JP2503040B2 - α-Substituted-γ-alkoxyallyl sulfide derivative and method for producing the same - Google Patents

Description

TECHNICAL FIELD The present invention relates to a novel α-substituted-γ-alkoxyallyl sulfide derivative and a method for producing the same.

The α-substituted-γ-alkoxyallyl sulfide derivative of the present invention is expected to be useful as an anti-asthma drug because it has a leukotriene production inhibitory action (E,
Z, Z, Z) -5- (2-carbamoylhydrazono) -6,8,1
(E, Z, Z, Z) -5- such as 1,14-eicosatetraenoic acid
Known to be a synthetic intermediate for the production of substituted-6,8,11,14-eicosatetraenoic acid (E, Z, Z, Z)
Useful as a synthetic intermediate for producing a hydroxypolyene compound having a defined geometrical isomerism such as 5-hydroxy-6,8,11,14-eicosatetraenoic acid methyl ester [Journal of Medicinal・ Chemistry (Journal of Medicinal Chemistry) Vol. 30, Vol.
See pages 1177 to 1186 (1987)].

2. Description of the Related Art Conventionally, among hydroxypolyene compounds whose geometrical isomerism is defined, (E, Z, Z, Z) -5-hydroxy-6,8,11,14
-Eicosatetraenoic acid methyl ester is obtained by reacting arachidonic acid with iodine in the presence of potassium carbonate and potassium iodide, and converting the resulting 6-iodolactone compound to 1,5-
By carrying out a dehydroiodination reaction in the presence of diazebicyclo [5.4.0] undec-5-ene (DBU) (E, Z, Z,
Z) -5-Hydroxy-6,8,11,14-ecosatetraenoic acid is known to be prepared by obtaining the delta-lactone and then reacting the delta-lactone with methanol in the presence of triethylamine.

[Tetrahedron Letters]
Vol. 22, pp. 299-302 (1981)] Problems to be Solved by the Invention The above conventional method is industrially advantageous because it is difficult to obtain a large amount of arachidonic acid used as a raw material. It is hard to say that it is a simple method.

Therefore, one of the objects of the present invention is to provide a novel compound which can be easily produced from readily available raw materials and can be derived into a hydroxypolyene compound having a defined geometrical isomerism. Another object of the invention is to provide a process for preparing the novel compounds.

Means for Solving the Problems According to the present invention, the above-mentioned object is represented by the general formula (In the formula, R ¹ represents a lower alkyl group or an aryl group which may have a substituent, and R ² , R ³ , R ⁶ , R ⁷ , R ⁸ and R ⁹ each represent a hydrogen atom or a substituent. Having an alkyl group which may have, an alkenyl group which may have a substituent, an aralkyl group which may have a substituent, an aryl group which may have a substituent or a substituent Optionally represents a cycloalkyl group, wherein R ⁶ together with R ⁷ or R ⁸ may represent an alkylene group which may have a substituent, and R ⁴ represents a lower alkyl group. R ⁵ is a hydrogen atom, an alkyl group which may have a substituent, an alkenyl group which may have a substituent, an aralkyl group which may have a substituent, and a substituent which has a substituent. Optionally an aryl group, a cycloalkyl group optionally having a substituent, a group represented by the formula-OR ⁴ or a formula-SR ¹ represents a group represented by 1 and n represents an integer of 0 or 1.), and a compound represented by the general formula: (In the formula, R ¹ , R ² , R ³ , R ⁴ and R ⁵ are as defined above.) After the γ-alkoxyallyl sulfide derivative represented by the formula is treated with a base, the presence of a strongly coordinating compound The general formula below (In the formula, R ⁶ , R ⁷ , R ⁸ , R ⁹ and n are as defined above.) Α-represented by the general formula (I) characterized by reacting with an oxygen-containing compound represented by This is accomplished by providing a method of making a substituted-γ-alkoxyallyl sulfide derivative.

