JPH04218384A - Production of optically active (-)-2-halo-1-(substituted phenyl)ethanol and (-)-substituted styrene oxide - Google Patents

Abstract

PURPOSE:To efficiently produce optically active (-1)-2-bromo-1-(3'-chlorophenyl) ethanol useful as a synthetic intermediate for medicines, agricultural chemicals, etc., and a (-)-substituted styrene oxide. CONSTITUTION:A fungus belonging to the genus Ashbya, Brettanomyces or other nine genuses is brought into contact with 2-bromo-1-(3'-chlorophenyl) ethanone and asymmetrically reduced to form (-1)-2-bromo-1-(3'-chlorophenyl) ethanol, which is isolated and purified. The prepared alcohol is subjected to ring closure under an alkali condition to give (-)-substituted styrene oxide.

Description

Detailed Description of the Invention [0001] [Industrial Application Field] The present invention relates to (-)-2-halo-1-
Regarding the production method of (substituted phenyl)ethanol and (-)-substituted styrene oxide, for more details, refer to 2-halo-
A method for efficiently producing (-)-2-halo-1-(substituted phenyl)ethanol by bringing a microorganism into contact with 1-(substituted phenyl)ethanone, and ring-closing the same under alkaline conditions to provide (-)- The present invention relates to a method for efficiently producing substituted styrene oxide. These compounds are useful as synthetic raw materials for drugs, agricultural chemicals, etc. that require optical activity. [0002] Regarding optically active (-)-2-halo-1-(substituted phenyl)ethanol, the present inventors have not found any patents, reports, etc. showing a method for producing the same. On the other hand, optically active chloro-substituted styrene oxide was obtained by epoxidation of chloro-substituted styrene with Nocaldea coralina to achieve an e.g. e. There is a report (Keizo Furuhashi: Organic Synthetic Chemistry, 43, 162 (1987)). There is also a method of synthesis by phase transfer reaction between chloro-substituted benzaldehyde and dimethylsulfonium methylide, but the optical purity is extremely poor (Hiroyuki Sawada: JP-A-51-105024). [0003] The present inventors have developed an efficient method for producing optically active (-)-2-halo-1-(substituted phenyl)ethanol and (-)-substituted styrene oxide. As a result of repeated studies for the development of 2-halo-1-(substituted phenyl)ethanone, we carried out stereospecific asymmetric reduction of (-)
The present invention was completed based on the discovery that a microorganism exists that has the ability to convert -2-halo-1-(substituted phenyl)ethanol. [Means for Solving the Problems] That is, the first aspect of the present invention is:
General formula [1] [0005] [Chemical formula 5] [0006] (wherein, Indicates the group.However, 3
Excludes cases where all substituents are hydrogen atoms. ) 2-halo-1-(substituted phenyl)ethanone represented by the general formula [2]
3 is the same as the general formula [1], * indicates an asymmetric carbon atom), which has the ability to asymmetrically reduce to (-)-2-halo-1-(substituted phenyl)ethanol, The microorganisms selected from the microorganisms belonging to the genera Brettanomyces, Candida, Cryptococcus, Geotrichum, Pichia, Rhodosporidium, Rhodotorula, Saccharomyces, Torulopsis, and Trigonopsis are brought into contact and produced. (-)-2-halo-1- characterized by collecting (-)-2-halo-1-(substituted phenyl)ethanol represented by general formula [2]
The second aspect of the present invention, which is a method for producing (substituted phenyl)ethanol, has the general formula [2] [Chemical 7]
3 is the same as general formula [1], * indicates an asymmetric carbon atom) (-)-2-halo-1-(substituted phenyl)ethanol is ring-closed under alkaline conditions to form general formula [3] 00
11] [0012] (-)-Substituted styrene oxide represented by (substituents R1, R2, R3 are the same as in general formulas [1] and [2], * indicates an asymmetric carbon atom) Each content is a method for producing (-)-substituted styrene oxide characterized by obtaining the following. The 2-halo-1-(substituted phenyl)ethanone used in the present invention is asymmetrically reduced to form (-)-2-halo-1-
Microorganisms that convert (substituted phenyl)ethanol can be found by the method described below. for example,
Glucose 40g, yeast extract 3g (NH4) 2H
PO4 13g, KH2PO47g, MgSO4 ・7
H2O 0.8g, ZnSO4 ・7H2O 60mg
, FeSO4 ・7H2O 90mg, CuSO4 ・
5H2O 5mg, MnSO4 ・4H2O 10mg
, 50 ml of A medium consisting of 0.1 g (per 1 liter) of NaCl was placed in a 500 ml Sakaguchi flask, and after sterilization, microorganisms were planted and cultured with shaking at 30° C. for 2 days. Thereafter, the bacterial cells were collected by centrifugation and 2-bromo-1-(3
25 ml of 0.1M phosphate buffer (pH 7.0) containing 0.5% of '-chlorophenyl)ethanone and 3% of glucose
and suspended in a 500 ml Sakaguchi flask for 2 to 3 days.
