合成路线1

7) The regio- and stereoselective carboxylation of the tricyclic ketone (LXVI) with dimethyl carbonate by means of t-BuOK in THF gives the keto ester (LXVII), which by treatment with acetic acid/H2SO4 is converted into the acetoxy keto ester (LXVIII). The reduction of (LXVIII) with NaBH4 in methanol followed by reaction with dihydropyran/PPTS yields the tetrahydropyranyl ether (LXIX), which is deacetylated with K2CO3 in methanol, and the resulting alcohol is protected again with TBDPS-Cl and imidazole in DMF to afford the protected dihydroxy ester (LXX). The reduction of (LXX) with DIBAL, followed by oxidation with CrO3/Pyr gives the aldehyde (LXXI), which is condensed with dimethyl 2-oxoheptylphosphonate (XV) by means of NaH in THF yielding the bicyclic enone (LXXII). Selective elimination of the THP group, followed by reduction of the keto group with DIBAL in toluene and flash column chromatography affords the diol (LXXIII) as a pure enantiomer. Protection of the two hydroxy groups with dihydropyran/PPTS, followed by desilylation with TBAF in THF gives the bicyclic alcohol (LXXIV), which is oxidized with CrO3/Pyr in DMF to the corresponding ketone (LXXV). The condensation of (LXXV) with 4-formylbutyric acid methyl ester (LXXVI) by means of lithium diisopropylamide in THF yields the oxocarbacycline derivative (LXXVII). The reductoisomerization of the enone (LXXVII) with NaBH4/CeCl4 in methanol affords the hydroxylated isocarbacycline derivative (LXXVIII), which is treated with phenoxythionocarbonyl chloride and DMAP to give the thiocarbonate (LXXIX) [intermediate for the elimination of the hydroxy group of (LXXVIII)]. The reductive cleavage of (LXXIX) with Bu3SnH/AIBN in refluxing benzene yields the bitetrahydropyranyl derivative of clinprost (LXXX), which is finally deprotected with acetic acid/THF/water.