Optically-active cyclopentenone derivatives

Abstract

The present invention provides: industrially desirable and novel optically-active cyclopentenone derivatives; and a novel industrial manufacturing method. The novel optically-active cyclopentenone derivatives and method for manufacturing the same are, respectively: an intermediate for industrially desirable and novel prostaglandin derivatives and the like; and a method for manufacturing the same. It is expected that the present invention will be commercialized and industrialized.

Claims

1. A method for producing the compound of formula (3) or the compounds of formula (4), comprising reacting the compound of formula (2) with a carboxylic acid ester of an unsaturated alcohol in the presence of a hydrolase to give a mixture of the compounds of formula (3) and formula (4), wherein the mixture of the compounds of formula (3) and formula (4) is then separated to produce an optically-active compound of formula (3) or an optically active compound of formula (4), wherein R.sup.1 is tert-butyldimethylsilyl or triphenylmethyl and R.sup.2 is an acyl group ##STR00010##

2. The method according to claim 1, wherein the carboxylic acid ester of an unsaturated alcohol is vinyl acetate, vinyl propionate, vinyl valerate, isopropenyl acetate, isopropenyl propionate, or isopropenyl valerate, and the hydrolase is lipase.

3. The method according to claim 1, wherein the carboxylic acid ester of an unsaturated alcohol is vinyl acetate, and the hydrolase is Amano Lipase PS or Amano Lipase AK.

4. A compound represented by formula (I) or an optically-active form thereof, ##STR00011## wherein, R.sup.1 is a tent-butyldimethylsilyl, and R.sup.2 is acetyl, propionyl, n-butyryl, iso-butyryl, n-valeryl or caproyl, and wherein the * represents an asymmetric carbon atom.

5. A compound represented by formula (I) or an optically-active form thereof, ##STR00012## wherein, R.sup.1 is triphenylmethyl, and R.sup.2 is an acyl group, and wherein the * represents an asymmetric carbon atom.

Description

EXAMPLE 1

Manufacture of 4-hydroxy-2-(tert-butyldimethylsilyl) oxymethyl) cyclopenta-2-en-1-one

(1) ##STR00005##

(2) Tert-butyldimethylsilyl chloride (3.29 g, 21.8 mmol) and triethylamine (3.8 mL, 27.3 mmol) were added at room temperature to a THF solution (20 mL) of 4-hydroxy-2-hydroxymethyl) cyclopenta-2-en-1-one (1.4 g, 10.9 mmol). After stirring the reaction solution at the same temperature for 24 hours, an aqueous solution of saturated ammonium chloride was added to stop the reaction. The mixture was separated using ethyl acetate (2×30 mL). The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The residue remaining after removal under reduced pressure was purified by silica gel chromatography (hexane/EtOAc 2:1.fwdarw.1:1). 4-hydroxy-2-(tert-butyldimethylsilyl) oxymethyl) cyclopenta-2-en-1-one (2.17 g, 82%) was obtained as a colorless to pale yellow oily substance.

(3) .sup.1H NMR (400 Mz, CDCl.sub.3): δ 0.080 (s, 3H), 0.085 (s, 3H), 0.92 (s, 3H), 1.91 (d, J=5.2 Hz), 2.37 (dd, J=2.0, 18.8 Hz, 1H), 2.86 (dd, J=6.0, 18.8 Hz, 1H), 4.37-4.38 (m, 2H), 4.99 (brs, 1H), 7.37-7.38 (m, 1H) ppm; .sup.13C NMR (100 Mz, CDCl.sub.3): δ 5.35, 5.32, 18.4, 26.0 (3C), 45.8, 58.0, 68.9, 148.4, 155.9, 204.8 ppm.

EXAMPLE 2

(4) Manufacture of an Optically-Active Cyclopentenone

(5) ##STR00006##

(6) Lipase AK amano (1.1 g) was added to acetone-vinyl acetate solution (26 mL, 1:1) of 4-hydroxy-2-(tert-butyldimethylsilyl) oxymethyl) cyclopenta-2-en-1-one (2.2 g, 9.04 mmol) at room temperature and stirred at the same temperature overnight. After removing the enzyme was by filtration, the filtrate was distilled off under reduced pressure. The residue obtained was purified with silica gel chromatography (hexane/EtOAc 3:1.fwdarw.1:1). 4R-acetoxy-2-(tert-butyldimethylsilyl) oxymethyl) cyclopenta-2-en-1-one ((R)-AC form) (1.25 g, 48%) and 4S-hydroxy-2-(tert-butyldimethylsilyl) oxysilyl) cyclopenta-2-en-1-one ((S)-mono TBS form) (1.1 g, 50%) were obtained, respectively.

(7) (R)-AC form:

(8) .sup.1H NMR (400 Mz, CDCl.sub.3): δ 0.084 (s, 3H), 0.086 (s, 3H), 0.92 (s, 9H), 2.10 (s, 3H), 2.41 (dd, J=2.0, 18.8 Hz, 1H), 2.91 (dd, J=6.0, 18.2 Hz, 1H), 4.40 (t, J=2.0 Hz, 2H), 5.78-5.82 (m, 2H), 7.36 (q, J=2.4, 1H) ppm; .sup.13C NMR (100 Mz, CDCl.sub.3) δ 5.36, 18.4, 21.1, 26.0 (3C), 42.6, 58.1, 70.5, 150.0, 152.1, 170.7, 203.6 ppm.

