JPH07233109A - Optically active alcohol derivative and its production - Google Patents

Abstract

PURPOSE:To obtain an optically active alcohol derivative useful as an intermediate for agrochemicals, pharmaceuticals or organic electronic materials (especially ferroelectric liquid crystals). CONSTITUTION:This optically active compound is expressed by formula I [R1 is a 1-20C saturated or unsaturated alkyl, a 2-20C saturated or unsaturated alkoxyalkyl, H or an OH-protecting group; R is H or COR2 (R2 is a lower alkyl); (m) and (q) each is 0 or 1; (n) is 0-8; A1 to A3 each is group of formula II to formula VI, etc.; q=0 when A1 or A2 is a condensed ring and q=1 when A1 and A2 each is a monocyclic group; atom marked with * is asymmetric C atom], e.g. (-)-2-(4'-hydroxy-1-heptynyl)-4-biphenyl)-5-octyloxypyrimidine. The compound can be produced by the asymmetric hydrolysis of an ester derivative of formula VII using an esterase capable of preferentially hydrolyzing either one of the optical isomers of the compound. The compound of formula VII can be produced by the reaction of a halogenated compound of formula VIII with an acetylene derivative of formula IX.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an optically active alcohol derivative useful as an intermediate for agricultural chemicals, pharmaceuticals, organic electronic (particularly, ferroelectric liquid crystal) materials, and a method for producing the same.

[0002]

2. Description of the Related Art Conventionally, various compounds have been developed as liquid crystal materials, but very few compounds have excellent characteristics such as fast response and become ferroelectric liquid crystal materials in a low temperature region. Development of the body is not yet sufficient, and it has been desired to develop the intermediate and its industrially advantageous production method.

[0003]

The present invention particularly provides a novel optically active alcohol derivative useful as an intermediate of a ferroelectric liquid crystal material which becomes a ferroelectric liquid crystal in a low temperature region and is excellent in the above properties, and its derivative. It provides a manufacturing method. Here, the above-mentioned ferroelectric liquid crystal material can be synthesized by the following steps.

[0004]

Incidentally, it is described in JP-A-4-178369 that an analogue of the compound represented by the general formula (8) is produced by the following method.

However, in such a Heck reaction, it has been clarified that positional isomers may be mixed in the reaction with an olefin, which requires purification and is not necessarily advantageous as a raw material. It was hard to say that it was always satisfactory in terms of industrial implementation.

[0007]

Based on the above, the present inventors have made various studies on new production methods of the compound represented by the general formula (8), and as a result, there is no possibility of inclusion of isomers. Moreover, they have found a new production method via a new intermediate. That is, the present invention has the general formula (1) (In the formula, R1 represents a saturated or unsaturated alkyl group having 1 to 20 carbon atoms, a saturated or unsaturated alkoxyalkyl group having 2 to 20 carbon atoms, a hydrogen atom or a hydroxyl-protecting group, and R represents hydrogen. An atom or a group COR ² , R ² represents a lower alkyl group, m and q represent 0 or 1, and
n represents an integer of 0 to 8, and A1, A2 and A3 are respectively And when A1 or A2 is a condensed ring, q is 0.
And when A1 and A2 are monocyclic, q is 1 and the * mark indicates an asymmetric carbon atom. ), An optically active alcohol derivative and a method for producing the same. Further, a general formula (8) using an alcohol derivative (Wherein R1, m, n, q, A1, A2, A3 and R
Represents the same meaning as described above. The present invention provides an optically active saturated alcohol and a method for producing the same.

The present invention will be described in detail below. The optically active alcohol derivative (1) has the general formula (2): (Wherein R1, m, n, q, A1, A2, A3 and R
2 has the same meaning as above. A) It is possible to produce by optically asymmetrically hydrolyzing either one of the optically active isomers of the ester derivative represented by the formula (1). The esterase in the present invention means an esterase in a broad sense including lipase.

The esterase-producing microorganism used in this reaction is not particularly limited as long as it is an esterase-producing microorganism having an ability to asymmetrically hydrolyze esters. Specific examples of such microorganisms include, for example, Enterobacter, Arthrobacter, Brevibacterium, Pseudomonas, Alcaligenes, Micrococcus, Chromobacterium, Microbacterium, Corynebacterium, Bacillus, Lactobacillus, Trichoderma, Candida, Saccharomyces, Rhodotorula, Cryptococcus, Torulopsis, Pichia,
Examples include microorganisms belonging to the genus Penicillium, Aspergillus, Rhizopus, Mucor, Aureobasidium, Actinomucor, Nocardia, Streptomyces, Hansenula and Achromobacter.

Cultivation of the above-mentioned microorganism is usually carried out according to a conventional method, and a liquid culture can be obtained by carrying out liquid culture. For example, a sterilized liquid medium [for molds and yeasts, a malt extract / yeast extract medium (5 g of heptone, 10 g of glucose, 3 g of malt extract, 3 g of yeast extract are dissolved in 1 L of water to obtain pH 6.5), For bacteria, sweetened broth medium (1 L of water, 10 g of glucose, 5 peptones)
g, 5 g of meat extract and 3 g of NaCl are dissolved to adjust the pH to 7.2. )] Is inoculated with a microorganism, and is usually 1 to 3 at 20 to 40 ° C.
The culture may be performed by reciprocal shaking culture for a day, and if necessary, solid culture may be performed. Some of these esterases originating from microorganisms are commercially available and can be easily obtained. Specific examples of commercially available esterases include the followings. Pseudomonas lipase [lipase P (manufactured by Amano Pharmaceuticals)], Aspergillus lipase [lipase AP
(Manufactured by Amano Pharmaceutical Co., Ltd.)], lipase of the genus Mucor [Lipase M
-AP (manufactured by Amano Pharmaceuticals)], lipase of Candida cylindrasse [lipase MY (manufactured by Meito Sangyo)], lipase of the genus Alcaligenes [lipase PL (manufactured by Meito Sangyo)], lipase of the genus Achromobacter [lipase AL]
(Manufactured by Meito Sangyo Co., Ltd.)], lipase of Arthrobacter genus [lipase joint BSL (purified joint liquor)], lipase of Chromobacterium genus (manufactured by Toyo Brewing Co.), lipase of Rhizopus dermer [talipase (manufactured by Tanabe Seiyaku)] , Rhizopus lipase [Lipase Saiken (Osaka Institute for Bacteria)].

Animal / plant esterases can also be used, and specific esterases thereof include the following. Steabsin, pancreatin, pig liver esterase, Wheat Germ esterase. As the esterase used in this reaction, an enzyme obtained from animals, plants, or microorganisms is used. It can be used as needed in various forms such as liquids and processed products thereof,
It is also possible to use a combination of enzymes and microorganisms. Alternatively, it can also be used as an immobilized enzyme or immobilized bacterium immobilized on a resin or the like. The asymmetric hydrolysis reaction is usually carried out by vigorously stirring a mixture of the starting ester derivative (2) and the enzyme or microorganism in a buffer solution. As the buffer solution, a commonly used buffer solution of an inorganic acid salt such as sodium phosphate and potassium phosphate, a buffer solution of an organic acid salt such as sodium acetate and sodium citrate, and the like are used. The pH of the culture broth or the alkaline esterase is preferably 8 to 11, and the pH of the culture broth of a non-alkalophilic microorganism or the esterase having no alkali tolerance is preferably 5 to 8. Concentration is usually 0.05-2
M, preferably in the range of 0.05-0.5M. The reaction temperature is usually 10 to 60 ° C., and the reaction time is generally 10 to 10.
70 hours, but is not limited to these. When a lipase belonging to the genus Pseudomonas or the genus Arthrobacter is used as the lipase in this asymmetric hydrolysis reaction, the optically active alcohol derivative (1) can be obtained with a relatively high optical purity. In addition, in the case of this asymmetric hydrolysis reaction, an organic solvent inert to the reaction such as toluene, chloroform, methyl isobutyl ketone, and dichloromethane may be used in addition to the buffer solution. The decomposition can be carried out advantageously.

By the asymmetric hydrolysis reaction, only one of the optically active isomers of the ester derivative (2) as a raw material is preferentially hydrolyzed to give an optically active alcohol derivative represented by the general formula (1). On the other hand, the optically active ester derivative, which is the other optically active substance in the ester derivative (2) as the raw material, remains as a hydrolysis residue. After completion of such a hydrolysis reaction, the hydrolysis reaction solution is subjected to extraction treatment with a solvent such as methyl isobutyl ketone, ethyl acetate, ethyl ether, etc., the solvent is distilled off from the organic layer, and the concentrated residue is treated with column chromatography. Etc., an optically active alcohol derivative (1) which is a hydrolysis product and an optically active ester derivative which is a hydrolysis residue [of the optically active substance in the starting ester derivative (2) which is not hydrolyzed. ] Can be separated. The optically active ester derivative obtained here may be further hydrolyzed, if necessary, to obtain an optically active alcohol derivative (1) which is an antipode to the previously obtained optically active alcohols.

Ester derivative (2) as a raw material compound
Is the general formula (6) (Wherein R1, m, n, q, A1, A2 and A3 have the same meanings as described above), and an alcohol derivative represented by the general formula (7) R2 COOH (7) (wherein R2 is It has the same meaning as the above) and can be produced by reacting it with a carboxylic acid or a derivative thereof. In such an acylation reaction,
As the lower alkyl carboxylic acid (ie, the carboxylic acid (7) or its derivative) as the acylating agent, an acid anhydride or acid halide of a lower alkyl carboxylic acid is usually used. Examples thereof include chloride or bromide, propionic acid chloride or bromide, butyryl chloride or bromide, valeroyl chloride or bromide, and the like. Esterification conditions are usually applied to the reaction between the alcohol derivative (6) and the lower alkylcarboxylic acid,
It is carried out by reacting with a catalyst in the presence or absence of a solvent. When a solvent is used in this reaction, the solvent is, for example, tetrahydrofuran,
Aliphatic or aromatic hydrocarbons such as ethyl ether, acetone, methyl ethyl ketone, toluene, benzene, chlorobenzene, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, dimethylformamide, hexane, ethers, ketones, halogenated hydrocarbons, aprotic Solvents such as polar solvents which are inert to the reaction may be used alone or as a mixture. The amount used can be used without particular limitation.