R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , in each of the above general formulas,
R ⁷ , R ⁸ and R ⁹ will be described in detail. Examples of the lower alkyl group represented by R ¹ and R ⁴ include a methyl group, an ethyl group, a propyl group, a butyl group, a t-butyl group and the like. Examples of the aryl group represented by R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ include, for example, a phenyl group,
Examples thereof include a tolyl group and a naphthyl group. R ² , R ³ , R ⁵ ,
Examples of the alkyl group represented by R ⁶ , R ⁷ , R ⁸ and R ⁹ include, for example, methyl group, ethyl group, propyl group, butyl group, pentyl group, hexyl group, heptyl group, octyl group, nonyl group and decyl group. Examples of the alkenyl group include a vinyl group, a propenyl group, a butenyl group, a pentenyl group, a hexenyl group, a heptenyl group, an octenyl group, an undecenyl group, an octadienyl group, and an undecadienyl group, and an aralkyl group. Examples of the group include a benzyl group, a phenethyl group,
Examples thereof include a naphthylmethyl group, and examples of the cycloalkyl group include a cyclohexyl group and a cyclopentyl group. Examples of the alkylene group represented by R ⁶ together with R ⁷ include a tetramethylene group,
Examples thereof include a pentamethylene group, and examples of the alkylene group represented by R ⁶ together with R ⁸ include a trimethylene group and a tetramethylene group. Substituents which these aryl group, alkyl group, alkenyl group, aralkyl group, cycloalkyl group and alkylene group may have include, for example, hydroxyl group; lower alkoxyl group such as methoxy group and ethoxy group; carboxyl group A lower alkoxycarbonyl group such as a methoxycarbonyl group and an ethoxycarbonyl group.

The γ-alkoxyallyl sulfide derivative represented by the general formula (II) is treated with a base and then reacted with the oxygen-containing compound represented by the general formula (III) to obtain the α-substituted-γ represented by the general formula (I). -Alkoxyallyl sulfide derivatives can be obtained. As the base, for example, an organic lithium compound such as butyllithium, s-butyllithium, t-butyllithium, or methyllithium can be used. The base is γ represented by the general formula (II)
-Usually used in an amount in the range of about 0.8 to 1.5 moles per mole of the alkoxyallyl sulfide derivative, especially about 1.
It is preferably used in an amount within the range of 0 to 1.3 mol. The treatment of the γ-alkoxyallyl sulfide derivative represented by the general formula (II) with a base is preferably carried out in an organic solvent, and examples of such an organic solvent include cyclic or chain-like ones such as tetrahydrofuran, dimethoxyethane and diethyl ether. It is possible to use an organic solvent which does not react with the base used, such as the ether-based solvent. The amount of the organic solvent used is not critical, but is usually in the range of about 5 to 20 times the weight of the γ-alkoxyallyl sulfide derivative represented by the general formula (II). The treatment with a base is usually carried out at a temperature in the range of about -100 to 0 ° C, particularly preferably at a temperature in the range of about -80 to -20 ° C.

The carbanion formed by treating the γ-alkoxyallyl sulfide derivative represented by the general formula (II) with a base is treated with the general formula (III) in the presence of a strongly coordinating compound without isolation from the reaction mixture. React with the indicated oxygenates. In this case, the reaction mixture containing the carbanion can be directly subjected to the reaction.
The strongly coordinating compound used here may be a compound having a high affinity for a cation derived from a previously used base such as lithium ion, and typical examples thereof include hexamethylphosphoramide and tetramethyl. Examples thereof include ethylenediamine and [2,2,2] -cryptate. The amount of the strongly coordinating compound to be used is usually in the range of about 0.9 to 10 mol, preferably about 1 mol, relative to 1 mol of the γ-alkoxyallyl sulfide derivative represented by the general formula (II) used initially. It is an amount within the range of 1 to 5 mol. The compound represented by the general formula (III) used in the reaction has the general formula (In the formula, R ⁶ and R ⁷ are as defined above.) And a general formula (In the formula, R ⁶ , R ⁷ , R ⁸ and R ⁹ are as defined above.), Which are roughly classified into epoxy compounds represented by the general formula (II) originally used. The amount of γ-alkoxyallyl sulfide derivative is usually about 0.
It is used in an amount in the range of 9 to 2.0 moles, particularly preferably in an amount in the range of about 1.0 to 1.5 moles. This reaction is preferably carried out in an organic solvent. Any organic solvent may be used as long as it does not inhibit the reaction, and an organic solvent such as an ether solvent which can be used in the treatment with the base of the γ-alkoxyallyl sulfide derivative represented by the general formula (II) is used To be done. The amount of the organic solvent used is not critical, but is usually about 5 with respect to the γ-alkoxyallyl sulfide derivative represented by the general formula (II) used initially.
It is in the range of up to 20 times the weight. Γ represented by the general formula (II)
-The reaction mixture obtained by treating the alkoxyallyl sulfide derivative with a base is used as it is in the general formula (II
It is convenient in terms of reaction operation to use the organic solvent used in the treatment with a base as it is in the next reaction by subjecting it to the reaction with the oxygen-containing compound represented by I). The strongly coordinating compound may be allowed to be present in the system during the treatment with the base in advance. The reaction temperature is usually about -100 to
It is in the range of 0 ° C, preferably in the range of about -80 to -20 ° C.

