JP3446225B2 - Cyclopentane derivative and method for producing the same - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an α- and β-position-substituted cyclopentane derivative useful as a pharmaceutical or agricultural chemical or an intermediate thereof, particularly a prostaglandin having a strong physiological activity or an intermediate thereof, and a method for producing the same.

[0002]

BACKGROUND OF THE INVENTION Cyclopentane derivatives have attracted attention as intermediates for pharmaceuticals, and are particularly useful as intermediates for prostaglandins having strong physiological activity.

Conventionally, the production of cyclopentane derivatives has been
For example, when synthesizing the following compound (VI), it was carried out according to the following reaction formula (tetrahedron letter, Vo.
l. 31, No. 24, p. 3425, 199
0).

[0004]

[Chemical 5]

That is, the aldehyde represented by the above formula (VIII) is synthesized from the corey lactone of the above formula (VII) by a 9-step reaction, and then the Wittig reaction (Witti reaction) is performed on this aldehyde.
ng reaction), and then proceed with a reduction reaction to synthesize the alcohol represented by the above formula (IX), and then the compound of the formula (VI) was produced through 5 steps of reaction.

However, in the above method, since the double bonds at the 5th and 6th positions of prostaglandin are in the cis configuration,
(CF ₃ CH ₂ O) ₂ P (O) CH ₂ CO _{2 which is} difficult to obtain in the Wittig reaction of the aldehyde of formula (VIII)
CH ₃ , toxic 18-Croom-6 and KN
[Si (CH _{3) 3]} must be used _2, such as a special reagent (Tetrahedron Letters, Vol. 2
4, No. 41, 4405, 1983).

Furthermore, even if the above-mentioned reagents are used, the by-products of trans configuration of the double bond at the 5th and 6th positions are by-produced by about 10%, so that the separation thereof becomes complicated and the yield of the target compound is also increased. However, there was a problem that

Therefore, it is desired to develop a cyclopentane derivative which can be produced industrially advantageously without the above-mentioned problems and which is useful as an optically active prostaglandin or its intermediate, and a production method thereof.

[0009]

Means for Solving the Problems The present inventors have conducted extensive studies in order to meet the above demands, and as a result, cyclopentane derivatives represented by the following general formulas (I) and (II) are optically active prostaglandins. It has been found that they are effective as compounds or synthetic intermediates thereof and can be produced industrially very advantageously.

[0010]

[Chemical 6] (However, in the formula, R ¹ is a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an i-butyl, a t-
Butyl group, amyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, 2-methylhexyl group, 2
-Hexyl group, cyclopentyl group, cyclohexyl group,
Cyclohexylmethyl group, hexa-4-in-2-yl group, hepta-4-in-2-yl group, 2,6-dimethyl-hepta-5-en-1-yl group, penta-1-ene-
1-yl group, penta-2-en-1-yl group, hexa-
1-en-2-yl group, 3-ethoxy-2-methyl-propan-2-yl group, ethoxyethyl group, 5-methoxyhexyl group, 2- (trimethylsilyloxy) -2-hexyl group, methyl halide group A halogenated n-butyl group, a halogenated n-pentyl group, a halogenated nonyl group,
Phenyl group, benzyl group, halogenated phenyl group, n-
Pentyloxymethyl group, 1-ethoxy-2-methyl-
Propan-2-yl group, phenoxymethyl group, benzyloxymethyl group, p-chlorophenoxymethyl group, 2-phenylethyl group, benzyloxyethyl group, p-fluorophenoxymethyl group, phenylacetylenyl group, m-chloro group Phenoxymethyl group, m-trifluoromethyl-phenoxymethyl group, 1-butyl-cyclopropyl group, 3
-Ethyl-cyclopentyl group, benzothiophenone-5
-Yl group, 2-octenyl group, 3-methoxycarbonylpropyl group or vinyl group, R ² and R ³ are each a hydroxyl group-protecting group, and R ⁴ is a hydrogen atom or a hydroxyl group-protecting group. )

That is, the cyclopentane derivative (cyclopentanone derivative) of the above formula (I) can be industrially advantageously produced by the present inventor as an optically active prostaglandin intermediate before. No. 128, a cyclopentenone derivative represented by the following general formula (III) is reacted with a nucleophilic reagent represented by the following general formula (V), and the protecting group of R ⁴ is deprotected as necessary. The cyclopentane derivative of formula (II) (cyclopentanol derivative) can be synthesized by reacting the cyclopentanone derivative of formula (I) with a reducing agent. It is possible.