The lower alkylcarboxylic acid used in the above reaction is required to be 1 equivalent or more with respect to the alcohol derivative (6) as a raw material, and the upper limit is not particularly limited.
It is preferably 4 equivalents. Examples of the catalyst used in the above reaction include dimethylaminopyridine, triethylamine, tri-n-butylamine, pyridine, picoline, imidazole, sodium carbonate, sodium methylate,
Examples include organic or inorganic basic substances such as potassium hydrogen carbonate. The amount used is not particularly limited, but is usually 1 to 5 equivalents relative to the alcohol derivative (6). When an organic amine is used as the solvent, the amine may act as a catalyst. Also, toluene sulfonic acid,
Acids such as methanesulfonic acid and sulfuric acid can also be used as a catalyst. The amount of catalyst used varies depending on the type of lower alkyl carboxylic acid and the combination of catalysts used,
Although not necessarily specified, when an acid halide is used as the lower alkylcarboxylic acid, for example, 1 equivalent or more is used with respect to the acid halide. The reaction temperature is usually -30 to 100 ° C, preferably -20 to 90 ° C.
Is. The reaction time is not particularly limited, and the time point at which the starting alcohol derivative (6) disappears can be used as the end point of the reaction. After completion of the reaction, usual separation means such as extraction,
The ester derivative (2) can be obtained in good yield by operations such as liquid separation, concentration, and recrystallization, and this can be purified by column chromatography or the like if necessary, but the reaction mixture is used as it is for the next step. It can also be used.

Further, the ester derivative (2) has the general formula (3) R 1-(O) m-A 1 -A 2-(A 3) q -X (3) (wherein R 1, m, q, A 1, A2 and A3 have the same meanings as described above, and X is a halogen atom or --OSO.
2 R'is shown. However, R ′ represents a lower alkyl group which may be substituted with a fluorine atom, or a phenyl group which may be substituted. ) And a general formula (4) It can also be obtained by reacting an acetylene represented by the formula (wherein R 2 and n have the same meanings as described above) in the presence of a palladium catalyst and a basic substance. still,
The raw material compounds represented by the general formulas (3) and (4) may be commercially available products or can be produced from the commercially available products according to known methods. In the above reaction, the amount of the acetylenes (4) used is usually the amount of the halide (3) used.
It is 0.9 to 10 times equivalent, preferably 1 to 2 times equivalent. As the metal catalyst, palladium-based catalysts such as palladium chloride, palladium acetate, triphenylphosphine palladium complex and palladium / carbon are used, and nickel- and rhodium-based catalysts similar to the above palladium-based catalysts are also used. The amount of these metal catalysts used is in the range of 0.001 to 0.1 times the equivalent of the raw material halide (3). In this reaction, in addition to the above metal catalyst, a trivalent phosphorus compound or a trivalent arsenic compound is required as a cocatalyst, and these compounds are represented by the general formula (11) R4- (R5-)-Y-R6 ( 11) (In the formula, Y represents a phosphorus atom or an arsenic atom, and R4, R
5 and R6 are the same or different and each represents an alkyl group, an aryl group, an alkoxy group, an aryloxy group or a halogen atom. ), Specifically exemplified are tri-n-butylphosphine, triphenylphosphine, tri-o-tolylphosphine, tri-o-tolylphosphite, phosphorus trichloride, triphenylarsenic and the like. It The amount of the phosphorus compound or arsenic compound used is 0.5 to 50 times equivalent, preferably 10 to 30 times equivalent to the above metal catalyst. Further, in addition to these catalysts, copper catalysts are used, and as such copper catalysts, copper iodide, copper bromide, copper chloride, copper oxide, copper cyanide, etc. are used. It is in the range of 0.001 to 0.1 times the equivalent of (3). Of course, it is possible to use more than that, but there is no merit of using a large amount.

Examples of the basic substance include alkali metal carbonates, carboxylates, alkoxides, hydroxides and organic bases, and tertiary amines or secondary amines (organic bases) are preferably used. Examples thereof include diethylamine, triethylamine, di-isopropylethylamine, tri-n-butylamine, tetramethylethylenediamine, dimethylaniline and the like. The amount of the base used is usually 1 to 3 with respect to the halide (3).
It is 5 times equivalent. If necessary, a suitable solvent such as acetonitrile, tetrahydrofuran, dimethylformamide, hexamethylphosphorylamide, N-methylpyrrolidone, methanol or the like can be used as a reaction solvent.

The amount of these reaction solvents used is not particularly limited. The above reaction is usually carried out in an inert gas such as nitrogen or argon. In the reaction, the yield of the target ester derivative can be improved by increasing the reaction temperature, but since the by-product increases at too high temperature, the reaction temperature is usually 15 to 160 ° C., preferably It is 30-140 degreeC. After completion of the reaction, the ester derivative (2) can be obtained by usual means such as extraction, distillation, recrystallization and the like. In order to obtain the optically active alcohol derivative (1) in the next step, the ester derivative (2) is not always required.
Is not required to be isolated, and the reaction mixture may be directly used in the next step.

The alcohol derivative (6) is a compound of the general formula (5) with the halide (3). (In the formula, n has the same meaning as described above.) And is obtained by reacting with an acetylene compound. This reaction can be carried out in the same manner as the reaction for reacting the halide (3) with the acetylenes (4) to obtain the ester derivative (2). That is, the same palladium catalyst, basic substance, and other catalysts used in the reaction can be used, and the reaction solvent, reaction temperature, and other reaction conditions are also applied. From the reaction mixture thus obtained, the alcohol derivative (6) can be obtained in good yield by operations such as liquid separation, concentration, distillation and crystallization, but the ester derivative (2) in the next step is obtained. In order to obtain it, it is not always necessary to isolate the alcohol derivative (6), and the reaction mixture may be directly used in the next step.

