JPH032141A - Cyclopentanecarboxylic acid derivative and antipode thereof - Google Patents

Abstract

NEW MATERIAL:A cyclopentanecarboxylic acid derivative of formula I [R<1> and R<2> are either such that when one of them is H, the other is hydroxyl, or form O; R<3> is isopropenyl, isopropyl, acetyl, 1-hydroxyethyl or acetyloxy; R<4> is H, alkyl or aryl (where, in case R<4> is H or methyl, R<3> is group other than isopropenyl); wavy line means either that stereochemistry is unclear or stereoisomer mixture] and its antipode. EXAMPLE:A compound of formula II. USE:Protective or therapeutic medicines for thrombosis. PREPARATION:For example, a compound of formula III (R<5> and R<6> are either such that when one of them is H, the other is hydroxyl, or form O; R<7> is isopropenyl, acetyl, isopropyl, 1-hydroxyethyl or acetyloxy) or its antipode is reacted with a compound of formula R<8>OH (R<8> is alkyl or aryl) to obtain the objective cyclopentanecarboxylic acid derivative of the formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to a novel cyclopentanecarboxylic acid derivative, its enantiomer, and a method for producing the same.

The inventors of the conventional technology filed an earlier application (Japanese Patent Application No. 186714/1982).
In the step, 4-isopropenyl-1-methyl-6-oxocyclohexane-1,2-epoxide (1) was treated with base O
After reacting with CHa (M=alkali metal), it is hydrolyzed to form 3
-Hydroxy-5-isopropenyl-2-methylcyclobencune-1-carboxylic acid (2), followed by oxidation and heating. -Carboxylic acid (3)
We offer the manufacturing method.

These compounds (2) and (3) have multiple asymmetric carbon atoms on the cyclobencune ring, and are known to be important intermediates in the synthesis of various compounds for agriculture, pharmaceuticals, fragrances, and the like. Furthermore, as disclosed in the above-mentioned earlier application by the inventors, these compounds themselves have anti-peptic ulcer activity as a physiological activity.

Problems to be Solved by the Invention Incidentally, thrombosis and the aftereffects thereof have been increasing in recent years, and the treatment and prevention of these diseases will be essential in the future aging society.

Means for Solving the Problems The inventors have conducted intensive research and studies with the aim of obtaining a compound useful for the prevention and treatment of thrombosis, and as a result, the above-mentioned 3-hydroxy-5-isopropenyl-2- A novel cyclobencune carboxylic acid derivative derived from methylcyclobencune-1-carboxylic acid (2) and 2-isopropenyl-5-methyl-4-isopentane-1-carboxylic acid (3), It was discovered that it has a physiological activity that effectively inhibits platelet aggregation, which causes thrombosis, leading to the present invention.

The object of the present invention is to provide compounds of the form (I) [wherein [, R1 represents a hydroxyl group when one is hydrogen, or R1 and R1 represent oxygen;
R3 represents an isopropenyl group, isopropyl group, acetyl group, 1-hydroxyethyl group, or acetyloxy group, and R4 represents hydrogen, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted aryl group. represents a hydrogen or methyl group, R3 is a group other than an isopropenyl group); represents a stereochemistry unknown or a mixture of stereoisomers]; The purpose is to provide its antipode.

Another object of the present invention is to convert a compound represented by the form (n) representing a biyl group, a 1-hydroxyethyl group or an acetyloxy group, or an enantiomer thereof, to An object of the present invention is to provide a method for producing a cyclopentanecarboxylic acid derivative and its enantiomer, which is characterized by reacting with a compound represented by an unsubstituted alkyl group or a substituted or unsubstituted aryl group.

Another object of the present invention is to provide -form (I) (wherein R5 and R8 are hydrogen and the other represents a hydroxy group, or R5 and R6 represent oxygen:
R7 is an isopropenyl group, an acetyl group, isopro (wherein R6 and R' have the same meanings as above, R11 is hydrogen,
A compound represented by a substituted or unsubstituted alkyl group or a substituted or unsubstituted aryl group or its enantiomer is oxidatively cleaved to form -form (IV) (wherein R', RI and R
An object of the present invention is to provide a method for producing a cyclopentanecarboxylic acid derivative and its enantiomer, characterized in that the compound is a compound represented by (4 has the same meaning as above) or its enantiomer.

Another object of the invention is that - of the form (I[[), where RI,
An object of the present invention is to provide a method for producing a cyclopentanecarboxylic acid derivative and its enantiomer, characterized in that the compound is a compound represented by (R2 and R4 have the same meanings as above) or its enantiomer.

Another object of the present invention is to reduce a compound represented by the -form (Vl) (in the formula, R5, Ra and Ra have the same meanings as above) or its enantiomer; , R', R'' and R9 have the same meanings as above) or its enantiomer is reduced to -form (in the formula,
An object of the present invention is to provide a method for producing a cyclopentanecarboxylic acid derivative and its enantiomer, characterized in that R1, R1 and R4 are the same as defined above) or its antipode.

Another object of the present invention is to provide a cyclopentane compound represented by the general formula (VI) (wherein R', R2 and R4 have the same meanings as above) or an enantiomer thereof. An object of the present invention is to provide a method for producing carboxylic acid derivatives and their enantiomers.

Another object of the present invention is to perform Bayer-Villiger oxidation of a compound represented by the general formula (IX) (wherein R5, Ra and R8 have the same meanings as above) or its enantiomer, (■) (wherein, R7 and Ro have the same meaning as Moeki) or its enantiomer is reduced, and the general formula (X) [1
) 1 (wherein R3 and R4 have the same meanings as above) or its enantiomer, to provide a method for producing a cyclopentanecarboxylic acid derivative and its enantiomer. It is in.

Another object of the present invention is to oxidize the compound represented by the general formula (XI) l (wherein R7 and R8 have the same meanings as above) or its enantiomer to obtain the effect of the general formula (yl). According to a preferred embodiment of the present invention, the alkyl group for R4 in general formula (I) includes a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, and a nonyl group. , denol group, etc., and examples of the aryl group include phenyl group. Each of these groups may be substituted.

Next, the manufacturing process will be explained.