[0012]

[Chemical 7] (However, in the formula, R ^{1 to} R ³ have the same meanings as described above.) (However, in the formula, R ⁴ has the same meaning as described above.)

According to these methods, an easily available and highly safe reagent is used with a small number of reaction steps and without using a special reagent, and further, an oxygen atom is at the 3-position,
It was found that the cyclopentane derivative of the formula (I) or (II) in which the double bond at the 5- and 6-positions has a completely cis orientation can be selectively synthesized in a high yield without a separation operation, and thus the present invention is made. I arrived.

Accordingly, the present invention provides (1) a cyclopentane derivative represented by the above formula (I) or (II), (2) a cyclopentenone derivative represented by the above formula (III) and a nucleophilic compound represented by the above formula (V). React with reagent and R ⁴ if necessary
A method for producing a cyclopentane derivative of the above formula (I), wherein the protecting group of the above formula is deprotected, (3) reacting the cyclopentenone derivative of the above formula (III) with a nucleophilic reagent of the above formula (V) A reducing agent is allowed to act on the obtained cyclopentane derivative of the above formula (I), and if necessary, the protecting group of R ⁴ is deprotected to form the above formula (I
A method for producing the cyclopentanone derivative of I) is provided.

The present invention will be described in more detail below. The cyclopentanone derivative of the present invention is represented by the above general formula (I) or (II).

[0016]

Here, R ¹ in the formula is a substituted or unsubstituted alkyl group having 1 to 15 carbon atoms, preferably 3 to 7 carbon atoms, or a substituted or unsubstituted phenyl group, for example, a methyl group, an ethyl group, n-propyl group, i-propyl group, n
-Butyl group, i-butyl group, t-butyl group, amyl group,
Hexyl group, heptyl group, octyl group, nonyl group, decyl group, 2-methylhexyl group, 2-hexyl group, cyclopentyl group, cyclohexyl group, cyclohexylmethyl group, hexa-4-in-2-yl group, hepta-4 -In-2-yl group, 2,6-dimethyl-hept-5-ene-
1-yl group, penta-1-en-1-yl group, penta-
2-en-1-yl group, hexa-1-en-2-yl group, 3-ethoxy-2-methyl-propan-2-yl group, ethoxyethyl group, 5-methoxyhexyl group, 2-
(Trimethylsilyloxy) -2-hexyl group, halogenated methyl group, halogenated n-butyl group, halogenated n
-Pentyl group, halogenated nonyl group, phenyl group, benzyl group, halogenated phenyl group, n-pentyloxymethyl group, 1-ethoxy-2-methyl-propan-2-yl group, phenoxymethyl group, benzyloxymethyl group , P
-Chlorphenoxymethyl group, 2-phenylethyl group,
Benzyloxyethyl group, p-fluorophenoxymethyl group, phenylacetylenyl group, m-chlorophenoxymethyl group, m-trifluoromethyl-phenoxymethyl group, 1-butyl-cyclopropyl group, 3-ethyl-cyclopentyl group, Benzothiophenon-5-yl group, 2-
Examples thereof include an octenyl group, a 3-methoxycarbonylpropyl group and a vinyl group.

R ² and R ³ are each a hydroxyl group-protecting group, and specifically, arylmethyl groups such as benzyl group and p-methoxybenzyl group, trialkyl groups such as trimethylsilyl group and t-butyldimethylsilyl group. Alkoxyalkyl groups such as silyl groups, methoxymethyl groups, ethoxyethyl groups, aralkyloxyalkyl groups such as benzyloxymethyl groups, trityl groups, tetrahydropyranyl (TH
P) group etc. are illustrated.

R ⁴ is a hydrogen atom or a hydroxyl-protecting group, and examples of the hydroxyl-protecting group include the same groups as the above R ² and R ^3, and R ⁴ is the same group as R ² and R ^3. Or they may be different groups.

