The esterification of 4alpha-carboxymethyl-5beta-benzyloxymethyl-cyclopent-2-en-1alpha-ol (I) with methyl iodide and K2CO3 in acetone gives the corresponding methyl ester (II), which by reaction with triethyl - orthoacetate (III) at 145 C is converted into 3-ethoxycarbonylmethyl-4-methoxycarbonylmethyl-5-benzyloxymethyl-1-cyclopentene (IV). The cyclization of (IV) with potassium tert-butoxide in benzene yields 6-benzyloxymethyl-cis-bicyclo[3.3.0]oct-7-ene-3-one (V), which by reaction with N-bromosuccinimide in DMSO - water affords 6-benzyloxymethyl-7-hydroxy-8-bromo-cis-bicyclo[3.3.0]octan-3-one (VI). Debromination of (VI) with tributyltin hydride and azobisisobutyronitrile in benzene irradiated with UV light gives 6-benzyloxymethyl-7-hydroxy-cis-bicyclo[3.3.0]octan-3-one (VII), which is treated with dihydropyran and p-toluenesulfonic acid in methylene chloride yielding the corresponding protected compound (VIII). Elimination of the benzyl group of (VIII) with H2 over Pd/C in acetic acid affords 6-hydroxymethyl-7-(tetrahydropyranyloxy)-cis-bicyclo[3.3.0]octan-3-one (IX), which is submitted to a Wittig condensation with (4-carboxybutyl) triphenylphosphonium bromide (X) and the sodium salt of DMSO in this solvent, followed by a methylation with diazomethane, affording 3-(4-methoxycarbonylbutylidene)-6-hydroxymethyl-7-tetrahydropyranyloxy)-cis-bicyclo[3.3.0]octane (XI). Oxidation of (XI) with CrO3 in methylene chloride gives the corresponding 6-formyl derivative (XII), which is submitted to a new Wittig condensation with dimethyl 2-oxo-2-cyclopentylethylphosphonate (XIII) and NaH in THF yielding methyl 6,9-methano-11-(tetrahydropyranyloxy)-15-oxo-15-cyclopentyl-16,17,18,19,20-pentanorprosta-3,5-dienoate (XIV). Deprotection of (XIV) with acetic acid in THF - water gives the corresponding 11-hydroxy compound (XVI), which is reduced with NaBH4 in methanol affording the 11,15-dihydroxy ester (XVI). Finally, this compound is hydrolyzed with NaOH in methanol - water.

The protection of bromoketol (VI) with dihydropyran and p-toluene sulfonic acid in methylene chloride gives the corresponding tetrahydropyranyl derivative (XVII), which is debrominated with tributyltin hydride as usual yielding (VIII), already obtained.

The protection of hydroxyester (II) with dihydropyran dihydropyran and p-toluene sulfonic acid in methylene chloride gives 1-(tetrahydropyranyloxy)-4-methoxycarbonylmethyl-6-benzyloxymethylcyclopent-2-ene (XVIII), which is condensed with ethyl acetate by means of butyllithium and diisopropyl amine in THF yielding 1-(tetrahydropyranyloxy)-4-(2-oxo-3-ethoxycarbonylpropyl)-5-benzyloxymethylcyclopent-2-ene (XIX). The reaction of (XIX) with p-toluenesulfonyl azide and triethylamine in acetonitrile affords 1-(tetrahydropyranyloxy)-4-(2-oxo-3-diazo-3-ethoxycarbonylpropyl)-5-benzyloxymethylcyclopent-2-ene (XX), which is cyclized by means of CuSO4 in refluxing benzene to 2-ethoxycarbonyl-6-benzyloxymethyl-7-(tetrahydropyranyloxy)-cis-tricyclo[3.3.0.0(2,8)]octan-3-one (XXI). Ring opening of (XXI) with tributyltin hydride and azobisisobutyronitrile in benzene irradiated with UV light affords 2-ethoxycarbonyl-6-benzyloxymethyl-7-(tetrahydropyranyloxy)-cis-bicyclo[3.3.0]octan-3-one (XXII), which is hydrolyzed and decarboxylated in HMPT - water at 160 C giving (VIII), already obtained.

The oxidative ring opening of 2-oxa-6-benzyloxymethyl-7-(tetrahydropyranyloxy)-cis-bicyclo[3.3.0]octan-3-one (XXIII) with NaOH in methanol, followed by a treatment with CrO2Cl2 in CCl4 gives 2-methoxycarbonylmethyl-3-benzyloxymethyl-4-(tetrahydropyranyloxy)-1-cyclopentanone (XXIV), which by reaction with methyl trimethylsilylacetate (XXV) by means of butyllithium and diisopropylamine in THF is converted into 1-(methoxycarbonylmethylidene)-2-methoxycarbonylmethyl-3-benzyloxymethyl-4-(tetrahydropyranyloxy)cyclopentane (XXVI). The hydrogenation of (XXVI) with H2 over Pd/C in ethanol affords 1,2-bis(methoxycarbonylmethyl)-3-benzyloxymethyl-4-(tetrahydropyranyloxy)cyclopentane (XXVII), which is cyclized by means of potassium tert-butoxide in refluxing benzene to 2 (or 4)-methoxycarbonyl-6-benzyloxymethyl-7-(tetrahydropyranyloxy)-cis-bicyclo[3.3.0]octan-3-one (XXVIII). Finally, this compound is hydrolyzed and decarboxylated in HMPT - water at 160 C giving the ketone (VIII), already obtained.