(9) Enantiomer excess: 92% ee (Chiral ART (YMC), Cellulose-SC, 250×4.6 mm I.D., hexane/i-propanol=90/10)

(10) (S)-mono TBS form:

(11) [α].sub.D.sup.19=−11.6 (c=1.0 in CHCl.sub.3)

EXAMPLE 3

Manufacture of 4S-hydroxy-2-(tert-butyldimethylsilyloxymethyl) cyclopenta-2-en-1-one

(12) ##STR00007##

(13) tert-butyldimethylsilyl chloride (405 mg, 2.69 mmol) and triethylamine (0.5 mmol, 3.58 mmol) were added to a THF solution (6 mL) of 4S-hydroxy-2-hydroxymethylcyclopenta-2-en-1-one (230 mg, 1.79 mmol) at room temperature. After stirring the reaction solution at the same temperature for 24 hours, an aqueous solution of saturated ammonium chloride was added to stop the reaction. The mixture was separated using ethyl acetate (2×10 mL). The organic layer is washed with saturated brine and dried over anhydrous magnesium sulfate. The residue remaining after the removal under reduced pressure was purified with silica gel chromatography (hexane/EtOAc 2:1.fwdarw.1:1). 4S-hydroxy-2-(tert-butyldimethylsilyloxymethyl) cyclopenta-2-en-1-one (306 mg, 70%) was obtained as a colorless to pale yellow oily substance. The various spectral data were the same as those in Example 1. Besides, the optical rotation matched well with that in Example 2. [α].sub.D.sup.19=−11.8 (c=1.0 in CHCl.sub.3)

EXAMPLE 4

Manufacture of 4-hydroxy-2-(triphenylmethyloxymethyl) cyclopenta-2-en-1-one

(14) ##STR00008##

(15) Triphenylmethyl chloride (993 mg, 3.56 mmol) and diisopropylethylamine (1.13 mL, 6.48 mmol) were added to a THF solution (20 mL) of 4-hydroxy-2-hydroxymethyl) cyclopenta-2-en-1-one (415 mg, 3.24 mmol) at room temperature. After stirring the reaction solution at the same temperature for 24 hours, an aqueous solution of saturated ammonium chloride was added to stop the reaction. The mixture was separated using ethyl acetate (2×30 mL). The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The residue remaining after removal under reduced pressure was purified with silica gel chromatography (hexane/EtOAc 1:1). 4-Hydroxy-2-(triphenylmethyloxymethyl) cyclopenta-2-en-1-one (390 mg, 32%) was obtained as a pale yellow amorphous to viscous oily substance.

(16) .sup.1H NMR (400 Mz, CDCl.sub.3): δ 1.85 (d, J=6.4 Hz, 1H), 2.30 (dd, J=2.0, 18.8 Hz, 1H), 2.80 (dd, J=6.0, 18.8 Hz, 1H), 3.93-3.94 (m, 2H), 4.98-5.02 (m, 1H), 7.22-7.45 (m, 15H), 7.61 (q, J=2.0 Hz, 1H) ppm; .sup.13C NMR (101 Mz, CDCl.sub.3) δ 45.2, 58.6, 68.8, 87.1, 127.2, 127.9, 128.5, 143.6, 145.8, 156.1, 204.5 ppm.

EXAMPLE 5

(17) Manufacture of an Optically-Active Cyclopentenone

(18) ##STR00009##

(19) Lipase AK amano (81 mg) was added to vinyl acetate-acetone solution (1:1, 2.2 mL) of 4-hydroxy-2-(triphenylmethyloxymethyl) cyclopenta-2-en-1-one (81.7 mg, 0.22 mmol) at room temperature and stirred at the same temperature for 24 hours. The enzyme was removed by filtration, and the filtrate was distilled off under reduced pressure. The obtained residue was purified with silica gel chromatography (hexane/EtOAc=2:1). 4R-acetoxy-2-(triphenylmethyloxymethyl) cyclopenta-2-en-1-one ((R)-AC form) (32 mg, 36%), and 4S-hydroxy-2-(triphenylmethyloxymethyl) cyclopenta-2-en-1-one ((S)-monotrityl form) (40 mg, 49%) were obtained, respectively.

(20) .sup.1H NMR (400 Mz, CDCl.sub.3): δ 2.13 (s, 3H), 2.36 (dd, J=2.0, 18.8 Hz), 2.86 (dd, J=6.0, 18.8 Hz, 1H), 3.92-3.93 (m, 2H), 5.81-5.84 (m, 1H), 7.22-7.44 (m, 15H) 7.63 (d, J=2.4, 1H) ppm; .sup.13C NMR (101 Mz, CDCl.sub.3) δ 20.9, 41.9, 58.7, 70 4, 87.1, 127.2, 127.9, 128.4, 143.4, 147.5, 152.0, 170.5, 203.1 ppm.