JP2000253897A - Production of optically active alpha-hydroxylactones - Google Patents

Abstract

PROBLEM TO BE SOLVED: To efficiently produce optically active lactones useful as a starting material or the like for a medicine, an agrochemical, or the like with a high optical purity and in a high yield by reacting a primary alcohol with specific α-hydroxylactones in the presence of a prescribed lipase to carry out a transesterification. SOLUTION: A primary alcohol such as n-propanol is reacted with α- hydroxylactones of formula I (R1 is H, a 1-12C alkyl or an aryl; R2 and R3 are each H or methyl) and being a mixture of (R) isomer and (S) isomer in an arbitrary ratio, in the presence of a lipase derived from Pseudomonas bacteria to carry out a transesterification to divide the Α-hydroxylactones into the (R)-isomer of the hydroxylactones of formula II and the (S)-isomer of esters of the Α-hydroxylactones of formula III which are antipodes, and to provide the objective optically active Α-hydroxylactones.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing optically active α-hydroxylactones useful as starting materials for optically active physiologically active substances and functional materials. (R) -α-hydroxy-γ-butyrolactone, which can be produced by the method for producing optically active α-hydroxylactones of the present invention, is useful as a starting material for 2,3-epoxysqualene (MA Adballah et al. al., J. C
hem. soc. Perkin Trans., 1 , 888 (1975)). Also, (S)-
α-Hydroxy-γ-butyrolactone can be easily converted to (R) -α-fluoro-γ-butyrolactone. It is useful as a starting material for the bioactive substance 1α, 25-dihydroxy-24 (R) -fluorocholecalciferol (SJ Shiuey
et al., J. Org. Chem., 53 , 1040 (1988)).

[0002]

2. Description of the Related Art Optically active compounds are useful as starting materials for physiologically active substances such as medicines and agricultural chemicals, or functional materials. However, due to the presence of optical isomers,
In practical use, it is an essential condition to use only one of the enantiomers. Here, when a racemate or a substance having a low optical purity is used, it is considered that there is a high possibility that the target substance does not exhibit sufficient physiological activity or functionality. It is also known that enantiomers that are not the target may inhibit the expression of physiological activity and functionality.
Therefore, the higher the optical purity of the optically active compound used as the starting material, the better.

However, although optically active α-hydroxylactones are very useful, there is no known method for effectively producing the (R) form with high optical purity. Currently known methods for producing (R) -form α-hydroxylactones include the following. (1) Method derived from malic acid produced naturally or its ester (K. Mori et al., Tetrahedron, 35 , 393)
(1979), H. Hayasi et al., J. Am. Chem. Soc., 95 , 874.
9 (1973), EJ Corey et al., J. Am. Chem. Soc., 10
0 , 1942 (1978), SJ Shiuey et al., J. Org. Chem.,
53 , 1040 (1988)), but only two carboxyl groups or esters need to be reduced. But,
No effective reduction method is known and is not industrially advantageous.

(2) Similarly, as a method of using a natural product as a raw material, a method using L-ascorbic acid as a raw material (KC L
uk et al., Synthesis., 3 , 226 (1988)). However, it has a disadvantage that it is not industrially advantageous because the number of steps is very large. (3) The following is known as a method for synthesizing α-hydroxylactones by performing asymmetric reduction. A method for obtaining (R) -3-hydroxybutyrolactone by asymmetric reduction using baker's yeast (D. Seebach, Synthesis., 1 , 37 (198
6)) has been found, but there is a problem that the efficiency of this reduction step is extremely low. That is, for example, to treat 35 g of substrate, 1 kg of baker's yeast, 1 k of saccharose
g and 8 l of water are required, which is not an industrially advantageous method.

