3,3a,4,5,6,6a-hexahydro-2H-pentalen-1-one

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

Procedure: By proceeding in a manner to that described in Reference Example 47, but replacing the starting material by the appropriate quantity of (E)-2-(3-tert-butyldimethylsilyloxy-4-phenoxybut-1-enyl)bicyclo[3,3,0]octan-6-one, prepared as described in Reference Example 52, and in the form of (±)-(E)-2β-[(mixture of 3α and 3β)-tert-butyldimethylsilyloxy-4-phenoxybut-1-enyl]bicyclo[3,3,0]octan-6-one, there was prepared 6-(E)-3-tert-butyldimethylsilyloxy-4-phenoxybut-1-enyl-3-(1-hydroxy-4-methoxycarbonylbut-1-yl)-bicyclo[3,3,0]octan-2-one, in the form of (±)-6β-[(E)-(mixture of 3α and 3β)-tert-butyldimethylsilyloxy-4-phenoxybut-1-enyl]-3-(1-hydroxy-4-methoxycarbonylbut-1-yl)bicyclo[3,3,0]octan-2-one. prepared

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

Procedure: A stirred solution of 6-[(E)-3-tert-butyldimethylsilyloxy-3-cyclohexylprop-1-enyl]-3-(5-ethoxycarbonyl-2-hydroxypent-2-yl)bicyclo[3,3,0]octan-2-one (26 mg), prepared as described in Reference Example 39 and in the form of 6β-[(E)-3β-tert-butyldimethylsilyloxy-3-cyclohexylprop-1-enyl]-3-(5-ethoxycarbonyl-2-hydroxypent-2-yl)bicyclo[3,3,0]octan-2-one, otherwise known as (±)-ethyl(13E)-(9S,15R)-6a-oxo-6,9-methano-15-tert-butyldimethylsilyloxy-15-cyclohexyl-5-hydroxy-5-methyl-16,17,18,19,20-pentanorprost-13-enoate, in benzene (0.19 ml) was treated with methanesulphonyl chloride (0.0048 ml) at the ambient temperature, followed by triethylamine (0.008 ml) and the mixture was stirred for 2 hours. It was then treated with 1,8-diazabicyclo[5,4,0]undec-7-ene (0.0446 ml) and the mixture was stirred for 2 hours. It was then treated with water (10 ml) and extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulphate, and concentrated under reduced pressure. The resulting residue was subjected to medium pressure, short column chromatography on silica gel, using a mixture of ethyl acetate and hexane (1:8 v/v) as eluant, to give 6-[(E)-3-tert-butyldimethylsilyloxy-3-cyclohexylprop-1-enyl]-3-{[mixture of (E) and (Z)]-5-ethoxycarbonylpentylid-2-ene}bicyclo[3,3,0]octan-2-one (22 mg), in the form of (±)-6β-[(E)-3β-tert-butyldimethylsilyloxy-3-cyclohexylprop-1-enyl]-3-{[mixture of (E) and (Z)]-5-ethoxycarbonylpentylid-2-ene}bicyclo[3,3,0]octan-2-one, otherwise known as (±)-ethyl [mixture of (5E and (5Z)],(13E)-(9S,15R)-6a-oxo-6,9-methano-5-methyl-15-tert-butyldimethylsilyloxy-15-cyclohexyl-16,17,18,19,20-pentanorprosta-5,13-dienoate. the mixture was stirred for 2 hours extracted with ethyl acetate The extract was washed with saturated aqueous sodium chloride solution dried over anhydrous sodium sulphate concentrated under reduced pressure a mixture of ethyl acetate and hexane (1:8 v/v) as eluant