The cyclopentane derivative (cyclopentanone derivative) represented by the above formula (I) of the present invention comprises a cyclopentenone derivative represented by the following general formula (III) and a nucleophilic compound represented by the following general formula (V). It can be synthesized by reacting with a reagent and optionally deprotecting.

[0021]

[Chemical 9] (However, in the formula, R ^{1 to} R ³ have the same meanings as described above.) (However, in the formula, R ⁴ has the same meaning as described above.)

In this case, the cyclopentenone derivative of the above formula (III) can be produced by the method previously proposed by the present inventor in JP-A-2-128.

[0023]

[0024]

[0025]

[0026]

[0027]

In the present invention, the nucleophilic reagent of the above formula (V) is used in an amount of 0.5 to 4 equivalents, particularly 0.8 to 1.2 equivalents, relative to the cyclopentenone derivative of the above formula (III). preferable. If the amount of the nucleophilic reagent used is less than 0.5 equivalent, a large amount of raw material may remain, and if it exceeds 4 equivalents, by-products may be produced.

The reaction of the compound of formula (III) with the nucleophilic reagent can be carried out in the presence of a solvent, and any solvent may be used as long as it does not inhibit the reaction, for example, tetrahydrofuran, hexane, pentane, Diethyl ether and the like can be mentioned.

The reaction temperature is usually -100 to 50 ° C,
It is preferably -80 to 0 ° C, and the reaction time is usually 5 minutes to
50 hours.

Further, the deprotection of the protecting group of R ⁴ may be carried out under the condition that the other part of the compound (I) is not damaged,
For example, a weak acidic catalyst such as p-toluenesulfonic acid or pyridinium p-toluenesulfonate, or ⁿ Bu ₄ N
It can be carried out in the presence of a fluorine ion represented by F.

The cyclopentanol derivative represented by the above formula (II) can be synthesized by reacting the cyclopentanone derivative represented by the above formula (I) with a reducing agent.

Here, the reducing agent is, for example, NaB.
H_Four, LiAlH_Four, NaBH₃CN, (iBu)₂Al
H, KB [CH (CH₃) C₂H_Five]₃H, KB [CH (C
H₃) CH (CH₃)₂]₃H, LiB [CH (CH₃) C₂
H_Five] H and the like.

The reducing agent is used in an amount of 0.1 to 10 equivalents relative to the cyclopentanone derivative of formula (I), especially 0.1.
It is preferable to use 3 to 3 equivalents.

The above reduction reaction is preferably carried out in the presence of a solvent, and examples of the solvent include tetrahydrofuran, hexane, pentane, diethyl ether, methanol, ethanol, dichloromethane, dichloroethylene and the like.

The reaction conditions are not particularly limited, but -5
It is desirable to react at 0 to 20 ° C. for 0.1 to 5 hours.

[0037]

INDUSTRIAL APPLICABILITY The cyclopentane derivative of the present invention, that is, the cyclopentanone derivative of the formula (I) and the cyclopentanol derivative of the formula (II) are represented by pharmaceuticals and agricultural chemicals or intermediates thereof, especially by the following formulas A and B. It is useful as a synthetic intermediate for prostaglandins having an oxygen atom at the 3-position. Further, according to the production method of the present invention, the above cyclopentane derivative is used in a small number of reaction steps, without using a special reagent, and has an oxygen atom at the 3-position, and the double bond at the 5- and 6-positions is cis. The compound can be synthesized in a high yield by a simple operation.

[0038]

[Chemical 12]

[0039]

[Examples of Actual Rotation] Hereinafter, the present invention will be described more specifically with reference to examples of actual rotation and reference examples, but the present invention is not limited to the following examples of actual rotation. EE is an ethoxyethyl group, TB
S is a t-butyldimethylsilyl group, t-Bu is a t-butyl group, and n-Bu is an n-butyl group.