The compounds represented by the general formula (1) obtained through the above steps are exemplified below. 4 "-alkyl-4
-(6-Hydroxy-1-heptinyl) -p-terphenyl, 4 "-alkyl-4- (6-acyloxy-1
-Heptinyl) -p-terphenyl, 4 "-alkyloxy-4- (6-hydroxy-1-heptinyl) -p-terphenyl, 4" -alkyloxy-4- (6-acyloxy-1-heptinyl) -p-terphenyl, 4 "-hydroxy-4- (6-hydroxy-1-heptynyl) ) -P-terphenyl, 4 ″ -hydroxy-4- (6-acyloxy-1-heptinyl) -p-terphenyl, 4 ″ -hydroxy-4- (6-hydroxy-1-heptinyl) -p-terphenyl, 4 ″ -hydroxy-4- (6-acyloxy-1-heptinyl)
-P-terphenyl, 5-alkyl-2- {4 '-(6
-Hydroxy-1-heptynyl) -biphenyl-4-yl} -pyridine, 5-alkyl-2- {4 '-(6-acyloxy-1-heptinyl) -biphenyl-4-yl} -pyridine, 5-alkyloxy-2- {4'-(6-hydroxy-1-heptenyl) -biphenyl-4
-Yl} -pyridine, 5-alkyloxy-2- {4 '
-(6-Acyloxy-1-heptenyl) -biphenyl-4-yl} -pyridine, 5-hydroxy-2- {4 '
-(6-Hydroxy-1-heptinyl) -biphenyl-4-yl} -pyridine, 5-hydroxy-2- {4 '
-(6-Acyloxy-1-heptinyl) -biphenyl-4-yl} -pyridine, 5-hydroxy-2- {4 '
-(6-Hydroxy-1-heptenyl) -biphenyl-4-yl} -pyridine, 5-hydroxy-2- {4 '-(6-acyloxy-1-heptenyl) -biphenyl-4-yl} -pyridine, 2- (4'-alkyl-biphenyl-4-yl) -5- ( 6-Hydroxy-1-heptynyl) -pyridine, 2- (4′-alkyl-biphenyl-4-yl) -5- (6-acyloxy-1-heptinyl) -pyridine, 2- (4′-alkyloxy-biphenyl-4-yl) -5- (6-hydroxy- 1-Heptinyl) -pyridine, 2- (4'-alkyloxy-biphenyl-4-yl) -5- (6-acyloxy-1-heptinyl) -pyridine, 2- (4'-hydroxy-biphenyl-4-yl) -5- (6-hydroxy-1-heptynyl ) -Pyridine, 2- (4'-Hydroxy-biphenyl-4-yl) -5- (6-acyloxy-1-heptinyl) -pyridine, 2- (4'-hydroxy-biphenyl-4-yl) -5- (6-hydroxy-1-heptinyl) -pyridine, 2- (4 '-Hydroxy-biphenyl-4-yl) -5- (6-acyloxy-1-heptinyl) -pyridine, 5-alkyl-2- {4'-(6-acyloxy-1-heptinyl) -biphenyl-4-yl} -pyrimidine, 5-alkyloxy-2- {4'- (6-Hydroxy-1-heptenyl) -biphenyl-4-yl} -pyrimidine, 5-alkyloxy-2- {4 '-(6-acyloxy-1-heptenyl)
-Biphenyl-4-yl} -pyrimidine, 5-hydroxy-2- {4 '-(6-hydroxy-1-heptinyl) -biphenyl-4-yl} -pyrimidine, 5-hydroxy-2- {4'-(6-acyloxy-1-heptinyl) -biphenyl-4-yl} -pyrimidine, 5-hydroxy-2- {4 '-(6-Hydroxy-1-heptenyl) -biphenyl-4-yl} -pyrimidine, 5-hydroxy-2- {4'-(6-acyloxy-1-heptenyl) -biphenyl-4-yl} -pyrimidine, 2
-{4 '-(6-hydroxy-1-heptinyl) -biphenyl-4-yl} -5-alkyl-pyrimidine, 2
-{4 '-(6-acyloxy-1-heptinyl) -biphenyl-4-yl} -5-alkyl-pyrimidine, 2
-{4 '-(6-Hydroxy-1-heptinyl) -biphenyl-4-yl} -5-alkyloxy-pyrimidine, 2- {4'-(6-acyloxy-1-heptinyl) -biphenyl-4-yl} -5-alkyloxy-pyrimidine, 2- {4 '-(6-Hydroxy-1-heptinyl) -biphenyl-4-yl} -5-hydroxy-pyrimidine, 2- {4'-(6-acyloxy-1-heptinyl) -biphenyl-4-yl} -5-hydroxy-pyrimidine, 2- {4 '-(6 -Hydroxy-1
-Heptinyl) -biphenyl-4-yl} -5-hydroxy-pyrimidine, 2- {4 '-(6-acyloxy-1-heptinyl) -biphenyl-4-yl} -5-hydroxy-pyrimidine, 5- (4-alkylphenyl)
-2- {4- (6-Hydroxy-1-heptinyl) -phenyl} -pyrimidine, 5- (4-alkylphenyl) -2- {4- (6-acyloxy-1-heptinyl) -phenyl} -pyrimidine, 5- (4-alkyloxyphenyl)- 2- {4- (6-hydroxy-1-heptinyl) -phenyl} -pyrimidine, 5- (4-alkyloxyphenyl) -2- {4- (6-acyloxy-1-heptinyl) -phenyl} -pyrimidine, 5- (4-hydroxyphenyl) -2 -{4- (6-hydroxy-1-heptinyl) -phenyl} -pyrimidine,
5- (4-hydroxyphenyl) -2- {4- (6-acyloxy-1-heptynyl) -phenyl} -pyrimidine, 5- (4-hydroxyphenyl) -2- {4- (6
-Hydroxy-1-heptynyl) -phenyl} -pyrimidine, 5- (4-hydroxyphenyl) -2- {4- (6-acyloxy-1-heptynyl) -phenyl}
-Pyrimidine, 2- (4-alkylphenyl) -5- {4- (6-hydroxy-1-heptinyl) -phenyl} -pyrimidine, 2- (4-alkylphenyl) -5
-{4- (6-Acyloxy-1-heptinyl) -phenyl} -pyrimidine, 2- (4-alkyloxyphenyl) -5- {4- (6-hydroxy-1-heptinyl)
-Phenyl} -pyrimidine, 2- (4-alkyloxyphenyl) -5- {4- (6-acyloxy-1-heptinyl) -phenyl} -pyrimidine, 2- (4-hydroxyphenyl) -5- {4- (6-hydroxy-1-heptinyl) -phenyl } -Pyrimidine, 2- (4-hydroxyphenyl) -5- {4- (6-acyloxy-1-heptinyl) -phenyl} -pyrimidine, 2- (4
-Hydroxyphenyl) -5- {4- (6-hydroxy-1-heptynyl) -phenyl} -pyrimidine, 2- (4-hydroxyphenyl) -5- {4- (6-acyloxy-1-heptynyl) -phenyl} -pyrimidine, 2- {4- (5-alkylpyrimidin-2-yl)
Phenyl} -5- (6-hydroxy-1-heptinyl)}-pyrimidine, 2- {4- (5-alkylpyrimidin-2-yl) phenyl} -5- (6-acyloxy-1-heptynyl)}-pyrimidine, 2- {4- (5
-Alkyloxypyrimidin-2-yl) phenyl} -5- (6-hydroxy-1-heptinyl)}-pyrimidine, 2- {4- (5-alkyloxypyrimidine-2)
-Yl) phenyl} -5- (6-acyloxy-1-heptinyl)}-pyrimidine, 2- {4- (5-hydroxypyrimidin-2-yl) phenyl} -5- (6-hydroxy-1-heptinyl)}-pyrimidine, 2- {4- ( 5-hydroxypyrimidin-2-yl) phenyl} -5- (6-acyloxy-1-heptinyl)}
-Pyrimidine, 2- {4- (5-hydroxypyrimidin-2-yl) phenyl} -5- (6-hydroxy-1
-Heptinyl)}-pyrimidine, 2- {4- (5-hydroxypyrimidin-2-yl) phenyl} -5- (6-acyloxy-1-heptynyl)}-pyrimidine, 5- (4-alkylphenyl) -2- {4- (6 -Hydroxy-1-heptinyl) phenyl} pyrazine, 5- (4
-Alkylphenyl) -2- {4- (6-acyloxy-1-heptinyl) phenyl} pyrazine, 5- (4-alkyloxyphenyl) -2- {4- (6-hydroxy-1-heptynyl) phenyl} pyrazine, 5- (4- Alkyloxyphenyl) -2- {4- (6-acyloxy-1-heptinyl) phenyl} pyrazine, 5- (4-hydroxyphenyl) -2- {4- (6-hydroxy-1-heptinyl) phenyl} pyrazine, 5- (4-hydroxy Phenyl) -2- {4- (6-acyloxy-1-heptinyl) phenyl} pyrazine, 5- (4-hydroxyphenyl) -2- {4- (6-hydroxy-1-heptynyl) phenyl} pyrazine, 5- (4-hydroxyphenyl) -2- {4- (6-acyloxy-1-heptynyl) phenyl } Pyrazine, 6- (4-alkylphenyl) -3- {4- (6-hydroxy-1-heptinyl) phenyl} pyridazine, 6- (4-alkylphenyl) -3- {4- (6-acyloxy-1-heptinyl) phenyl} pyridazine , 6- (4-alkyloxyphenyl) -3- {4- (6-hydroxy-1-heptinyl) phenyl} pyridazine, 6- (4-alkyloxyphenyl) -3- {4- (6-acyloxy-1-heptinyl) phenyl} pyridazine , 6- (4-hydroxyphenyl) -3- {4- (6-hydroxy-1-heptinyl) phenyl} pyridazine, 6- (4-hydroxyphenyl) -3- {4- (6-acyloxy-1-heptynyl) phenyl} pyridazine, 6- (4-hydroxyphenyl) -3- {4- (6-hydroxy) Sea 1-heptynyl) phenyl} pyridazine, 6- (4-hydroxyphenyl) -3- {4- (6-acyloxy-1-heptinyl) phenyl} pyridazine, 2- (6-alkylnaphthalen-2-yl) -5- (6-hydroxy- 1-Heptynyl) -pyridine, 2- (6-alkylnaphthalen-2-yl) -5- (6-acyloxy-1-heptinyl) -pyridine, 2- (6-alkyloxynaphthalen-2-yl) -5- (6-hydroxy-1-heptynyl) -Pyridine, 2- (6-alkyloxynaphthalen-2-yl) -5- (6-acyloxy-1-heptinyl) -pyridine, 2- (6-hydroxynaphthalen-2-yl) -5- (6-hydroxy-1-heptinyl) -pyridine, 2 -(6-hydroxynaphthalene- -Yl) -5- (6-acyloxy-1-heptinyl) -pyridine, 2- (6-hydroxynaphthalen-2-yl) -5- (6-hydroxy-1-heptinyl) -pyridine, 2- (6-hydroxynaphthalen-2-yl)- 5- (6-Acyloxy-1-heptinyl) -pyridine, 5- (6-alkylnaphthalen-2-yl) -2- (6-hydroxy-1-heptinyl)
-Pyridine, 5- (6-Alkylnaphthalen-2-yl) -2- (6-acyloxy-1-heptinyl) -pyridine, 5- (6-Alkyloxynaphthalene-2)
-Yl) -2- (6-hydroxy-1-heptinyl)
-Pyridine, 5- (6-alkyloxynaphthalen-2-yl) -2- (6-acyloxy-1-heptinyl) -pyridine, 5- (6-hydroxynaphthalene-2)
-Yl) -2- (6-hydroxy-1-heptinyl) -pyridine, 5- (6-hydroxynaphthalen-2-yl) -2- (6-acyloxy-1-heptinyl) -pyridine, 5- (6-hydroxynaphthalene-2-yl) -2- (6-Hydroxy-1-heptynyl) -pyridine, 5- (6-hydroxynaphthalen-2-yl) -2- (6-acyloxy-1-heptinyl) -pyridine, 2-alkyl-5- {6- (6-hydroxy-1
-Heptinyl) naphthalen-2-yl) -pyridine,
2-alkyl-5- {6- (6-acyloxy-1-
Heptinyl) naphthalen-2-yl) -pyridine, 2
-Alkyloxy-5- {6- (6-hydroxy-1
-Heptinyl) naphthalen-2-yl) -pyridine,
2-alkyloxy-5- {6- (6-acyloxy-1-heptinyl) naphthalene-2-yl) -pyridine, 2-hydroxy-5- {6- (6-hydroxy-1
-Heptynyl) naphthalen-2-yl) -pyridine, 2-hydroxy-5- {6- (6-acyloxy-1-yl-heptinyl) naphthalen-2-yl) -pyridine, 2-hydroxy-5- {6- (6-hydroxy-1)
-Heptinyl) naphthalen-2-yl) -pyridine, 2-hydroxy-5- {6- (6-acyloxy-1-yl-heptynyl) naphthalen-2-yl) -pyridine, 5-alkyl-2- {6- (6-hydroxy-1)
-Heptinyl) naphthalen-1-yl} -pyridine,
5-alkyl-2- {6- (6-acyloxy-1-
Heptinyl) naphthalen-1-yl} -pyridine, 5
-Alkyloxy-2- {6- (6-hydroxy-1
-Heptinyl) naphthalen-1-yl} -pyridine,
5-Alkyloxy-2- {6- (6-acyloxy-1-heptinyl) naphthalene-1-yl} -pyridine, 5-hydroxyalkyl-2- {6- (6-hydroxy-1-heptinyl) naphthalene-1-yl} -pyridine, 5-hydroxy-2- {6 -(6-Acyloxy-1-heptinyl) naphthalene-1-yl} -pyridine, 5-hydroxy-2- {6- (6-hydroxy-1-heptinyl) naphthalene-1-yl} -pyridine, 5-hydroxy-2- {6- (6-acyloxy-1-heptynyl) naphthalene-1-yl } -Pyridine, 7-alkyl-3- {4- (6-hydroxy-1-heptinyl) -phenyl} -isoquinoline, 7-alkyl-3- {4- (6-acyloxy-1-heptinyl) -phenyl} -iso Quinoline, 7-alkyloxy-3- {4- (6-hydroxy-1-heptinyl) -phenyl} -isoquinoline, 7-alkyloxy-3- {4- (6-acyloxy-1-heptinyl)
-Phenyl} -isoquinoline, 7-hydroxy-3- {4- (6-hydroxy-1-heptinyl) -phenyl} -isoquinoline, 7-hydroxy-3- {4- (6
-Acyloxy-1-heptynyl) -phenyl} -isoquinoline, 7-hydroxy-3- {4- (6-hydroxy-1-heptinyl) -phenyl} -isoquinoline, 7-hydroxy-3- {4- (6-acyloxy-1-heptinyl) -phenyl} -isoquinoline, 3- (4-alkynyl) Rouphenyl) -7- (6-hydroxy-1-heptinyl) -isoquinoline, 3- (4-alkyl-phenyl) -7- (6-acyloxy-1-heptenyl) -isoquinoline, 3- (4-alkyloxy-phenyl) -7- (6-hydroxy- 1-heptynyl) -isoquinoline, 3- (4-alkyloxy-phenyl)
-7- (6-acyloxy-1-heptinyl) -isoquinoline, 3- (4-hydroxy-phenyl) -7- (6-hydroxy-1-heptinyl) -isoquinoline,
3- (4-Hydroxy-phenyl) -7- (6-acyloxy-1-heptenyl) -isoquinoline, 3- (4-hydroxy-phenyl) -7- (6-hydroxy-1-heptinyl) -isoquinoline, 3- (4-hydroxy-phenyl)- 7- (6-acyloxy-1-heptinyl) -isoquinoline, 6-alkyl-2- {4- (6-hydroxy-1-heptinyl) -phenyl} -quinoline, 6-alkyl-2- {4- (6-acyloxy-1
-Heptinyl) -phenyl} -quinoline, 6-alkyloxy-2- {4- (6-hydroxy-1-heptinyl) -phenyl} -quinoline, 6-alkyloxy-2- {4- (6-acyloxy-1-heptinyl) -phenyl} -quinoline, 6-hydroxy-2- {4- (6-Hydroxy-1-heptinyl) -phenyl} -quinoline, 6-hydroxy-2- {4- (6-acyloxy-1-heptinyl) -phenyl} -quinoline, 6
-Hydroxy-2- {4- (6-hydroxy-1-heptynyl) -phenyl} -quinoline, 6-hydroxy-2- {4- (6-acyloxy-1-heptinyl) -phenyl} -quinoline, 2- (4-alkyl-phenyl) -6- (6-hydroxy-1) -Heptenyl) -quinoline, 2- (4-alkyl-phenyl) -6- (6-acyloxy-1-heptenyl) -quinoline, 2- (4-alkyloxy-phenyl) -6- (6-hydroxy-1-heptinyl) -quinoline, 2- (4-) Alkyloxy-phenyl) -6- (6-acyloxy-1-heptinyl) -quinoline, 2- (4-hydroxy-phenyl) -6- (6-hydroxy-1-heptenyl) -quinoline, 2- (4-hydroxy-phenyl) -6- (6-acyloxy- 1-Hep Nil) Kinorin,
2- (4-hydroxyphenyl) -6- (6-hydroxy-1-heptinyl) -quinoline, 2- (4-hydroxyphenyl) -6- (6-acyloxy-1-heptinyl) -quinoline, 5-alkyl-5- {6- (6
-Hydroxy-1-heptynyl) naphthalene-2-yl} -pyrimidine, 5-alkyl-5- {6- (6-acyloxy-1-heptinyl) naphthalene-2-yl} -pyrimidine, 5-alkyloxy-5- {6- (6-hydroxy-1-heptinyl) naphthalene-2-yl} -pyrimidine, 5-Alkyloxy-5- {6- (6-acyloxy-1-heptenyl) naphthalene-2-yl} -pyrimidine, 5-hydroxy-5
-{6- (6-Hydroxy-1-heptinyl) naphthalene-2-yl} -pyrimidine, 5-hydroxy-5
-{6- (6-Acyloxy-1-heptenyl) naphthalene-2-yl} -pyrimidine, 5-hydroxy-5- {6- (6-hydroxy-1-heptinyl) naphthalene-2-yl} -pyrimidine, 5-hydroxy-5- {6- (6-acyloxy-1-heptenyl) naphthalene-2 -Yl} -pyrimidine, 3-alkyl-7- {4- (6-hydroxy-1-heptenyl) -phenyl} -quinoxaline, 3-alkyl-7- {4- (6-acyloxy-1-heptynyl) -phenyl}
-Quinoxaline, 3-alkyloxy-7- {4- (6
-Hydroxy-1-heptinyl) -phenyl} -quinoxaline, 3-alkyloxy-7- {4- (6-acyloxy-1-heptinyl) -phenyl} -quinoxaline, 2-alkyl-6- {4- (6-hydroxy-1)
-Heptinyl) -phenyl} -quinazoline, 2-alkyl-6- {4- (6-acyloxy-1-heptinyl) -phenyl} -quinazoline, 2-alkyloxy-6- {4- (6-hydroxy-1-phenyl) -phenyl} -quinazoline, 2-alkyloxy-6- { Four
-(6-acyloxy-1-heptinyl) -phenyl} -quinazoline, 3-hydroxy-7- {4- (6-hydroxy-1-heptenyl) -phenyl} -quinoxaline, 3-hydroxy-7- {4- (6-acyloxy-1-heptynyl) -phenyl} -quinoxaline,
3-hydroxy-7- {4- (6-hydroxy-1-heptinyl) -phenyl} -quinoxaline, 3-hydroxy-7- {4- (6-acyloxy-1-heptinyl) -phenyl} -quinoxaline, 2-hydroxy-6
-{4- (6-Hydroxy-1-heptinyl) -phenyl} -quinazoline, 2-hydroxy-6- {4- (6
-Acyloxy-1-heptynyl) -phenyl} -quinazoline, 2-hydroxy-6- {4- (6-hydroxy-1-heptinyl-phenyl} -quinazoline, 2-hydroxy-6- {4- (6-acyloxy-1-heptynyl) -phenyl} -quinazoline, and the above-mentioned The substituted (6-hydroxy-1-heptinyl) group is 3-hydroxy-1-butynyl, 4-hydroxy-1-pentynyl, 5-hydroxy-1-hexynyl, 6-hydroxy-1-heptinyl, 7-hydroxy-1-octynyl, 8-hydroxy-1-nonenyl, 9-hydroxy-1-undecenyl, 10-hydroxy-1-undecenyl. Compounds replacing any of the 11-hydroxy-1-dodecenyl groups, and also substituted (6-alkoxy-1-heptinyl) groups , 3 Arukokishi 1 Buchiniru, 4 Arukokishi 1 Penchiniru, 5
-Alkoxy-1 -hexynyl, 6-alkoxy-1
-Heptinyl, 7-alkoxy-1-octynyl,
8-alkoxy-1-nonyl, 9-alkoxy-1
-Decenyl, 10-alkoxy-1-undecenyl, compounds substituting any of 11-alkoxy-1-dedecenyl groups, and the above-mentioned substituted (6-acyloxy-1-heptinyl) groups having 3-acyloxy-1-butynyl, 4-acyloxy-1-pentynyl, 5-acyloxy-1-hexynyl, It is a compound substituted with any of 6-acyloxy-1-heptinyl, 7-acyloxy-1-octynyl, 8-acyloxy-1-nonyl, 9-acyloxy-1-decenyl, 10-acyloxy-1-undecenyl and 11-acyloxy-1-dedecenyl groups. Further, it is a compound in which the alkyl group and the alkyloxy group of the above compounds replace the alkenyl group and the alkenyloxy group, respectively.