An object of the present invention is to provide a method for producing a cyclopentanecarboxylic acid derivative and its enantiomer, characterized in that it is a compound represented by the formula (wherein R3 and R4 have the same meanings as above) or its enantiomer. .

(If) (I) This step is an esterification step, and it is desirable to react the carboxylic acid and the corresponding alcohol in the presence of a dehydration condensation agent such as dicyclohexylcarbodiimide or diisopropylcarbodiimide.

desirable.

R5 R' (III) (IV) This step is an oxidative cleavage step, and the oxidizing agent is a carbon-carbon double bond such as osmium tetroxide-sodium periodate, ozone, ruthenium tetroxide, potassium permanganate, etc. An oxidizing agent that oxidizes and cleaves can be used.

(VT) (■) This process is the process of reducing ketones to alcohol,
The reducing agent is preferably a metal hydride such as sodium borohydride.

(V) This step is a step of reducing carbon-carbon double bonds,
The reaction with hydrogen in the presence of a catalyst such as platinum, palladium, ronium, or Raney nickel is (VI) (■) This process is a Bayer-Villiger oxidation process.
As the oxidizing agent, peracids such as trifluoroperacetic acid, metachloroperbenzoic acid, monopermaleic acid, monoperphthalic acid, and peracetic acid can be used.

(IX) (X) This step is a step of reducing a ketone to an alcohol, and the reducing agent is preferably a metal hydride such as sodium borohydride.

(X[) (XI[) This process is a process of oxidizing alcohol to ketone, and the oxidizing agents include chromic acid-sulfuric acid, pyridinium chlorochromate, pyridinium dichromate, dimethyl sulfoxide-oxalyl chloride, dimethyl sulfoxide-trifluoroacetic anhydride. You can also use something like

The cyclopentanecarboxylic acid derivative according to the present invention obtained as described above was proved to have an inhibitory effect on platelet aggregation.

In order to further explain the present invention in detail, some examples will be illustrated next, but the present invention is not limited thereto.

In some of the following examples, (IS, 5R)-2-methyl-5(1-methylethynyl)-3-oxocyclopentanecarboxylic acid (raw material 1), (IS, 3R,5R)-3-hydroxy-
2-Methyl-5-(1-methylethynyl)cyclopentanecarboxylic acid (raw material 2) and each enantiomer were prepared according to the invention described in the earlier patent application (Japanese Patent Application No. 62186714) related to the present application. prepared.

Example 1 P-H (IS, 5R)-2-methyl-5-(1-methylethynyl)3-oxocyclopentanecarboxylic acid 5.469(
30x*ol) and 1-hexanol 5.75i (!(
45+ uol) was dissolved in ethyl acetate, and dimethylaminopyridine 0.379 (3xxol) and dicyclohexylcarbodiimide 6.809 (33xxol) were dissolved under water cooling.
was added and stirred for 3 hours.

An appropriate amount of diluted hydrochloric acid was added to the reaction solution, stirred for 30 minutes, and filtered. The solution was extracted with ethyl acetate, the extract was washed successively with aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography (hexane-acetic acid). ethyl-1
0+1) to obtain compound (MP-11)3.
609 (45% yield) was obtained as a colorless oil.

IRv "IC"(cjI-'): 1710 (br
) ax 'H-NMR (60 MHz, CC12-) δ: 1.
73 (3H, S, CH3).

4.03(2)! , t, J: 6Hz, 0CHt).

4.77 (2H, s, C-CH*) MS (C,,H,,03): Theoretical value m/z 266.
1882 (M) Actual value cIl/z 266.1883
(M”) Example 2 P-12 (IS, 5R)-2-methyl-5-(1-methylethynyl)=3-oxocyclopentanecarboxylic acid 7, 22
9(40xxo1) and l-pentanol 6.52+v
((60xxol) was dissolved in ethyl acetate, dimethylaminopyrinone 0.499(4+uyol) and dicyclohexylcarbodiimide 9.089(44xx
ol) was added and stirred for 3 hours.

An appropriate amount of diluted hydrochloric acid was added to the reaction solution, stirred for 30 minutes, and filtered. The furnace solution was extracted with ethyl acetate, and the extract was washed successively with an aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography (petroleum ether-acetic acid). Ethyl =
Compound (MP-12) 8.4
29 (84% yield) was obtained as a colorless oil.

, R, cocc3(c,-ri: 1700ax'H-NMR (60MHz, CCQ-) δ: 1.7
3 (3H, S, CH3).

4.07 (2H, t, J=6Hz, 0CHt).

4.80 (2H, s, C=CHt) MS (CI5H-40s): Theoretical value m/z 252.
1725 (M”) Actual measurement value tn/z 252.1726 (
M) Example 3 (15,5R)-2-methyl-5-(1-methylethynyl)3-oxocyclopentanecarboxylic acid 5.469(
3011 L) and 1-Heptatur 6.54 Pass (45
1101) was dissolved in ethyl acetate, 0.37 g (3xxol) of dimethylaminopyridine and 6.80g (33xxol) of dicyclohexylcarbodiimide were added under water cooling, and the mixture was stirred for 24 hours.

An appropriate amount of diluted hydrochloric acid was added to the reaction solution, stirred for 30 minutes, and filtered. Extract the furnace liquid with ethyl acetate, wash the extract with an aqueous sodium bicarbonate solution and saturated brine, dry over anhydrous magnesium sulfate, remove the solvent, and purify the residue by silica gel column chromatography (benzene). Compound (MP-13) 3.869 (yield 46%) was obtained as a colorless oil.

IRv CHCQ'(C1-'): 1710aX'H-NMR (60MHz, CCIJδ: 1.67(
3H, S, CH3) 3.97 (2H, t, J=6Hz,
0C)It).

4.73(2H,s,C=CHt) MS(C,,l(,,0,):Theoretical value tn/z 28
0.2036 (M”) Actual value m/z 211!0.20
34(M+) Example 4 (IS, 5R)-2-Methyl-5-(1-methylethynyl)3-oxocyclopentanecarboxylic acid 1.009(
6mxo1) and 2-pentanol 1. oox12(7
, 5+ uol) in ethyl acetate, dimethylaminopyridine Q, Q79 (0.5 imol) and synchrohexylcarbodiimide 1.404 F (5,5x
xol) was added and stirred for 24 hours.