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred solution of (E)-2-[(mixture of 3α and 3β)-tert-butyldimethylsilyloxy-3-cyclohexylprop-1-enyl]bicyclo[3,3,0]-octan-6-one (0.22 g; prepared as described in Reference Example 33 and predominantly in the 2β-configuration) in dry diethyl ether (3 ml) at -78° C. in an atmosphere of argon was treated with a solution of lithium diisopropylamide in diethyl ether (0.5 ml; 1.38M). The solution was stirred for 10 minutes at -78° C. and then treated with 4-methoxycarbonylbutanal (112 mg) at -78° C. After stirring for 10 minutes at -78° C. the reaction mixture was treated with a solution of glacial acetic acid (200 mg) in diethyl ether (400 mg) and the resulting white suspension was allowed to warm to room temperature. The mixture was then diluted with diethyl ether (20 ml) and poured into water (10 ml). The organic phase was separated and washed with aqueous sodium bicarbonate solution (5 ml; 10% w/v) and then with saturated aqueous sodium chloride solution, dried over magnesium sulphate and concentrated in vacuo. The resulting oil (0.4 g) was dissolved in benzene (0.2 ml) at 20° C. and treated with methanesulphonyl chloride (83 mg). The stirred mixture was then treated dropwise with triethylamine (0.095 ml) and stirred for a further period of 40 minutes in an argon atmosphere. The mixture was then treated with 1,8-diazabicyclo[ 5,4,0]undec-7-ene (0.51 g) and it was stirred for a further period of 2 hours. The mixture was then treated with diethyl ether (20 ml). glacial acetic acid (2 ml) and water (20 ml). The organic phase was separated and the aqueous layer was extracted with diethyl ether (2×10 ml). The combined organic solutions were washed with saturated aqueous sodium bicarbonate solution and then dried over anhydrous sodium sulphate. Concentration in vacuo, followed by chromatography on a silica gel column, using a mixture of ethyl acetate and hexane (1:9 v/v) as eluant, gave 6-[(E)-(mixture of 3α and 3β)-tert-butyldimethylsilyloxy-3-cyclohexylprop-1-enyl]-3-[(E)-4-methoxycarbonylbutylidene]bicyclo[3,3,0]octan-2-one (54 g), predominantly in the 6β-configuration, otherwise known as (±)-methyl (5E,13E)-(9S), [mixture of (15R) and (15S)]-6a-oxo-6,9-methano-15-tert-butyldimethylsilyloxy-15-cyclohexyl-16,17,18,19,20-pentanorprosta-5,13-dienoate. prepared After stirring for 10 minutes at -78° C. the reaction mixture to warm to room temperature The organic phase was separated washed with aqueous sodium bicarbonate solution (5 ml; 10% w/v) with saturated aqueous sodium chloride solution, dried over magnesium sulphate concentrated in vacuo The resulting oil (0.4 g) was dissolved in benzene (0.2 ml) at 20° C. treated with methanesulphonyl chloride (83 mg) The stirred mixture was then treated dropwise with triethylamine (0.095 ml) stirred for a further period of 40 minutes in an argon atmosphere The mixture was then treated with 1,8-diazabicyclo[ 5,4,0]undec-7-ene (0.51 g) and it was stirred for a further period of 2 hours The mixture was then treated with diethyl ether (20 ml) The organic phase was separated the aqueous layer was extracted with diethyl ether (2×10 ml) The combined organic solutions were washed with saturated aqueous sodium bicarbonate solution dried over anhydrous sodium sulphate Concentration in vacuo a mixture of ethyl acetate and hexane (1:9 v/v) as eluant

