JPS632251B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel cyclopentene derivative and a method for producing the same. More specifically, it is a compound obtained from dl-4-hydroxy-2-cyclopenten-1-one, which leads to optically active 4-hydroxy-2-cyclopenten-1-one, which is an important intermediate of prostaglandins. The present invention relates to a novel cyclopentene derivative and a method for producing the same.

4-Hydroxy-2-cyclopentene-1-
As previously shown by the present inventors [Tetrahedron Lett., 1535 (1975)], ion and its derivatives are extremely useful compounds as synthetic intermediates for prostaglandins. optically active 4-hydroxy-
As a method for synthesizing 2-cyclopenten-1-one derivatives, the method proposed by the present inventors involves limited hydrolysis of 3,5-diacetoxycyclopentene using an enzyme, followed by two steps [Tetrahedron, 32 , 1713].
(1976)] and RW Rickards et al.
Using 3,5-trichlorophenol as a starting material,
A method is known in which four steps are performed after optically splitting Hantscha cid [Tetrahedron Lett., 1539 (1979)]. However, these methods are known to have several drawbacks, such as difficulty in synthesizing starting materials and setting reaction conditions, use of heavy metal compounds, and low reaction yields. It is hard to say that this is an advantageous method. The inventors dl-
By optically resolving 4-hydroxy-2-cyclopenten-1-one, optically active 4-hydroxy-2-cyclopenten-1-one is obtained.
As a result of intensive research on obtaining 1-on,
The present invention was achieved by discovering that various new cyclopentene derivatives can be obtained in the optical resolution process.

The novel cyclopentene derivative provided by the present invention has the following formula [] [In the formula, R represents a hydrogen atom, a lower alkyl group, or an optically active aminium ion of an amine, and the symbol * indicates that the absolute configuration of the carbon atom is R configuration or S
Represents coordination and their mixing in any ratio. ] It is expressed as .

In the novel cyclopentene derivative represented by the above formula [], R represents a hydrogen atom, a lower alkyl group, or an aminium ion of an optically active amine. Such lower alkyl group has 1 to 4 carbon atoms.
Examples include alkyl groups such as methyl, ethyl, propyl, isopropyl,
Examples include butyl group and t-butyl group. What is the aminium ion of an optically active amine?
It represents a protonated cation of an optically active amine that can form a salt with a carboxyl group, and forms a pair with a carboxylate anion. Examples of optically active amines that form such aminium salts include natural alkaloids such as cinchonine, cinchonidine, brucine, strychnine, quinine, quinidine, and morphine; lysine;
Examples include optically active amino acids and amino acid derivatives such as phenylalanine methyl ester and phenylglycine ethyl ester, and synthetic resolving agents such as (R)-α-phenylethylamine and (S)-α-phenylethylamine. .

The symbol * in the above formula [] represents that the absolute configuration of the carbon atom is R configuration or S configuration, or a mixture of these in an arbitrary ratio. Specifically, S
It means that the ratio of coordination and R coordination compounds includes mixtures with any mixing ratio from 1:0 to 0:1.

If the compounds represented by the above formula [] are described in more detail, they are preferably exemplified as the following three compound groups.

The following formula [-a] A novel cyclopentene derivative represented by the following formula [-b] [In the formula, R ¹ represents an optically active aminium ion of an amine, and the symbol * represents that the carbon atom contains a large amount of R coordination and/or S coordination. ] A novel cyclopentene derivative represented by the following formula [-c] [In the formula, R ² represents a hydrogen atom or a lower alkyl group, and the symbol * represents that the carbon atom contains a large amount of R coordination and/or S coordination. ] This is a novel cyclopentene derivative represented by

Examples of the compound represented by the above formula [] include (1) 4-(o-carboxybenzoyloxy)-2
-cyclopenten-1-one (2) 4-(o-carboxybenzoyloxy)-2
- cinchonine salt of cyclopenten-1-one,
Cinchonidine salt, brucine salt, strychnine salt, quinine salt, quinidine salt, morphine salt, lysine salt, (R)-α-phenethylamine salt, and (S)-α-phenethylamine salt (3) 4-(o-methoxycarbonylbenzoyl) oxy)-2-cyclopenten-1-one (4) 4-(o-ethoxycarbonylbenzoyloxy)-2-cyclopenten-1-one (5) 4-(o-isopropyloxycarbonylbenzoyloxy)-2-cyclopenten- 1-
(6) 4-(ot-butyloxycarbonylbenzoyloxy)-2-cyclopenten-1-one and the like. These compounds have R with respect to the carbon atom of symbol * in the above formula
It includes all coordination compounds, S-coordination compounds, and mixtures thereof in arbitrary ratios.