[0040]

[Chemical 13]

(Z) -1-iodo-3-of the above formula (1)
(1-Ethoxyethyloxy) -1-propene (1.6
To a solution of 6 g (6.48 mmol) in ether (13 ml) was added dropwise a solution of tert-butyllithium in pentane (7.6 ml, 0.7M, 12.97 mmol) at -78 ° C, and the mixture was stirred for 40 minutes, and then ( 2-thienyl) Cu
(CN) Li in THF (tetrahydrofuran) solution (3
3.7 ml, 0.25M, 8.43 mmol) was added. After stirring at -78 ° C for 15 minutes, (3R, 4R) -2-methylene-3-[(S, E) -3 of the above formula (2) was used.
-Cyclohexyl-3- (tert-butyldimethylsiloxy) -1-propen-1-yl] -4- (tert
-Butyldimethylsiloxy) cyclopentan-1-one (2.07 g, 4.32 mmol) ether (15
ml) solution was added dropwise. After the temperature was raised to room temperature over about 1 hour with stirring, the reaction solution was poured into a mixed solution of hexane (10 ml) and a saturated aqueous solution of NaCO ₃ (100 ml) with stirring, the organic layer was separated, and the aqueous layer was separated. Hexane (50
ml). The organic layer obtained was dried over MgSO ₄ and filtered. The crude product obtained by concentrating the filtrate under reduced pressure was purified by silica gel column chromatography to obtain 1.79 g of the compound of the above formula (3) in a yield of 68.
Obtained in%. The NMR and R of the compound of formula (3)
The measurement results of the f value are as follows.

[0042]

[Chemical 14] ¹ H NMR (CDCl ₃ , 300 MHz) δ:-
0.01, 0.03, 0.04 and 0.05 (4s, 1
2H), 0.87 and 0.89 (2s, 18H), 1.
20 (t, J = 7.1 Hz, 3H), 1.31 (d,
J = 5,4 Hz, 3H), 0.93-1.82 (m,
11H), 2.00-2.08 (m, 1H), 2.15
(Dd, J = 8.2, 18.2 Hz, 1H), 2.2
4-2.57 (m, 3H), 2.63 (dd, J = 6.
9, 18.2 Hz, 1H), 3.41-3.69
(M, 2H), 3.80-3.87 (m, 1H), 4.
00-4.20 (m, 3H), 4.70 (q, J = 5.
4 Hz, 1H), 5.40-5.67 (m, 4H) Rf: 0.50 (hexane / ether = 4/1)

[0043]

[Chemical 15]

1 of the above formula (3) synthesized in the actual rotation example 1
2,3,16,17,18,19,20-octanoyl
-4- (1-ethoxyethyloxy) -15-cyclohe
Kicil PGE₂11,15-bis (tert-butyldi)
Methylsilyl) ether (1.66 g, 2.73 mm
ol) in THF (13.6 ml) cooled to -78 ° C.
L-Select [LiB [CH (C
H₃) C₂H_Five] H] (3.55 ml, 1M in THF
Liquid, 3.55 mmol) was added dropwise. 1 hour at -78 ° C
After stirring for 1 hour, the temperature was raised to room temperature over about 1 hour. 35%
After dropping hydrogen peroxide solution (3 ml) at room temperature,
Stir for minutes. Saturated NH_FourCl aqueous solution (50 ml) and
Ether (50 ml), then the organic layer is separated and the aqueous layer is separated.
Was extracted with ether (30 ml). The obtained organic layer
MgSO_FourAfter drying with a filter, it was filtered. Reduce the pressure of the filtrate
The crude product obtained by concentrating under
When purified by means of the matography, the product of the above formula (4)
1.12 g of the compound was obtained with a yield of 67%. NMR measurement
The results were as follows.

[0045]

[Chemical 16] ¹ H NMR (CDCl ₃ , 300 MHz) δ:-
0.01, 0.02, 0.05 and 0.10 (4s, 1
2H), 0.87 and 0.89 (2s, 18H), 1.
21 (t, J = 7.0 Hz, 3H), 1.32 (d,
J = 5.2 Hz, 3H), 0.90-1.35 (m,
6H), 1.38-2.50 (m, 11H), 3.43.
-3.69 (m, 2H), 3.74-3.80 (m, 1)
H), 3.98-4.25 (m, 4H), 4.74.
(Q, J = 5.2 Hz, 1H), 5.32 (dd, J
= 8.8, 15.4 Hz, 1H), 5.45 (dd,
J = 6.0, 15.4 Hz, 1H), 5.52-5.
68 (m, 2H).