Further, in the above compounds, the hydroxy group substituted by A1 also includes a compound protected by a hydroxyl group protecting group, and examples of such protecting group are as follows. Substituted with an aliphatic acyl group such as acetyl, propionyl, butyryl, pentylyl, a halogen atom such as chlorine atom, bromine atom, an alkyl group such as methyl, ethyl, propyl, butyl, or an alkoxy group such as methoxy, ethoxy, propoxy, butoxy. A benzoyl group which may be present,
Chlorine atom, halogen atom such as bromine atom, alkyl group such as methyl, ethyl, propyl, butyl or benzyl group which may be substituted with methoxy, ethoxy, propoxy, butoxy group such as butoxy, trimethylsilyl group, triethylsilyl group, Trialkylsilyl group such as dimethylphenylsilyl group, dimethylbenzylsilyl group, methyldibenzylsilyl group, tribenzylsilyl group, dimethylbutylsilyl group, methyldiphenylsilyl group, triphenylsilyl group, dialkylphenylsilyl group, alkyldiphenylsilyl A group, a triphenylsilyl group, an aralkyldialkylsilyl group, a diaralkylalkylsilyl group, a triaralkylsilyl group,
The phenyl group and aralkyl group may be substituted with a halogen atom, an alkyl group, an alkoxy group or the like. Further examples include a tetrahydropyranyl group, a tetrahydrofuranyl group, and further ethers such as a 1- (alkoxy) ethyl group such as ethoxyethyl and propoxyethyl. Here, in the compound names, alkyl, alkenyl, and alkoxy represent a group having 1 to 20 carbon atoms, and an acyloxy group represents a lower alkyl group having 1 to 5 carbon atoms.