The compounds represented by the above formula [] and the compounds represented by the above formulas [-a], [-b], and [-c] contained therein are dl-4-hydroxy-2
- Optical resolution of cyclopenten-1-one to produce optically active 4-hydroxy-2-cyclopentene-
These compounds are obtained in the process of obtaining 1-one, and the method for producing these compounds is shown as follows in a flow sheet.

That is, in the first step, dl-4-hydroxy-2-cyclopenten-1-one is reacted with phthalic anhydride in the presence of a base to form the following formula [-
a] A new cyclopentene derivative represented by is obtained, and in the second step, this is reacted with an optically active amine, followed by fractional recrystallization to obtain the following formula [-b] [In the formula, R ¹ represents an optically active amine aminium ion, and the symbol * represents that the carbon atom contains a large amount of R coordination and/or S coordination. ] A new cyclopentene derivative represented by is obtained, and then in the third step, it is treated with acid to be deamined, and if necessary, esterified to form the following formula [-c] [In the formula, R ² represents a hydrogen atom or a lower alkyl group, and the symbol * indicates that the carbon atom is in R coordination or S
Indicates that there is a large amount of coordination or one of the two. ] A new cyclopentene derivative represented by is obtained, which is then reduced in the fourth step and optionally esterified to form the following formula [-d] [In the formula, R ² represents a hydrogen atom or a lower alkyl group, one of X ¹ and Y ¹ is a hydrogen atom and the other represents a hydroxyl group, and the symbol * indicates that the carbon atom is in R coordination. Or, it represents containing a large amount of S coordination or either one of them. ] A novel cyclopentene derivative represented by the following is obtained.

Next, this is protected in the fifth step, and hydrolyzed in the sixth step to form the following formula [] [In the formula, Z represents a protecting group, and the two substituents on the cyclopentene ring, OZ group and OH group, are cis or trans to each other. ] Optically active 4-hydroxy-2-cyclopentene-1 is obtained by oxidizing the optically active cyclopentene derivative represented by the formula in the seventh step.
A protected form of -one, ie, a lower trialkylsilyl form or a tetrahydropyranyl form, can be produced.

dl-4-hydroxy-2-cyclopenten-1-one used in the first step of the present invention is produced by a method separately proposed by the present inventors, namely, 2-methylfuran is brominated and then treated with a phosphate buffer. Method, Alternatively, a method of isomerizing 3-cyclopenten-1-one using a palladium compound after epoxidizing it, However, any other method may be used. The other raw material, phthalic anhydride, is a known compound.

In addition, as the base used in the first step,
Pyridine, collidine, lutidine, 4-dimethylaminopyridine, triethylamine, triptylamine, 1,5-diazabicyclo[5,4,0]undec-5-ene (DBU), 1,5-diazapicyclo[4,3,0] ] Organic bases such as non-5-ene and mixtures thereof are used, especially pyridine, 4-
Dimethylaminopyridine is preferably used.
The solvent varies depending on the base used, but when using the base itself as a solvent, carbon tetrachloride, chloroform,
Preferably used are halogen solvents such as methylene chloride, ether solvents such as diethyl ether and tetrahydrofuran, hydrocarbon solvents such as benzene, toluene, xylene and hexane, or mixtures thereof.

Phthalic anhydride is usually used in a molar amount of 0.8 to 4 times the amount of 4-hydroxy-2-cyclopenten-2-one, preferably 1 to 2 times the amount of 4-hydroxy-2-cyclopenten-2-one. It is used in an amount of about 0.8 to 10 times the mole, but if the base also serves as a solvent, it may be used in an amount of about 100 times the mole.

The reaction temperature ranges from -50°C to 60°C, preferably from -20°C to 40°C. The reaction time varies depending on the reaction temperature and the base used, but is usually about 1 hour to 4 days.

The reaction in the first step is carried out in this manner, and the product is isolated by a conventional extraction operation followed by column chromatography or the like.