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

Procedure: A stirred solution of crude (E)-2-[(mixture of 3α and 3β)-tert-butyldimethylsilyloxy-3-cyclohexylprop-1-enyl]-6-hydroxybicyclo[3,3,0]octane (0.36 g; prepared as described in Reference Example 32 and predominantly in the 2β-configuration) in dichloromethane (15 ml) was treated with pyridinium chlorochromate (0.42 g) at 20° C. under an argon atmosphere and stirred for a further period of 3.5 hours. The mixture was then treated with silica gel (2 g) and carefully concentrated in vacuo. The resulting powder was placed onto a column of silica gel and eluted with a mixture of ethyl acetate and hexane (1:4 v/v), to give (E)-2-[(mixture of 3α and 3β)-tert-butyldimethylsilyloxy-3-cyclohexylprop-1-enyl]bicyclo[3,3,0]octan-6-one (0.22 g), predominantly in the 2β-configuration. prepared The mixture was then treated with silica gel (2 g) carefully concentrated in vacuo eluted with a mixture of ethyl acetate and hexane (1:4 v/v)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (E)-2-[(mixture of 3α and 3β)-tert-Butyldimethylsilyloxyoct-1-enyl]bicyclo[3,3,0]octan-6-one (290 mg), prepared as described in Reference Example 19 or 26 and predominantly in the 2β-configuration, was dissolved, with stirring, in anhydrous diethyl ether (5 ml) at -78° C. in an argon atmosphere, and the solution was then treated with a freshly prepared solution of lithium diisopropylamide in diethyl ether (1.1 ml; 0.9M) at -78° C. and the mixture was stirred at -78° C. for 10 minutes. The mixture was then treated with 4-methoxycarbonylbutanal (208 mg) at -78° C. and stirred for a further period of 10 minutes. The reaction mixture was then treated with a solution of glacial acetic acid (100 mg) in diethyl ether (0.1 ml) at -78° C., and was then warmed to 20° C. The mixture was then diluted with ethyl acetate (25 ml), washed with aqueous ammonium chloride solution (2M) and then with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulphate and concentrated in vacuo. The resulting oil (480 mg) was dissolved with stirring in dry benzene (5 ml) and then was treated with methanesulphonyl chloride (124 mg) and then, dropwise, with a solution of triethylamine (101 mg) in benzene (0.5 ml) at 20° C. The mixture was stirred for 1 hour at 20° C. and then was treated with 1,8-diazabicyclo[5,4,0]undec-7-ene (1.0 ml) and the resulting mixture was stirred for a further period of 1.5 hours at 20° C. The mixture was concentrated in vacuo to give a residue which was subjected to chromatography on a silica gel column using a mixture of hexane and ethyl acetate (1:9 v/v) as eluant, to give 6-[(E)-(mixture of 3α and 3β)-tert-butyldimethylsilyloxyoct-1-enyl]3-[(E)-4-methoxycarbonylbutylidene]-bicyclo[3,3,0]octan-2-one (92.4 mg), predominantly in the 6β-configuration, otherwise known as (±)-methyl (5E,13E)-(9S), [mixture of (15R) and (15S)]-6a-oxo-6,9-methano-15-tert-butyldimethylsilyloxy-prosta-5,13-dienoate. predominantly in the 2β-configuration, was dissolved stirred for a further period of 10 minutes was then warmed to 20° C washed with aqueous ammonium chloride solution (2M) with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulphate concentrated in vacuo The resulting oil (480 mg) was dissolved with stirring in dry benzene (5 ml) was treated with methanesulphonyl chloride (124 mg) at 20° C The mixture was stirred for 1 hour at 20° C. was treated with 1,8-diazabicyclo[5,4,0]undec-7-ene (1.0 ml) the resulting mixture was stirred for a further period of 1.5 hours at 20° C The mixture was concentrated in vacuo to give a residue which