The α − represented by the general formula (I) thus obtained
Separation / purification of the substituted-γ-alkoxyallyl sulfide derivative from the reaction mixture can be carried out, for example, by the following method. The reaction mixture is mixed with an aqueous solution such as an aqueous solution of ammonium chloride or water and then extracted with an organic solvent such as ethyl acetate, the organic solvent is distilled off from the extract, and the residue is then subjected to silica gel column chromatography, alumina column chromatography, etc. The α-substituted-γ-alkoxyallyl sulfide derivative represented by the general formula (I) can be obtained by subjecting to the purification operation of.

The γ-alkoxyallyl sulfide derivative represented by the general formula (II) can be synthesized by the method described in, for example, the 52nd Organic Synthesis Symposium Lectures, pages 75 to 78 (published on October 22, 1987). According to the general formula (In the formula, R ² , R ³ , R ⁴ and R ⁵ are as defined above, and R
¹⁰ represents a lower alkyl group. ) Is represented by the general formula R ¹¹ _m Sn (SR ⁻¹ ) _4-m (V) in the presence of boron trifluoride etherate (wherein R ¹ is as defined above and R ¹¹ is alkyl). Group, and m represents an integer of 2 or 3.), thereby easily producing the compound.

The α-substituted-γ-alkoxyallyl sulfide derivative represented by the general formula (I) can be obtained by reacting with a general formula (In the formula, R ² , R ³ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ and n are as defined above, and R ² and R ³ are a carbon atom-carbon atom double bond. In the trans position with respect to each other.) Is induced to an α, β-unsaturated carbonyl compound. Examples of the peroxide include organic peracids such as m-chloroperbenzoic acid, peracetic acid, and perbenzoic acid or sodium metaperiodate, hydrogen peroxide, diperoxo-oxohexamethylphosphoramide molybdenum (VI), and the like. Inorganic peroxides are used, but it is particularly preferable to use sodium metaperiodate. The peroxide is usually used in an amount within the range of about 0.9 to 3.0 mol, particularly about 1.0 to 2.0 mol, based on 1 mol of the α-substituted-γ-alkoxyallyl sulfide derivative represented by the general formula (I). It is preferred to use an amount within the range. Α-Substitution represented by the general formula (I)
The reaction between the γ-alkoxyallyl sulfide derivative and the peroxide is carried out by using a water-soluble organic solvent such as a cyclic ether such as dioxane and tetrahydrofuran, a lower alkanol such as methanol and ethanol; a water-insoluble solvent such as a hydrocarbon dihydrogen such as dichloromethane and dichloroethane. Organic solvent; or a solvent that does not inhibit the reaction, such as a mixed solvent of a water-soluble or water-insoluble organic solvent and water. The amount of the solvent used is not critical, but the general formula (I)
The amount is usually 5 to 20 times the weight of the α-substituted-γ-alkoxyallyl sulfide derivative. The reaction temperature is usually in the range of about -20 ° C to 80 ° C, preferably about 0 to 40 ° C.

Α obtained by the general formula (VI) thus obtained,
Separation of β-unsaturated carbonyl compound from the reaction mixture
Purification can be performed, for example, by the following method. The reaction mixture or the solvent is distilled off from the organic layer obtained by extracting the reaction mixture with a solvent such as ethyl acetate and then washing with a sodium hydrogen carbonate solution, and subjecting the residue to purification operations such as silica gel column chromatography and alumina column chromatography. Thereby, the α, β-unsaturated carbonyl compound represented by the general formula (VI) can be obtained.

