defined above, to produce a fatty acid ester of an unsaturated secondary alcohol which is an optically active (R) form, and General formula (IV) Wherein R ¹ and R ² have the same meanings as described above, and the unreacted (S) -form unsaturated secondary alcohol is allowed to remain in the reaction solution without being reacted. From the general formula (I
The optically active unsaturated secondary alcohol fatty acid ester of II) is separated, and the obtained ester of general formula (III) is hydrolyzed to obtain the following general formula (V) Wherein R ¹ and R ² have the same meanings as described above, which is characterized by producing an optically active (R) -form unsaturated secondary alcohol represented by the formula: A method for producing the optically active unsaturated secondary alcohol of the above general formula (V). 2. The lipase used is a genus Pseudomonas, a genus Aspergillus,
Mucor, Rhizopus, Alcaligenes, Achromobacter
The method according to claim 1, which is a lipase derived from the genus acter) or the genus Candida. 3. The asymmetric transesterification reaction is carried out without a solvent,
The reaction according to claim 1, wherein the reaction is carried out at a temperature of 70 ° C, the reaction is stopped when the conversion to the ester of the general formula (III) reaches 35 to 45%, and the lipase is removed from the reaction solution by vacuum filtration. Method. 4. The vinyl ester of the general formula (II) is vinyl acetate, vinyl propionate, vinyl octanoate, vinyl laurate or isopropenyl acetate.
The method described in.