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (E)-2-[(mixture of 3α and 3β)-tert-Butyldimethylsilyloxyoct-1-enyl]bicyclo[3,3,0]octan-6-one (290 mg), prepared as described in Reference Example 19 or 26 and predominantly in the 2β-configuration, was dissolved, with stirring, in anhydrous diethyl ether (5 ml) at -78° C. in an argon atmosphere, and the solution was then treated with a freshly prepared solution of lithium diisopropylamide in diethyl ether (1.1 ml; 0.9M) at -78° C. and the mixture was stirred at -78° C. for 10 minutes. The mixture was then treated with 4-methoxycarbonylbutanal (208 mg) at -78° C. and stirred for a further period of 10 minutes. The reaction mixture was then treated with a solution of glacial acetic acid (100 mg) in diethyl ether (0.1 ml) at -78° C., and was then warmed to 20° C. The mixture was then diluted with ethyl acetate (25 ml), washed with aqueous ammonium chloride solution (2M) and then with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulphate and concentrated in vacuo. The resulting oil (480 mg) was dissolved with stirring in dry benzene (5 ml) and then was treated with methanesulphonyl chloride (124 mg) and then, dropwise, with a solution of triethylamine (101 mg) in benzene (0.5 ml) at 20° C. The mixture was stirred for 1 hour at 20° C. and then was treated with 1,8-diazabicyclo[5,4,0]undec-7-ene (1.0 ml) and the resulting mixture was stirred for a further period of 1.5 hours at 20° C. The mixture was concentrated in vacuo to give a residue which was subjected to chromatography on a silica gel column using a mixture of hexane and ethyl acetate (1:9 v/v) as eluant, to give 6-[(E)-(mixture of 3α and 3β)-tert-butyldimethylsilyloxyoct-1-enyl]3-[(E)-4-methoxycarbonylbutylidene]-bicyclo[3,3,0]octan-2-one (92.4 mg), predominantly in the 6β-configuration, otherwise known as (±)-methyl (5E,13E)-(9S), [mixture of (15R) and (15S)]-6a-oxo-6,9-methano-15-tert-butyldimethylsilyloxy-prosta-5,13-dienoate. predominantly in the 2β-configuration, was dissolved stirred for a further period of 10 minutes was then warmed to 20° C washed with aqueous ammonium chloride solution (2M) with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulphate concentrated in vacuo The resulting oil (480 mg) was dissolved with stirring in dry benzene (5 ml) was treated with methanesulphonyl chloride (124 mg) at 20° C The mixture was stirred for 1 hour at 20° C. was treated with 1,8-diazabicyclo[5,4,0]undec-7-ene (1.0 ml) the resulting mixture was stirred for a further period of 1.5 hours at 20° C The mixture was concentrated in vacuo to give a residue which

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred solution of (E)-2-[(mixture of 3α and 3β)-tert-butyldimethylsilyloxyoct-1-enyl]-6-hydroxybicyclo[3,3,0]octane (430 mg prepared as described in Reference Example 25 and predominantly in the 2β-configuration) in dry dichloromethane (15 ml) was treated with potassium acetate (127 mg), potassium carbonate (110 mg) and pyridinium chlorochromate (561 mg), and the mixture was stirred for 150 minutes at 20° C. A further quantity of pyridinium chlorochromate (120 mg) was then added and the mixture was stirred for a further period of 1 hour. The mixture was then concentrated in vacuo and subjected to chromatography on a silica gel column, using a mixture of ethyl acetate and hexane (1:4 v/v) as eluant, to give (E)-2-[(mixture of 3α and 3β)-tertbutyldimethylsilyloxyoct-1-enyl]bicyclo[3,3,0]octan-6-one (330 mg), predominantly in the 2β-configuration. the mixture was stirred for a further period of 1 hour The mixture was then concentrated in vacuo a mixture of ethyl acetate and hexane (1:4 v/v) as eluant

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

Procedure: 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 (20 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 methanol (3.2 ml) was treated with lithium hydroxide (33.8 mg) and water (1.1 ml) at 20° C. and stirred for 2 hours. The mixture was then concentrated in vacuo. The resulting residue was diluted with water (5 ml) and then acidified to pH 3 by treatment with dilute hydrochloric acid (2N). The aqueous layer was then extracted with ethyl acetate (5×5 ml). The combined organic extracts were dried over anhydrous 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 formic 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]bicyclo[3,3,0]octan-2-one (10 mg), predominantly in the 6β-configuration, otherwise known as (±)-(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-dienoic acid [NMR in deuterochloroform: multiplets at 6.5, 5.5, 4.2-3.5, 3.0-0.7 p.p.m⟧ The mixture was then concentrated in vacuo The resulting residue was diluted with water (5 ml) The aqueous layer was then extracted with ethyl acetate (5×5 ml) The combined organic extracts were dried over anhydrous sodium sulphate concentrated in vacuo a mixture of ethyl acetate, hexane and formic acid (50:50:1 by volume) as eluant