Next, the production method for obtaining the optically active saturated alcohol (8) by reducing the optically active alcohol derivative (1) obtained here will be described. The reduction can be carried out by hydrogenating the optically active alcohol derivative (1) with hydrogen and a hydrogenation catalyst. In the above reaction, a Raney nickel palladium metal catalyst is preferably used as the hydrogenation catalyst, and specific examples thereof include palladium-carbon, palladium oxide, palladium black or palladium chloride. The hydrogenation catalyst is usually used in an amount of 0.001 to 0.5 times by weight, preferably 0.005 to 0.3 times by weight, of the optically active alcohol derivative (1). The reaction is carried out in a solvent, and examples of the solvent include water, dioxane, tetrahydrofuran, methanol, ethanol, n-propyl alcohol, acetone, dimethylformamide, toluene, dichloromethane, ethyl acetate and other hydrocarbons, alcohols, ethers, ketones and esters. Solvents such as halogenated hydrocarbons and amides which are inert to the reaction may be used alone or as a mixture.

The above reaction is carried out under normal or elevated pressure of hydrogen, and the reaction end point is reached when the amount of absorbed hydrogen is 1 to 1.2 equivalent times that of the optically active alcohol derivative (1) as a raw material. Is preferred. Reaction is -10 to 100
C., preferably 10 to 60.degree. After the reaction is completed, the desired optically active saturated alcohol (8) can be obtained by an operation such as removing the catalyst from the reaction mixture by filtration and then concentrating it. It can also be purified by chromatography or the like. The optically active saturated alcohols (8) are separately hydrogenated with an ester derivative represented by the general formula (2) using hydrogen and a hydrogenation catalyst to obtain the general formula (9). (Wherein R1, R2, m, n, q, A1, A2 and A
3 has the same meaning as above. It can also be produced by asymmetrically hydrolyzing an ester represented by the formula (1) and then using an esterase having the ability to preferentially hydrolyze any one of the optically active substances of the ester. This reaction can be carried out by a method similar to the method for producing the optically active alcohol (1) from the ester derivative (2). The hydrogenation reaction from the ester derivative to the ester is also hydrogenation according to the hydrogenation reaction used in the reaction for obtaining the optically active saturated alcohol (8) from the optically active alcohol derivative (1) and the reaction conditions. Done by

Further, the above-mentioned esters (9) are hydrogenated by separately hydrogenating the racemic alcohol derivative (6) using hydrogen and a hydrogenation catalyst to obtain the general formula (10). (Wherein R1, R2, m, n, q, A1, A2 and A
3 has the same meaning as above. ) And then reacting with the carboxylic acid represented by the general formula (7) or its derivative. Both the hydrogenation reaction and the reaction with the carboxylic acid or its derivative are carried out according to the reaction conditions described above. By the above reaction, extremely high-purity racemic or optically active saturated alcohols can be obtained from the novel racemic or optically active alcohol derivative of the present invention, and if necessary, racemic ester derivative, and further esters. After that, an optically active saturated alcohol can be obtained by an asymmetric hydrolytic reaction.

[0024]

INDUSTRIAL APPLICABILITY The compound of the present invention is not only useful as an intermediate for liquid crystal materials but also as an intermediate for agricultural chemicals, pharmaceuticals and the like. Further, according to the method of the present invention, the optically active alcohol derivative (1) can be industrially advantageously produced. Further, from such an optically active alcohol derivative, an extremely highly pure optically active saturated alcohol can be obtained.

[0025]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto. Example 1 In a four-necked flask equipped with a stirrer and a thermometer, 2- (4'-bromo-4-biphenyl) -5-octyloxypyrimidine (3-1) 8.8 g (0.02 mol), 1-heptin- 6-ol (5-1) 3.4 g (0.03 mol), bis (triphenylphosphine) palladium chloride 0.13
g, copper iodide 0.13 g, triphenylphosphine 0.26 g and triethylamine 40 ml were charged, and under a nitrogen stream,
React at 80 ° C. for 8 hours. After completion of the reaction, the reaction mixture was poured into 200 ml of water and extracted with 200 ml of toluene.
The obtained toluene layer was washed with 3% HCl water and water, and then concentrated under reduced pressure to obtain a brown residue. This was purified by silica gel column chromatography (eluent: toluene-ethyl acetate) to give 2- (4 '-(6-hydroxy-1-heptinyl) -4-biphenyl) -5-octyloxypyrimidine (6-1). ) 7.3 g (yield 78%) was obtained. Obtained (6-1) 4.7 g (10 mmol), acetic anhydride 2
Then, 15 g of pyridine and 15 ml of pyridine are charged and reacted at 50 ° C. for 4 hours. After the reaction was completed, the reaction solution was poured into 50 ml of water and 5% HC
After adjusting the pH to 3 with water, the mixture is extracted with 100 ml of toluene. The organic layer is washed with water and then concentrated under reduced pressure to give 2- (4'-
5.0 g of (6-acetoxy-1-heptinyl) -4-biphenyl) -5-octyloxypyrimidine (2-1)
(Yield 97%) was obtained. Obtained (2-1) 2.6 g (5
0.3 mM phosphate buffer (pH 7.0) 80
ml, chloroform 3 ml, and Pseudomonas lipase (lipase "P" Amano) 0.8 g, and the mixture was vigorously stirred at 30 to 35 ° C for 60 hours. The obtained mixture was extracted with 100 ml of toluene, and the organic layer was washed with water and then concentrated under reduced pressure. The residue was separated by silica gel column chromatography (eluent: toluene-ethyl acetate),
(-)-2- (4 '-(6-Hydroxy-1-heptinyl) -4-biphenyl) -5-octyloxypyrimidine (1-1) 0.9 g (38%), [α] _D ²⁰ = -2.3 °
(C = 1, chloroform) and (-)-2- (4'-
1.5 g of (6-acetoxy-1-heptinyl) -4-biphenyl) -5-octyloxypyrimidine (yield 58
%), [Α] _D ²⁰ = -1.8 ° (c = 1, chloroform)
To get

Example 2 2- (4 '-(6-hydroxy-1) obtained in Example 1
-Heptinyl) -4-biphenyl) -5-octyloxy
2.4 g (5 mmol) of cypyrimidine (6-1), methano
10 ml, 20 ml ethyl acetate and 5% palladium on charcoal
Hydrogen pressure of 10g / cm2, 25-30
Hydrogenate at ℃. After the reaction was completed, the catalyst was filtered off and the filtrate
Was concentrated under reduced pressure to give 2- (4 '-(6-hydroxy-1-hexyl).
(Putyl) -4-biphenyl) -5-octyloxypyri
2.4 g (yield 98%) of the midine (10-1) is obtained. next
(10-1) 1.9 g (4 mmol), triethylamine 3
g and 25 g of dichloromethane were charged, and acetyl chloride was added.
0.5 g (6 mmol) of the lid is added below 10 ° C. same
The reaction is carried out for 1 hour at temperature and 2 hours at 30 ° C. End of reaction
After completion, the reaction solution is poured into ice water and the organic layer is separated. Organic
The layers are washed sequentially with 3% hydrochloric acid water, water, 3% heavy soda water, and water
And further concentrate. Column chromatography of the resulting residue
2- (4 '-(6-
Acetoxy-1-heptyl) -4-biphenyl) -5-
Octyloxypyrimidine (9-1) 1.8 g (yield 98
%). Next, 1.5 g of (9-1) obtained above (3 mi
Limol), 0.2M phosphate buffer (pH 7.5) 70m
1, toluene 5 ml and Pseudomonas lipase 0.5
The g mixture is stirred at 35-40 ° C. for 30 hours. Less than
By post-treatment and purification according to Example 1,
(-)-2- (4 '-(6-hydroxy-1-hepti
Le) -4-biphenyl) -5-octyloxypyrimidi
(1-1) 0.6 g (39%), [α]_D ²⁰= -2.1 °
(C = 1, chloroform) and (-)-2- (4'-
(6-acetoxy-1-heptyl) -4-biphenyl)
-5-octyloxypyrimidine 0.9 g (yield 56
%), [Α] _D ²⁰= -2.0 ° (c = 1, chloroform)
To get

Example 3 0.9 g (2) of the optically active 2- (4 '-(6-hydroxy-1-heptinyl) -4-biphenyl) -5-octyloxypyrimidine (1-1) obtained in Example 1 Mmol), methanol (2 ml), ethyl acetate (10 ml) and 5% palladium on carbon (0.1 g) were mixed at a hydrogen pressure of 5 kg / cm ² , 3
Hydrogenate at 5 ° C. for 3 hours. By post-treatment and purification according to Example 2, the optically active 2- (4′-
(6-hydroxy-1-heptyl) -4-biphenyl)
-5-octyloxypyrimidine (8-1) 0.9 g (yield 98%) is obtained. Similarly, optically active 2- (4 '-(6
Optically active 2- (4 '-(6-acetoxy-1-heptyl) -4-biphenyl) -5-octyloxypyrimidine is obtained from -acetoxy-1-heptinyl) -4-biphenyl) -5-octyloxypyrimidine.