An appropriate amount of diluted hydrochloric acid was added to the reaction solution, stirred for 30 minutes, and filtered. The furnace solution was extracted with ethyl acetate, and the extract was washed successively with an aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography (hexane-ethyl acetate). =5:
1), compound (MP-14) 0.709 (
Yield: 50%) was obtained as a colorless oil.

IRνCH"3Cam-'): 1700ax 'H-NMR (60MHz, CC12-) δ: 1.
70(31(,S,CH3)4.8G(28,s,C;
CHt) Ms(clsHt4os): Theoretical value m/z 252.
1?25 (M+) Actual value m/z 252.1730 (M
”) Example 5 MP(5 (LS, 5R)-2-methyl-5-(1-methylethynyl)=3-oxocyclopencunecarboxylic acid 5.46 g
(30x*ol) and 2-hexanol 115IlIQ
(90IIIol) was dissolved in ethyl acetate, and dimethylaminopyridine 0.379 (32!7101) was dissolved under water cooling.
and synchhexylcarboimide L2. a69(6
0itxoL) was added and stirred at room temperature for 5 days. An appropriate amount of diluted hydrochloric acid was added to the reaction solution, stirred for 30 minutes, and filtered. The furnace solution was extracted with ethyl acetate, and the extract was washed successively with an aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography (hexane-ethyl acetate). -1oll
) to obtain compound (MP-15) 6.309 (yield 79%) as a colorless oil.

IRv C""3Can-'): 1700,164
0ax H-NMR (60MHz, CCL) δ: 1.77 (3
H, S, CH3).

4.77 (2t(, s, MS of C=CI (C1etlts03): Theoretical value m/z 2fJ
, 1832 (M+) Actual value trr/z 266.188
2(M”) Example 6 (IS, 5R)-2-Methyl-5-(1-methylethynyl)-3-oxocyclopentanecarboxylic acid 5.4h(
30zxol) and 2-heptatool13. l*Q(
90xxol) in ethyl acetate, dimethylaminopyridine 0.379 (31101) and dicyclohexylcarbodiimide 12.369 (601101) were dissolved under water cooling.
) and stirred at room temperature for 5 days. An appropriate amount of diluted hydrochloric acid was added to the reaction solution, stirred for 30 minutes, and filtered. The furnace solution was extracted with ethyl acetate, and the extract was washed successively with an aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography (hexane-ethyl acetate). = 10:1) to obtain compound (MP-16) 3.309 (yield 39%) as a colorless oil.

! RνCHC123(ctx-tx: 1710ax'l(-NMR(60Mflz, C(J!,) δ:
1.73 (3H, 5, CH3).

4.80 (2H, s, C=Cllt) MS (C, 711,, o,): Theoretical value m/z 280
．． 2038 (M+) Actual value m/z 280.2038 (
M+) Example 7 MP-25 (IS, 5R)-2-methyl-5-(1-methylethynyl)-3-oxocyclopentanecarboxylic acid 4.55 g
(25xxol) was dissolved in excess ethanol, dimethylaminopyridine 0.319(2,5xx
ol) and noisopropyl carbonimide 3.479 (
28ixol) was added and stirred overnight. An appropriate amount of diluted hydrochloric acid was added to the reaction solution, stirred for 30 minutes, then the solvent was distilled off, ethyl acetate was added to the residue, and the mixture was filtered. The furnace solution was extracted with ethyl acetate, and the extract was washed successively with an aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography (cyclohexane-ethyl acetate). =40+1) to obtain compound (MP-25) 4.329 (yield 82%).
) was obtained as a colorless oil.

IRv Ox (cr'): 1725 (br)'H-
NMR (60M) Iz, CCQ4) δ: 1.07 (3
H, d, J: 6Hz, CH3) 1.25 (3H, t, J
・7H2,C)+3)1.75(3H,s,CHs).

4.10 (2H, q, J=6Hz, 0CHz) 4.77
(20,s,C:CHt) MS(C,,H,,0,): Theoretical value m/z 210.
1257 (M+) Actual value m/z 210.1257 (M
”) Example 8 (IS, 5R)-2-methyl-5-(1-methylethynyl)=3=oxocyclopentanecarboxylic acid 4.119
(22x*ol,) was dissolved in excess 1-propanol, and dimethylaminopyridine 0.279 (2,2
■ol) and synchrohequinlecarbodiimide 5.00
@(24,v+xol) was added and stirred for 1 hour. An appropriate amount of diluted hydrochloric acid was added to the reaction solution, stirred for 30 minutes, then the solvent was distilled off, ethyl acetate was added to the residue, and the mixture was filtered. The furnace solution was extracted with ethyl acetate, and the extract was washed successively with an aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was subjected to silica gel column chromatography (cyclohexane-ethyl acetate). -10
Compound (MP-26) 3.769
(yield 74%) was obtained as a colorless oil.

11(y2',', (Cm-'): 1720(
br) H-NMR (60MHz, CCl24) δ:
0.88 (3H, br dJJHz, CH3) 1.07 (3H1br t J・61 (Z, CH3).

1.77 (3H, s, CH3).

4.03(2H,br　t.

J=6Hz, 0CHz) 4.80(2H,s, CmCI(-) !+1S(C,3H,,03): Theoretical value m/z 22
4.1411 (M”) Actual value I! IHz 224.14
11(M”) Example 9 MP-27 (IS, 5R)-2-methyl-5-(1-methylethynyl)-3-oxocyclopentanecarboxylic acid 4,709
(26iio1) was dissolved in excess butanol and dimethylaminopyridine 0.319 (2,5xxol) was dissolved under water cooling.
) and diisopropylcarbodiimide 3.609 (29
xxol) was added and stirred for 2 hours. An appropriate amount of diluted hydrochloric acid was added to the reaction solution, stirred for 30 minutes, then the solvent was distilled off, ethyl acetate was added to the residue, and the mixture was filtered. The furnace solution was extracted with ethyl acetate, and the extract was washed successively with an aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography (petroleum ether-acetic acid). ethyl=10:1) to obtain 4.469 (yield 73%) of compound (MP-27) as a colorless oil.