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred solution of 6-[(E)-(mixture of 3β and 3β)-hydroxyoct-1-enyl]-3-[(E)-4-methoxycarbonylbutylidene]bicyclo[3,3,0]octan-2-one (90 mg), prepared as described in Example 4 and predominantly in the 6β-configuration, otherwise known as (±)-methyl(5E,13E)-(9S),[mixture of (15R) and (15S)]-6a-oxo-6,9-methano-15-hydroxyprosta-5,13-dienoate, in methanol (2 ml) at 5° C. was treated with aqueous lithium hydroxide solution (1.5 ml; 1.0N). The resulting solution was stirred for 3.3 hours at 10° C. and was then treated with glacial acetic acid (0.1 ml). The methanol was removed in vacuo and the residue was diluted with ethyl acetate (10 ml), washed with hydrochloric acid (2N), then with water, and then with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulphate and concentrated in vacuo, to give 3-[(E)-4-carboxybutylidene]-6-[(E)-(mixture of 3α and 3β)-hydroxyoct-1-enyl]bicyclo[3,3,0]octan-2-one (70.0 mg), thought to be in the 6β-configuration, otherwise known as (±)-(5E,13E)-(9S),[mixture of (15R) and (15S)]-6a-oxo-6,9-methano-15-hydroxyprosta-5,13-dienoic acid [NMR in deuterochloroform: multiplets at 6.6, 5.5, 4.8-3.7, 3.0-1.1, 1.1-0.7 p.p.m⟧ The methanol was removed in vacuo the residue was diluted with ethyl acetate (10 ml) washed with hydrochloric acid (2N) with water, and then with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulphate concentrated in vacuo

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

Procedure: By proceeding in a manner to that described in Reference Example 47, but replacing the starting material by the appropriate quantity of (E)-2-(3-tert-butyldimethylsilyloxy-4-phenoxybut-1-enyl)bicyclo[3,3,0]octan-6-one, prepared as described in Reference Example 52, and in the form of (±)-(E)-2β-[(mixture of 3α and 3β)-tert-butyldimethylsilyloxy-4-phenoxybut-1-enyl]bicyclo[3,3,0]octan-6-one, there was prepared 6-(E)-3-tert-butyldimethylsilyloxy-4-phenoxybut-1-enyl-3-(1-hydroxy-4-methoxycarbonylbut-1-yl)-bicyclo[3,3,0]octan-2-one, in the form of (±)-6β-[(E)-(mixture of 3α and 3β)-tert-butyldimethylsilyloxy-4-phenoxybut-1-enyl]-3-(1-hydroxy-4-methoxycarbonylbut-1-yl)bicyclo[3,3,0]octan-2-one. prepared

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

Procedure: A stirred solution of 6-[(E)-3-tert-butyldimethylsilyloxy-3-cyclohexylprop-1-enyl]-3-(5-ethoxycarbonyl-2-hydroxypent-2-yl)bicyclo[3,3,0]octan-2-one (26 mg), prepared as described in Reference Example 39 and in the form of 6β-[(E)-3β-tert-butyldimethylsilyloxy-3-cyclohexylprop-1-enyl]-3-(5-ethoxycarbonyl-2-hydroxypent-2-yl)bicyclo[3,3,0]octan-2-one, otherwise known as (±)-ethyl(13E)-(9S,15R)-6a-oxo-6,9-methano-15-tert-butyldimethylsilyloxy-15-cyclohexyl-5-hydroxy-5-methyl-16,17,18,19,20-pentanorprost-13-enoate, in benzene (0.19 ml) was treated with methanesulphonyl chloride (0.0048 ml) at the ambient temperature, followed by triethylamine (0.008 ml) and the mixture was stirred for 2 hours. It was then treated with 1,8-diazabicyclo[5,4,0]undec-7-ene (0.0446 ml) and the mixture was stirred for 2 hours. It was then treated with water (10 ml) and extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulphate, and concentrated under reduced pressure. The resulting residue was subjected to medium pressure, short column chromatography on silica gel, using a mixture of ethyl acetate and hexane (1:8 v/v) as eluant, to give 6-[(E)-3-tert-butyldimethylsilyloxy-3-cyclohexylprop-1-enyl]-3-{[mixture of (E) and (Z)]-5-ethoxycarbonylpentylid-2-ene}bicyclo[3,3,0]octan-2-one (22 mg), in the form of (±)-6β-[(E)-3β-tert-butyldimethylsilyloxy-3-cyclohexylprop-1-enyl]-3-{[mixture of (E) and (Z)]-5-ethoxycarbonylpentylid-2-ene}bicyclo[3,3,0]octan-2-one, otherwise known as (±)-ethyl [mixture of (5E and (5Z)],(13E)-(9S,15R)-6a-oxo-6,9-methano-5-methyl-15-tert-butyldimethylsilyloxy-15-cyclohexyl-16,17,18,19,20-pentanorprosta-5,13-dienoate. the mixture was stirred for 2 hours extracted with ethyl acetate The extract was washed with saturated aqueous sodium chloride solution dried over anhydrous sodium sulphate concentrated under reduced pressure a mixture of ethyl acetate and hexane (1:8 v/v) as eluant

