The partial protection of cyclohexane-1,4-diol (I) with dihydropyran (DHP) and p-toluenesulfonic acid in dichloromethane gives the monotetrahydropyranyloxy derivative (II), which is oxidized with oxalyl chloride in DMSO - dichloromethane to 4-(tetrahydropyranyloxy)cyclohexanone (III). The condensation of (III) with propyldiphenylphosphonium bromide by means of n-butyllithium in THF affords the 4-propenyl derivative (V), which is deprotected with p-toluenesulfonic acid in methanol giving 4-propenylcyclohexanol (VI). The hydrogenation of (VI) with H2 over Pd/C in methanol, followed by column chromatography over Lobar (trademark of Merck & Co., Inc.) affords trans-4-propylcyclohexanol (VII), which is mesylated with mesyl chloride and triethylamine in dichloromethane to the corresponding mesylate (VIII). The reaction of (VIII) with NaCN in hot DMSO gives cis-4-propylcyclohexanecarbonitrile (IX), which is hydrolyzed with H2SO4 - water at 130 C yielding cis-4-propylcyclohexanecarboxylic acid (X). Esterification of (X) with diazomethane in ether affords the corresponding methyl ester (XI), which is condensed with dimethyl methylphosphonate (XII) by means of n-butyllithium in THF to give the phosphonate (XIII). The Wittig condensation of (XIII) with 1alpha-acetoxy-2alpha-[6-(methoxycarbonyl)hex-2(Z)-enyl]-3beta-formyl-4alpha-(tetrahydropyran-2-yloxy)cyclopentane (XIV) by means of NaH in THF yields the protected 15-oxo-prostaglandin (XV), which is reduced with LiAlH4 and S-2,2'-dihydroxy-1,1'-binaphthyl (SBN) affording the 15alpha-hydroxy compound (XVI). The methyl cis-4-propylcyclohexanecarboxylate (XI) can also be obtained by a cis-selective hydrogenation of methyl 4-propylbenzoate (XXIV) with hydrogen in hexane as organic phase and a buffer solution at pH 7.6 containing a quaternary salt as phase-transfer catalyst, and the dimer chloro(1,5-cyclooctadiene)rhodium [RhCl(COD)]2 as hydrogenation catalyst.

The protection of (XVI) with dihydropyran as usual gives the fully protected compound (XVII), which is deacetylated with K2CO3 in methanol to the 9alpha-hydroxy derivative (XVIII). The formylation of (XVIII) with diethyl azodiformate (XIX) and triphenylphosphine - formic acid in THF gives the 9beta-formyloxy compound (XX), which is hydrolyzed with K2CO3 as before to the 9beta-hydroxy compound (XXI). The tosylation of (XXI) with tosyl chloride in pyridine yields the tosylate (XXII), which is deprotected with p-toluenesulfonic acid affording the 9beta-tosyloxy-11alpha,15alpha-dihydroxyprostaglandin (XXIII). Finally, this compound is cyclized with sodium azide in hot DMSO.

The partial protection of cyclohexane-1,4-diol (I) with dihydropyran (DHP) and p-toluenesulfonic acid in dichloromethane gives the monotetrahydropyranyloxy derivative (II), which is oxidized with oxalyl chloride in DMSO - dichloromethane to 4-(tetrahydropyranyloxy)cyclohexanone (III). The condensation of (III) with propyldiphenylphosphonium bromide by means of n-butyllithium in THF affords the 4-propenyl derivative (V), which is deprotected with p-toluenesulfonic acid in methanol giving 4-propenylcyclohexanol (VI). The hydrogenation of (VI) with H2 over Pd/C in methanol, followed by column chromatography over Lobar (trademark of Merck & Co., Inc.) affords trans-4-propylcyclohexanol (VII), which is mesylated with mesyl chloride and triethylamine in dichloromethane to the corresponding mesylate (VIII). The reaction of (VIII) with NaCN in hot DMSO gives cis-4-propylcyclohexanecarbonitrile (IX), which is hydrolyzed with H2SO4 - water at 130 C yielding cis-4-propylcyclohexanecarboxylic acid (X). Esterification of (X) with diazomethane in ether affords the corresponding methyl ester (XI), which is condensed with dimethyl methylphosphonate (XII) by means of n-butyllithium in THF to give the phosphonate (XIII). The Wittig condensation of (XIII) with 1alpha-acetoxy-2alpha-[6-(methoxycarbonyl)hex-2(Z)-enyl]-3beta-formyl-4alpha-(tetrahydropyran-2-yloxy)cyclopentane (XIV) by means of NaH in THF yields the protected 15-oxo-prostaglandin (XV), which is reduced with LiAlH4 and S-2,2'-dihydroxy-1,1'-binaphthyl (SBN) affording the 15alpha-hydroxy compound (XVI). The methyl cis-4-propylcyclohexanecarboxylate (XI) can also be obtained by a cis-selective hydrogenation of methyl 4-propylbenzoate (XXIV) with hydrogen in hexane as organic phase and a buffer solution at pH 7.6 containing a quaternary salt as phase-transfer catalyst, and the dimer chloro(1,5-cyclooctadiene)rhodium [RhCl(COD)]2 as hydrogenation catalyst.