The optically active amines used in the second step of optical resolution include natural alkaloids such as cinchonine, zinconidine, brucine, strychnine, quinine, quinidine, and morphine, and optically active amino acids such as lysine, phenylalanine methyl ester, and phenylglycine ethyl ester. and amino acid derivatives, (R)-α-phenylethylamine, (S)-α
- Synthetic resolving agents such as phenylethylamine are used, but are not limited thereto.

Usually, optically active amine and 4-(o-carboxybenzoyloxy) represented by the above formula [-a]
The reaction for forming a salt of -2-cyclopenten-1-one is carried out by mixing the two in a suitable solvent. Examples of the solvent that can be used include halogen solvents such as chloroform, methylene chloride and carbon tetrachloride, alcohol solvents such as methanol and ethanol, acetonitrile and acetone.

After distilling off the solvent, the salt thus obtained is divided by repeated fractional recrystallization from an appropriate solvent. The recrystallization solvent used for the separation varies depending on the optically active amine used, but cannot be generalized, but examples include alcohol solvents such as methanol, ethanol, propanol, and isopropanol, ether solvents such as ether and tetrahydrofuran, acetone, Carbonyl compounds such as methyl ethyl ketone, acetic acid, and ethyl acetate, halogenated solvents such as methylene chloride, chloroform, and carbon tetrachloride, acetonitrile, dimethylformamide, dimethyl sulfoxide, and the like are used.

The absolute coordination of the compound obtained by fractional recrystallization varies depending on the optically active amine used or, in some cases, the solvent used for recrystallization, and cannot be generalized, but for example, it can be determined by fractionation in methanol using brucine. When recrystallization is performed, (4S)-4-(o-
The brucine salt of carboxybenzoyloxy)-2-cyclopenten-1-one is obtained. Also,
In some cases, a compound whose absolute coordination is opposite to that of the crystal may be obtained from the mother liquor of fractional recrystallization.
In addition, the number of fractional recrystallizations varies depending on the optically active amine used and the recrystallization solvent, and also varies depending on the required optical purity, although it cannot be generalized.
Usually it is about 1 to 30 times.

The third step is carried out by treating the salt represented by the above formula [-b] with an acid. For example, the following method is preferably carried out. First, the salt represented by the above formula [-b] is dissolved or suspended in a suitable solvent, such as methylene chloride or ether, and extracted by adding 1 to 10 equivalents of a mineral acid such as dilute hydrochloric acid or dilute sulfuric acid. do. After washing the organic layer with water, it is dried and concentrated to obtain optically active 4-(o-carboxybenzoyloxy)-2-cyclopenten-1-one.

The optically active 4-(o-carboxybenzoyloxy)-2-cyclopentene-1 thus obtained
Since -one is unstable to strong alkalis such as sodium hydroxide and potassium hydroxide, phthalic acid residues cannot be removed under normal alkaline hydrolysis conditions. The inventors of the present invention conducted intensive studies on a method for removing this phthalic acid residue, and as a result, they were able to discover that it can be removed by the reaction described below.

First, the third and fourth steps are steps of esterification of a carboxy group and selective reduction of a carbonyl group, but it does not matter which of these two steps is carried out first.

The esterification reaction is carried out under normal esterification conditions, using diazo compounds such as diazomethane and diazoethane, methanol, ethanol, propanol, and acid catalysts such as sulfuric acid, hydrochloric acid, p-toluenesulfonic acid, and boron trifluoride etherate.
A method using a solvent such as isopropanol or butanol is used, but a method using diazomethane is particularly preferred.

The selective reduction reaction is based on the double bond present in the molecule,
This is a reaction that selectively reduces carbonyl groups without damaging functional groups that are easily reduced, such as ester groups and carboxyl groups. Examples of such selective reducing agents include aluminum amalgam/ether-water, diborane-ethylenediamine complex, aluminum triisopropoxide/isopropanol, sodium borohydride and lanthanide metal salts, and particularly sodium borohydride and lanthanide metal salts. A method using a lanthanide metal salt is preferably used.