The esterification of 4alpha-carboxymethyl-5beta-benzyloxymethyl-cyclopent-2-en-1alpha-ol (I) with methyl iodide and K2CO3 in acetone gives the corresponding methyl ester (II), which by reaction with triethyl - orthoacetate (III) at 145 C is converted into 3-ethoxycarbonylmethyl-4-methoxycarbonylmethyl-5-benzyloxymethyl-1-cyclopentene (IV). The cyclization of (IV) with potassium tert-butoxide in benzene yields 6-benzyloxymethyl-cis-bicyclo[3.3.0]oct-7-ene-3-one (V), which by reaction with N-bromosuccinimide in DMSO - water affords 6-benzyloxymethyl-7-hydroxy-8-bromo-cis-bicyclo[3.3.0]octan-3-one (VI). Debromination of (VI) with tributyltin hydride and azobisisobutyronitrile in benzene irradiated with UV light gives 6-benzyloxymethyl-7-hydroxy-cis-bicyclo[3.3.0]octan-3-one (VII), which is treated with dihydropyran and p-toluenesulfonic acid in methylene chloride yielding the corresponding protected compound (VIII). Elimination of the benzyl group of (VIII) with H2 over Pd/C in acetic acid affords 6-hydroxymethyl-7-(tetrahydropyranyloxy)-cis-bicyclo[3.3.0]octan-3-one (IX), which is submitted to a Wittig condensation with (4-carboxybutyl) triphenylphosphonium bromide (X) and the sodium salt of DMSO in this solvent, followed by a methylation with diazomethane, affording 3-(4-methoxycarbonylbutylidene)-6-hydroxymethyl-7-tetrahydropyranyloxy)-cis-bicyclo[3.3.0]octane (XI). Oxidation of (XI) with CrO3 in methylene chloride gives the corresponding 6-formyl derivative (XII), which is submitted to a new Wittig condensation with dimethyl 2-oxo-2-cyclopentylethylphosphonate (XIII) and NaH in THF yielding methyl 6,9-methano-11-(tetrahydropyranyloxy)-15-oxo-15-cyclopentyl-16,17,18,19,20-pentanorprosta-3,5-dienoate (XIV). Deprotection of (XIV) with acetic acid in THF - water gives the corresponding 11-hydroxy compound (XVI), which is reduced with NaBH4 in methanol affording the 11,15-dihydroxy ester (XVI). Finally, this compound is hydrolyzed with NaOH in methanol - water.

The protection of bromoketol (VI) with dihydropyran and p-toluene sulfonic acid in methylene chloride gives the corresponding tetrahydropyranyl derivative (XVII), which is debrominated with tributyltin hydride as usual yielding (VIII), already obtained.

The protection of hydroxyester (II) with dihydropyran dihydropyran and p-toluene sulfonic acid in methylene chloride gives 1-(tetrahydropyranyloxy)-4-methoxycarbonylmethyl-6-benzyloxymethylcyclopent-2-ene (XVIII), which is condensed with ethyl acetate by means of butyllithium and diisopropyl amine in THF yielding 1-(tetrahydropyranyloxy)-4-(2-oxo-3-ethoxycarbonylpropyl)-5-benzyloxymethylcyclopent-2-ene (XIX). The reaction of (XIX) with p-toluenesulfonyl azide and triethylamine in acetonitrile affords 1-(tetrahydropyranyloxy)-4-(2-oxo-3-diazo-3-ethoxycarbonylpropyl)-5-benzyloxymethylcyclopent-2-ene (XX), which is cyclized by means of CuSO4 in refluxing benzene to 2-ethoxycarbonyl-6-benzyloxymethyl-7-(tetrahydropyranyloxy)-cis-tricyclo[3.3.0.0(2,8)]octan-3-one (XXI). Ring opening of (XXI) with tributyltin hydride and azobisisobutyronitrile in benzene irradiated with UV light affords 2-ethoxycarbonyl-6-benzyloxymethyl-7-(tetrahydropyranyloxy)-cis-bicyclo[3.3.0]octan-3-one (XXII), which is hydrolyzed and decarboxylated in HMPT - water at 160 C giving (VIII), already obtained.

The oxidative ring opening of 2-oxa-6-benzyloxymethyl-7-(tetrahydropyranyloxy)-cis-bicyclo[3.3.0]octan-3-one (XXIII) with NaOH in methanol, followed by a treatment with CrO2Cl2 in CCl4 gives 2-methoxycarbonylmethyl-3-benzyloxymethyl-4-(tetrahydropyranyloxy)-1-cyclopentanone (XXIV), which by reaction with methyl trimethylsilylacetate (XXV) by means of butyllithium and diisopropylamine in THF is converted into 1-(methoxycarbonylmethylidene)-2-methoxycarbonylmethyl-3-benzyloxymethyl-4-(tetrahydropyranyloxy)cyclopentane (XXVI). The hydrogenation of (XXVI) with H2 over Pd/C in ethanol affords 1,2-bis(methoxycarbonylmethyl)-3-benzyloxymethyl-4-(tetrahydropyranyloxy)cyclopentane (XXVII), which is cyclized by means of potassium tert-butoxide in refluxing benzene to 2 (or 4)-methoxycarbonyl-6-benzyloxymethyl-7-(tetrahydropyranyloxy)-cis-bicyclo[3.3.0]octan-3-one (XXVIII). Finally, this compound is hydrolyzed and decarboxylated in HMPT - water at 160 C giving the ketone (VIII), already obtained.