[(1R,2S)-2-(hydroxymethyl)cyclopentyl]methanol

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 127 ml of a 1.2 molar solution of diisobutylaluminum hydride in toluene is instilled in a solution of 8.7 g of 2-hydroxymethyl-cyclopentanecarboxylic acid lactone (O. Caamano et al., Euro. J. Med. Chem. 22, 311 (1987)) in 127 ml of toluene at 0° C. under argon and stirred for 50 minutes at 0° C. Then, 25 ml of isopropanol and 63 ml of water are instilled, stirred for 2 hours at 22° C., filtered washed with methylene chloride and concentrated by evaporation in a vacuum. The residue is purified by chromatography on silica gel. With ethyl acetate/hexane (4+1), 7 g of cis-1,2-dihydroxymethyl-cyclopentane is obtained as colorless liquid. filtered washed with methylene chloride concentrated by evaporation in a vacuum The residue is purified by chromatography on silica gel

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 127 ml of a 1.2 molar solution of diisobutylaluminum hydride in toluene is instilled in a solution of 8.7 g of 2-hydroxymethyl-cyclopentanecarboxylic acid lactone (O. Caamano et al., Euro. J. Med. Chem. 22, 311 (1987)) in 127 ml of toluene at 0° C. under argon and stirred for 50 minutes at 0° C. Then, 25 ml of isopropanol and 63 ml of water are instilled, stirred for 2 hours at 22° C., filtered washed with methylene chloride and concentrated by evaporation in a vacuum. The residue is purified by chromatography on silica gel. With ethyl acetate/hexane (4+1), 7 g of cis-1,2-dihydroxymethyl-cyclopentane is obtained as colorless liquid. filtered washed with methylene chloride concentrated by evaporation in a vacuum The residue is purified by chromatography on silica gel

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 127 ml of a 1.2 molar solution of diisobutylaluminum hydride in toluene is instilled in a solution of 8.7 g of 2-hydroxymethyl-cyclopentanecarboxylic acid lactone (O. Caamano et al., Euro. J. Med. Chem. 22, 311 (1987)) in 127 ml of toluene at 0° C. under argon and stirred for 50 minutes at 0° C. Then, 25 ml of isopropanol and 63 ml of water are instilled, stirred for 2 hours at 22° C., filtered washed with methylene chloride and concentrated by evaporation in a vacuum. The residue is purified by chromatography on silica gel. With ethyl acetate/hexane (4+1), 7 g of cis-1,2-dihydroxymethyl-cyclopentane is obtained as colorless liquid. filtered washed with methylene chloride concentrated by evaporation in a vacuum The residue is purified by chromatography on silica gel

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Glycine (18.8 grams) is dissolved in 2 liters of deionized water, and the pH is adjusted by the addition of 10% sodium hydroxide to 9.0. Cis-1,2-cyclopentane dimethanol (10.0 grams) is added to the glycine solution with stirring until dissolution occurs, followed by the addition of β-NAD+ (Sigma, 2 grams) and flavin mononucleotide (Sigma, 30 grams). To the resulting clear orange solution is added horse liver alcohol dehydrogenase (Sigma, 250 mg, approximately 400 units). After the enzyme has dissolved the pH is readjusted to 9.0 with 10% sodium hydroxide, and the reaction mixture is stirred at 30° C. During the reaction, the pH is maintained at 9.0 with a pH-stat by the addition of 10% sodium hydroxide. Progress of the reaction is monitored by thin layer chromatography (Silica gel plates, eluent 1:1 ethyl acetate-methylene chloride; visualization by dipping in a solution of 5% anisaldehyde in ethanol and heating). When the reaction is complete as judged by thin layer chromatography, the reaction mixture is adjusted to a pH of 13 with 10 M sodium hydroxide and then extracted 3 times with 250 ml of methylene chloride. The pH of the aqueous mixture is then adjusted to 3 with concentrated HCl, followed by continuous extraction with 1 liter of ethyl acetate for 24 hours. The ethyl acetate extract is dried over anhydrous magnesium sulfate and evaporated under reduced pressure to yield (1R,5S)-(+)-7-oxabicyclo[3.3.0]octan-6-one (9 grams) as an orange oil. The product may be further purified by distillation at reduced pressure to yield a colorless oil. After the enzyme has dissolved the pH the reaction mixture is stirred at 30° C During the reaction heating) extracted 3 times with 250 ml of methylene chloride followed by continuous extraction with 1 liter of ethyl acetate for 24 hours The ethyl acetate extract is dried over anhydrous magnesium sulfate evaporated under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 46 ml of a 1.2 molar solution of diisobutylaluminum hydride in toluene is instilled in a solution of 2.8 g of 2-hydroxymethyl-cyclobutanecarboxylic acid lactone (C. C. Schroff et al., J. Org. Chem. 36, 3356 (1971)) in 70 ml of toluene at 0° C. under argon and stirred for 50 minutes at 0° C. Then, 20 ml of 2-propanol and 23 ml of water are instilled, stirred for 2 hours at 22° C. filtered washed with dichloromethane and concentrated by evaporation in a vacuum. The residue is purified by chromatography on silica gel. With ethyl acetate/hexane (4+1), 2.1 g of cis-1,2-dihydroxymethyl-cyclopentane is obtained as colorless liquid. stirred for 2 hours at 22° C. filtered washed with dichloromethane concentrated by evaporation in a vacuum The residue is purified by chromatography on silica gel

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Glycine (18.8 grams) is dissolved in 2 liters of deionized water, and the pH is adjusted by the addition of 10% sodium hydroxide to 9.0. Cis-1,2-cydopentane dimethanol (10.0 grams) is added to the glycine solution with stirring until dissolution occurs, followed by the addition of β-NAD+ (Sigma, 2 grams) and flavin mononucleotide (Sigma, 30 grams). To the resulting dear orange solution is added horse liver alcohol dehydrogenase (Sigma, 250 mg, approximately 400 units). After the enzyme has dissolved the pH is readjusted to 9.0 with 10% sodium hydroxide, and the reaction mixture is stirred at 30° C. During the reaction, the pH is maintained at 9.0 with a pH-stat by the addition of 10% sodium hydroxide. Progress of the reaction is monitored by thin layer chromatography (Silica gel plates, eluent 1:1 ethyl acetate-methylene chloride; visualization by dipping in a solution of 5% anisaldehyde in ethanol and heating). When the reaction is complete as judged by thin layer chromatography, the reaction mixture is adjusted to a pH of 13 with 10 M sodium hydroxide and then extracted 3 times with 250 ml of methylene chloride. The pH of the aqueous mixture is then adjusted to 3 with concentrated HCl, followed by continuous extraction with 1 liter of ethyl acetate for 24 hours. The ethyl acetate extract is dried over anhydrous magnesium sulfate and evaporated under reduced pressure to yield (1R,5S)-(+)-7-oxabicyclo[3.3.0]octan-6-one (9 grams) as an orange oil. The product may be further purified by distillation at reduced pressure to yield a colorless oil. After the enzyme has dissolved the pH the reaction mixture is stirred at 30° C During the reaction heating) extracted 3 times with 250 ml of methylene chloride followed by continuous extraction with 1 liter of ethyl acetate for 24 hours The ethyl acetate extract is dried over anhydrous magnesium sulfate evaporated under reduced pressure