[0046]

[Chemical 17]

1 of the above formula (4) synthesized in the actual rotation example 2
2,3,16,17,18,19,20-Octanoyl-4- (1-ethoxyethyloxy) -15-cyclohexyl PGF (2α) 11,15-bis (tert-butyldimethylsilyl) ether (318.8 mg , 0.
52 mmol of isopropyl alcohol (2.6 m
l) and ether (2.6 ml) in a solution of pyridinium p-toluenesulfonate (13.1 mg, 0.052).
(m mol) and the mixture was stirred at room temperature for 20 hours. Ether (10 ml), followed by saturated aqueous NaHCO ₃ (15
(ml) and then extracted with ether (2 × 10 ml). The obtained organic layer was dried over MgSO ₄ and then filtered. The filtrate was concentrated under reduced pressure, the resulting crude product was purified by silica gel column chromatography,
250 mg of the compound of the above formula (5) was obtained with a yield of 89%. The results of measurement of NMR, IR, optical rotation and Rf value were as follows.

¹ H NMR (CDCl ₃ , 300 MH
z) δ: −0.01, 0.03, 0.06 and 0.07
(4s, 12H), 0.88 and 0.89 (2s, 18
H), 1.02-1.41 (m, 6H), 1.43-
1.92 (m, 8H), 2.03 (dt, J = 13.
7, 3.8 Hz, 1H), 2.20 (dt, J = 2.
0, 7.1 Hz, 1H), 2.29 (t, J = 8.5)
Hz, 1H), 2.52-2.80 (m, 3H),
3.73-3.90 (m, 2H), 4.10 (brs,
2H), 4.33-4.47 (m, 1H), 5.34.
(Dd, J = 8.7, 15.3 Hz, 1H), 5.4
5 (dd, J = 6.1, 15.3 Hz, 1H), 5.
55 (dt, J = 4.9, 11.0 Hz, 1H),
5.70-5.89 (m, 1H). ¹³ C NMR (CDCl ₃ , 75 MHz) δ: 13
3.1, 132.4, 131.1, 129.2, 80.
2,74.5,57.4,56.7,52.0,44.
9, 42.6, 29.0, 28.7, 26.7, 26.
3, 25.9, 25.8, 18.2, 17.9, -4.
1, -4.6, -4.8, -4.9. IR (neat): 3340, 2940, 2860, 1
740, 1658, 1463, 1390, 1385, 1
300,1255,1110,1050,1010,9
70,950,900,840,775 cm ^-1 . [Α] ²⁶ _D : +22.70 (c 0.80, CHC
l ₃ ). Rf: 0.43 (hexane / AcOEt = 2/1)

[0049]

[Chemical 18]

1, 2, 3, 16, 17, in the above equation (5),
18,19,20-Octanoyl-4-hydroxy-1
5-Cyclohexyl PGF (2α) 11,15-bis (tert-butyldimethylsilyl) ether (49
2.7 mg, 0.914 mmol) and Bu ₄ N.HS
A solution of O ₄ (31 mg, 0.091 mmol) in toluene (5 ml) / aqueous NaOH solution (5 ml) was added with 2-
Bromoacetic acid t-butyl ester (0.37 ml, 2.2
(9 mmol) was added, and the mixture was stirred at room temperature for 4 hours. The organic layer was separated, and the aqueous layer was extracted with hexane (15 ml). The obtained organic layer was washed with saturated aqueous NH ₄ Cl solution (10 ml), dried over MgSO ₄ , and then filtered. The filtrate was concentrated under reduced pressure, and the obtained crude product was purified by silica gel column chromatography to obtain 480.4 mg of the compound of the above formula (6) in a yield of 80.5%. N
The measurement results of MR, IR, optical rotation and Rf value were as follows.