(4) A method for obtaining optically active pantolactone by asymmetric reduction of a prochiral ketone using optically active 4-methyl-1,4-dihydropyridine (AI Meyer
s, Tetrahedoron Lett., 29 , 5617 (1988)), but has the drawback of being impractical due to poor optical purity (~ 72% ee). (5) A method of performing optical resolution using lipase is known. As one of them, a method of performing asymmetric transesterification with lipase to obtain (R)-or (S) -pantolactone (HS Bevinakatti, J. Org. Chem., 54 , 2
453 (1989)). According to this method, it is possible to obtain both enantiomers, which seem to be excellent at first glance. However, there is a problem that the optical purity of the (R) form is as low as 70% ee.

(6) The present applicant discloses in Japanese Patent Application Laid-Open No. 7-51090 that α- or β-hydroxylactones are esterified with lipase and optically resolved. However, in this method, the optical purity of the (R) form is only about 94% ee in one reaction. For this reason, when alcohols with higher optical purity are required, there is a problem that the steps in the patent publication must be repeated a plurality of times.

[0007]

SUMMARY OF THE INVENTION An object of the present invention is to provide a method for producing optically active α-hydroxylactones of high purity by overcoming the above-mentioned drawbacks of the prior art and by simple operation and high yield. It is to provide.

[0008]

Means for Solving the Problems The present invention has been studied diligently in order to solve the above-mentioned problems, and obtained an ester of hydroxylactone, which is a mixture of the (R) -form and the (S) -form in any ratio, derived from Pseudomonas spp. In the presence of lipase, by performing a transesterification by acting a primary alcohol, optical activity (R) -α-
The inventors have found that only hydroxylactones can be selectively obtained, and have completed the present invention. That is, the present invention provides a transesterification reaction by reacting a primary alcohol with a racemic α-hydroxylactone represented by the general formula (1) in the presence of a lipase derived from Pseudomonas fluorescens to perform a transesterification reaction. The α-hydroxylactone of the (R) form represented by the formula (2) and the α-hydroxylactone ester of the (S) form represented by the general formula (3), which is an enantiomer thereof, can be resolved. A process for producing optically active α-hydroxylactones characterized by the following.

[0009]

Embedded image

(In the general formula (1), R ₁ is a hydrogen atom and has 1 carbon atom.
12 alkyl group, or an aryl group, R ₂
And R ₃ represent a hydrogen atom or a methyl group. )

[0011]

Embedded image

(In the general formula (2), R ₁ is a hydrogen atom and has 1 carbon atom.
12 alkyl group, or an aryl group, R ₂
And R ₃ represent a hydrogen atom or a methyl group. )

[0013]

Embedded image

(In the general formula (3), R ₁ is a hydrogen atom and has 1 carbon atom.
Represents an alkyl group or an aryl group, and R ₂ and R ₃ represent a hydrogen atom or a methyl group. )

[0015]

BEST MODE FOR CARRYING OUT THE INVENTION In the process for producing optically active α-hydroxylactones of the present invention, water is not actively added. Therefore, side reactions such as hydrolysis of the raw material ester and ring opening of the lactone hardly occur. Further, separation and reuse of the water-soluble enzyme after the reaction can be easily performed. Further, since the reaction is carried out under a condition with a small water content, microorganisms do not propagate, so that a special device, a preservative, a sterilization treatment and the like are not required. In addition to this, the substrate concentration in the method for producing optically active α-hydroxylactones of the present invention can be performed at a substrate concentration equal to or higher than that of ordinary organic synthesis.