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred solution of (E)-2-[(mixture of 3α and 3β)-tert-butyldimethylsilyloxy-3-cyclohexylprop-1-enyl]bicyclo[3,3,0]-octan-6-one (0.22 g; prepared as described in Reference Example 33 and predominantly in the 2β-configuration) in dry diethyl ether (3 ml) at -78° C. in an atmosphere of argon was treated with a solution of lithium diisopropylamide in diethyl ether (0.5 ml; 1.38M). The solution was stirred for 10 minutes at -78° C. and then treated with 4-methoxycarbonylbutanal (112 mg) at -78° C. After stirring for 10 minutes at -78° C. the reaction mixture was treated with a solution of glacial acetic acid (200 mg) in diethyl ether (400 mg) and the resulting white suspension was allowed to warm to room temperature. The mixture was then diluted with diethyl ether (20 ml) and poured into water (10 ml). The organic phase was separated and washed with aqueous sodium bicarbonate solution (5 ml; 10% w/v) and then with saturated aqueous sodium chloride solution, dried over magnesium sulphate and concentrated in vacuo. The resulting oil (0.4 g) was dissolved in benzene (0.2 ml) at 20° C. and treated with methanesulphonyl chloride (83 mg). The stirred mixture was then treated dropwise with triethylamine (0.095 ml) and stirred for a further period of 40 minutes in an argon atmosphere. The mixture was then treated with 1,8-diazabicyclo[ 5,4,0]undec-7-ene (0.51 g) and it was stirred for a further period of 2 hours. The mixture was then treated with diethyl ether (20 ml). glacial acetic acid (2 ml) and water (20 ml). The organic phase was separated and the aqueous layer was extracted with diethyl ether (2×10 ml). The combined organic solutions were washed with saturated aqueous sodium bicarbonate solution and then dried over anhydrous sodium sulphate. Concentration in vacuo, followed by chromatography on a silica gel column, using a mixture of ethyl acetate and hexane (1:9 v/v) as eluant, gave 6-[(E)-(mixture of 3α and 3β)-tert-butyldimethylsilyloxy-3-cyclohexylprop-1-enyl]-3-[(E)-4-methoxycarbonylbutylidene]bicyclo[3,3,0]octan-2-one (54 g), predominantly in the 6β-configuration, otherwise known as (±)-methyl (5E,13E)-(9S), [mixture of (15R) and (15S)]-6a-oxo-6,9-methano-15-tert-butyldimethylsilyloxy-15-cyclohexyl-16,17,18,19,20-pentanorprosta-5,13-dienoate. prepared After stirring for 10 minutes at -78° C. the reaction mixture to warm to room temperature The organic phase was separated washed with aqueous sodium bicarbonate solution (5 ml; 10% w/v) with saturated aqueous sodium chloride solution, dried over magnesium sulphate concentrated in vacuo The resulting oil (0.4 g) was dissolved in benzene (0.2 ml) at 20° C. treated with methanesulphonyl chloride (83 mg) The stirred mixture was then treated dropwise with triethylamine (0.095 ml) stirred for a further period of 40 minutes in an argon atmosphere The mixture was then treated with 1,8-diazabicyclo[ 5,4,0]undec-7-ene (0.51 g) and it was stirred for a further period of 2 hours The mixture was then treated with diethyl ether (20 ml) The organic phase was separated the aqueous layer was extracted with diethyl ether (2×10 ml) The combined organic solutions were washed with saturated aqueous sodium bicarbonate solution dried over anhydrous sodium sulphate Concentration in vacuo a mixture of ethyl acetate and hexane (1:9 v/v) as eluant