[0051]

[Chemical 19] ¹ H NMR (CDCl ₃ , 300 MHz) δ:-
0.01, 0.03, 0.05 and 0.06 (4s, 1
2H), 0.87 and 0.88 (2s, 18H), 1.
48 (s, 9H), 1.10-1.98 (m, 14
H), 2.15 (dt, J = 5.1, 14.1 Hz,
1H), 2.30 (dt, J = 2.7, 8.7 Hz, 1
H), 2.35-2.52 (m, 1H), 3.74-
3.81 (m, 1H), 3.95 (s, 2H), 3.9
8-4.50 (m, 2H), 4.12 (dd, J = 5.
8, 11.6 Hz, 1H), 4.22 (dd, J =
6.3, 11.6 Hz, 1H), 5.32 (dd, J
= 8.8, 15.2 Hz, 1H), 5.44 (dd,
J = 6.0, 15.2 Hz, 1H), 5.50-5.
74 (m, 2H). ¹³ C NMR (CDCl ₃ , 75 MHz) δ: 16
9.5, 133.5, 133.2, 131.4, 12
5.6, 81.4, 79.7, 73.9, 67.7, 6
6.6, 56.1, 51.3, 44.8, 42.8, 2
9.0, 28.6, 28.0, 26.8, 26.6, 2
6.2, 25.8, 25.7, 18.1, 17.8,-
4.1, -4.7, -4.8. IR (neat): 3500, 2940, 2850, 1
750, 1665, 1468, 1375, 1300, 1
255, 1170, 1130, 1060 cm ^-1 . [Α]
_{^{21 D: +11.80 (c 1.061,}} CHCl 3). Rf: 0.45 (hexane / AcOEt = 4/1)

[0052]

[Chemical 20]

The compound of the above formula (6) (273.4 mg,
0.419 mmol of methylene chloride solution (1.1 m
1) at 0 ° C. to DMAP (N, N-dimethylaminopyridine) (153.6 mg, 1.67 mmol) and p-
TsCl (p-toluenesulfonyl chloride) (23
9.6 mg, 1.26 mmol) was added, the temperature was raised to room temperature, and the mixture was stirred for 5 hours. Saturated NaHCO ₃ aqueous solution (10 m
1) and hexane (15 ml) were added, the mixture was stirred for 10 minutes, and then the organic layer was separated. The obtained organic layer is MgSO ₄
After drying in, it was filtered. The filtrate was concentrated under reduced pressure and the resulting crude product was passed through a short silica gel column chromatography. This was concentrated, and the obtained product was directly used in the next reaction.

The crude product DMF (4
ml) solution with n-Bu ₄ NCl (582 mg, 2.10).
(m mol) and the mixture was stirred at 40 ° C. for 5 hours. After adding saturated saline (10 ml), hexane (2 x 10 m
Extracted in l). The obtained organic layer was dried using MgSO ₄ and then filtered. The crude product obtained by concentrating the filtrate under reduced pressure was passed through a short silica gel column chromatography. The product obtained by concentrating this was directly used in the next reaction.

Acetonite of the crude product obtained in the above reaction
Pyridine (0.83 ml) was added to the ril (14.1 ml) solution at 0 ° C.
ml) and (HF) _n・ Add pyridine (0.7ml)
Then, the mixture was stirred for 4 hours while warming to room temperature. Acetic acid as the reaction solution
Ethyl (15 ml) / saturated NaHCO₃Aqueous solution (15m
l) with stirring, then the organic layer was separated and the aqueous layer was separated.
Was extracted with ethyl acetate (10 ml). Obtained organic layer
To MgSO_FourAfter drying with a filter, it was filtered. Reduce filtrate
The crude product obtained by concentrating under pressure is purified by silica gel column chromatography.
Romanography (toluene / isopropyl alcohol
Was used as a solvent) to obtain a compound of the formula (7) above.
75.4 mg of the product was obtained in a three-step yield of 40.6%.
The NMR and IR measurement results were as follows. Naoko
In this case, 39.1 mg of the compound of the following formula (8) (yield 22.
9%) was a byproduct.