The α, β-unsaturated carbonyl compound represented by the general formula (VI) has a double bond between the α-position carbon atom and the β-position carbon atom. (Wherein R ⁶ , R ⁷ , R ⁸ , R ⁹ and n are as defined above) and a group having a hydroxyl group and a formula (In the formula, R ⁵ is as defined above.) Since the group having a carbonyl group and the group having a carbonyl group are arranged in the trans position, (E, Z, Z, Z) -5-hydroxy −6,8,11,14
-Derived to hydroxypolyene compounds with defined geometrical isomerism, such as eicosatetraenoic acid methyl ester. For example, (E) -5-hydroxy- which is one of the α, β-unsaturated carbonyl compounds represented by the general formula (VI).
Methyl 8-oxo-6-octenoate may be prepared in an inert solvent such as tetrahydrofuran, diethyl ether or toluene at a temperature within the range of -80 to 50 ° C, preferably about -30 to 0.
At a temperature within the range of about 0.8 to about 1 mol of the methyl (E) -5-hydroxy-8-oxo-6-octenoate.
(E, Z, Z, Z) -5-hydroxy-6,8,11 by reacting with an amount of (Z, Z) -3,6-dodecadienylidenetriphenylphosphorane in the range of 1.2 moles. Induced by methyl 14,14-eicosatetraenoic acid ester.

EXAMPLES Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited to these examples.

Example 1 1-ethoxy-3-phenylthio-1 under a nitrogen atmosphere
-In a solution consisting of 1.94 g of propene, 6.8 ml of hexamethylphosphoramide and 20 ml of tetrahydrofuran, at -78 ° C,
5 ml of a 2.2 M pentane solution of t-butyllithium was gradually added dropwise. After continuing the stirring at the same temperature for 3 minutes after the dropping,
A solution of 1.59 g of benzaldehyde in 5 ml of tetrahydrofuran was gradually added dropwise, and stirring was continued for another 30 minutes at the same temperature.
Aqueous ammonium chloride solution (10 ml) was added to the obtained reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, low-boiling substances were distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography treated with ammonia to give the following: 4-Ethoxy-1-phenyl- having physical properties
2.40 g of 2-phenylthio-3-buten-1-ol was obtained (yield 80%).

IR spectrum (neat): 3450cm ^-1 0.73 (t, J = 7.08Hz, 1.5H), 0.77 (t, J = 6.83Hz, 1.5
H), 3.16 (m, 2H), 3.45 (br, 1H), 3.75 (m, 1H), 4.64 (m,
2H), 5.83 (d, J = 12.4Hz, 0.5H), 5.92 (d, J = 12.4Hz, 0.5
H), 6.9-7.4 (m, 10H) FD mass spectrum: [MH ₂ O] ⁺ 282 Example 2 In Example 1, benzaldehyde 1.59 g (15 mmo)
2.13 g (15 mmol) of 1,2-epoxyheptane instead of l)
By performing the reaction and separation and purification in the same manner as in Example 1 except that was used, 1.31 g of 1-ethoxy-3-phenylthio-1-decen-5-ol having the following physical properties was obtained (yield 43%). .

IR spectrum (neat): 3400cm ^-1 0.88 (t, J = 6.10Hz, 3H), 1.17 (t, J = 7.08Hz, 3H), 1.29 (m, 8H), 1.76 (m, 3H), 3.65 (m, 4H), 4.61 (m, 1
H), 6.06 (d, J = 12.4Hz, 0.5H), 6.10 (d, J = 12.6Hz, 0.5
H), 7.32 (m, 5H) Example 3 In Example 1, benzaldehyde 1.59 g (15 mmo
1-Ethoxy-3-phenylthio-1-dodecene-4- having the following physical properties was obtained by carrying out the reaction and separation and purification in the same manner as in Example 1 except that 2.60 ml (15 mmol) of nonylaldehyde was used instead of l). 2.28 g of oat was obtained (yield 7
1%).