Example 4 In a 4-necked flask equipped with a stirrer and a thermometer, a 5- (4
-Nonylphenyl) -2- (4-bromophenyl) pyrimidine (3-2) 8.7 g (0.02 mol), 6-acetoxy-1-heptin 6.2 g (0.04 mol), bis (triphenylphosphine) palladium chloride 0.15 g, iodine Copper 0.
2 g, triphenylphosphine (0.3 g) and triethylamine (50 ml) were charged, and the mixture was reacted under a nitrogen stream under reflux for 9 hours. After completion of the reaction, post-treatment and purification were carried out according to Example 1, and 5- (4-nonylphenyl) -2- (4- (6-
Acetoxy-1-heptynyl) phenyl) pyrimidine)
(2-2) 8.0 g (yield 78%) is obtained. 2.6 g (5 mmol) of (2-2) obtained here, 60 ml of 0.2 M phosphate buffer (pH 7.5), 4 ml of chloroform and Pseudomonas lipase (lipase "PS" Amano)
0.5 g of the mixture is vigorously stirred at 35-40 ° C. for 50 hours. The reaction solution is extracted with 100 ml of ethyl acetate, the organic layer is washed with water and then concentrated under reduced pressure. The obtained residue was separated by silica gel column chromatography (eluent: toluene-ethyl acetate), and (-)-5- (4-nonylphenyl) -2- (4- (6-hydroxy-1-heptynyl).
Phenyl) pyrimidine (1-2) 0.84 g (36%),
[Α] _D ²⁰ = −2.3 ° (c = 1, chloroform) and (−)-5- (4-nonylphenyl) -2- (4- (6
-Acetoxy-1-heptynyl) phenyl) pyrimidine
1.5 g (yield 58%), [α] _D ²⁰ = -1.7 ° (c =
1, chloroform) is obtained. Obtained here (1-2)
The optically active ester derivative and the optically active ester derivative can be reduced according to Example 3 to obtain an optically active 5- (4-nonylphenyl) -2- (4- (6-hydroxy-1-heptyl) phenyl) pyrimidine (8-2). And optically active 5- (4-nonylphenyl) -2- (4- (6-acetoxy-1-heptyl) phenyl) pyrimidine, respectively.

Example 5 5- (4-nonylphenyl) -2- (4- (6-acetoxy-1-heptynyl) phenyl) obtained in Example 4
A mixed solution of 5.1 g (0.01 mol) of pyrimidine (2-2), 40 ml of ethyl acetate and 0.24 g of 5% palladium carbon was hydrogenated at 20-25 ° C under normal pressure. The catalyst was filtered off and the filtrate was concentrated to give 5- (4-nonylphenyl) -2.
-(4- (6-acetoxy-1-heptyl) phenyl)
5.0 g (97%) of pyrimidine (9-2) are obtained. Then, 2.6 g (5 mmol) of (9-2) obtained here, 0.2 M
A mixture of 100 ml of phosphate buffer (pH 7.0) and 0.5 g of Pseudomonas lipase (lipase “P” Amano) is vigorously stirred at 30 to 40 ° C. for 60 hours. By carrying out post-treatment and purification according to Example 4 below,
Optically active (−)-5- (4-nonylphenyl) -2- (4- (6-hydroxy-1-heptyl) phenyl) pyrimidine (1-2) 0.89 g (38%), [α] _D ²⁰ = −
1.9 ° (c = 1, chloroform) and (−)-5- (4-nonylphenyl) -2- (4- (6-acetoxy-1-heptyl) phenyl) pyrimidine 1.4 g (yield 5
6%), [α] _D ²⁰ = −1.5 ° (c = 1, chloroform).

Example 6 4.1 g (0.01 mol) of 6- (4-dodecyloxyphenyl) -2-bromonaphthalene (3-3), 3-butyl-2
-All 1.1 g (0.015 mol), copper iodide 0.15, triphenylphosphine 0.2 g, bis (triphenylphosphine) palladium chloride 0.1 g, triethylamine 5
Charge 0 ml and stir under reflux under nitrogen for 10 hours. After completion of the reaction, the reaction solution is poured into ice-hydrochloric acid water and extracted with 150 ml of ethyl acetate. The organic layer is further washed with water and concentrated under reduced pressure. The obtained residue is purified by column chromatography to give 6- (4-dodecyloxyphenyl) -2.
-(3-Hydroxy-1-butynyl) naphthalene (6-
3) 3.2 g (81% yield) are obtained. Next, 3.2 g (8 mmol) of (6-3) obtained above was mixed with propionic anhydride.
1.3 g (0.01 mol) and 20 ml of pyridine are added and reacted at 30 ° C. for 4 hours. Then, post-treatment and purification were conducted according to Example 1 to obtain 6- (4-dodecyloxyphenyl) -2- (3
-Propionyloxy-1-butynyl) naphthalene (2
-3) 3.5 g (yield 97%) is obtained. Next, a mixed solution of 2.28 g (5 mmol) of (2-3) obtained above, 60 ml of 0.3M phosphate buffer (pH 7.0), 5 ml of dichloromethane and 0.7 g of Arthrobacter lipase (Nippon Kagaku) Is stirred at 30 ° C. for 60 hours. Reaction completion liquid,
By carrying out post-treatment and purification according to Example 1,
Optically active 6- (4-dodecyloxyphenyl) -2-
(3-Hydroxy-1-butynyl) naphthalene (1-
3) 0.74 g (yield 37%), [α] _D ²⁰ = + 11.7 °
2.5 g (58% yield) of (c = 1, chloroform) and 6- (4-dodecylocyphenyl) -2- (3-propionyloxy-1-butynyl) naphthalene are obtained. Then 0.4 g (1 mmol) of the optically active 6- (4-dodecyloxyphenyl) -2- (3-hydroxy-1-butynyl) naphthalene (1-3) obtained above, 10 ml of tetrahydrofuran (THF) and 0.05 g of 5% palladium carbon is hydrogenated under normal pressure. The reaction is completed in 4 hours at 20 ° C. The catalyst was filtered off, concentrated, and purified by chromatography to give 6- (4-dodecyloxyphenyl) -2- (3-hydroxy-1-butyl) naphthalene (8-3) 0.4 g (yield 98%), [α] _D ²⁰ =-
Obtain 5.8 ° (c = 1, chloroform). Similarly, optically active 6- (4-dodecyloxyphenyl) -2- (3-
6 from propionyloxy-1-butynyl) naphthalene
-(4-dodecyloxyphenyl) -2- (3-propionyloxy-1-butyl) naphthalene is obtained.

Example 7 In a four-necked flask equipped with a stirrer and a thermometer, 6- (4-bromophenyl) -2-decyloxyquinoxaline (3-4) 8, 8 g (0.02 mol), 4-pentyne -2
-All 2.5 g (0.03 mol), copper iodide 0.16 g, triphenylphosphine 0.3 g, bis (triphenylphosphine) palladium (II) chloride 0.15 g, and diethylamine 80 ml were charged, and the mixture was heated and stirred in a nitrogen atmosphere for 10 hours. After the reaction was completed, the reaction mixture was poured into 100 ml of water,
It was neutralized with dilute sulfuric acid and extracted with a mixed solution of toluene-ethyl acetate. The obtained organic solvent layer is washed with water and then concentrated under reduced pressure to obtain a yellowish brown residue. This was purified by silica gel column chromatography (eluent: toluene-ethyl acetate) to give 6- (4- (4-hydroxy-1-pentynyl).
Phenyl) -2-decyloxyquinoxaline (6-4)
6.8 g (77% yield) are obtained. Obtained here (6-4)
4.4 g (0.01 mol), acetic anhydride 2.80 g, pyridine 50 ml
And stirred at 40 to 50 ° C. for 5 hours. After completion of the reaction, the reaction mixture was poured into 100 ml of water, neutralized with dilute sulfuric acid, and extracted with a mixed solution of toluene-ethyl acetate. The obtained organic solvent layer was washed with water and then concentrated under reduced pressure to give 6- (4-
4.7 g (yield 96%) of (4-acetyloxy-1-pentynyl) phenyl) -2-decyloxyquinoxaline (2-4) is obtained. 3.9 g (8 mmol) of (2-4) obtained here was added to 140 m of 0.8 M phosphate buffer (pH 7.0).
l, 5 ml of chloroform and 1.0 g of Pseudomonas lipase (lipase Amano "PS") are added to the mixture, and the mixture is vigorously stirred at 30 to 35 ° C for 60 hours. The resulting mixture is extracted with 100 ml of toluene-ethyl acetate, the organic layer is washed with water and then concentrated under reduced pressure. The obtained mixture was subjected to silica gel column chromatography (eluent: toluene-
The reaction mixture was separated with ethyl acetate) and the optically active (−)-6- (4-
(4-Hydroxy-1-pentynyl) phenyl) -2-decyloxyquinoxaline (1-4) 1.4 g (yield 40
%), [Α] _D ²⁶ = -2.6 ° (c = 1, chloroform)
And (-)-6- (4- (4-acetyloxy-1-
Pentynyl) phenyl) -2-decyloxyquinoxaline 2.1 g (yield 55%), [α] _D ²⁰ = -3.4 ° (c =
1, chloroform) is obtained. The optically active (1-4) and 6- (4- (4-acetyloxy-1
If each of -pentynyl) phenyl) -2-decyloxyquinoxaline is reduced according to Example 2, the following compounds can be synthesized. 6- (4- (4-hydroxy-1-pentyl) phenyl) -2-decyloxyquinoxaline (8-4) [α] _D ²⁶ = −2.1 ° (c = 1,
Chloroform) and 6- (4- (4-acetyloxy-1-pentyl) phenyl) -2-decyloxyquinoxaline