The lanthanide metal salts used in the reduction reaction using sodium borohydride and lanthanide metal salts are mainly cerium trichloride, europium trichloride, and samarium trichloride. Sodium borohydride is used 1.0 to 3.0 times the mole of the raw material, and lanthanide metal salt is used 0.9 to 1.1 times the mole of sodium borohydride. Reaction solvents are metal, water, ethanol, tetrahydrofuran,
Chloroform or a mixed solvent thereof is used, and the reaction temperature is -50°C to 50°C, preferably -30°C.
~20°C, and the reaction time is 5 minutes to 2 hours, preferably 10 minutes to 1 hour.

The reduction product thus obtained can be purified by a conventional method, that is, by an extraction operation followed by column chromatography or the like.

The alcohol protection reaction in the fifth step is carried out using a suitable silylating agent or dihydropyran. Examples of the silylating agent include trialkylsilyl chlorides such as trimethylsilyl chloride, triethylsilyl chloride, and t-butyldimethylsilyl chloride, trimethylsilylimidazole, and bis(trimethylsilyl)acetamide. Furthermore, when using trialkylsilyl chloride, it is preferable to add a suitable base such as imidazole, pyridine, triethylamine, etc. The reaction solvent may be a general aprotic solvent such as dimethylformamide, ether, tetrahydrofuran, chloroform, methylene chloride, benzene, or depending on the reaction reagent, the reaction may be carried out without a solvent. The reaction temperature and reaction time vary depending on the silylating agent used, but are usually -30°C to 40°C for 1 minute to 3 days. The silylating agent is used in an amount of 1 to 30 equivalents based on the raw material, and when a group is used, 1 to 30 equivalents are used.

When protecting alcohol with tetrahydropranyl ether, in the presence of an acid catalyst such as para-toluene sulfonic acid, hydrogen chloride, or a cation exchange resin,
The reaction is carried out in a solvent such as chloroform, ethyl ether, benzene, dioxane, ethyl acetate, dimethylformamide, etc. or without a solvent. Dihydropyran is usually used in an amount of 1 equivalent to a solvent amount based on the raw material.
The reaction temperature is -20℃ to 40℃, and the reaction time is 30 minutes to 5 minutes.
It is days.

For the ester hydrolysis reaction in the sixth step, alkaline hydrolysis or reductive hydrolysis is usually used. Alkaline hydrolysis is a commonly used method,
For example, it is carried out in a mixed solvent of an aqueous alkaline solution such as sodium hydroxide, potassium hydroxide, lithium hydroxide, etc. and a suitable organic solvent. As the organic solvent, methanol, ethanol, tetrahydrofuran, dioxane, acetone, or a mixture thereof can be used. Alkaline aqueous solution is 0.1 normal or more
A concentration of about 4N is used, and it is usually used in an amount of 1 to 10 equivalents based on the raw material. The reaction temperature and reaction time are usually -10 to 80°C and 10 minutes to 1 day.

In addition, examples of reducing agents used when performing reductive hydrolysis include lithium aluminum hydride, triethoxylithium aluminum hydride, tri-t-butyloxylithium aluminum hydride, bis(methoxyethoxy) sodium aluminum hydride, Diisobutylaluminum hydride and the like are used, and diethyl ether, dioxane, diglyl, tetrahydrofuran, benzene, toluene, hexane, xylene and the like are used as the reaction solvent. The reducing agent is 1% for the raw material.
~10 equivalents are used, the reaction temperature is -78 to 40°C, and the reaction time is 5 minutes to 2 hours.

The hydrolyzed product thus obtained can be subjected to an alcohol oxidation reaction in the seventh step to yield the desired optically active 4-hydroxy-2-cyclopenten-1-one. The oxidation reaction of this compound can be achieved by using manganese dioxide as already shown by the present inventor, but other oxidizing agents include pyridinium dichlorochromate (PDC), chromium trioxide,
Pyridine complex, pyridinium chlorochromate (PCC), dichlorodicyanoquinone, carbon silver, dimethyl sulfoxide-dicyclohexylcarbodiimide, dimethyl sulfoxide-acetic anhydride,
Examples include dimethyl sulfoxide-oxalyl chloride and dimethyl sulfoxide-trifluoroacetic anhydride. As a reference example
An oxidation example using PDC is shown.

The optically active 4-hydroxy-2-cyclopenten-1-one thus obtained is an extremely useful compound as a synthetic intermediate for prostaglandins. The present invention will be described in detail below with reference to specific examples, but the present invention is not limited thereto.