Incidentally, specific examples of the α-hydroxylactones of the general formula (1) include α-methoxycarbonyl-
γ-butyrolactone, α-acetoxy-γ-butyrolactone, α-propoxycarbonyl-γ-butyrolactone, α-
Butoxycarbonyl-γ-butyrolactone, α-pentoxycarbonyl-γ-butyrolactone, α-hexoxycarbonyl-γ-butyrolactone, α-heptoxycarbonyl-
γ-butyrolactone, α-octoxycarbonyl-γ-butyrolactone, α-nonoxycarbonyl-γ-butyrolactone, α-decoxycarbonyl-γ-butyrolactone, α-undecoxycarbonyl-γ-butyrolactone, α-dodecaxycarbonyl -γ-butyrolactone, α-phenyloxycarbonyl-γ-butyrolactone, α-methoxycarbonyl-β, β'-dimethyl-γ-butyrolactone, α-acetoxy-β, β'-dimethyl-γ-butyrolactone, α-propoxycarbonyl -β, β'-dimethyl-γ-butyrolactone, α
-Butoxycarbonyl-β, β'-dimethyl-γ-butyrolactone, α-pentoxycarbonyl-β, β'-dimethyl-γ-
Butyrolactone, α-hexoxycarbonyl-β, β′-dimethyl-γ-butyrolactone, α-heptoxycarbonyl-
β, β'-dimethyl-γ-butyrolactone, α-octoxycarbonyl-β, β'-dimethyl-γ-butyrolactone, α-nonoxycarbonyl-β, β'-dimethyl-γ-butyrolactone, α-decaxycarbonyl -β, β'-dimethyl-γ-butyrolactone, α-undecoxycarbonyl-β, β'-dimethyl-γ-butyrolactone, α-dodecaxycarbonyl-
β, β'-dimethyl-γ-butyrolactone, α-phenyloxycarbonyl-γ-butyrolactone and the like, α-methoxycarbonyl-γ-butyrolactone, α-acetoxy-
γ-butyrolactone, α-propoxycarbonyl-γ-butyrolactone, α-methoxycarbonyl-β, β′-dimethyl-
γ-butyrolactone, α-acetoxy-β, β'-dimethyl-
γ-butyrolactone, α-propoxycarbonyl-β, β'-
Dimethyl-γ-butyrolactone can be mentioned. Further, the primary alcohol used for the transesterification in the method for producing the optically active α-hydroxylactone of the present invention may be a commercially available product that can be easily obtained, and specifically, methanol, ethanol, n-propanol, and n-propanol. Butanol, isobutyl alcohol, n-amyl alcohol, 1-hexanol, benzyl alcohol, ethylene glycol, propanediol, butanediol, glycerin, 2-methoxy
-Ethanol, 1-hydroxy-2-methoxy-propane, 1-
Hydroxy-3-methoxy-propane, 1-hydroxy-2-methoxy-butane, 1-hydroxy-3-methoxy-butane, 1-
Hydroxy-4-methoxy-butane, 1-hydroxy-2-methoxypentane, 1-hydroxy-3-methoxypentane, 1-