Example 8 4.0 g (0.01 mol) of 4- (4-octyloxyphenyl) -4'-bromobiphenyl (3-5), 3.9 g (0.02 mol) of 5-acetoxy-1-hexyne, bis (tri) Phenylphosphine) palladium chloride 0.1 g, copper iodide
Charge 0.2 g, triphenylphosphine 0.15 g, triethylamine 60 ml, dimethylformamide 10 ml,
The reaction is carried out at 90 ° C for 12 hours under a nitrogen stream. After completion of the reaction, the reaction mixture is poured into 100 ml of water, ethyl acetate is added, and the mixture is made weakly acidic with 10% aqueous hydrochloric acid. After liquid separation, the organic layer is further washed with water and then concentrated under reduced pressure to obtain 4
3.7 g of-(4-octyloxyphenyl) -4 '-(5-acetoxy-1-hexynyl) biphenyl (2-5)
(Yield 80%) is obtained. Then obtained above (2-5)
2.3 g (5 mmol), 3 ml of chloroform, 90 ml of 2M phosphate buffer (pH 7.0) and 1.0 g of Arthrobacter lipase (manufactured by Shin Nippon Kagaku Co., Ltd.) are stirred at 30 to 35 ° C. for 40 hours. After completion of the reaction, the reaction solution was extracted with ethyl acetate, further concentrated under reduced pressure, and the residue was purified by chromatography to give optically active 4- (4-octyloxyphenyl) -4 '-(5-hydroxy- 1-hexynyl) biphenyl (1-5) 0.7 g (yield 35
%), [Α] _D ²⁰ = −2.2 ° (c = 1, CHCl 3), and optically active 4- (2,3-difluoro-4-octyloxyphenyl) -4 ′-(5-acetoxy-1-hexynyl). Biphenyl 1.3 g (yield 56%), [α] _D ²⁰ =
-1.6 ° (c = 1, CHCl3) is obtained. The above optically active (1-5) and ester form are reduced according to Example 3 to give the following optically active form. Optically active 4- (4-octyloxyphenyl) -4 '-(5-hydroxy-1-hexyl) biphenyl (8-5),
[Α] D 20 = -2.0 ° (c = 1, chloroform) and optically active 4- (4-octyloxyphenyl) -4'-
(5-acetoxy-1-hexyl) biphenyl, [α]
D 20 = -1.2 ° (c = 1, chloroform).

Example 9 In a 4-necked flask equipped with a stirrer and a thermometer, 2- (6
-Decyloxy-naphthalen-2-yl) -5-bromopyrimidine (3-6) 4.6 g (0.01 mol), 6-acetoxy-1-heptin 3.1 g (0.02 mol), bis (triphenylphosphine) palladium chloride 0.1 g , 0.2 g of copper iodide, 0.2 g of triphenylphosphine and 50 ml of diethylamine were charged, and the mixture was refluxed under a nitrogen stream at 89%.
React for hours. After completion of the reaction, post-treatment and purification were carried out in accordance with Example 1 to give 2- (6-siloxy-naphthalene-2-
Yield) -5- (6-acetoxy-1-heptynyl) pyrimidine (2-6) (3.9 g, yield 73%) is obtained. 2.7 g (5 mmol) of (2-6) obtained here, 100 ml of 0.2 M phosphate buffer (pH 7.5), dichloromethane 6
ml and Pseudomonas lipase (lipase "PS"
Amano) 0.85 g of the mixture is vigorously stirred at 30-40 ° C. for 60 hours. The reaction solution was extracted with 60 ml of ethyl acetate,
The organic layer is washed with water and then concentrated under reduced pressure. The obtained residue was separated by silica gel column chromatography (eluent: toluene-ethyl acetate), and optically active 2- (6-decyloxy-naphthalen-2-yl) -5- (6-hydroxy-1-heptinyl). Pyrimidine (1-6) 0.9 g
(37%), [α] _D ²⁰ = −2.1 ° (c = 1, chloroform) and optically active 2- (6-decyloxy-naphthalen-2-yl) -5- (6-acetoxy-1-heptinyl). 1.5 g of pyrimidine (yield 56%) is obtained. The (1-6) and the optically active ester derivative obtained here can be reduced according to Example 3 to give an optically active 2- (6-decyloxy-naphthalen-2-yl) -5.
-(6-hydroxy-1-heptyl) pyrimidine (8-
2) and the optically active 2- (6-decyloxy-naphthalen-2-yl) -5- (6-acetoxy-1-heptyl) pyrimidine, respectively.

Example 10 1.1 g (2 mmol) of 2- (6-decyloxy-naphthalen-2-yl) -5- (6-acetoxy-1-heptinyl) pyrimidine (2-6) obtained in Example 9 A mixed solution of 15 ml of ethyl acetate and 0.1 g of 5% palladium-carbon was hydrogenated at 25 to 30 ° C. under normal pressure. The catalyst is filtered off,
By concentrating the filtrate, 2- (6-decyloxy-
Naphthalen-2-yl) -5- (6-acetoxy-1-
1.1 g (98%) of heptyl) pyrimidine (9-6) are obtained. Then, 0.8 g (1.5 mmol) of (9-6) obtained here, 30 ml of 0.2 M phosphate buffer (pH 7.0) and Pseudomonas lipase (lipase "P" amano)
0.2 g of the mixture is stirred vigorously at 30-35 ° C. for 60 hours. By post-treatment and purification according to Example 9 below, optically active 2- (6-decyloxy-naphthalen-2-yl) -5- (6-hydroxy-1-heptyl) pyrimidine (8-2) is obtained. 0.25g (34%), [α] _D
²⁰ = -1.8 ° (c = 1, chloroform) is obtained.

Example 11 2-Pentyloxy-6- (2- (5-trifluorometa
Sulfonyloxypyrimidyl)) quinoxaline (3-
7) 8.8 g (0.02 mol), 4-acetoxy-1-pliers
5 g (0.04 mol), bis (triphenylphosphine)
Palladium chloride 0.2g, Copper iodide 0.2g, Triphe
Nylphosphine 0.4 g, triethylamine 20 ml, N-
Charge 30 ml of methylpyrrolidone and react at 80 ° C for 9 hours
Let After completion of the reaction, post-treatment and purification are carried out according to Example 1.
2-pentyloxy-6- (2- (5-
(4-acetoxy-1-pentynyl) pyrimidyl)) ki
6.8 g (yield 81%) of noxalin (2-7) is obtained. Next
(2-7) 4.2 g (0.01 mol) obtained here, methanol
20 ml of ethyl acetate, 20 ml of ethyl acetate and 2% platinum-carbon
 Return 0.1g under hydrogen pressure of 1kg / cm2, 10-20 ℃
Origin After the reaction was completed, the catalyst was filtered off and the filtrate was concentrated.
2-pentyloxy-6- (2- (5- (4-
Acetoxy-1-pentyl) pyrimidyl)) quinoxali
This gives 4.2 g (98% yield) of benzene (9-7). Then (9
-7) 2.1 g (5 mmol), dichloromethane 2 ml, 3
80 ml of M phosphate buffer (pH 7.0) and pseudo
Monas lipase (Amano "P") 0.5g 35-40
Stir vigorously at 55 ° C. for 55 hours. According to Example 5 below
Optically active 2-pentylio by post-treatment and purification
Kishi 6- (2- (5- (4-hydroxy-1-pliers
Le) pyrimidyl)) quinoxaline (8-7) 0.7 g (yield
38%), [α]_D ²⁰= -2.3 ° (c = 1, chloropho
Rum) and optically active 2- (2,3-difluoro-4-)
Decylphenyl) -5- (4-acetoxy-1-pentyl
1.1 g (53% yield) of nyl) pyridazine are obtained. on the other hand,
2.1 g (5 mmol) of (2-7) obtained earlier is also the same.
Asymmetric hydrolysis under conditions, post-treatment, purification, the following compounds
To get Optically active 2-pentyloxy-6- (2-
(5- (4-hydroxy-1-pentynyl) pyrimidi
)) Quinoxaline (1-7) (yield 35%),
[Α]_D ²⁰= -2.6 ° (c = 1, chloroform) and
Optically active 2-pentyloxy-6- (2 (5- (4-
Acetoxy-1-pentynyl) pyrimidyl)) quinoxa
Phosphorus (yield 57%)

Example 12 5- (4'-bromo-4-biphenyl) -2-dodecyloxypyridine (3-8) 4.9 g (0.01 mol), 4-acetoxy-1-pentyne 2.5 g (0.02 mol), bis ( Triphenylphosphine) palladium chloride 0.2 g, copper iodide 0.2 g, triphenylphosphine 0.4 g, triethylamine 20 ml, and N-methylpyrrolidone 30 ml are charged and reacted at 80 ° C. for 12 hours. After completion of the reaction, by post-treatment and purification according to Example 1, 5- (4'-
(4-acetoxy-1-pentynyl) -4-biphenyl) -2dodecyloxypyridine (2-8) 4.2 g
(Yield 78%) is obtained. Then obtained here (2-8) 2.7
g (5 mmol), methanol 20 ml, ethyl acetate 30
ml and 5% palladium-carbon 0.1g hydrogen pressure 5kg
/ Cm2, reduction under the condition of 20 to 30 ° C. After completion of the reaction, the catalyst was filtered off and the filtrate was concentrated to give 5- (4 '-(4-acetoxy-1-pentyl) -4-biphenyl) -2dodecyloxypyridine (9-8) 2.7.
g (98% yield) are given. Next (9-8) 1.6 g (3
Mmol), 2 ml of dichloromethane, 60 ml of 3M phosphate buffer (pH 7.0), and 0.5 g of Pseudomonas lipase (Amano "P") are vigorously stirred at 35-40 ° C for 50 hours. The following optically active 5- (4 ′-(4-hydroxy-
1-pentyl) -4-biphenyl) -2 dodecyloxypyridine (8-8) 0.55 g (yield 37%) [α] _D
²⁰ = −2.3 ° (c = 1, chloroform) and optically active 5- (4 ′-(4-acetoxy-1-pentyl) -4
-Biphenyl) -2 dodecyloxypyridine 0.9 g
(Yield 54%) is obtained. On the other hand, previously obtained (2-8)
Asymmetric hydrolysis of 1.1 g (2 mmol) under the same conditions,
Post-treatment and purification give the following compounds. Optically active 5- (4 '-(4-hydroxy-1-pentynyl) -4-biphenyl) -2dodecyloxypyridine (1-8)
(Yield 36%), [α] _D ²⁰ = −2.5 ° (c = 1, chloroform) and optically active 5- (4 ′-(4-acetoxy-1-pentynyl) -4-biphenyl) -2dodecyl. Oxypyridine (yield 55%)