Example 1 dl-4-(o-carboxybenzoyloxy)-
2-cyclopenten-1-one dl-4-hydroxy-2-cyclopentene-
Dissolve 5.42 g of 1-one in 70 ml of anhydrous pyridine,
9.14 g of phthalic anhydride was added while stirring under ice cooling, and the mixture was stirred at the same temperature overnight. After distilling off the pyridine under reduced pressure,
Extraction was performed by adding ethyl acetate and 1N hydrochloric acid. The organic layer was washed twice with water, then with saturated brine, and dried over Glauber's salt. After concentrating this, it was subjected to silica gel column chromatography and chloroform-
From the methanol (30:1) elution part, dl-4-
6.16 g of (o-carboxybenzoyloxy)-2-cyclopenten-1-one was obtained.

NMR ( _CDCl3 , δ value) 2.46 (dd, 1H, J=2.5, 19Hz) 2.96 (dd, 1H, J=6, 19Hz) 5.96-6.25 (m, 1H) 6.36 (dd, 1H, J=1.5, 5.5Hz) 7.3~8.05 (m, 5H) 11.8 (s, 1H) IR (neat) 2000~3600, 1660~1720 1585, 1403, 1348cm ^-1 Also, dl-4-hydroxy-2-cyclopenten-1-one Dissolve 490mg in 6ml of pyridine,
After adding 50 mg of 4-dimethylaminopyridine, 800 mg of phthalic anhydride was added under ice-cooling and stirring, and the mixture was stirred overnight at the same temperature and separated and purified in the same manner.479
mg dl-4-(o-carboxybenzoyloxy)
-2-cyclopenten-1-one was obtained.

Example 2 dl-4-(o-carboxybenzoyloxy)-
Resolution of 2-cyclopenten-1-one with brucine dl-4-(o-carboxybenzoyloxy)-
4.24 g of 2-cyclopenten-1-one was dissolved in 40 ml of methylene chloride, 7.42 g of brucine dihydrate was added, and the mixture was stirred until completely dissolved. After concentrating this, fractional recrystallization from methanol was performed 5 times.
1.71 g of 4-(o-carboxybenzoyloxy)
-2-Cyclopenten-1-one brucine salt was obtained.

Optical rotation [α] ²² _D = 17.3° (C = 2.0, CH ₂ Cl ₂ ) 1.18 g of the above brucine salt was dissolved in methylene chloride, washed 4 times with 2N hydrochloric acid, and washed 2 times with water. , washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated to obtain 415 mg of optically active 4-(o-carboxybenzoyloxy)-2-cyclopenten-1-one.

Optical rotation [α] ²⁴ _D = -13.8° (C = 1.6, CH ₂ Cl ₂ ) The NMR spectrum and IR spectrum were consistent with those of the dl form.

Reference Example 1 4-(o-methoxycarbonylbenzoyloxy)-2-cyclopenten-1-ol 152 mg of the optically active 4-(o-carboxybenzoyloxy)-2-cyclopenten-1-one obtained in Example 2 was added. It was dissolved in methanol, and an ether solution of diazomethane was added until spots of the raw material disappeared using thin layer chromatography. This was concentrated under reduced pressure and separated by silica gel column chromatography, and 151 mg of 4-(o-methoxycarbonylbenzoyloxy)-2-cyclopenten-1-one was extracted from the fraction eluted with benzene-ethyl acetate (4:1). I got it.

NMR (CDCl ₃ , δ value) 2.40 (dd, 1H, J=2.5, 19Hz) 2.92 (dd, 1H, J=6, 19Hz) 3.83 (s, 3H) 5.9-6.2 (m, 1H) 6.32 (dd, 1H, J=1.5, 5.5Hz) 7.4-7.9 (m, 4H) Dissolve this in 2ml of methanol, add and dissolve 217mg of cerium trichloride heptahydrate, and add 22mg of sodium borohydride while stirring on ice. was added over a period of 4 minutes. The mixture was further stirred for 15 minutes, extracted with water and ethyl acetate, and the organic layer was washed with water and then dried and concentrated using sodium sulfate. The concentrated residue was subjected to silica gel column chromatography, and (cis)-4 was extracted from the hexane-ethyl acetate (2:1) to (1:1) eluate.
-(o-methoxycarbonylbenzoyloxy)-
92 mg of 2-cyclopenten-1-ol and 35 mg of (trans)-4-(o-methoxycarbonylbenzoyloxy)-2-cyclopen-1-ol were obtained.

