2-羟基环戊烷甲酸乙酯

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2-hydroxy-cyclopentanecarboxylic acid ethyl ester (3.5 g, 22.12 mmol) in methylene chloride (147.5 mL) was treated with 3,4-dihydro-2H-pyran (3.03 mL, 33.1 mmol) and pyridiniump-toluenesulfonate (556 mg, 2.21 mmol). This solution was stirred at 25° C. for 5 h. The reaction was then washed with a half-saturated aqueous sodium chloride solution (2×75 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 90/10 hexanes/ethyl acetate) afforded 2-(tetrahydro-pyran-2-yloxy)-cyclopentanecarboxylic acid ethyl ester (4.7 g, 87.7%) as a clear liquid: EI-HRMS m/e calcd for C13H22O4 (M+) 242.1518. found 242.1521. The reaction was then washed with a half-saturated aqueous sodium chloride solution (2×75 mL) dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2-oxo-cyclopentanecarboxylic acid ethyl ester (10 g, 64.0 mmol) in ethanol (106.7 mL) cooled to 0° C. was treated with 98% sodium borohydride (686 mg, 17.78 mmol). The reaction was stirred at 0° C. for 30 min. At this time, the reaction mixture was poured into water (53 mL) and was extracted into diethyl ether 3×100 mL). The organics were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 75/25 ethyl acetate/hexanes) afforded 2-hydroxy-cyclopentanecarboxylic acid ethyl ester (8.5 g, 83.9%) as a clear liquid. was extracted into diethyl ether 3×100 mL) The organics were dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2-oxo-cyclopentanecarboxylic acid ethyl ester (10 g, 64.0 mmol) in ethanol (106.7 mL) cooled to 0° C. was treated with 98% sodium borohydride (686 mg, 17.78 mmol). The reaction was stirred at 0° C. for 30 min. At this time, the reaction mixture was poured into water (53 mL) and was extracted into diethyl ether 3×100 mL). The organics were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 75/25 ethyl acetate/hexanes) afforded 2-hydroxy-cyclopentanecarboxylic acid ethyl ester (8.5 g, 83.9%) as a clear liquid. was extracted into diethyl ether 3×100 mL) The organics were dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 1st method: 10 g of sodium borohydride are added to a solution of 62.4 g (0.4 mole) of 2-oxo-cyclopentylcarboxylic acid ethyl ester in 200 ml of methanol cooled to 0° C. When the reaction, which is followed by thin layer chromatography, is completed, the reaction mixture is poured with caution into an aqueous solution saturated with NaH2PO4. By extracting with ethyl ether and subsequently evaporating off the solvent, a residue is obtained which is purified by under vacuum distillation yielding 44 g of 2-hydroxy-cyclopentylcarboxylic acid ethyl ester (b.p. 87° C./0.3 mmHg). When the reaction, which By extracting with ethyl ether subsequently evaporating off the solvent a residue is obtained which is purified by under vacuum distillation

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 1st method: 10 g of sodium borohydride are added to a solution of 62.4 g (0.4 mole) of 2-oxo-cyclopentylcarboxylic acid ethyl ester in 200 ml of methanol cooled to 0° C. When the reaction, which is followed by thin layer chromatography, is completed, the reaction mixture is poured with caution into an aqueous solution saturated with NaH2PO4. By extracting with ethyl ether and subsequently evaporating off the solvent, a residue is obtained which is purified by under vacuum distillation yielding 44 g of 2-hydroxy-cyclopentylcarboxylic acid ethyl ester (b.p. 87° C./0.3 mmHg). When the reaction, which By extracting with ethyl ether subsequently evaporating off the solvent a residue is obtained which is purified by under vacuum distillation

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 1st method: 10 g of sodium borohydride are added to a solution of 62.4 g (0.4 mole) of 2-oxo-cyclopentylcarboxylic acid ethyl ester in 200 ml of methanol cooled to 0° C. When the reaction, which is followed by thin layer chromatography, is completed, the reaction mixture is poured with caution into an aqueous solution saturated with NaH2PO4. By extracting with ethyl ether and subsequently evaporating off the solvent, a residue is obtained which is purified by under vacuum distillation yielding 44 g of 2-hydroxy-cyclopentylcarboxylic acid ethyl ester (b.p. 87° C./0.3 mmHg). When the reaction, which By extracting with ethyl ether subsequently evaporating off the solvent a residue is obtained which is purified by under vacuum distillation