Example 13 In a four-necked flask equipped with a stirrer and a thermometer, 5- (4-bromophenyl) -2- (4-hexylphenyl) pyridine (3-9) 7.9 g (0.02 mol), 5-hydroxy-1-hexyne 2.9 g (0.03 mol), copper iodide 0.
16 g, triphenylphosphine 0.3 g, bis (triphenylphosphine) palladium (II) chloride 0.2 g,
70 ml of triethylamine was charged, and the mixture was heated and stirred in a nitrogen atmosphere for 9 hours. After the reaction was completed, the reaction mixture was added to 100 ml of water.
And extracted with a mixed solution of toluene and ethyl acetate. The obtained organic solvent layer is washed with water and then concentrated under reduced pressure to obtain a yellowish brown residue. This was purified by silica gel column chromatography (eluent: toluene-ethyl acetate) and 5- (4- (5-hydroxy-1-hexynyl) phenyl) -2- (4-hexylphenyl) pyridine (6
-9) Obtain 6.4 g. (Yield 79%) 4.1 g (0.01 mol) of (6-9) obtained here, acetic anhydride 2.
Charge 80 g and pyridine 50 ml, and stir at 40-50 ° C. for 5 hours. After completion of the reaction, the reaction mixture was poured into 100 ml of water, neutralized with dilute sulfuric acid, and extracted with a mixed solution of toluene-ethyl acetate. The obtained organic solvent layer was washed with water and then concentrated under reduced pressure to give 5- (4- (5-acetoxy-1-hexynyl) phenyl) -2- (4-hexylphenyl) pyridine (2
-9) Obtain 4.4 g. (Yield 97%) 3.6 g (8 mmol) of (2-4) obtained here was mixed with 150 ml of 0.8 M phosphate buffer (pH 7.0), chloroform 3 ml and 1.0 g of Pseudomonas lipase (lipase Amano "P"). Add to the mixture and add 6 at 30-35 ° C.
Stir vigorously for 0 hours. The resulting mixture is extracted with 100 ml of toluene-ethyl acetate, the organic layer is washed with water and then concentrated under reduced pressure. The obtained mixture was separated by silica gel column chromatography (eluent: toluene-ethyl acetate), and the optically active (−)-5- (4- (5-hydroxy-
1-hexynyl) phenyl) -2- (4-hexylphenyl) pyridine (1-9) 1.2 g (yield 36%),
[Α] _D ²⁰ = −2.3 ° (c = 1, chloroform) and (−)-5- (4- (5-acetoxy-hexynyl) phenyl) -2- (4-hexylphenyl) pyridine 1.9
g (yield 53%), [α] _D ²⁰ = −3.1 ° (c = 1, chloroform) are obtained. The optically active (1-
9) and 5- (4- (5-acetoxy-1-hexynyl) phenyl) -2- (4-hexylphenyl) pyridine can be reduced according to Example 2 to synthesize the following compound. . 5- (4- (5-hydroxy-1-hexyl) phenyl) -2- (4-hexylphenyl) pyridine (8-9), [α] _D ²⁵ = −2.1 °
(C = 1, chloroform) and 5- (4- (5-acetoxy-1-hexyl) phenyl) -2- (4-hexylphenyl) pyridine

Examples 14 to 21 When the reaction and the post-treatment are carried out in order according to Example 4 except that the starting materials shown in Table 1 are used, the optically active alcohol derivative (1) shown in Table 1 is obtained. And optically active saturated alcohols (8) are obtained.

Examples 22 to 25 Reactions and post-treatments were sequentially carried out according to Example 9 except that the starting materials shown in Table 2 were used, and the optically active saturated alcohols (8) shown in Table 2 were obtained. Is obtained.

Examples 26 to 31 Reactions and post-treatments were sequentially carried out in accordance with Examples 5 and 7 except that the starting materials shown in Table 3 were used, and the optically active alcohol derivative (1 ) And an optically active saturated alcohol (8) were obtained.

[0041]

[Table 1]

[Table 2]

[Table 3]

[Table 4]

[Table 5]

[Table 6]

[Table 7]

[Table 8]

[Table 9]

Continuation of the front page (51) Int.Cl. ⁶ Identification code Office reference number FI Technical display location C07C 33/18 33/24 43/178 C 7419-4H 69/24 9279-4H C07D 213/30 213/64 215 / 14 217/16 237/08 237/10 239/26 239/34 239/74 239/80 241/12 241/18 241/42 241/44 C12P 17/12 7432-4B // C07B 61/00 300 C07M 7:00 (72) Inventor Masayoshi Minai 2-10-1 Tsukahara, Takatsuki City, Osaka Prefecture Sumitomo Kagaku Kogyo Co., Ltd.

Claims (13)

[Claims] 1. A general formula (1) (In the formula, R1 represents a saturated or unsaturated alkyl group having 1 to 20 carbon atoms, a saturated or unsaturated alkoxyalkyl group having 2 to 20 carbon atoms, a hydrogen atom or a hydroxyl-protecting group, and R represents hydrogen. An atom or a group COR ² , R ² represents a lower alkyl group, m and q represent 0 or 1, and
n represents an integer of 0 to 8, and A1, A2 and A3 are respectively And when A1 or A2 is a condensed ring, q is 0.
And when A1 and A2 are monocyclic, q is 1 and the * mark indicates an asymmetric carbon atom. ) Is an optically active alcohol derivative. 2. General formula (2) (In the formula, R1, R2, A1, A2, A3, m, n and q have the same meanings as described above). 3. A general formula (6) (Wherein R1, m, n, q, A1, A2 and A3 have the same meanings as described above). 4. A general formula (8) (Wherein R ¹ , m, n, q, A ¹ , A ² , A ³ and R
Represents the same meaning as described above. The * mark indicates an asymmetric carbon atom. ) Optically active saturated alcohols represented by. 5. General formula (9) (Wherein R1, R2, m, n, q, A1, A2 and A
3 has the same meaning as above. ) The ester shown by. 6. An asymmetric hydrolysis using an esterase having the ability to preferentially hydrolyze either one of the optically active isomers of the ester derivative represented by the general formula (2). A method for producing an optically active alcohol derivative represented by (1). 7. A general formula (3) R1- (O) m-A1-A2- (A3) q-X (3) (wherein R1, m, q, A1, A2 and A3 have the same meanings as described above. And X is a halogen atom or -OSO
₂ R'is shown. Here, R'represents a lower alkyl group optionally substituted with a fluorine atom or a phenyl group optionally substituted. ) And a general formula (4) Wherein an acetylene represented by the formula (wherein R ² and n have the same meanings as described above) is reacted in the presence of a vanadium catalyst and a basic substance to obtain an ester derivative represented by the general formula (2). Item 7. A method for producing an optically active alcohol derivative according to Item 6. 8. A halide represented by the general formula (3) and a general formula (5) (In the formula, n has the same meaning as described above.) The acetylene compound is reacted in the presence of a palladium catalyst and a basic substance to obtain an alcohol represented by the general formula (6), The ester represented by the general formula (2) is obtained by reacting with a carboxylic acid represented by the formula (7) R2 COOH (7) (wherein R2 has the same meaning as described above) or a derivative thereof. 7. The method for producing an optically active alcohol derivative according to item 6. 9. An optically active saturated alcohol represented by the general formula (8), which is obtained by hydrogenating the optically active alcohol derivative represented by the general formula (1) in the presence of a hydrogenation catalyst. Manufacturing method. 10. An ester derivative represented by the general formula (2) is hydrogenated in the presence of a hydrogenation catalyst to obtain an ester represented by the general formula (9), which is an optically active substance of the ester. A process for producing an optically active saturated alcohol represented by the general formula (8), which comprises asymmetric hydrolysis using an esterase having the ability to preferentially hydrolyze either one. 11. A halide represented by the general formula (3) is reacted with an acetylene represented by the general formula (4) in the presence of a palladium catalyst and a basic substance to form the compound represented by the general formula (2). The method for producing an optically active saturated alcohol represented by the general formula (8) according to claim 10, wherein an ester derivative is obtained. 12. A halide represented by the general formula (3) and an acetylene represented by the general formula (5) are reacted with each other in the presence of a palladium catalyst and a basic substance, and represented by the general formula (6). The formula (8) according to claim 10, wherein an alcohol derivative is obtained and then reacted with a carboxylic acid represented by the formula (7) or a derivative thereof to obtain an ester represented by the formula (2). Method for producing optically active saturated alcohols. 13. A halogenated compound represented by the general formula (3) is reacted with an acetylene compound represented by the general formula (5) in the presence of a palladium catalyst and a basic substance to form a compound represented by the general formula (6). The alcohol derivative is obtained and then hydrogenated using hydrogen and a hydrogenation catalyst to give a compound of general formula (10) (Wherein R1, R2, m, n, q, A1, A2 and A
3 has the same meaning as above. ) To obtain a racemic saturated alcohol, which is further reacted with a carboxylic acid represented by the general formula (7) or a derivative thereof to obtain an ester represented by the general formula (9), and an optical activity of the ester. A method for producing an optically active saturated alcohol represented by the general formula (8), which comprises asymmetric hydrolysis using an esterase having the ability to preferentially hydrolyze one of the bodies.