Hydroxy-4-methoxy-pentane, 1-hydroxy-5-methoxypentane, 1-hydroxy-2-methoxyhexane, 1
-Hydroxy-3-methoxyhexane, 1-hydroxy-4-methoxy-hexane, 1-hydroxy-5-methoxyhexane,
1-hydroxy-6-methoxyhexane, 2-ethoxy-ethanol, 1-hydroxy-2-ethoxy-propane, 1-hydroxy-3-ethoxy-propane, 1-hydroxy-2-ethoxy-butane, 1-hydroxy-3 -Ethoxy-butane, 1-hydroxy
-4-ethoxy-butane, 1-hydroxy-2-ethoxypentane, 1-hydroxy-3-ethoxypentane, 1-hydroxy-
4-ethoxy-pentane, 1-hydroxy-5-ethoxypentane, 1-hydroxy-2-ethoxyhexane, 1-hydroxy-
3-ethoxyhexane, 1-hydroxy-4-ethoxy-hexane, 1-hydroxy-5-ethoxyhexane, 1-hydroxy-
6-ethoxyhexane, 2-propoxy-ethanol, 1-hydroxy-2-propoxy-propane, 1-hydroxy-3-propoxy-propane, 1-hydroxy-2-propoxy-butane, 1-hydroxy-3-propoxy-butane , 1-hydroxy
-4-propoxy-butane, 1-hydroxy-2-propoxypentane, 1-hydroxy-3-propoxypentane, 1-hydroxy-4-propoxy-pentane, 1-hydroxy-5-propoxypentane, 1-hydroxy-2- Propoxyhexane, 1-hydroxy-3-propoxyhexane, 1-hydroxy-4-propoxy-hexane, 1-hydroxy-5-propoxyhexane, 1-hydroxy-6-propoxyhexane, 2-
Butoxy-ethanol, 1-hydroxy-2-butoxypropane, 1-hydroxy-3-butoxy-propane, 1-hydroxy
2-butoxy-butane, 1-hydroxy-3-butoxy-butane, 1-hydroxy-4-butoxy-butane, 1-hydroxy-2
-Butoxypentane, 1-hydroxy-3-butoxypentane, 1-hydroxy-4-butoxy-pentane, 1-hydroxy
-5-butoxypentane, 1-hydroxy-2-butoxyhexane, 1-hydroxy-3-butoxyhexane, 1-hydroxy-
4-butoxy-hexane, 1-hydroxy-5-butoxyhexane, 1-hydroxy-6-butoxyhexane, 2-pentoxy-
Ethanol, 1-hydroxy-2-pentoxypropane, 1-
Hydroxy-3-pentoxy-propane, 1-hydroxy-2-
Pentoxy-butane, 1-hydroxy-3-pentoxy-butane, 1-hydroxy-4-pentoxy-butane, 1-hydroxy
2-pentoxypentane, 1-hydroxy-3-pentoxypentane, 1-hydroxy-4-pentoxy-pentane, 1-hydroxy-5-pentoxypentane, 1-hydroxy-2-pentoxyhexane, 1-hydroxy -3-pentoxyhexane, 1
-Hydroxy-4-pentoxy-hexane, 1-hydroxy-5-
Pentoxyhexane, 1-hydroxy-6-pentoxyhexane, and the like, among which R ₃ in the general formula (4)
= H methanol, R ₃ = CH ₃ ethanol,
In R ₃ = C ₂ H ₅ is n- _{propanol, R 3 = CH 3 CH 2} C
Preference is given to n-butanol being H ₂ and ethylene glycol being R ₃ ＣＨCH ₂ OH.

