This compound can be obtained in two different ways: 1) The hydrolysis of 2-oxa-3-oxo-6-syn-hydroxymethyl-7-anti-acetoxy-cis-bicyclo[3.3.0] octane (I) with KOH in methanol gives the dihydroxylactone (II), which by partial acetylation with acetic anhydride in pyridine yields the acetoxymethyl lactone (III). The reaction of (III) with dihydropyran by means of p-toluenesulfonic acid in CH2Cl2 gives the fully protected lactone (IV), which is reduced with diisobutylaluminium hydride in toluene at -60 C to give 2-oxa-3-hydroxy-6-syn-hydroxymethyl-7-anti-(2-tetrahydropyranyloxy)-cis-bicyclo[3.3.0]octane (V) [this compound can also be obtained by reductive debenzylation of 2-oxa-3-hydroxy-6-syn-benzyloxymethyl-7-anti-(2-tetrahydropyranyloxy)-cis-bicyclo[3.3.0]octane (VI) with H2 over Pd/C in MeOH]. The Wittig reaction of (V) with (4-carboxybutyl)triphenylphosphonium bromide (VII) by means of NaH in DMSO affords 2alpha-(6-carboxyhex-cis-2-enyl)-3beta-hydroxymethyl-4alpha-(2-tetrahydropyranoyloxy) cyclopentan-1alpha-ol (VIII), which is methylated to the corresponding methyl ester (IX) with diazomethane in ether. Partial acetylation of (IX) with acetyl chloride in CH2Cl2 - pyridine gives the acetoxymethyl compound (X), which is treated with dihydropyran as before yelding the fully protected compound (XI). Partial hydrolysis of (XI) with K2CO3 in MeOH affords compound (XII) with the free hydroxymethyl group. The reaction of (XII) with diphenyldiselenide (A) by means of lithiumdiisopropylamine in hexane - THF gives 1alpha,4alpha-bis(2-tetrahydropyranyloxy)-2alpha-(6-phenylseleno-6-methoxycarbonylhex-cis-2-enyl)-3beta-hydroxymethylcyclopentane (XIII).
Compound (XIII) is treated with 30% H2O2 in EtOAc - MeOH yielding 1alpha,4alpha-bis(2-tetrahydropyranyloxy)-2alpha-(6-methoxycarbonylhex-cis-2,trans-5-dienyl)-3beta-hydroxymethylcyclopentane (XIV). The oxidation of (XIV) with N-chlorosuccinimide in toluene affords the 3beta-formyl compound (XV), which by a Wittig reaction with dimethyl 2-oxo-3-(3-chlorophenoxy)propylphosphonate (XVI) [obtained by reaction of ethyl (3-chlorophenoxy)acetate (XVIII) with dimethyl methylphosphonate (XIX) by means of butyllithium in THF], using NaH in THF, is converted into methyl 9alpha,11alpha-bis(2-tetrahydropyranyloxy)-15-oxo-16-(3-chlorophenoxy)-17,18,19,20-tetranorprosta-trans-2,cis-5,trans-13-trienoate (XVII). The reduction of (XVII) with NaBH4 in MeOH affords methyl 9alpha,11alpha-bis(2-tetrahydropyranyloxy)-15-hydroxy-16-(3-chlorophenoxy)-17,18,19,20-tetranorprosta-trans-2,cis-5,trans-13-trienoate (XX). Finally the tetrahydropyranyl groups of (XX) are eliminated by treatment with acetic acid in THF - water.
2) The silylation of (IX) with trimethylchlorosilane in methylene chloride - pyridine gives the trimethylsilyloxymethyl compound (XXI), which by acetylation with acetyl chloride and elimination of the silyl group yields 1alpha-acetoxy-2alpha-(6-methoxycarbonylhex-cis-2-enyl)-3alpha-hydroxymethyl-4alpha-(2-tetrahydropyranyloxy)cyclopentane (XXII). The oxidation of (XXII) with CrO3 - pyridine in methylene chloride affords the formyl derivative (XXIII), which by a Wittig condensation with dimethyl 2-oxo-3(3-chlorophenoxy)propylphosphonate (XVI) using NaH in THF gives methyl 9alpha-acetoxy-11alpha-bis(2-tetrahydropyranyloxy)-15-oxo-16-(3-chlorophenoxy)-17,18,19,20-tetranor-prosta-cis-5,trans-13-dienoate (XXIV). The reduction of the keto group of (XXIV) with NaBH4 in methanol yields the 15-hydroxy compound (XXV), which is deacetylated by means of K2CO3 in methanol affording the dihydroxy compound (XXVI). The protection of the free hydroxyl groups of (XXVI) with dihydropyran by means of p-toluenesulfonic acid in CH2Cl2 gives the tris-tetrahydropyranyl derivative (XXVII), which by reaction with diphenyldiselenide (A) by means of lithiumdiisopropylamine in hexane - THF gives the 2-phenylseleno derivative (XXVIII).
The reaction of (XXVIII) with H2O2 in ethyl acetate - methanol yields methyl 9alpha,11alpha,15alpha-tris(2-tetrahydropyranyloxy)-16-(3-chlorophenoxy)-17,18,19,20-tetranorprosta-trans-2,cis-5,trans-13-trienoate (XXIX). Finally this compound is deprotected by treatment with acetic acid in THF - water.