IR spectrum (neat): 3350cm ^-1 0.96 (m, 6H), 1.29 (m, 14H), 2.44 (br, 1H), 3.30
(M, 2H), 3.69 (m, 2H), 4.74 (m, 1H), 6.13 (d, J = 12.4Hz, 0.5
H), 6.34 (d, J = 12.6Hz, 0.5H), 7.03 (m, 3H), 7.44 (m, 2
H) FD mouse spectrum: [M] ⁺ 336 Example 4 Consists of 416 mg (2 mmol) of 2-ethyl-1-methoxy-3-phenylthio-1-propene, 1.36 ml of hexamethylphosphoramide and 4 ml of tetrahydrofuran under a nitrogen atmosphere. 1.18 ml (2.6 mmol) of a 2.2 M pentane solution of t-butyllithium was gradually added dropwise to the solution at -78 ° C. After the dropwise addition was completed, stirring was continued for 3 minutes at the same temperature, and then a solution of 0.36 ml (3 mmol) of 1,2-epoxy-2-methyl-3-butene in 1 ml of tetrahydrofuran was slowly added dropwise, and the mixture was stirred at the same temperature for 30 minutes. Continued. 2 ml of an ammonium chloride aqueous solution was added to the obtained reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, low-boiling substances were distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography treated with ammonia to give the following: 2-Ethyl having physical properties
1-methoxy-5-methyl-3-phenylthio-1,6-
479 mg of heptadien-5-ol was obtained (yield 82%).

IR spectrum (neat): 3420cm ^-1 1.48 (m, 6H), 2.00 (m, 2H), 2.32 (m, 2H), 2.98 (s,
1,5H), 3.00 (s, 1.5H), 3.86 (m, 1H), 5.05 (m, 1H), 5.4-6.
0 (m, 3H), 7.06 (m, 3H), 7.44 (m, 2H) FD mass spectrum: [M] ⁺ 292 Example 5 In Example 4, 1,2-epoxy-2-methyl-3
-2-hexenal instead of butene 0.36 ml (3 mmol)
It has the following physical properties by performing the reaction and separation and purification in the same manner as in Example 4 except that 0.35 ml (3 mmol) was used.
244 mg of -ethyl-1-methoxy-3-phenylthio-1,5-nonadien-4-ol was obtained (yield 40%).

IR spectrum (neat): 3430cm ^-1 0.88 (m, 3H), 1.28 (m, 5H), 1.94 (m, 2H), 2.34 (m, 3
H), 3.01 (s, 1.5H), 3.06 (s, 1.5H), 3.54 (d, J = 8.30Hz,
0.5H), 3.67 (d, J = 6.83Hz, 0.5H), 4.26 (m, 1H), 5.73 (m, 3H), 7.03 (m, 3H), 7.42 (m, 2H) FD mass spectrum: [M ] ⁺ 306 Example 6 In Example 4, 2-ethyl-1-methoxy-3-
2-ethyl-1-methoxy-3-phenylthio-1-butene 444 mg (2 mmol) was used in place of phenylthio-1-propene 416 mg (2 mmol), and 1,2-epoxy-2-
2-Ethyl-1-methoxy having the following physical properties was obtained by performing the same reaction and separation and purification as in Example 4 except that 0.32 ml (3 mmol) of pentanal was used instead of 0.36 ml (3 mmol) of methyl-3-butene. 220 mg of -3-methyl-3-phenylthio-1-octen-4-ol was obtained (yield 3
Five%).

IR spectrum (neat): 3450cm ^-1 0.73-1.64 (m, 12H), 1.13 (m, 3H), 2.09 (m, 3H), 3.25 (s, 1.5H), 3.30 (m.1H), 3.42 (s, 1.5H), 5.15 (s, 0.5H), 5.69 (s, 0.5H), 7.25 (m, 5H) Examples 7 and 8 In Example 4, 2-ethyl-1-methoxy-3-
Phenylthio-1-propene 416 mg (2 mmol) was replaced with 1-methoxy-2-methyl-3-phenylthio-1-butene 388 mg (2 mmol), and 1,2-epoxy-2-
Instead of 0.36 ml (3 mmol) of methyl-3-butene, 0.46 ml (3 mmol) of octanal or 0,2-epoxy-octane.
By performing the reaction and separation and purification in the same manner as in Example 4 except that 46 mo (3 mmol) was used, 1-methoxy-
2-Methyl-3-phenylthio-1-undecene-4-
All (Example 7) and 1-methoxy-2-methyl-3
-Cenylthio-1-undecen-5-ol (Example 8) was obtained. The results are shown in Table 1.