The enzyme used in the method for producing the optically active α-hydroxylactone of the present invention is preferably a lipase derived from Pseudomonas fluorescens, and more preferably a lipase derived from Pseudomonas fluorescens. Enzymes that are commercially available as lipases derived from fluorescens include Amano Pharmaceutical Lipase PS, Amano Pharmaceutical Lipas
e PS CI or Lipase PS CII manufactured by Amano Pharmaceutical.

Next, the present invention will be described in detail. In the method for producing an optically active α-hydroxylactone of the present invention, a mixture of the (R) -form and the (S) -form of the general formula (1) as a raw material can be easily produced by a general organic chemical technique. For example, a method of exchanging bromine of a commercially available α-bromo-γ-butyrolactone with an acetoxy group by a nucleophilic substitution reaction, a method of esterifying a commercially available α-hydroxy-γ-butyrolactone, and the like can be mentioned. However, the present invention is not limited to this. In the method for producing an optically active α-hydroxylactone of the present invention, a reaction is carried out by mixing a racemic compound with a primary alcohol and efficiently contacting the mixture with an enzyme. The racemic compound and primary alcohol used here can be used without any special treatment.

In the process for producing an optically active α-hydroxylactone of the present invention, the reaction of mixing a racemic compound with an alcohol and performing a transesterification reaction may be performed without a solvent. For efficient contact, it is desirable to use an ester and carbon number 5
-12 straight-chain, branched or cyclic alkanes, 6-1 carbon atoms
Preferably, the reaction is performed in an aromatic hydrocarbon or ether. Specific examples of the solvent include methyl formate, ethyl formate, propyl formate, butyl formate, pentyl formate, hexyl formate, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, pentyl acetate, hexyl acetate, hexyl acetate, methyl propionate, and propion. Ethyl acid, propyl propionate, butyl propionate, pentyl propionate, hexyl propionate, pentane, hexane, heptane, octane, nonane, decane, undecane, dodecane, cyclopentane, cyclohexane, cycloheptane, methylcyclopentane, ethylcyclo Pentane, propylcyclopentane, butylcyclopentane, methylcyclohexane, ethylcyclohexane, butylcyclohexane, benzene, toluene, xylene, ethylbenzene, pyridine, furan, pyrrole, diethyl Ether, dipropyl ether, dibutyl ether, dipentyl ether, dihexyl ether, methyl ethyl ether, methyl propyl ether, methyl butyl ether, methyl pentyl ether, methyl hexyl ether, ethyl propyl ether, ethyl butyl ether, ethyl pentyl ether, ethyl to ethyl Xyl ether, propyl butyl ether, propyl pentyl ether, propyl hexyl ether, pentyl hexyl ether, tetrahydrofuran and the like are mentioned, and ethyl acetate and isopropyl ether are preferable.

The amount of the solvent is preferably about 0.5 to 50 times the volume of the racemic compound of the general formula (1), and 1 to 10 times the volume of the racemic compound is used. Is particularly preferred. The transesterification reaction is preferably performed in a temperature range of 0 ° C to 80 ° C, and 15 ° C to 50 ° C
Is particularly preferred. The transesterification can be performed in an air atmosphere, but is preferably performed in an atmosphere of an inert gas such as nitrogen, argon, helium, or xenon.

In the process for producing optically active α-hydroxylactones of the present invention, after asymmetric transesterification,
The enzyme can be removed from the system by a usual operation. Further, by immobilizing the enzyme on a suitable carrier, it can be easily reused after removal. After removing the enzyme, the reaction solution is distilled, column chromatography,
It can be separated into optically active alcohols and their enantiomeric esters by general techniques such as extraction. Further, the obtained optically active ester can be converted into an enantiomeric optically active alcohol by performing a decarboxylation reaction under mild conditions not containing a Lewis base or Bronsted base.

In the method for producing optically active α-hydroxylactones of the present invention, silica, silica whose surface is methylated, alumina, magnesia, or the like can be used as a carrier for immobilizing the enzyme. Anything is fine. This fixation generally involves electrostatic interaction between polar sites present on the carrier surface and polar amino acid residues present on the protein surface, or hydrophobic sites present or introduced on the carrier. It is performed by hydrophobic interaction with a hydrophobic group on the protein surface.

[0023]

EXAMPLES Hereinafter, the present invention will be described specifically with reference to typical examples, but the present invention is not limited to these examples. In this example, the optical purity was measured by attaching a chiral cell OD manufactured by Daicel to a liquid chromatograph.

Example 1 α-acetoxy-γ-butyrolactone (in the general formula (1), R ₁ = CH ₃ , R ₂ = H, R ₃
= H) was optically split as follows. Racemic α-acetoxy-γ-butyrolactone 1.0 g, n-propanol 1.0
g, 2.0 g of ethyl acetate as a solvent, and 0.5 g of Lipase PS manufactured by Amano Pharmaceutical Co., Ltd. were stirred at 25 ° C. for 24 hours under an argon atmosphere. After removing the enzyme by suction filtration,
The extraction operation was performed in water-chloroform. This allows
(R) -α-hydroxy-γ-butyrolactone and its enantiomer ester were obtained. The conversion of (R) -α-acetoxy-γ-butyrolactone was 88%. The optical purity of (R) -α-hydroxy-γ-butyrolactone is 100% ee.

Example 2 Optical resolution was carried out according to Example 1, except that the solvent was changed from 2.0 g of ethyl acetate to 2.0 g of isopropyl ether. The conversion of (R) -α-acetoxy-γ-butyrolactone was 93%. The optical purity of (R) -α-hydroxy-γ-butyrolactone is 100% ee.