The protection of (XVI) with dihydropyran as usual gives the fully protected compound (XVII), which is deacetylated with K2CO3 in methanol to the 9alpha-hydroxy derivative (XVIII). The formylation of (XVIII) with diethyl azodiformate (XIX) and triphenylphosphine - formic acid in THF gives the 9beta-formyloxy compound (XX), which is hydrolyzed with K2CO3 as before to the 9beta-hydroxy compound (XXI). The tosylation of (XXI) with tosyl chloride in pyridine yields the tosylate (XXII), which is deprotected with p-toluenesulfonic acid affording the 9beta-tosyloxy-11alpha,15alpha-dihydroxyprostaglandin (XXIII). Finally, this compound is cyclized with sodium azide in hot DMSO.

The partial protection of cyclohexane-1,4-diol (I) with dihydropyran (DHP) and p-toluenesulfonic acid in dichloromethane gives the monotetrahydropyranyloxy derivative (II), which is oxidized with oxalyl chloride in DMSO - dichloromethane to 4-(tetrahydropyranyloxy)cyclohexanone (III). The condensation of (III) with propyldiphenylphosphonium bromide by means of n-butyllithium in THF affords the 4-propenyl derivative (V), which is deprotected with p-toluenesulfonic acid in methanol giving 4-propenylcyclohexanol (VI). The hydrogenation of (VI) with H2 over Pd/C in methanol, followed by column chromatography over Lobar (trademark of Merck & Co., Inc.) affords trans-4-propylcyclohexanol (VII), which is mesylated with mesyl chloride and triethylamine in dichloromethane to the corresponding mesylate (VIII). The reaction of (VIII) with NaCN in hot DMSO gives cis-4-propylcyclohexanecarbonitrile (IX), which is hydrolyzed with H2SO4 - water at 130 C yielding cis-4-propylcyclohexanecarboxylic acid (X). Esterification of (X) with diazomethane in ether affords the corresponding methyl ester (XI), which is condensed with dimethyl methylphosphonate (XII) by means of n-butyllithium in THF to give the phosphonate (XIII). The Wittig condensation of (XIII) with 1alpha-acetoxy-2alpha-[6-(methoxycarbonyl)hex-2(Z)-enyl]-3beta-formyl-4alpha-(tetrahydropyran-2-yloxy)cyclopentane (XIV) by means of NaH in THF yields the protected 15-oxo-prostaglandin (XV), which is reduced with LiAlH4 and S-2,2'-dihydroxy-1,1'-binaphthyl (SBN) affording the 15alpha-hydroxy compound (XVI). The methyl cis-4-propylcyclohexanecarboxylate (XI) can also be obtained by a cis-selective hydrogenation of methyl 4-propylbenzoate (XXIV) with hydrogen in hexane as organic phase and a buffer solution at pH 7.6 containing a quaternary salt as phase-transfer catalyst, and the dimer chloro(1,5-cyclooctadiene)rhodium [RhCl(COD)]2 as hydrogenation catalyst.

The protection of (XVI) with dihydropyran as usual gives the fully protected compound (XVII), which is deacetylated with K2CO3 in methanol to the 9alpha-hydroxy derivative (XVIII). The formylation of (XVIII) with diethyl azodiformate (XIX) and triphenylphosphine - formic acid in THF gives the 9beta-formyloxy compound (XX), which is hydrolyzed with K2CO3 as before to the 9beta-hydroxy compound (XXI). The tosylation of (XXI) with tosyl chloride in pyridine yields the tosylate (XXII), which is deprotected with p-toluenesulfonic acid affording the 9beta-tosyloxy-11alpha,15alpha-dihydroxyprostaglandin (XXIII). Finally, this compound is cyclized with sodium azide in hot DMSO.