Shake at 0°C. After that, an equal amount of ethyl acetate is added and extracted, and the generated (-)-2-bromo-1-(3'-chlorophenyl)ethanol is extracted by gas chromatography (column: silicon OV-7, φ0.3 x 200 cm, column temperature Analyze at 190°C, N2 gas pressure 1.2kg/cm2). The optical purity of (-)-2-bromo-1-(3'-chlorophenyl)ethanol was determined by distillation and purification of the extracted oil, followed by high performance liquid chromatography (column: JASCO Corporation, Chiralcel-OJ, elution solvent: hexane-isopropanol). (50:1), flow rate 1.0ml/
min, detection 220 nm), the (-) body is 44.8
The (+) form is separated with a retention time of 54.9 minutes and the optical purity can be determined. Microorganisms that can be used in the present invention include 2-
Asymmetric reduction of halo-1-(substituted phenyl)ethanone (-
)-2-Halo-1-(substituted phenyl)ethanol can be converted to ethanol. For example, Ashbya gossippy
sypii) IFO 0560, Brettanomyces
Castelicianus (Brettanomyces cu)
stersianus) IFO 1585, Candida humicol
a) CBS 2774, Candida intermedia I
FO 0761, Candida Krusay (Cand
ida krusei) IFO 0011, Candida magnoliae (Candida magnoliae)
iae) IFO 0705, Candida pinus (
Candida pinus) IFO 0741, Candida saitoa
na) IFO 0768, Candida Salmon (C
andida sake) CBS 2219, Candida tropicalis (Candida tropicis)
calis) IFO 1403, Cryptococcus albidus
us) IFO 0378, Cryptococcus terreus I
FO 0727, Geotrichum hirtum
CBS 189, 53,
Geotrichum rouvieri (Geotrichum l)
Pichia farinosa (Pichia farinosa) IFO
0574, Pichia membranaefaciens (Pi
chia membranaefaciens) IF
O 0460, Rhodosporidium toruroides (
Rhodosporidium toruloides
) IFO 0871, Rhodotorula glutinis (R
hodotorula glutinis) IFO
1099, Rhodotorula glutinis
var. dairenensis) IFO 04
15. Rhodotoru graminis
la graminis) IFO 0190, Rhodotorula minuta (Rhodotorula minu
ta) IFO 0387, Road Torla Lubra (R
hodotorula rubra) IFO0383
, Saccharomyces cerevisiae
yces cerevisiae) IFO 0614
, Trigonopsis variabilis
sis variabilis) IFO 0671
etc. can be used. [0015] For culturing these microorganisms, any nutrient source that can be assimilated by these microorganisms can be used. For example, carbohydrates such as glucose and sucrose, alcohols such as ethanol and glycerol; hydrocarbons such as paraffin, organic acids such as acetic acid and propionic acid; carbon sources such as soybean oil or mixtures thereof, yeast extract, peptone, meat extract, Nitrogen-containing inorganic organic nutrients such as corn steep liquor, ammonium sulfate, and ammonia; phosphates, magnesium, iron,
A conventional medium containing an appropriate amount of inorganic nutrients such as manganese and potassium; and vitamins such as biotin and thiamine is used. The culture method is to adjust the pH of the nutrient medium to 4.0 to 9.5.