Examples 9 to 12 In Example 4, 2-ethyl-1-methoxy-3-
Phenylthio-1-propene (416 mg, 2 mmol) was replaced with 1-methoxy-3-phenylthio-1-butene, 388 mg (2
mmol) and 1,2-epoxy-2-methyl-3-
The reaction and separation / purification were carried out in the same manner as in Example 4 except that 1,2-epoxyoctane, cyclohexene epoxide, octanal or cyclohexanone was used in an amount of 3 mmol instead of 0.36 ml (3 mmol) of butene.
-Methoxy-3-methyl-3-phenylthio-1-undecen-5-ol (Example 9), 2- (3-methoxy-1-methyl-1-phenylthio-2-propenyl) cyclohexan-1-ol (implementation) Example 10), 1-methoxy-3-methyl-3-phenylthio-1-undecene-4
-Ol (Example 11) and 1- (3-methoxy-1-methyl-1-phenylthio-2-propenyl) cyclohexan-1-ol (Example 12) were obtained. The results are shown in Table 2.

Examples 13 and 14 In Example 1, 1.59 g of benzaldehyde (15 mmo
l) was replaced by 1.50 g (15 mmol) of hexanal, and 1-ethoxy-3-phenylthio-1-propene 1.94.
1-ethoxy-3- (4-methylphenyl) thio-1-propene or 1-ethoxy-3 instead of g (10 mmol)
1-Ethoxy-3- (4-methylphenyl) thio-1-nonene-4- was prepared by carrying out the reaction and separation and purification in the same manner as in Example 1 except that 10 mmol of each of -t-butylthio-1-propene was used. All (Example 13) and 1
-Ethoxy-3-t-butylthio-1-nonen-4-ol (Example 14) was obtained. The results are shown in Table 3.

Examples 15 and 16 In Example 1, benzaldehyde 1.59 g (15 mmo
8-ethoxy-6 was obtained by carrying out the reaction and separation and purification in the same manner as in Example 1 except that 15 mmol of 4-methoxycarbonylbutanal or (Z) -3-nonen-1-al was used instead of l). Methyl -hydroxy-7-phenylthio-7-octenoate (Example 15) and (6Z) -1-ethoxy-3-phenylthio-1,6-dodecadien-4-ol (Example 16) were obtained. The results are shown in Table 4.

Examples 17 and 18 In Example 1, benzaldehyde 1.59 g (15 mmo
l) was replaced by 1.50 g (15 mmol) of hexanal, and 1-ethoxy-3-phenylthio-1-propene 1.94.
Example 1 except that 10 mmol of 1,1-diethoxy-3-phenylthio-1-propene or 2-ethoxy-4-phenylthio-2-butene was used instead of g (10 mmol), respectively.
By performing the reaction and separation and purification in the same manner as in 1,
1-diethoxy-3-phenylthio-1-nonene-4-
All (Example 17) and 2-ethoxy-4-phenylthio-2-decen-5-ol (Example 18) were obtained. The results are shown in Table 5.

Reference Example 1 4-Ethoxy-1-phenyl-2 obtained in Example 1
-Phenylthio-3-buten-1-ol 300 mg (1 mm
ol), 4 ml of dioxane and 1 ml of water, 428 mg of sodium metaperiodate was added, and the mixture was stirred at room temperature for 20 hours. After confirming the disappearance of raw materials, ethyl acetate was added to the reaction mixture.
40 ml was added for extraction. The extract was washed successively with 10 ml of saturated aqueous sodium hydrogen carbonate and 10 ml of saturated brine, dried over anhydrous sodium sulfate, and the low-boiling substances were distilled off from this. The resulting residue has the following physical properties by being purified by silica gel column chromatography treated with ammonia (E)-
144 m of 4-hydroxy-4-phenyl-2-butenal
g was obtained (yield 89%).