IRν(cr'): 1720(br)H-NMR
(60MHz, CCff-) δ: 1.03 (3H,
br tJ=6Hz, CH3) 1.77 (3H, s, cl13).

4.10(2)1. br t ,b6Hz,0CHt) 4.83(21(,s,C:C11,)MS(C14H
00,); Theoretical value m/z 238.1570 (M”) Actual value m/z 23 g, 1571 (M+) Example 10 (IS, 5R)-2-Methyl-5-(1-methylethynyl)3- 2.75 g of oxocyclopentanecarboxylic acid (
15x*ol) and 17.43g (105xxol) of methyl p-hydroxyphenylacetate were dissolved in ethyl acetate, and dimethylaminopyridine 2.209g (105xxol) was dissolved under water cooling.
18xxol) and dicyclohequinolcarbonimide &
, :(69(41x*ol)) was added and stirred for 4 hours.

An appropriate amount of diluted hydrochloric acid was added to the reaction solution, stirred for 30 minutes, and filtered. The furnace solution was extracted with ethyl acetate, and the extract was washed successively with an aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography (petroleum ether-acetic acid). Ethyl
Compound (MP-31) 2.4
09 (yield 48%) was obtained.

1l IRv (cx-'): 1730(br)a
x'H-NMR (60MHz, CCC4) δ: 1.12
(3H, br d.

J=6Hz, CH3) 1.73 (3H, S, CH3).

3.45 (2H, s, CHt) 3.55 (3H, s, 0CH3) 4.85 (2H, s, C=CH=) 6.82-7.23 (4H, m, 4XArH) MS (C
+IIHtffiOs): Theoretical value m/z 330.1
465 (M+) Actual value m/z 330.1462 (M+
) Example 11 P-32 (IS, 5R) -2-methyl-5-(1-methylethynyl)3-oxocyclopentanecarboxylic acid 2.90
9 (16xmol) and methyl 4-hydroxybenzoate 24.09 (160*xol) were dissolved in ethyl acetate, and dicyclohexylcarbodiimide 3.30% was dissolved under water cooling.
9 (16xxol) was added and stirred overnight. An appropriate amount of diluted hydrochloric acid was added to the reaction solution, stirred for 30 minutes, and filtered. The furnace liquid was extracted with ethyl acetate, and the extract was washed successively with an aqueous sodium bicarbonate solution, a 1N aqueous sodium hydroxide solution, and saturated brine. After drying over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was subjected to silica gel column chromatography. - (petroleum ether-ethyl acetate-4:1), the obtained crystals were recrystallized from cyclohexane, and the compound (MP-32
) 1.589 (yield 32%) was obtained as colorless crystals at mp 60°C.

IRv "CQ'(aI!-'): 1710(br
), 1595ax 'H-NMR (60MHz, CCj4) δ: 1,2
5 (3Hbr dJ=6Hz, CHs) 1.83 (3H, s, CH3) 3.90 (3H, s, 0CH3) 4.95 (2H2s, C=CHt) 7.09 and 8.04 (2H, respectively) Each d.

MS (C1aH-oos) 'Theoretical value m/z 316.
1309 (M+) Actual value m/z 316.130g (M
”) Example 12 (is, 3R,5R)-3-hydroxy-2-methyl-5-(l-methylethynyl)cyclopencune carboxylic acid 18.49 (100xxo1) and 1-pentanol 16JxQ (1501113101) Dissolved in ethyl acetate and dimethylaminopyridine 1.229 (1
0ffJ+ol) and 22.79 (110 ixol) of dicyclohexylcarbodiimide were added, and the mixture was stirred for 3 hours. An appropriate amount of diluted hydrochloric acid was added to the reaction solution, stirred for 30 minutes, and filtered. The furnace solution was extracted with ethyl acetate, and the extract was washed successively with an aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was subjected to silica gel column chromatography (cyclohexane-ethyl acetate). = 5:1) to obtain compound (MP-24C)2
0.09 (yield 79%) was obtained as a colorless oil.

1l IRν(C3I-'): 3375(br), 171
5(br)ax'H-NMR (60MHz, CCl24) δ: 0.8
3-1.20 (6H, m, 2XC113) 1.73 (3
H, s, CH3) 4.02 (2H, t, J=6Hz, 0CHt) 4.69
(2H, s, C=CH=) Ms(clsHteo-): Theoretical value m/z 254.
1880 (M”) Actual value m/z 254.186g (M
+) Example 13 MP-2111 (IS, 3R, 5R)-3-hydroxy-2-methyl-
5(1-methylethynyl)cyclopencunecarboxylic acid 4
．． 309 (23zxol) was dissolved in excess ethanol and dimethylaminopyridine 0, 289 (2,
3mxo1. ) and synchhexylcarbodiimide 5
．． 209 (25*xol) was added and stirred for 4 hours. An appropriate amount of diluted hydrochloric acid was added to the reaction solution, stirred for 30 minutes, then the solvent was distilled off, ethyl acetate was added to the residue, and the mixture was filtered. The P solution was extracted with ethyl acetate, and the extract was washed successively with an aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography (petroleum ether ethyl acetate). =3:1)
was purified to obtain compound (MP-28) 3.229 (yield 65%) as a colorless oil.

w1 1Rv (cTl-') + 3300(
br), 1720(br)ax'If-NMR (60MHz, CC124) δ 1.
25 (3H, br t, J=7HzCH3).

1.70(3H,s,C[+3) 3.70(1)1. m, Cll0) I) 4.07 (2H
,br q,J=7HzOCH,) 4.65(2H,s,C;Ct(,) MS(Cl tLo03): Theoretical value m/z 212.
1409 (M+) Actual value m/z 212.1410 (M
”) Example 14 MP-29 (IS, 3R, 5R)-3-hydroxy-2-methyl-
5=(1-methylethynyl)cyclopencunecarboxylic acid 4. 10g (22yxol) was dissolved in excess 1-propatol, and dimethylaminopyridine 0.279% was dissolved under water cooling.
(2.2 ml ol) and dicyclohexylcarboimide 5.009 (24 xx ol) were added and stirred for 4 hours. An appropriate amount of diluted hydrochloric acid was added to the reaction solution, stirred for 30 minutes, then the solvent was distilled off, ethyl acetate was added to the residue, and the mixture was filtered.