[0056]

[Chemical 21]

[0057]

[Chemical formula 22] ¹ H NMR (CDCl ₃ , 300 MHz) δ: 0.
82-1.46, (m, 6H), 1.48 (s, 9
H), 1.59-1.90 (m, 5H), 1.95-
2.42 (m, 6H), 3.74 (t, J = 7.1H
z, 1H), 3.96 (s, 2H), 3.92-4.1.
0 (m, 2H), 4.11 (d, J = 5.7Hz, 2
H), 5.43 (dd, J = 7.8, 15.2 Hz,
1H), 5.52 (dd, J = 15.2, 7.4H
z, 1H), 5.55-5.75 (m, 2H). ¹³ C NMR (CDCl ₃ , 75 MHz) δ: 16
9.6, 134.5, 133.2, 130.1, 12
7.6, 81.7, 77.5, 75.0, 67.8, 6
6.5, 59.5, 56.1, 53.2, 43.4, 4
3.2, 28.8, 28.7, 28.1, 266.4, 2
6.0, 25.9. IR (neat): 3400, 2990, 2940, 2
860, 1740, 1450, 1400, 1375, 1
310, 1240, 1160, 1130, 1000, 9
75,895,845,760 cm ^-1 .

[0058]

[Chemical formula 23]

The compound of the above formula (7) (75.4 mg,
0.171 mmol of methanol (5.7 ml) /
LiOH.H ₂ O (lithium hydroxide-hydrate) (35.9 mg) was added to the water (0.57 ml) solution, and the mixture was stirred at room temperature for 4 hours. After adding ethyl acetate (5 ml), add 0.1
N hydrochloric acid was added little by little to bring the pH to 6.5. To this (N
H ₄ ) ₂ SO ₄ (2 g) was added, followed by ethyl acetate (2 x 7
ml). The obtained organic layer was dried using MgSO ₄ and then filtered. The filtrate was concentrated under reduced pressure, and the obtained crude product was purified by silica gel column chromatography (using ethyl acetate / methanol as a solvent) to obtain 58.6 mg of the compound of the above formula (9) in a yield of 8
Obtained in 9%. The NMR measurement results were as follows.

[0060]

[Chemical formula 24] ¹ H NMR (CDCl ₃ , 300 MHz) δ: 0.
85-1.45, (m, 6H), 1.57-1.92
(M, 5H), 1.95-2.43 (m, 6H), 3.
77-3.85 (m, 1H), 4.09 (s, 2H),
4.01-4.35 (m, 7H), 5.48 (dd, J
= 8.5, 15.5 Hz, 1H), 5.56 (dd,
J = 15.5, 6.0 Hz, 1H), 5.58-5.
75 (m, 2H).

─────────────────────────────────────────────────── ─── Continuation of the front page (56) References Japanese Patent Laid-Open No. 48-67257 (JP, A) Tokuhyo 2-502009 (JP, A) J. Am. Chem. Soc. , 1975, 97 (21), 6260-6261 J. Am. Chem. Soc. , 1975, 97 (16), 4745-4746 (58) Fields investigated (Int.Cl. ⁷ , DB name) C07C 405/00 CA (STN) REGISTRY (STN)

Claims (3)