IR spectrum (neat): 3400,1680,1635cm ^-1 2.95 (br, s, 1H), 5,41 (br, d, J = 3.9Hz, 1H), 6.35 (d
dd, J = 1.46,7,8,15.6Hz, 1H), 6.87 (dd, J = 3.9,15.6Hz,
1H), 7.33 (s, 5H), 9.49 (d, J = 7.8Hz, 1H) Reference Examples 2, 3 and 4 In Reference Example 1, 4-ethoxy-1-phenyl-2
-Phenylthio-3-buten-1-ol 300 mg (1 mmo
1-ethoxy-3-phenylthio-1-in place of l)
Decen-5-ol, 1-ethoxy-3-phenylthio-1-dodecen-4-ol or 2-ethyl-1-methoxy-5-methyl-3-phenylthio-1,6-heptadien-5-ol, respectively. By performing the reaction and separation and purification in the same manner as in Reference Example 1 except that 1 mmol was used, (E) -5-hydroxy-2-decenal (Reference Example 2) and (E) -4-hydroxy-2-dodecenal ( Reference Example 3) and (E) -2-ethyl-5-hydroxy-5
-Methyl-2,6-heptadienal (Reference Example 4) was obtained. The results are shown in Table 6.

Reference Example 5 Under a nitrogen atmosphere, a solution of 200 mg of 2-ethyl-1-methoxy-3-phenylthio-1,5-nonadiene-4-ol and 5 ml of methylene chloride was added to diperoxo-oxohexamethylphosphoramide under ice cooling. 571 mg of molybdenum-pyridine complex was added and stirred for 1 hour. 5 ml of diethyl ether was added to the resulting reaction mixture, and the mixture was passed through Celite. The liquid is concentrated under reduced pressure, and the obtained concentrate is purified by silica gel column chromatography treated with ammonia to have the following physical properties (2E) -2-
90 mg of ethyl-4-hydroxy-2,5-nonadienal
Obtained (yield 75%).

IR spectrum (neat): 3400,1682,1638cm ^-1 0.89 (t, J = 7.32Hz, 3H), 0.97 (t, J = 7.81Hz, 3H), 1.41 (m, 2H), 2,17 (m, 4H), 5.08 (m, 1H), 5.64 (m , 2
H), 6.34 (d, J = 8.3 Hz, 1H), 9.38 (s, 1H) Reference Examples 6 to 12 In Reference Example 1, 4-ethoxy-1-phenyl-2
-Phenylthio-3-buten-1-ol 300 mg (1 mmo
2-ethyl-1-methoxy-3-methyl-3-phenylthio-1-octen-4-ol in place of l), 1-
Methoxy-2-methyl-3-phenylthio-1-undecen-4-ol, 1-methoxy-2-methyl-3-phenylthio-1-undecen-5-ol, 1-methoxy-3-methyl-3-phenylthio- 1-Undecen-
5-ol, 2- (3-methoxy-1-methyl-1-phenylthio-2-propenyl) cyclohexane-1-ol, 1-methoxy-3-methyl-3-phenylthio-
1-undecen-4-ol or 1- (3-methoxy-
By performing the reaction and separation and purification in the same manner as in Reference Example 1 except that 1 mmol of 1-methyl-1-phenylthio-2-propenyl) cyclohexan-1-ol was used,
(E) -2-Ethyl-4-hydroxy-3-methyl-2-octenal (Reference Example 6), (E) -4-hydroxy-2-methyl-2-undecenal (Reference Example 7), (E) -5-hydroxy-2-methyl-2-undecenal (Reference Example 8), (E) -5-hydroxy-3
-Methyl-2-undecenal (Reference Example 9), (E)-
3- (2-Hydroxycyclohexyl) -2-butenal (Reference Example 10), (E) -4-hydroxy-3-methylundecenal (Reference Example 11) and (E) -3- (1-hydroxycyclohexyl) -2- Butenal (Reference Example 1
2) got. The results are shown in Table 7.