Cultivate aerobically at a temperature of 20 to 40°C for 1 to 5 days. [0016] Reduction methods include using the culture solution as it is, separating the bacterial cells by centrifugation, etc., resuspending them in phosphate buffer or water, etc., and adding 2-halo-1.
-(Substituted phenyl)ethanone is added and reacted, etc. During this reaction, a carbon source such as glucose or sucrose may be added as an energy source. Furthermore, the bacterial cells may be kept as viable cells, or may be treated with acetone, freeze-drying, or the like. Moreover, these microbial cells can also be immobilized on a carrier and used. 2-Hello-
1-(Substituted phenyl)ethanone may be added as is, dissolved in an organic solvent and added all at once from the beginning of the reaction, or added in portions so as not to affect the reaction. The reaction is carried out at a temperature of 10 to 60°C at a pH of 5 to 9.
Carry out under stirring for 0 hours. (-)-2-halo- produced by the reaction
1-(Substituted phenyl)ethanol can be collected directly from the reaction solution, or after bacterial cell isolation, extraction with a solvent such as ethyl acetate or dichloromethane, dehydration, and purification by distillation or silica gel chromatography. −)
-2-halo-1-(substituted phenyl)ethanol is easily obtained. Furthermore, the optical purity is determined by column, Chiral
It can be measured in the same manner as above by high performance liquid chromatography using cel-OJ and an elution solvent of hexane/isopropanol (30 to 50/1). The (-)-2-halo-1-(substituted phenyl)ethanol obtained as described above can be easily ring-closed by heating it or leaving it at room temperature in the coexistence of an alkali such as NaOH in equal moles or more. , (−)-substituted styrene oxide. [Examples] The present invention will be explained in more detail based on Examples below, but the present invention is not limited to these examples. In the following description, "%" means "% by weight" unless otherwise specified. Example 1 After sterilizing 50 ml of the above medium A in a 500 ml Sakaguchi flask, each microorganism shown in Table 1 was inoculated. Then, aerobic shaking culture was performed at 30°C for 2 days. Bacterial cells were collected from this culture solution by centrifugation, and 2-bromo-1
-(3'-chlorophenyl)ethanone 0.5% to 0.3
0.1M phosphate buffer containing % glucose (pH 7.0)
The suspension was suspended in 25 ml, placed in a 500 ml Sakaguchi flask, and reacted with shaking at 30° C. for 48 hours. After the reaction, (-)-2-bromo-1-(3'-
Chlorophenyl) ethanol was extracted twice, and the ethyl acetate layer was analyzed by gas chromatography to determine the reaction rate. Next, after dehydrating the ethyl acetate with anhydrous sodium sulfate, the solvent was removed.
(-)-2-bromo-1-(3'-chlorophenyl)ethanol was obtained. This was dissolved in methylene chloride and the optical purity was measured by high performance liquid chromatography. The results are shown in Table 1. [Table 1] Example 2 A 5 liter mini-jar fermenter containing 3 liters of medium A was inoculated with Rhodotorula glutinis bar dyrenensis IFO 0415 and incubated at 30° C. with 1 aeration.
The cells were cultured for 24 hours at a stirring speed of 500 rpm. After culturing, the bacterial cells were collected by centrifugation, suspended in 750 ml of water, 7.5 g of 2-bromo-1-(3'-chlorophenyl)ethanone and 38 g of glucose were added, and the pH was maintained at 7.0 with NaOH. while stirring at 30℃ and 150 rpm.