The p solution was extracted with ethyl acetate, the extract was washed successively with an aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography (cyclohexane-ethyl acetate). −
7; Purified by 1), compound (MP29) 4.359
(yield 86%) was obtained as a colorless oil.

1l IRv (cm-ri: 3300(br), 170
0(br), 1630aX 1(-NWR(6t1MIIz, CCl24)δ: 0
．． 137(3)1. d, J-5Hz, CH3).

1.03 (3H, t, J=6Hz, CHl).

170 (31 (, s, CL) 4.00 (2H, t, J=6Hz, 0CHt) 4.67
(2t(,s,C=C1,) MS(C+3HttO3): Theoretical value m/z 226.
1567 (M”) Actual value m/z 226.1566 (M
”) Example 15 MP-30 (IS, 3R, 5R)-3-hydroxy-2-methyl-
5(1-methylethynyl)cyclopentanecarphonic acid 3
．． 80g (21xiol) was dissolved in excess 1-butanol, and dimethylaminopyridine 0.269 (21xiol) was dissolved under water cooling.
, 1xffol) and 4.709 (23xjlol) of synchhexylcarbodiimide were added and stirred for 4 hours. An appropriate amount of diluted hydrochloric acid was added to the reaction solution, stirred for 30 minutes, then the solvent was distilled off, ethyl acetate was added to the residue, and the mixture was filtered.

The furnace solution was extracted with ethyl acetate, and the extract was washed successively with an aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography (cyclohexane-ethyl acetate). −
5=1), compound (MP30) 4.801
? (Yield 97%) was obtained as a colorless oil.

1l IR Ccx-'): 3300 (br), 1720
(br), 1640IIax'H-NMR (60MHz, CCL) δ2 1.7
3 (3H, S, CH3) 3.58-3.88 (1B, m
, CHOH) 4.05 (2H, t, J=6Hz, 0CI
lt)4.6111(2)1. s, C=CHJMS(C
,,H,403) :Theoretical value m/z 240,1?24
(M+) Actual value m/z 240.1723 (M”) Example 16 Example 17 P-42 (IS, 5R)-2-methyl-5-(1-methylethynyl)-3-oxocyclopentanecarboxylic acid 1.009
(5,5xxol) was dissolved in acetone and stirred at -400C for 1 hour in an ozone stream. Dimethyl sulfide 0.8xQ (1,1xxol) was added to the reaction solution, stirred for 1 hour, and the solvent of the reaction solution was distilled off. The obtained crystals were recrystallized from benzene to convert compound (MP-42) into mp125-
It was obtained quantitatively as colorless crystals at 127°C.

IRν(cr'): 1710(br)ax'H-NMR (60MHz, CDCl23) δ: 1
．． ．． 21 (3H, d, J = 7Hz, C) 13) 2.23
(3H,S,CH3) 6, (2(1)1.br s, COtH)MS(C6H
12O6): Theoretical value m/z 184.0736 (M
”) Actual value tn/z 184.0736 (M”) Compound obtained in Example 2 (MP-12) 0.199 (3,
6ziol) in tert-butanol and diluted with 0.5
N-sodium metaperiodate aqueous solution 30RL2 (0,4
x mol) and 1 x Q (15 xx mol) of a 0.4N olmium tetroxide/carbon tetrachloride solution were added thereto, and the mixture was vigorously stirred at room temperature for 1 hour. The reaction solution was extracted with ethyl acetate, the extract was washed successively with an aqueous sodium thiosulfate solution and saturated brine, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography (cyclohexane-ethyl acetate). = 2:1), and the compound (MP3
4) was quantitatively obtained as a colorless oil.

IRv0il(c,w-'): 1720(br)
aX'H-NMR (60MHz, CCQ4) δ: 0.95
(3H, d, J=6t(z,cH3)1.08(3H3
t, 6Hz, CI+3) 2.17(3H,s, CH3
) 4.09 (2H, t, J・6Hz, OCHt) MS (C
, 4H, t04): Theoretical value m/z 254.1517
(M+) Actual value m/z 254.1511 (M+) Example 18 P-40 (IS, 3R,5R)-3-hydroquino-2-methyl-5=(l-methylethynyl)cyclopentanecarboxylic acid 10. 19 (55xxol) was dissolved in tert-butanol, and 0.5N sodium metaperiodate aqueous solution 2
50x12 (125xjIol) and 14m of 0.4N osmium tetroxide carbon tetrachloride solution (1(0,56*zol)
) and stirred vigorously at room temperature for 1.5 hours. The reaction solution was extracted with ethyl acetate, the extract was washed successively with an aqueous sodium thiosulfate solution and saturated brine, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography (ethyl acetate). Purify the compound (
MP-40) 4.909 (yield 48%) was obtained as a colorless oil.

1l IRv (cm-ri: 3300(br), 16
95(br)flaX'H-NMR (60MHz, CDC123) δ: 1.
13 (3H, d, J□7Hz, CH3) 2.23 (3H
, s, CH3).

6.98 (2H, s, OH and Co2H) MS (CII
H1!03): Theoretical value m/z 168.0785 (M”
-HtO) Actual value m/z 168.0777 (M”-H
,0) Example 19 P P-24C Compound obtained in Example 12 (MP-24C) 10.0
9 (39xxol) was dissolved in tert-butanol,
0.5N sodium metaperiodate aqueous solution 216 Pass (1
08x next o1) and 1.4 m (2 (0.56 tmol) of 0.4 N osmium tetroxide and carbon tetrachloride solution were added, and the mixture was vigorously stirred at room temperature for 4 days. The reaction solution was extracted with ethyl acetate, and the extract was diluted with thiosulfuric acid. After washing successively with an aqueous sodium solution and a saturated saline solution and drying over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography (cyclohexane-ethyl acetate-1:1) to obtain the compound (MP-35). -A) 9.09 (yield 89%), (M
P-35B) 0.269 (yield 3%) were obtained as colorless oils.