Reference Examples 13 to 18 In Reference Example 1, 4-ethoxy-1-phenyl-2
-Phenylthio-3-buten-1-ol 300 mg (1 mmo
1-ethoxy-3- (4-methylphenyl) thio-1-nonen-4-ol, 1-ethoxy-3 instead of l)
-T-Butylthio-1-nonen-4-ol, methyl 8-ethoxy-6-hydroxy-7-phenylthio-7-octenoate, (6Z) -1-ethoxy-3-phenylthio-1,6-dodecadiene-4 -All, 1,1-diethoxy-
By performing reaction and separation / purification in the same manner as in Reference Example 1 except that 1 mmol of 3-phenylthio-1-nonen-4-ol or 2-ethoxy-4-phenylthio-2-decen-5-ol was used, respectively. (E) -4-Hydroxy-2-octenal (Reference Example 13), (E) -4-
Hydroxy-2-octenal (Reference Example 14), (E)-
Methyl 5-hydroxy-8-oxo-6-octenoate (Reference Example 15), (E, Z) -4-hydroxy-2,6-dodecadienal (Reference Example 16), (E) -4-hydroxy-2
-Ethyl octenoate (Reference Example 17) and (E) -5-hydroxy-3-nonen-2-one (Reference Example 18) were obtained. Table 8 shows the results.

EFFECTS OF THE INVENTION The α-substituted-γ-alkoxyallyl sulfide derivative represented by the general formula (I) of the present invention can be easily produced from readily available raw materials, as is apparent from the above examples. The α-substituted-γ-alkoxyallyl sulfide derivative represented by the general formula (I) can be easily and favorably produced by the α, β-unsaturated α, β-alkoxyaryl sulfide derivative represented by the general formula (VI). Derived to saturated carbonyl compounds. Since a hydroxypolyene compound having a defined geometrical isomerism is derived from the α, β unsaturated carbonyl compound represented by the general formula (VI), the α-substituted-compound represented by the general formula (I) is-
The γ-alkoxyallyl sulfide derivative is useful as a synthetic intermediate for producing the hydroxypolyene compound.

Claims (2)

(57) [Claims] 1. A general formula (In the formula, R ¹ represents a lower alkyl group or an aryl group which may have a substituent, and R ² , R ³ , R ⁶ , R ⁷ , R ⁸ and R ⁹ each represent a hydrogen atom or a substituent. Having an alkyl group which may have, an alkenyl group which may have a substituent, an aralkyl group which may have a substituent, an aryl group which may have a substituent or a substituent Optionally represents a cycloalkyl group, wherein R ⁶ together with R ⁷ or R ⁸ may represent an alkylene group which may have a substituent, and R ⁴ represents a lower alkyl group. R ⁵ is a hydrogen atom, an alkyl group which may have a substituent, an alkenyl group which may have a substituent, an aralkyl group which may have a substituent, and a substituent which has a substituent. Optionally an aryl group, a cycloalkyl group optionally having a substituent, a group represented by the formula-OR ⁴ or a formula-SR ^The α-substituted-γ-alkoxyallyl sulfide derivative represented by 1 represents a group represented by 1 and n represents an integer of 0 or 1.). 2. General formula (In the formula, R ¹ represents a lower alkyl group or an aryl group which may have a substituent, R ² and R ³ respectively represent a hydrogen atom, an alkyl group which may have a substituent, and a substituent. An alkenyl group which may have, an aralkyl group which may have a substituent, an aryl group which may have a substituent or a cycloalkyl group which may have a substituent, R ⁴ Represents a lower alkyl group, R ⁵ represents a hydrogen atom, an alkyl group which may have a substituent, an alkenyl group which may have a substituent, an aralkyl group which may have a substituent, a substituent A aryl group which may have a group, a cycloalkyl group which may have a substituent, a group represented by the formula -OR ⁴ or a group represented by the formula -SR ¹ ). After the alkoxyallyl sulfide derivative is treated with a base, it becomes strongly coordinated. General formula in the presence of compound (In the formula, R ⁶ , R ⁷ , R ⁸ and R ⁹ each represent a hydrogen atom, an alkyl group which may have a substituent, an alkenyl group which may have a substituent, and a substituent which may have a substituent. Optionally represents an aralkyl group, an aryl group which may have a substituent or a cycloalkyl group which may have a substituent, wherein
R ⁶ together with R ⁷ or R ⁸ may represent an alkylene group which may have a substituent, and n represents an integer of 0 or 1. ] The method for producing an α-substituted-γ-alkoxyallyl sulfide derivative according to claim 1, characterized in that the oxygen-containing compound represented by