The reaction was carried out for 24 hours at m. After the reaction was completed, the mixture was extracted twice with 750 mm of ethyl acetate. After dehydrating the ethyl acetate layer with anhydrous sodium sulfate, the solvent was removed under reduced pressure to obtain 5.2 g of an oily substance. This was distilled (130° C./3 mmHg) to obtain 3.9 g of (-)-2-bromo-1-(3'-chlorophenyl)ethanol as a colorless oil. Its specific optical rotation is [α] (
20,D)-25.5°(c=1.02CH3OH)
According to high performance liquid chromatography analysis, the optical purity is 100% e. e. Met. H-NMR (90MH
z, CDCl3) δppm 2.88 (br. S
, 1H), 3.35 - 3.90 (m, 4H),
4.90 (d.d, J=315, 8Hz, 1
H) 6.98-7.51 (m, 4H) 0023
Example 3 Using the microorganisms shown in Table 2, 2-bromo-1-
The culture reaction and analysis were carried out in the same manner as in Example 1 except that 2-bromo-1-(2'-chlorophenyl)ethanone was used instead of (3'-chlorophenyl)ethanone.
)-2-bromo-1-(2'-chlorophenyl)ethanol was obtained. The results are shown in Table 2. [0024] [Table 2] [0025] Example 4 Loading the microorganism Torula glutinis IFO 1099
The culture reaction and analysis were carried out in the same manner as in Example 2, except that 2-bromo-1-(2'-chlorophenyl)ethanone was used as the substrate, and (-)-2-bromo-1-(
4.2 g of 2'-chlorophenyl)ethanol was obtained. Specific optical rotation [α] (20, D) -41.5° (C = 1.02
, CH3OH), optical purity 100% e.g. according to high performance liquid chromatography analysis. e. Met. H-NMR (
90MHz, CDCl3) δppm 2.78~3
．． 06 (m, 1H), 3.39 (d.d, J=9
, 10Hz, 1H), 3.73(d.d, J=2
．． 5, 10Hz, 1H), 5.04 ~ 5.39
(m, 1H), 6.68 ~ 7.68 (m, 4H
) Example 5 Using the microorganisms shown in Table 3, 2-bromo-1-
The culture reaction and analysis were carried out in the same manner as in Example 1 except that 2-bromo-1-(4'-chlorophenyl)ethanone was used instead of (3'-chlorophenyl)ethanone.
)-2-bromo-1-(4'-chlorophenyl)ethanol was obtained. Table 3 shows the results. [Table 3] Example 6 2-bromo-1-(3'-chlorophenyl) as substrate
The culture reaction and analysis were carried out in the same manner as in Example 2 except that 2-bromo-1-(4'-chlorophenyl)ethanone was used instead of ethanone.
'-chlorophenyl) ethanol (3.6 g) was obtained. Boiling point 115-120℃/4mmHg, specific optical rotation [α] (
20,D) -26.6℃ (c=1.10, CH3OH)
, the result of optical purity analysis by high performance liquid chromatography was 100% e. e. Met. H-NMR (90MHz
, CDCl3) δppm 2.77 (br, S,
1H), 3.18 - 3.70 (m, 2H),
4.82 (d.d, J=3.5, 7.5Hz, 1
H), 6.82-7.44 (m, 4H) 002
9] Example 7 2-bromo-1-(3'-chlorophenyl) as a substrate
2-chloro-1-(2'-chlorophenyl)ethanone, 2-chloro-1-(3'-chlorophenyl)ethanone, and 2-chloro-1-(4'-chlorophenyl)ethane were used instead of ethanone in 3. The culture reaction and analysis were carried out in the same manner as in Example 2, except that 25 g each was used, and the corresponding (-)-2-chloro-1-(2'-chlorophenyl)ethanol and (-)-2-chloro-1 -(3'-chlorophenyl)ethanol and (-)-2-chloro-1-
(4'-chlorophenyl)ethanol was obtained. The yield and physical property values of each are shown in Table 4. [Table 4] Example 8 (-)-2-halo-1- obtained in Examples 2, 4, 6 and 7
(chlorosubstituted phenyl)ethanol 10g each 40%
The mixture was mixed with 5 ml of NaOH aqueous solution and 10 ml of methylene chloride, and reacted at 50° C. for 6 hours. After cooling, methylene chloride 20m
After washing the methylene chloride layer with saturated brine and dehydrating and filtrating the methylene chloride layer, the methylene chloride was removed under reduced pressure to obtain a crude epoxide oil. This was purified by vacuum distillation and Table 5
Each (-)-chloro-substituted styrene oxide shown below was obtained. [Table 5] Example 9 500 ml of the above medium A was placed in a 2-liter Sakaguchi flask, and Rhodotorula glutinis bar dyrenensis IFO 0415 was inoculated and cultured in the same manner as in Example 1. The body was collected, and 1.5 g of 2-chloro-1-(4'-fluorophenyl)ethanone was added to 0.5 g of 2-chloro-1-(4'-fluorophenyl)ethanone containing 0.3% glucose.