MP-35A IR+, 0"(cm-'): 3400 (br)
, 1700(br)ax'H-NMR(60Mt(z,CC4-)δ: 1.
Q3 (3H, t, J near Hz, cL).

1.08(3H, d, J=7t(z, CHJ2.13(
3H, s, CHs) 4.05 (2) 1. t, J=6) 1z, QC) 1d
s(C,,H140,): Theoretical value m/z 256. L
675 (M) Actual value m/z 256.1681 (M”
) MP-35B 1l IRν (c “”) + 3400 (br), 170
0(br)aX'H-NMR (60MHz, CCσ4) δ: 0.9
1-1.22 (6H, m, 2XCH*).

MS (CI48-to+) 2.13 (3)! , S, C) 13) 4.05 (2B, t, J=7Hz, 0CHt) Theoretical value m
/z 238.1569 (M -HzO) Actual value m/z
238.1574 (M”LO) Example 20 P-17 (IS, 5R)-2-Methyl-5-(1-methylethynyl)3-oxonclopentanecarboxylic acid 1049(5
6JIJIOI) was dissolved in methanol, 10% palladium-carbon io, Qg was added, and the mixture was stirred at room temperature under a hydrogen atmosphere for 3 hours. After the reaction, the palladium-carbon was removed from the furnace, and the solvent in the furnace solution was distilled off. The residue was dissolved in ethyl acetate, an aqueous solution of 84 g (I mol) of sodium hydrogen carbonate was added, and after stirring, the aqueous layer was separated, acidified with concentrated hydrochloric acid under water cooling, extracted with ethyl acetate, and the extract was After washing with saturated brine and drying over anhydrous magnesium sulfate, the solvent was distilled off. The obtained crystals were recrystallized from acetone, benzene, and cyclohexane to obtain compound (MP-17) 10.09 (yield 96%) as colorless crystals with a temperature of mp 97-103°C.

[α] Hole” 141.5° (C・2.00.CHCρ3
)I Rv C)l C123(Cx-ri: 1730
(br)aX'H-NMR (60Ml(z,cDcI24)δ: 0
．． 95 and 0.98 (31 (each).

each d, each J=6Hz.

2XCH3).

1.18 (3H, dj = 8Hz, CH3) 9.87 (k
t(,s,C0tH) As elemental analysis value (CIOH1s03): Calculated value C65
,19,)I 8.75 Measured value CB5.20. ) I 8.86 Example 21 was dissolved in methanol and 10% palladium-carbon 1
．． 001+ was added, and the mixture was stirred at room temperature overnight under a hydrogen atmosphere. After the reaction, the palladium-carbon was removed, the solvent in the furnace solution was distilled off, and the residue was purified by silica gel column chromatography (cyclohexane-ethyl acetate = 10+1) to obtain compound (MP-36) 1.007 (yield). rate 99%)
was obtained as a colorless oil.

il +Rν (cr'): 1725ax 't NMR (60MHz, CCf24) δ・0.75-
1.08 (12H, m, 4XCH3) 4.08 (28, t, J=6Hz, OCHt) MS (C
1s)lzeO3): Theoretical value m/z 254.18
82 (M”) Measured value m/z 254.1883 (M+)
Example 22 P-12 P-36 Compound (MP-12) L obtained in Example 2, QQ9 (
4mxol) Compound obtained in Example 12 (MP-24
C) 1.0 (19 (4 wool)) was dissolved in methanol, 1.00 g of 10% palladium-carbon was added, and the mixture was stirred at room temperature under a hydrogen atmosphere for 9 hours. After the reaction, the palladium-carbon was removed in the oven. The solvent of the p solution was distilled off, and the residue was purified by silica gel column chromatography (cyclohexane ethyl acetate-LO:l) to obtain the compound (MP-3
7) was quantitatively obtained as a colorless oil.

IRv: CR: 3300 (br), 17LO
(br)'H-NMR (60MHz, CCQ-) δ:
0.77-1.20 (12H, m, 4XCHa) 4.13 (2H, t, J-6Hz, OCHz) MS (C
=sHtsO3): Theoretical value m/z 256.20
37 (M”) Measured value m/z 256.2034 (M+)
Example 23 I did. An appropriate amount of ammonium chloride aqueous solution was added to the reaction solution, and the solvent of the reaction solution was distilled off. The residue was extracted with ethyl acetate and
The extract was washed successively with an aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography (cyclohexane-diyl acetate 1=1). , Compound (MP-38) was quantitatively obtained as a colorless oil.

1l IRν (cr'): 3325 (br), 17
20(br)ax'H-NMR (60Milz, CC) δ: 0.68
-1.25 (9H, m, 3XCH3) 3.18-3.90 (4H, m, 2xCHOH, and 2XOH) 4.07
(2H, t, J: 6) 1z, 0CH7) Theoretical value m/z
240.1725 (M+-H,O) Measured value m/z 24
0.1725(M+1lzO)ills(CI-824
03): Example 24 Compound obtained in Example 19 (MP-35A) 1.00
Dissolve g (3,9 zmol) in methanol and add 0.109 (2,6xxol) of sodium borohydride under water cooling.
and stirred overnight P-39 P-39 Compound obtained in Example 19 (MP-35A) 0.10
g (0,4zxol) was dissolved in methylene chloride, 0.494J (2,8xzol) of metachloroperbenzoic acid was added, and the mixture was stirred at room temperature for 20 days. Excess sodium hydrogen carbonate was added to the reaction solution and stirred for 4 hours, then 0.08y (1*xol) of dimethyl sulfoxide was added and stirred for 2 hours. After filtering the reaction solution, the solvent of the p solution was distilled off, and the residue was subjected to silica gel column chromatography (cyclohexane-
The compound (MP-3
9) 30s 9 (yield 27%) was obtained as a colorless oil.