(57) [Claims] 1. A cyclopentane derivative represented by the following general formula (I) or (II). [Chemical 1] (However, in the formula, R ¹ is a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an i-butyl, a t-
Butyl group, amyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, 2-methylhexyl group, 2
-Hexyl group, cyclopentyl group, cyclohexyl group,
Cyclohexylmethyl group, hexa-4-in-2-yl group, hepta-4-in-2-yl group, 2,6-dimethyl-hepta-5-en-1-yl group, penta-1-ene-
1-yl group, penta-2-en-1-yl group, hexa-
1-en-2-yl group, 3-ethoxy-2-methyl-propan-2-yl group, ethoxyethyl group, 5-methoxyhexyl group, 2- (trimethylsilyloxy) -2-hexyl group, halogenated methyl group A halogenated n-butyl group, a halogenated n-pentyl group, a halogenated nonyl group,
Phenyl group, benzyl group, halogenated phenyl group, n-
Pentyloxymethyl group, 1-ethoxy-2-methyl-
Propan-2-yl group, phenoxymethyl group, benzyloxymethyl group, p-chlorophenoxymethyl group, 2-phenylethyl group, benzyloxyethyl group, p-fluorophenoxymethyl group, phenylacetylenyl group, m-chloro group Phenoxymethyl group, m-trifluoromethyl-phenoxymethyl group, 1-butyl-cyclopropyl group, 3
-Ethyl-cyclopentyl group, benzothiophenone-5
-Yl group, 2-octenyl group, 3-methoxycarbonylpropyl group or vinyl group, R ² and R ³ are each a hydroxyl group-protecting group, and R ⁴ is a hydrogen atom or a hydroxyl group-protecting group. ) 2. A cyclopentenone derivative represented by the following general formula (III) is reacted with a nucleophilic reagent represented by the following general formula (V), and the protecting group of R ⁴ is deprotected as necessary. A method for producing a cyclopentane derivative represented by the following general formula (I): [Chemical 2] (However, in the formula, R ¹ is a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an i-butyl, a t-
Butyl group, amyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, 2-methylhexyl group, 2
-Hexyl group, cyclopentyl group, cyclohexyl group,
Cyclohexylmethyl group, hexa-4-in-2-yl group, hepta-4-in-2-yl group, 2,6-dimethyl-hepta-5-en-1-yl group, penta-1-ene-
1-yl group, penta-2-en-1-yl group, hexa-
1-en-2-yl group, 3-ethoxy-2-methyl-propan-2-yl group, ethoxyethyl group, 5-methoxyhexyl group, 2- (trimethylsilyloxy) -2-hexyl group, halogenated methyl group A halogenated n-butyl group, a halogenated n-pentyl group, a halogenated nonyl group,
Phenyl group, benzyl group, halogenated phenyl group, n-
Pentyloxymethyl group, 1-ethoxy-2-methyl-
Propan-2-yl group, phenoxymethyl group, benzyloxymethyl group, p-chlorophenoxymethyl group, 2-phenylethyl group, benzyloxyethyl group, p-fluorophenoxymethyl group, phenylacetylenyl group, m-chloro group Phenoxymethyl group, m-trifluoromethyl-phenoxymethyl group, 1-butyl-cyclopropyl group, 3
-Ethyl-cyclopentyl group, benzothiophenone-5
-Yl group, 2-octenyl group, 3-methoxycarbonylpropyl group or vinyl group, and R ² and R ³ are each a hydroxyl group-protecting group. ) (However, in the formula, R ⁴ is a hydrogen atom or a hydroxyl-protecting group.) (However, in the formula, R ^{1 to} R ⁴ have the same meanings as described above.) 3. A cyclopentane represented by the following general formula (I) obtained by reacting a cyclopentenone derivative represented by the following general formula (III) with a nucleophilic reagent represented by the following general formula (V). A method for producing a cyclopentane derivative represented by the following general formula (II), wherein a reducing agent is allowed to act on the derivative, and the protective group for R ⁴ is deprotected as necessary. [Chemical 3] (However, in the formula, R ¹ is a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an i-butyl, a t-
Butyl group, amyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, 2-methylhexyl group, 2
-Hexyl group, cyclopentyl group, cyclohexyl group,
Cyclohexylmethyl group, hexa-4-in-2-yl group, hepta-4-in-2-yl group, 2,6-dimethyl-hepta-5-en-1-yl group, penta-1-ene-
1-yl group, penta-2-en-1-yl group, hexa-
1-en-2-yl group, 3-ethoxy-2-methyl-propan-2-yl group, ethoxyethyl group, 5-methoxyhexyl group, 2- (trimethylsilyloxy) -2-hexyl group, halogenated methyl group A halogenated n-butyl group, a halogenated n-pentyl group, a halogenated nonyl group,
Phenyl group, benzyl group, halogenated phenyl group, n-
Pentyloxymethyl group, 1-ethoxy-2-methyl-
Propan-2-yl group, phenoxymethyl group, benzyloxymethyl group, p-chlorophenoxymethyl group, 2-phenylethyl group, benzyloxyethyl group, p-fluorophenoxymethyl group, phenylacetylenyl group, m-chloro group Phenoxymethyl group, m-trifluoromethyl-phenoxymethyl group, 1-butyl-cyclopropyl group, 3
-Ethyl-cyclopentyl group, benzothiophenone-5
-Yl group, 2-octenyl group, 3-methoxycarbonylpropyl group or vinyl group, and R ² and R ³ are each a hydroxyl group-protecting group. ) (However, in the formula, R ⁴ is a hydrogen atom or a hydroxyl-protecting group.) (However, in the formula, R ^{1 to} R ⁴ have the same meanings as described above.) (However, in the formula, R ^{1 to} R ⁴ have the same meanings as described above.)