Suspend in 300 ml of 1M phosphate buffer (pH 7.0),
The mixture was placed in a 2-liter Sakaguchi flask and reacted with shaking at 30° C. for 48 hours. After the reaction was completed, the mixture was extracted twice with 300 ml of ethyl acetate. After dehydrating the ethyl acetate layer with anhydrous sodium sulfate, the solvent was removed under reduced pressure to obtain an oily substance. This is distilled (105℃/
(4 mmHg) and (-)-2-chloro- as a colorless oil.
1.3 g of 1-(4'-fluorophenyl)ethanol was obtained. Its specific optical rotation is [α](20,D)-38.81°
(c=1.01CH3OH), and according to high performance liquid chromatography analysis, the optical purity was 100% e. e. Met. Next, this (-)-2-chloro-1-(4'-
(fluorophenyl) 1 g of ethanol equivalent to an equimolar amount of NaO
Mix 40% H aqueous solution with 5 ml of methylene chloride and heat at 50°C.
It reacted for 6 hours. After cooling, 5 ml of methylene chloride was added, and the methylene chloride layer was washed with saturated brine, dehydrated and filtered, and the methylene chloride was removed as a solvent under reduced pressure to obtain a crude epoxide oil. This was purified by vacuum distillation (85°C, 4 mmHg) to obtain 0.65 g of (-)-4'-fluorostyrene oxide in the form of a colorless oil. Its specific optical rotation is [α]
(20,D)-20.96°(c=1.04CHCl3
)Met. (-)-2-chloro-1-(4'-fluorophenyl)ethanol H-NMR (90MHz, CDCl3) δppm
3.00 (S, 1H), 3.40 ~ 3.83 (m
, 2H), 4.85 (d.d, J=4.5, 7
．． 5Hz, 1H) 6.83~7.53 (m, 4
H) (-)-4'-fluorostyrene oxide H-NMR (
90MHz, CDCl3) δppm 2.72(d
．． d, J=2.5, 6.0Hz, 1H), 3.
08 (d.d, J=4.5, 6.0Hz, 1H)
, 3.82 (d.d, J=2.5, 4.0Hz,
1H), 6.85 ~ 7.45 (m, 4H) [
Example 10 The substrates were 2-chloro-1-(2',4'-dichlorophenyl)ethanone, 2-chloro-1-(3',4'-dichlorophenyl)ethanone, 2-chloro-1-(2',5'
Example 9 except that -dichlorophenyl)ethanone was used.