IRvCHCQ"(cr'): 3380 (br)
, 1700ax 'H-NMR (60MHz, CC+24) δ: 0.8
9-1.28 (6H, m, 2XCHa) 2.09 (3B, S, CH3) 4.19 (2H, t, J-6Hz, 0CHt) 5, 20
-5.60 (IH, m, CH) MS (C1tHto0
3): Theoretical value rn/z 212.1411 (M”
CJaOt) Measured value mHz 212.1408 (M” C*H*Ot) Example 25 P-12 MP-24A MP-248MP-2
4C Compound obtained in Example 2 (MP-12) 0.40
Dissolve @(1,6ixol) in methanol and dissolve sodium borohydride 0.03i+(0,8xxol) under water cooling.
) and stirred for 30 minutes. An appropriate amount of ammonium chloride aqueous solution was added to the reaction solution, and the solvent of the reaction solution was distilled off. The residue was extracted with ethyl acetate, the extract was washed successively with an aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was subjected to silica gel column chromatography (cyclohexane- Ethyl acetate = 5:
l) and purified by compound (MP-24A), (MP-
24B) and (MP-24C) were obtained, respectively. The compound (MP-24C) obtained here was identical to the compound (MP-24C) obtained in Example 12.

P-24A IRvCH""(cr'):1720aX') l-NMR (60Hz, CCL) δ: 0.92 (
3)1. d, j-6Hz, cl(3)1.66(3H,
s, CH,) 4.00 (3H, t, J: 6Hz, 0CHt) 4.97
(2H,s,C=CH*) MS(C,,H!,03): Theoretical value m/z 25
4.1881 (M+) Measured value m/z 254.1876
(M”)P-24B [RνCtlCI2+ (C,-1): 1715a
X'H-NMR (60 MHz, CC (!4) δ: 0.
85 (3H, d, J-6Hz, CHe) 0.93 (3H
,t,J=6t(z,CH3)1.66(3H,S,C
H3) 3.92 (3H, t, J-6Hz, 0CHt) 4.62
(2H, s, C; CHt) MS (C1sHt60*) ' Theoretical value m/z 25
4.1881 (M”) Measured value mHz 254.1886
(M'') Example 26 MP-42MP-43 Compound obtained in Example 16 (MP-42) 1.019
(5,5 zmol) and methyl p-hydroxyphenylacetate 1.839 (llxxol) were dissolved in ethyl acetate, and dimethylaminopyridine 0.079 (llxxol) was dissolved under water cooling.
0,6xxol) and dicyclohexylcarbodiimide 1.131+(5,53IIO1) were added, and the mixture was stirred at room temperature for 4 days. An appropriate amount of diluted hydrochloric acid was added to the reaction solution, stirred for 30 minutes, and filtered. Extract the furnace liquid with ethyl acetate, and dilute the extract with 2
% sodium hydroxide aqueous solution and saturated saline solution,
After drying over anhydrous magnesium sulfate, the solvent was distilled off, the residue was purified by silica gel column chromatography (cyclohexane-ethyl acetate = 2:l), and the obtained crystals were recrystallized from benzene to obtain compound (MP-43). )0.7
09 (yield 38%) was obtained.

IRv "■ (cz-re: 1720 (br) ax H-NMR (60 MHz, CCl24) δ: 1.
27 (3H, d, J・6Hz, CH3) 2.23 (3)
1. s, CHs) 3.60 (2H, s, CHs) 3.69 (3H, s, OcH+) 6.95-7.35 (4H, m, 4XArl()ys(
c+autooJ: Theoretical value m/z 332.12
60 (M+) Actual value m/z 332.1260 (M”)
Example 27 Compound obtained in Example 18 (MP-40) 3.899
(21xxol) and methyl p-hydroxyphenylacetate 6,249 (38, w*ol) were dissolved in ethyl acetate and dimethylaminopyridine 0.269 (2,
1xxol) and synchhexylcarbodiimide4.
33g (21zxol) was added and stirred at room temperature for 24 hours. An appropriate amount of diluted hydrochloric acid was added to the reaction solution, stirred for 30 minutes, and filtered. The furnace solution was extracted with ethyl acetate, and the extract was washed successively with an aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was subjected to silica gel column chromatography (cyclohexane-ethyl acetate). = 2:3) to obtain compound (MP-41A)
3,649 (52% yield) was obtained as a colorless oil.

IRv Ox (cr'): 3350 (br), 1700
(br)'H-NMR (60MHz, CC(!4)δ:
1.15 (3H, d, J□6) 1z, CH3) 2.1
0(3H,S,CH3) 3.53(2)1. s, CHt) 3.63 (3H, s, 0CL) 6.93-7.32 (4B, m, 4XArH) MS (C
+a)12toe): Theoretical value m/z 334.1
417 (M”) Actual value m/z 334.1420 (M+
) Example 28 υ P-41A Example 29 O P-43 Compound obtained in Example 27 (MP-41A) 0.25
9(7,5JI[11) was dissolved in acetone, 1.31 liters of 8N Jones reagent was added dropwise under water cooling, and the mixture was stirred for 2.5 hours. An appropriate amount of isopropanol was added to the reaction solution, stirred for 30 minutes, then an appropriate amount of water was added, and acetone was distilled off. The residue was extracted with ethyl acetate, the extract was washed with saturated brine, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography (cyclohexane-ethyl acetate-2:1). Purify the compound (M
P-43) 0.229 (yield 87%) was obtained as a colorless oil. This compound is the compound MP obtained in Example 26.
-43 matched.

P-101 (IR,5S)-2-methyl-5-(1-methylethynyl)3-oxocyclopentanecarboxylic acid 9.09(5
0a+Rol) in the same manner as in Example 2, compound (M
P-101) 6, 19 (yield 47%: colorless oil). Various spectral data of this compound matched with various spectral data of the compound (MP-12) obtained in Example 2.

Example 30 P-102 (IR, 3S, 5S)-3-hydroxy-2-methyl-
5(1-methylethynyl)cyclopentanecarboxylic acid 1
Compound (MP-102) 169 (yield 64%; colorless oil) was obtained using h(0,1xol) in the same manner as in Example 12.
Converted to.

Various spectral data of this compound matched with various spectral data of the compound (MP-24C) obtained in Example 12.

Example 31 P-103 (IR,5S)-2-methyl-5-(1-methylethynyl)3-oxocyclopentanecarboxylic acid 5.59(3
0u01) in the same manner as in Example 10, compound (MP
-103) 80 g (yield: 80%; colorless oil). Various spectral data of the compound are shown in Example 1O.
It matched with various spectral data of the compound (MP-31) obtained in .

