Acetic Acid → Octahydropentalenol

Participants

Reaction Steps

A stirred solution of 6-[(E)-3-cyclohexyl-(mixture of 3α and 3β)-hydroxyprop-1-enyl]-3-[(E)-4-methoxycarbonylbutylidene]bicyclo[3,3,0]octan-2-one (6.7 mg), prepared as described in Example 8 and predominantly in the 6β-configuration, otherwise known as (±)-methyl(5E,13E)-(9S),[mixture of (15R) and (15S)]-6a-oxo-6,9-methano-15-cyclohexyl-15-hydroxy-16,17,18,19,20-pentanorprosta-5,13-dienoate, in tetrahydrofuran (0.5 ml) at -78° C. was treated dropwise with a solution of lithium tri-sec-butylborohydride in tetrahydrofuran (0.0196 ml; 1.0M). The stirred solution was allowed to warm to 0° during 2 hours and then it was stirred for a further period of 2 hours. Glacial acetic acid (0.15 ml) and water (0.2 ml) were then added to the mixture, which was then concentrated in vacuo. The resulting residue was dissolved in ethyl acetate (10 ml), washed with aqueous sodium bicarbonate solution (2M) and then with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulphate and concentrated in vacuo. The resulting oil was treated with a solution of sodium hydroxide in 50% v/v aqueous methanol (0.1 ml; 2.5N) and stirred for 150 minutes at 20° C. The mixture was then carefully concentrated in vacuo, and diluted with water (6 ml) and diethyl ether (3 ml). The aqueous phase was separated, acidified to pH 3 by treatment with hydrochloric acid (2N), and extracted with ethyl acetate (4×10 ml). The combined organic extracts were dried over sodium sulphate and concentrated in vacuo. The resulting residue was subjected to chromatography on a silica gel column, using a mixture of ethyl acetate, hexane and glacial acetic acid (50:50:1 by volume) as eluant, to give 3-[(E)-4-carboxybutylidene]-6-[(E)-3-cyclohexyl-(mixture of 3α and 3β)-hydroxyprop-1-enyl]-2-hydroxybicyclo[3,3,0]octane (3.6 mg), predominantly in the 6β,6α-configuration, otherwise known as (±)-(5E,13E)-(6aS,9S),[mixture of (15R) and (15S)]-6a,15-dihydroxy-6,9-methano-15-cyclohexyl-16,17,18,19,20-pentanorprosta-5,13-dienoic acid [NMR in deuterochloroform: multiplets at 5.5, 3.5, 2.7-0.7 p.p.m⟧

Provenance & Evidence