Cultured, reacted and purified in the same manner as (-)-2-chloro-1
-(2',4'-dichlorophenyl)ethanol, (-
)-2-chloro-1-(3,4'-dichlorophenyl)
Ethanol, (-)-2-chloro-1-(2',5'-
Dichlorophenyl)ethanol was obtained. The yield, specific rotation, and optical purity as determined by high performance liquid chromatography analysis are shown in Table 6. Next, epoxidize in the same manner as in Example 9,
(-)-2',4'-dichlorostyrene oxide, (
-)-3',4'-dichlorostyrene oxide, (-
)-2',5'-dichlorostyrene oxide was obtained. The yield and specific rotation are shown in Table 6. [Table 6] Example 11 Culture and reaction were carried out in the same manner as in Example 9 except that 2-chloro-1-(2',3',4'-trichlorophenyl)ethanone was used as the substrate. After the reaction was completed, the mixture was extracted twice with 300 ml of ethyl acetate. After dehydrating the ethyl acetate layer with anhydrous sodium sulfate, the solvent was removed under reduced pressure to obtain an oily substance. This was purified by silica gel chromatography (hexane-ethyl acetate 7:1) to give a colorless oil (-)-2-chloro-1-(2',3
1.1 g of ethanol (',4'-trichlorophenyl) was obtained. Its specific optical rotation is [α](20,D)-52.29
° (c=1.07CH3OH), and the optical purity was 100% e.g. according to high performance liquid chromatography analysis. e.
Met. (-)-2'-chloro-1-(2',3',4'-trichlorophenyl)ethanol H-NMR (90MHz, CDCl3) δppm
3.10 (br, S, 1H), 3.50 (d.d
, J=9.0, 11.0Hz, 1H) 3.85
(d.d, J=3.0, 11.0Hz, 1H)
5.25 (d.d, J=3.0, 8.5Hz, 1
H) 7.35 to 7.59 (m, 2H) 003
7] Example 12 The substrates were 2-chloro-1-(2'-methylphenyl)ethanone, 2-chloro-1-(3'-methylphenyl)ethanone, and 2-chloro-1-(4'-methylphenyl). Cultivation, reaction, and purification were carried out in the same manner as in Example 9 except that ethanone was used. '-methylphenyl)ethanol, (-)-2-chloro-1-(
4'-methylphenyl)ethanol was obtained. The yield, specific rotation, and optical purity as determined by high performance liquid chromatography analysis are shown in Table 7. Next, epoxidation was carried out in the same manner as in Example 9 to produce (-)-2'-methylstyrene oxide, (-)-
3'-methylstyrene oxide and (-)-4'-methylstyrene oxide were obtained. Table 7 shows the yield and specific rotation.
It was shown to. [Table 7] Example 13 The substrates were 2-chloro-1-(2',4'-dimethylphenyl)ethanone and 2-chloro-1-(3',4'-dimethylphenyl)ethanone. Culture, reaction, and purification were carried out in the same manner as in Example 9 except that (-)-2-chloro-1-(2'
,4'-dimethylphenyl)ethanol, (-)-2-
Chloro-1-(3',4'-dimethylphenyl)ethanol was obtained. The yield, specific rotation, and optical purity as determined by high performance liquid chromatography analysis are shown in Table 8. Next, epoxidation was carried out in the same manner as in Example 9 to obtain (-)-2',4'-dimethylstyrene oxide and (-)-3',4'-dimethylstyrene oxide. The yield and specific rotation are shown in Table 8. [Table 8] Example 14 The substrates were 2-chloro-1-(2'-methoxyphenyl)ethanone and 2-chloro-1-(3'-methoxyphenyl).