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 1st method: 10 g of sodium borohydride are added to a solution of 62.4 g (0.4 mole) of 2-oxo-cyclopentylcarboxylic acid ethyl ester in 200 ml of methanol cooled to 0° C. When the reaction, which is followed by thin layer chromatography, is completed, the reaction mixture is poured with caution into an aqueous solution saturated with NaH2PO4. By extracting with ethyl ether and subsequently evaporating off the solvent, a residue is obtained which is purified by under vacuum distillation yielding 44 g of 2-hydroxy-cyclopentylcarboxylic acid ethyl ester (b.p. 87° C./0.3 mmHg). When the reaction, which By extracting with ethyl ether subsequently evaporating off the solvent a residue is obtained which is purified by under vacuum distillation

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2-hydroxy-cyclopentanecarboxylic acid ethyl ester (3.5 g, 22.12 mmol) in methylene chloride (147.5 mL) was treated with 3,4-dihydro-2H-pyran (3.03 mL, 33.1 mmol) and pyridinium p-toluenesulfonate (556 mg, 2.21 mmol). This solution was stirred at 25° C. for 5 h. The reaction was then washed with a half-saturated aqueous sodium chloride solution (2×75 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 90/10 hexanes/ethyl acetate) afforded 2-(tetrahydro-pyran-2-yloxy)-cyclopentanecarboxylic acid ethyl ester (4.7 g, 87.7%) as a clear liquid: EI-HRMS m/e calcd for C13H22O4 (M+) 242.1518 found 242.1521. The reaction was then washed with a half-saturated aqueous sodium chloride solution (2×75 mL) dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2-hydroxy-cyclopentanecarboxylic acid ethyl ester (3.5 g, 22.12 mmol) in methylene chloride (147.5 mL) was treated with 3,4-dihydro-2H-pyran (3.03 mL, 33.1 mmol) and pyridinium p-toluenesulfonate (556 mg, 2.21 mmol). This solution was stirred at 25° C. for 5 h. The reaction was then washed with a half-saturated aqueous sodium chloride solution (2×75 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 90/10 hexanes/ethyl acetate) afforded 2-(tetrahydro-pyran-2-yloxy)-cyclopentanecarboxylic acid ethyl ester (4.7 g, 87.7%) as a clear liquid: EI-HRMS m/e calcd for C13H22O4 (M+) 242.1518 found 242.1521. The reaction was then washed with a half-saturated aqueous sodium chloride solution (2×75 mL) dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2-oxo-cyclopentanecarboxylic acid ethyl ester (10 g, 64.0 mmol) in ethanol (106.7 mL) cooled to 0° C. was treated with 98% sodium borohydride (686 mg, 17.78 mmol). The reaction was stirred at 0° C. for 30 min. At this time, the reaction mixture was poured into water (53 mL) and was extracted into diethyl ether (3×100 mL). The organics were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 75/25 ethyl acetate/hexanes) afforded 2-hydroxy-cyclopentanecarboxylic acid ethyl ester (8.5 g, 83.9%) as a clear liquid. was extracted into diethyl ether (3×100 mL) The organics were dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2-oxo-cyclopentanecarboxylic acid ethyl ester (10 g, 64.0 mmol) in ethanol (106.7 mL) cooled to 0° C. was treated with 98% sodium borohydride (686 mg, 17.78 mmol). The reaction was stirred at 0° C. for 30 min. At this time, the reaction mixture was poured into water (53 mL) and was extracted into diethyl ether (3×100 mL). The organics were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 75/25 ethyl acetate/hexanes) afforded 2-hydroxy-cyclopentanecarboxylic acid ethyl ester (8.5 g, 83.9%) as a clear liquid. was extracted into diethyl ether (3×100 mL) The organics were dried over sodium sulfate filtered concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The asymmetric reduction of ethyl 2-oxocyclopentanecarboxylate was carried out by using this reductase (1). Namely, 4 ml of the reaction mixture containing the reductase (1) (2U), NADPH (0.8 μmol), ethyl 2-oxocyclopentanecarboxylate (100 μmol, 16 mg), phosphate buffer solution (pH 7.0, 400 μmol), glucose dehydrogenase [manufactured by Sigma, Co., U.S.A.; 2U (wherein 1U is defined as the amount of the enzyme which reduces 1 μmol of NADP+ per 1 minute in the presence of glucose)] and glucose (100 μmol) was incubated at 30° C. with gentle shaking to promote the enzymatic reaction. After 6 hour-incubation, the reaction mixture was extracted according to the same manner as in Example 3. The extract was analyzed by gas chromatography described in Example 1. As a result, the yield of the cis isomer was 15.9 mg (reduction yield >99%), and neither the remaining substrate nor the trans isomer was detected. On the other hand, the extract above was distilled off according to the the same manner as in Example 3 to obtain the reduction product, ethyl 2-hydroxycyclopentane-carboxylate. The resulting reduction product was analyzed by high performance liquid chromatography as described in Example 1. As a result, only the cis 2 isomer was detected and no other isomers were detected. per 1 minute was incubated at 30° C. the enzymatic reaction the reaction mixture was extracted On the other hand, the extract above was distilled off