Example 3 The solvent was changed from 2.0 g of ethyl acetate to n-
Optical resolution was performed in the same manner as in Example 1, except that 2.0 g of hexane was used. 87% conversion of (R) -α-acetoxy-γ-butyrolactone. The optical purity of (R) -α-hydroxy-γ-butyrolactone is 100% ee.

Example 4 The enzyme was used as Lipase P manufactured by Amano Pharmaceutical Co., Ltd.
Optical resolution was performed in the same manner as in Example 1 except that 0.5 g of S was replaced with 0.5 g of Lipase PS CI manufactured by Amano Pharmaceutical Co., Ltd. 97% conversion of (R) -α-acetoxy-γ-butyrolactone. The optical purity of (R) -α-hydroxy-γ-butyrolactone is 100% ee.

Example 5 An enzyme was used as Lipase P manufactured by Amano Pharmaceutical Co., Ltd.
Optical resolution was performed according to Example 1, except that 0.5 g of S was replaced with 0.5 g of Lipase PS CII manufactured by Amano Pharmaceutical Co., Ltd. (R) -α-
Conversion of acetoxy-γ-butyrolactone is 94%. (R) -α-
100% ee optical purity of hydroxy-γ-butyrolactone.

[Example 6] (R) form rich α-acetoxy-
γ-butyrolactone (in the general formula (1), R ₁ ＣＨCH ₃ , R ₂
= H, R ₃ = H) was optically split as follows. (R) form rich α-acetoxy-γ-butyrolactone (85% ee) 1.0 g, n
-Propanol 1.0g, ethyl acetate 2.0g, Amano Pharmaceutical Li
0.5 g of pase PS was mixed and stirred at 25 ° C. for 24 hours under an argon atmosphere. After removing the enzyme by suction filtration, an isolation operation was performed using a silica gel column. This allows
(R) -Hydroxy-γ-butyrolactone and its enantiomeric ester were obtained. The conversion of (R) -acetoxy-γ-butyrolactone was 89%, and the optical purity of (R) -α-hydroxy-γ-butyrolactone was 100% ee.

Example 7 (S) Form Rich α-Acetoxy-
γ-butyrolactone (in the general formula (1), R ₁ ＣＨCH ₃ , R ₂
= H, R ₃ = H) were optically split as follows. (S) form rich α-acetoxy-γ-butyrolactone (70% ee) 1.0
g, n-propanol 1.0 g, isopropyl ether 1.4 g,
0.5 g of Lipase PS manufactured by Amano Pharmaceutical Co., Ltd. was mixed and stirred at 25 ° C. under an argon atmosphere for 24 hours. After removing the enzyme by suction filtration, an isolation operation was performed using a silica gel column. Thus, (R) -hydroxy-γ-butyrolactone and its enantiomer ester were obtained. The conversion of (R) -acetoxy-γ-butyrolactone was 94%, and the optical purity of (R) -α-hydroxy-γ-butyrolactone was 99% ee.

Example 8 α-Propoxycarbonyl-γ
-Butyrolactone (in the general formula (1), R ₁ = C ₂ H ₅ , R ₂
= H, R ₃ = H) was optically split as follows. Substrate is α
From 1.0 g of -acetoxy-γ-butyrolactone to α-propoxycarbonyl-γ-butyrolactone (in the general formula (1), R ₁
= C ₂ H _5, R ₂ = H) Optical division was carried out in the same manner as in Example 1 except that 1.1 g was used. (R) -propoxycarbonyl-γ-butyrolactone conversion 95% (R) -α-hydroxy-γ-butyrolactone optical purity 99% ee

Example 9 Optical resolution was performed according to Example 1 except that the primary alcohol was changed from n-propanol to n-butanol. (R) -acetoxy-γ-butyrolactone conversion 87% (R) -α-hydroxy-γ-butyrolactone optical purity 100% ee

