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 compound represented by formula (I) or an optically-active form thereof, ##STR00010## wherein R.sup.1 is silyl group represented by formula (i), an alkyl group, an aryl group, an arylalkyl group, or a group that forms an acetal bond together with the oxygen atom of a hydroxyl group, wherein R.sup.2 is a hydrogen atom or an acyl group wherein the * represents an asymmetric carbon atom, wherein formula (i) is: ##STR00011## wherein R.sup.3, R.sup.4 and R.sup.5 are an alkyl group, which may have a substituent, an aryl group, which may have a substituent, and an arylalkyl group which may have a substituent, respectively.

2. A compound or an optically-active form thereof according to claim 1, wherein R.sup.1 is silyl group represented by formula (i) and wherein R.sup.3, R.sup.4 and R.sup.5 are an alkyl group, which may have a substituent, an aryl group, which may have a substituent, and an arylalkyl group or arylalkyl group.

3. A compound or an optically-active form thereof according to claim 1, wherein R.sup.3, R.sup.4 and R.sup.5 are a C.sub.1-C.sub.6 alkyl group which may have a substituent, a C.sub.6-C.sub.10 aryl group which may have a substituent, and a C.sub.7-C.sub.14 arylalkyl group which may have a substituent, respectively.

4-7. (canceled)

8. A method for manufacturing a compound of formula (2), wherein, R.sup.1 is a silyl group represented by formula (i), an alkyl group, an aryl group, an arylalkyl group, or a group that forms an acetal bond together with the oxygen atom of a hydroxyl group or an optically-active form thereof, characterized in that a compound of formula (1) is reacted with a silyl halide or an arylalkyl halide in the presence of a base ##STR00012## wherein (i) has the formula: ##STR00013## wherein R.sup.3, R.sup.4 and R.sup.5 are an alkyl group, which may have a substituent, an aryl group, which may have a substituent, and an arylalkyl group which may have a substituent, respectively.

9. A method wherein the compound of formula (2) and a carboxylic acid ester of an unsaturated alcohol are reacted in the presence of a hydrolase to give a mixture of the compounds of formula (3) and formula (4), wherein, R.sup.1 is silyl group represented by formula (i), an alkyl group, an aryl group, an arylalkyl group, or a group that forms an acetal bond together with the oxygen atom of a hydroxyl group, and R.sup.2 is acyl group, which is then separated to manufacture the optically-active cycloeptenone of formula (3) and formula (4) ##STR00014##

10. A method according to claim 9, 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.

11. A method according to claim 9, wherein the carboxylic acid ester of an unsaturated alcohol is vinyl acetate, and the hydrolase is Lipase PS (Amano) or Lipase AK (Amano).

12. The compound according to claim 1, or an optically-active form thereof, wherein R.sup.1 is a tert-butyldimethylsilyl (TBS) group and R.sup.2 is a hydrogen atom.

13. The compound according to claim 1, or an optically-active form thereof, wherein R.sup.1 is a triphenylmethyl group and R.sup.2 is a hydrogen atom.

14. The compound according to claim 1, or an optically-active form thereof, wherein R.sup.1 is a tert-butyldimethylsilyl (TBS) group and R.sup.2 is an acyl group.

15. The compound according to claim 1, or an optically-active form thereof, wherein R.sup.1 is a tert-butyldimethylsilyl (TBS) group and R.sup.2 is an acetyl group, a proponyl group, an n-butyryl group, an iso-butyryl group, an n-valeryl group or a caproyl group.

16. The compound according to claim 1, or an optically-active form thereof, wherein R.sup.1 is a tert-butyldimethylsilyl (TBS) group and R.sup.2 is an acetyl group.

17. The compound according to claim 1, or an optically-active form thereof, wherein R.sup.1 is a triphenylmethyl group and R.sup.2 is an acyl group.

18. The compound according to claim 1, or an optically-active form thereof, wherein R.sup.1 is a triphenylmethyl group and R.sup.2 is an acetyl group, a proponyl group, an n-butyryl group, an iso-butyryl group, an n-valeryl group or a caproyl group.

19. The compound according to claim 1, or an optically-active form thereof, wherein R.sup.1 is a triphenylmethyl group and R.sup.2 is an acetyl group.

Description

EXAMPLE 1

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

[0071] ##STR00005##

[0072] 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.

[0073] .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

[0074] Manufacture of an Optically-Active Cyclopentenone

##STR00006##

[0075] 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.

[0076] (R)-AC form:

[0077] .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.

[0078] Enantiomer excess: 92% ee (Chiral ART (YMC), Cellulose-SC, 250×4.6 mm I.D., hexane/i-propanol=90/10)

[0079] (S)-mono TBS form:

[0080] [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

[0081] ##STR00007##

[0082] 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

[0083] ##STR00008##

[0084] 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.

[0085] .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

[0086] Manufacture of an Optically-Active Cyclopentenone

##STR00009##

[0087] 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.

[0088] .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.