Example 32 P-102 P-104 Example 30 Lareta compound (MP-102) 7.69
(30zxol), the same reaction as in Example 19 was carried out, and compound (MP-104) 5.99 (yield 77%)
was obtained as a mixture of stereoisomers.

1l IRv (cr: 3400(br), 1710
(br)ax'H-NMR (60MHz, CCl24) δ: 0.8
6-1.20 (6H, m, 2XCH3) 2.12 (3H
, s, CH3) 4.03 (2H, t, J=6Hz, OCtlt) MS(
C,,H,,0,): Theoretical value m/z 256.1
675(!d+) Measured value m/z 256.1680(M
”) Example 33 Examination of platelet aggregation inhibitory effect The platelet aggregation inhibitory effect of the cyclopentanecarboxylic acid derivative obtained in the above example was evaluated according to the following test method.

[Test method: Male rabbits weighing 2.5 to 3.2 to 9 were used;
In the presence of 8% citric acid (1 volume of citric acid per 10 volumes of blood)
Carotid artery blood was collected. The collected blood was immediately centrifuged to separate platelet-rich plasma (PRP) and platelet-poor plasma (PP).
P) was separated. The centrifugation conditions were PRP near 6Or
pm for 15 minutes, PPP: 26QQrpm for 10 minutes. Measurement of platelet aggregation was carried out by nephelometry, with the permeability of PRP set to 0 and the permeability of PPP set to 100.
Manufactured by Bingen Bioscience: Hematotracer V).

The inhibitory effect of the test substance on platelet aggregation was measured according to the following procedure. That is, 200μQ of PRP was prewarmed for 1 minute (37°C, 101000rpL), 2μρ of test substance solution towM (initial concentration: water or 10-50% ethanol solution) was added (final concentration: 100μM), and 3 minutes later. Collagen (Horn Co., final concentration 10μ9) was used as a flocculant.
/ Toge) was added.

[Evaluation] The effect of each test substance was evaluated by calculating the inhibition rate using the following formula.

Inhibition rate (%) - ((maximum aggregation rate of aggregation addition - maximum aggregation rate of test substance addition)/maximum aggregation rate of solvent addition) x 100 The obtained results are shown in the following table.

Similarly, when the platelet aggregation inhibiting effects of Raw Material 1 and Raw Material 2 were evaluated, the inhibition rate was 0% for each.

Effects of the Invention The cyclopentanecarboxylic acid derivative according to the present invention has a lower cyclopentanecarboxylic acid derivative than the raw materials 2-isopropenyl-5-methyl-4oxocyclopencune-1-carboxylic acid and 3hydroxy-2-methylcyclopentane-t-carboxylic acid. Although it has a similar structure, unlike these substances, it has a platelet aggregation effect and is a useful substance in the prevention and treatment of thrombosis.

Claims (1)

[Claims] 1 General formula (I) ▲ Numerical formulas, chemical formulas, tables, etc. ^1 and R^2 represent oxygen; R^3 represents isopropenyl group, isopropyl group, acetyl group, 1-hydroxyethyl group, acetyloxy group; R^4 represents hydrogen, substituted or unsubstituted alkyl group , or represents a substituted or unsubstituted aryl group (however, R
When ^4 represents hydrogen or a methyl group, R^3 is a group other than isopropenyl);
cyclopentanecarboxylic acid derivatives and their enantiomers represented by: 2 General formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R^5 and R^6 are hydrogen and the other represents a hydroxy group, or R^5 and R^6 represents oxygen; R^7 represents isopropenyl group, acetyl group, isopropyl group, 1-hydroxyethyl group, or acetyloxy group) or its enantiomer, with the general formula R^6OH (formula The cyclopentanecarboxylic acid derivative according to claim 1, wherein R^6 represents a substituted or unsubstituted alkyl group or a substituted or unsubstituted aryl group. How to prepare its antipode. 3 General formula (III) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R^5 and R^6 have the same meanings as above, and R^
9 is hydrogen, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted aryl group) or its enantiomer is oxidatively cleaved to obtain the general formula (IV) ▲ mathematical formula, chemical formula,
Claim 1, characterized in that the compound is a compound represented by (wherein R^1, R^2 and R^4 have the same meanings as above) or its enantiomer. A method for producing a cyclopentanecarboxylic acid derivative and its enantiomer. 4 General formula (III) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R^5, R^6 and R^9 have the same meanings as above) or its enantiomer Reduced to a compound represented by the general formula (V) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (wherein R^1, R^2 and R^4 have the same meanings as above) or a pair thereof. 2. The method for producing a cyclopentanecarboxylic acid derivative and its enantiomer according to claim 1, wherein the cyclopentanecarboxylic acid derivative and its enantiomer are prepared as an enantiomer. 5 General formula (IV) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R^5, R^6 and R^9 have the same meanings as above) or its enantiomer Reduced to a compound represented by the general formula (VII) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (wherein R^1, R^2 and R^4 have the same meanings as above) or a pair thereof 2. The method for producing a cyclopentanecarboxylic acid derivative and its enantiomer according to claim 1, wherein the cyclopentanecarboxylic acid derivative and its enantiomer are prepared as an enantiomer. 6 General formula (VI) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R^5, R^6 and R^9 have the same meanings as above) or its enantiomer After Bayer-Villiger oxidation, a compound represented by the general formula (VIII) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (wherein R^1, R^2 and R^4 have the same meanings as above) The method for producing a cyclopentanecarboxylic acid derivative and its enantiomer according to claim 1, characterized in that the cyclopentanecarboxylic acid derivative and its enantiomer are used as 7 General formula (IX) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R^7 and R^9 have the same meanings as above) or its enantiomer is reduced, General formula (X) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R^3 and R^4 have the same meanings as above) A compound represented by or its enantiomer do,
A method for producing the cyclopentanecarboxylic acid derivative and its enantiomer according to claim 1. 8 General formula (X I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R^7 and R^9 have the same meanings as above) or its enantiomer is oxidized. , general formula (XI
I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R^3 and R^4 have the same meanings as above) Characterized by being a compound or its enantiomer,
A method for producing the cyclopentanecarboxylic acid derivative and its enantiomer according to claim 1.