Ethanone, 2-chloro-1-(4'-methoxyphenyl)ethanone was cultured, reacted, and purified in the same manner as in Example 9, and (-)-2-chloro-1-(2'-methoxyphenyl) ) ethanol, (-)-2-chloro-1-(3
'-methoxyphenyl)ethanol and (-)-2'-chloro-1-(4'-methoxyphenyl)ethanol were obtained. The yield, specific rotation, and optical purity as determined by high performance liquid chromatography analysis are shown in Table 9. Next, epoxidation was performed in the same manner as in Example 9 to form (-)-2'-methoxystyrene oxide, (-)-3'-methoxystyrene oxide,
(-)-4'-methoxystyrene oxide was obtained. The yield and specific rotation are shown in Table 9. [Table 9] Example 15 The substrates were 2-chloro-1-(2',5'-dimethoxyphenyl)ethanone and 2-chloro-1-(3',4'-dimethoxyphenyl)ethanone. Culture, reaction, and purification were carried out in the same manner as in Example 9 except that (-)-2-chloro-1-(
2',5'-dimethoxyphenyl)ethanol, (-)
-2-chloro-1-(3',4'-dimethoxyphenyl)ethanol was obtained. The yield, specific rotation, and optical purity as determined by high performance liquid chromatography analysis are shown in Table 10. Next, (-)-2-chloro-1-(2',5'-dimethoxyphenyl)ethanol was epoxidized in the same manner as in Example 9 to obtain (-)-2',5'-dimethoxystyrene oxide. The yield and specific rotation are shown in Table 10. [Table 10] Example 16 The substrates were 2-chloro-1-(2',3',4'-trimethoxyphenyl)ethanone, 2'-chloro-1-(3',
Culture and reaction were carried out in the same manner as in Example 9 except that 4',5'-trimethoxyphenyl)ethanone was used.
Extracted twice with 00 ml of ethyl acetate. After dehydrating the ethyl acetate layer with anhydrous sodium sulfate, the solvent was removed under reduced pressure, and the resulting oily substance was purified by silica gel chromatography (hexane-ethyl acetate 7:1) to obtain (-)-2-chloro-1-(2 ′、
3',4'-trimethoxyphenyl)ethanol, (-
)-2-chloro-1-(3',4',5'-trimethoxyphenyl)ethanol was obtained. The yield and specific rotation are shown in Table 11. [Table 11] [Effects of the Invention] According to the present invention, as shown in Examples, optically active (-)-2-halo-1-(substituted phenyl)ethanol and (-)-substituted Styrene oxide can be efficiently produced.

Claims (3)

[Claims] Claim 1 General formula [1] [Formula 1] (wherein, X represents a chlorine atom or a bromine atom, and the substituent R1
, R2 and R3 represent a hydrogen atom, a chlorine atom, a fluorine atom, a methyl group, or a methoxy group. However, cases in which all three substituents are hydrogen atoms are excluded. ) 2-halo-1-(substituted phenyl)ethanone represented by the general formula [2] [Chemical formula 2] (wherein, asymmetric carbon atom) having the ability to asymmetrically reduce to (-)-2-halo-1-(substituted phenyl)ethanol,
The microorganisms selected from the microorganisms belonging to the genera Brettanomyces, Candida, Cryptococcus, Geotrichum, Pichia, Rhodosporidium, Rhodotorula, Saccharomyces, Torulopsis, and Trigonopsis are brought into contact and produced. (-)-2-halo-1 characterized by collecting (-)-2-halo-1-(substituted phenyl)ethanol represented by general formula [2]
- A method for producing (substituted phenyl)ethanol. [Claim 2] The microorganism is Asibia gossippii, Brettanomyces casterisianus, Candida humicola, Candida intermedia, Candida krusei, Candida magnoliae, Candida pinus, Candida cytoana, Candida salmon, Candida tropicalis, Cryptococcus albidus, Cryptococcus terreus, Geotrichum hirtum, Geotrichum rowvieri, Pichia farinosa, Pichia membranaefaciens, Rhodosporidium toruroides, Rhodotorula glutinis, Rhodotorula - Glutinis bar dyrenensis, Rhodotorula graminis, Rhodotorula minuta, Rhodotorula rubra, Saccharomyces.
2. The method according to claim 1, which is Trigonopsis variabilis. Claim 3: General formula [2] [Chemical formula 3] (wherein, X and substituents R1, R2, R3 are the same as in general formula [1], * indicates an asymmetric carbon atom) (- )-2-halo-1-(substituted phenyl)ethanol is ring-closed under alkaline conditions to form the general formula [3] [Chemical formula 4] (The substituents R1, R2, and R3 are of the general formula [1], [
A method for producing (-)-substituted styrene oxide, which is the same as 2], wherein * indicates an asymmetric carbon atom).