[Comparative Example 1] (R) form rich α-acetoxy-
γ-butyrolactone (in the general formula (1), R ₁ = CH ₃ ,
R ₂ = H, R ₃ = H) were hydrolyzed as follows. (R) form rich α-acetoxy-γ-butyrolactone (98% ee) 1.0
g, pH7.2, 1M phosphate buffer 15ml, Amano Pharmaceutical Lip
0.1 g of ase PS was mixed, and the mixture was stirred at 25 ° C. under an argon atmosphere for 28 hours. After removing the enzyme by suction filtration, the conversion to α-hydroxy-γ-butyrolactone and the optical purity of α-hydroxy-γ-butyrolactone were measured. 94% conversion of (R) -acetoxy-γ-butyrolactone Optical purity of (R) -hydroxy-γ-butyrolactone 16.5% ee

Comparative Example 2 α-acetoxy-β, β′-dimethyl-γ butyrolactone (in the general formula (1), R ₁ = CH
₃ , R ₂ = CH ₃ , R ₂ = CH ₃ ) was optically resolved using yeast-derived lipase as follows. α-acetoxy-
2.34 g of β, β′-dimethyl-γ butyrolactone, 45 ml of isopropyl ether, 4.4 g of n-butanol, and 3.0 g of yeast-derived lipase were mixed and mixed for 14 days. α-acetoxy-β, β′-dimethyl-γ butyrolactone conversion rate 34%,
α-hydroxy-β, β'-dimethyl-γ butyrolactone Optical purity 70% ee

Comparative Example 3 α-acetoxy-γ butyrolactone (In the general formula (1), R ₁ = CH ₃ , R ₂ = H, R ₂ =
CH ₃ ) was optically resolved using yeast-derived lipase as follows. α-acetoxy-γ-butyrolactone 1.
84 g, isopropyl ether 45 ml, n-propanol 3.6
g and yeast lipase 3.0 g were mixed and stirred for 7 days. After completion of the stirring, the reaction rate and the optical purity were measured using a gas chromatography method and a liquid chromatography method without purification. α-acetoxy-γ-butyrolactone conversion 25%, α-hydroxy-γ-butyrolactone optical purity 60% ee

[0036]

The effects of the present invention are listed below. (1) Since water is not actively added to the reaction system, the amount of water present in the reaction system is small. Therefore, the rate of the racemization of the target alcohol due to the unnecessary hydrolysis of the ester and the rate of the cleavage reaction of the lactone as a side reaction are negligibly small. (2) Since there is almost no free water in the system, it is easy to collect and reuse water-soluble enzymes. (3) Since the reaction can be performed at a relatively low temperature, no special equipment is required. (4) An optically pure enantiomer can be obtained by a one-step reaction. (5) Since a buffer solution or the like is not required, the salt strength is not a factor that determines the concentration of the reaction solution. Therefore, the substrate concentration can be increased irrespective of the biochemical reaction. For this reason, an extremely large capacity reaction vessel is not required for the substrate. Further, the efficiency of concentration of purification of the reaction product can be greatly increased. As described above, the present invention is a method for producing high-purity optically active α-hydroxylactones under simple operation and high yield, and the produced optically active compound is useful as a starting material for various useful compounds. is there.

Claims (1)

[Claims] (1) A primary alcohol is added to an α-hydroxylactone of a mixture of the (R) form and the (S) form represented by the general formula (1) in an arbitrary ratio in the presence of a lipase derived from Pseudomonas sp. And by transesterification, the general formula
(R) -form α-hydroxylactone represented by (2) and its enantiomer (S) represented by formula (3) represented by (S) form α-hydroxylactone esters A process for producing optically active α-hydroxylactones, characterized by the following. Embedded image (In the general formula (1), R ₁ represents a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, or an aryl group, and R ₂ and R ₃ represent a hydrogen atom or a methyl group.) (In the general formula (2), R ₁ represents a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, or an aryl group, and R ₂ and R ₃ represent a hydrogen atom or a methyl group.) (In the general formula (3), R ₁ represents a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, or an aryl group, and R ₂ and R ₃ represent a hydrogen atom or a methyl group.)