(cis)-4-(o-methoxycarbonylbenzoyloxy)-2-cyclopenten-1-ol NMR ( _CDCl3 , δ value) 1.74 (dt, 1H, J=15, 3.5Hz) 2.81 (dt, 1H, J = 15, 7.5Hz) 3.0 (br, s, 1H) 3.86 (s, 3H) 4.4 - 4.9 (m, 1H) 5.52 - 5.80 (m, 1H) 5.89 - 6.22 (m, 2H) 7.39 - 7.86 (m, 4H) Mass spectrum m/l262 (M ⁺ ) (trans)-4-(o-methoxycarbonylcybenzoyloxy)-2-cyclopentene-1-
All NMR ( _CDCl3 , δ value) 2.0-2.35 (m, 2H) 2.4 (br, s, 1H) 3.84 (s, 3H) 4.8-5.25 (m, 1H) 5.88-6.25 (m, 3H) 7.39-7.90 (m, 4H) Mass spectrum m/l262 (M ⁺ ) Reference example 2 4-(o-methoxycarbonylbenzoyloxy)-2-cyclopenten-1-ol Optically active 4-(o- Dissolve 220 mg of carboxybenzoyloxy)-2-cyclopenten-1-one in 3 ml of methanol,
Add and dissolve 400 mg of cerium trichloride heptahydrate, -
Sodium borohydride 41mg after cooling to 10℃
was added over 9 minutes. After stirring for 30 minutes after addition
The mixture was extracted with 0.5N hydrochloric acid and ethyl acetate, washed with water, further washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The concentrated residue was dissolved in a small amount of methanol, and an ether solution of diazomethane was added to convert it into methyl ester, followed by concentration. This was subjected to silica gel column chromatography, and (cis)-
4-(o-methoxycarbonylbenzoyloxy)
-2-cyclopenten-1-ol 129 mg and (trans)-4-(o-methoxycarbonylbenzoyloxy)-2-cyclopenten-1-ol 40
I got mg.

The R values and NMR spectra of these compounds in thin layer chromatography completely matched those of the two compounds obtained in Reference Example 1, respectively.

Reference Example 3 (cis)-1-(t-butyldimethylsilyloxy)-2-cyclopenten-4-ol (cis)-4 obtained in Reference Example 1 and Reference Example 2
-(o-methoxycarbonylbenzoyloxy)-
Dissolve 142 mg of 2-cyclopenten-1-ol in 2 ml of anhydrous dimethylformamide, add 96 mg of imidazole and 106 mg of t-butyldimethylsilyl chloride.
mg and stirred overnight at room temperature. Water and ethyl acetate were added to this for extraction, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated to produce (cis)-1-(t-butyldimethylsilyloxy).
214 mg of a crude product of -4-(o-methoxycarbonylbenzoyloxy)-2-cyclopentene was obtained.

NMR 0.77 (s, 9H) 1.67 (dt, 1H, J = 14, 5Hz) 2.79 (dt, 1H, J = 14, 7Hz) 3.74 (s, 3H) 4.63 (dd, 1H, J = 5, 7Hz) 5.56 (dd, 1H, J = 5, 7Hz) 5.87 (s, 2H) 7.62-7.76 (m, 4H) The above (cis)-1-(t-butyldimethylsilyloxy)-4-(o-methoxycarbonylbenzoyl 214 mg of oxy)-2-cyclopentene,
The mixture was stirred for 1 hour in 4 ml of THF, 2 ml of methanol, and 2 ml of 1N potassium hydroxide, and the reaction mixture was extracted with ethyl acetate and water. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated to give 120 mg of (cis)-1.
-(t-butyldimethylsilyloxy)-2-cyclopenten-4-ol was obtained.

NMR (CDCl ₃ , δ value) 0.09 (s, 6H) 0.90 (s, 9H) 1.72 (br, s, 1H) 2.0 (m, 2H) 4.7-5.2 (m, 2H) 5.92 (s, 2H) Mass spectrum 214 (M ⁺ ) Reference example 4 (trans)-1-(t-butyldimethylsilyloxy)-2-cyclopenten-4-ol Reference example 1 and reference example 2 (trans)-4- obtained in Example 4 (o-methoxycarbonylbenzoyloxy)-2-cyclopenten-1-ol 70
mg was t-butyldimethylsilylated in the same manner as in Reference Example 3 to obtain 105 mg of (trans)-1-(t-butyldimethylsilyloxy)-4-(o-methoxycarbonylbenzoyloxy)-2-cyclopentene. .

NMR (CDCl ₃ , δ value) 0.09 (s, 6H) 0.90 (s, 9H) 2.0~2.35 (m, 2H) 3.85 (s, 3H) 5.05 (m, 1H) 5.8~6.3 (m, 3H) 7.4~ 7.9 (m, 5H) 3 ml of 105 mg of the above (trans)-1-(t-butyldimethylsilyloxy)-4-(o-methoxycarbonylbenzoyloxy)-2-cyclopentel
Lithium aluminum hydride in anhydrous ether solution
Drop into a suspension of 40 mg in 1 ml of anhydrous ether under ice cooling.
Stirred for 1.5 hours. Saturated sodium sulfate solution was added dropwise to the reaction mixture under ice-cooling to decompose excess lithium aluminum hydride, and insoluble materials were filtered and washed using ether.
The liquid and washing liquid were combined, dried over anhydrous magnesium sulfate, and concentrated. This was subjected to silica gel column chromatography and benzene-ethyl acetate (4:
1) 16 mg of (trans)-1-(t-
Butyldimethylsilyloxy)-2-cyclopenten-4-ol was obtained. The R values of this compound in NMR spectrum, IR spectrum, and thin layer chromatography matched those of a standard product obtained by the method separately proposed by the present inventors.

Reference Example (S)-4-(t-butyldimethylsilyloxy)-2-cyclopenten-1-one (cis)-1-(t-butyldimethylsilyloxy)-2-cyclopenten-1-one obtained in Reference Example 3
60 mg of 4-ol was dissolved in 1 ml of anhydrous methylene chloride, 180 mg of PDC was added, and the mixture was stirred at room temperature for 50 minutes. Ether was added to the reaction solution to remove insoluble matter, the solution was concentrated, and separated by silica gel thin layer chromatography (developed with benzene-ethyl acetate 19:1).
mg of (S)-4-(t-butyldimethylsilyloxy)-2-cyclopenten-1-one was obtained.

Optical rotation [α] ²⁴ _D = +6.1° (C = 0.75, MeOH) The NMR spectrum and IR spectrum of this compound matched those of the dl form.

Claims (1)

[Claims] 1. The following formula [] [In the formula, R represents a hydrogen atom, a lower alkyl group, or an optically active aminium ion of an amine, and the symbol * indicates that the absolute configuration of the carbon atom is R configuration or S
It represents the coordination or a mixture of them in the ratio of arbitrary positions. ] A novel cyclopentene derivative represented by. 2 The following formula [-a] The cyclopentene derivative according to claim 1, which is represented by: 3 The following formula [-b] [In the formula, R ¹ represents an optically active aminium ion of an amine, and the symbol * represents that the carbon atom contains a large amount of R coordination and/or S coordination. ] A novel cyclopentene derivative according to claim 1. 4 The following formula [-c] [In the formula, R ² represents a hydrogen atom or a lower alkyl group, and the symbol * represents that the carbon atom contains a large amount of R coordination and/or S coordination. ] A novel cyclopentene derivative according to claim 1. 5 The following formula [-a] characterized by reacting dl-4-hydroxy-2-cyclopenten-1-one with phthalic anhydride in the presence of a base. A method for producing a novel cyclopentene derivative represented by 6 The following formula [-a] The following formula [-b] is characterized in that the novel cyclopentene derivative represented by is converted into an optically active amine salt and then fractionally recrystallized. [In the formula, R ¹ represents an optically active amine aminium ion, and the symbol * represents that the carbon atom contains a large amount of R coordination and/or S coordination. ] A method for producing a novel cyclopentene derivative represented by: 7 The following formula [-b] [In the formula, R ¹ and the symbol * are the same as defined above. ] The following formula [-c], which is characterized by treating a novel cyclopentene derivative represented by with an acid and esterifying it as necessary. [In the formula, R ² represents a hydrogen atom or a lower alkyl group, and the symbol * represents that the carbon atom contains a large amount of R coordination or S coordination, or one of them. ] A method for producing a novel cyclopentene derivative represented by: