合成路线1

12) The ketalization of (R)-2-(2-oxocyclopentyl)acetic acid methyl ester (XCVII) with butane-2,3-diol gives the expected acetal (XCVIII), which is converted into the beta-keto ester (XCIX) in the usual way. Transesterification of (XCIX) with benzyl alcohol yields the benzyl ester (C), which is converted into the alpha-diazo ester (CI) with p-toluenesulfonyl azide. The cyclization of (CI) by means of rhodium acetate in dichloromethane affords the bicyclic keto ester (CII), which is condensed with 3(S)-(TBDMS-O)-1(E)-octenyl mercury (CIII) by means of lead tetraacetate giving the alkylated bicyclic beta-keto ester (CIV). The decarboxylation of (CIV) with Raney Ni and triethylamine in ethanol yields the bicyclic ketone (CV), which is reduced with NaBH4 and deacetalized with HCl to afford the hydroxy ketone (CVI). The silylation of the hydroxy group of (CVI) with TBDMS-Cl and DMAP in DMF gives the disilylated ketone (CVII), which is treated with diphenyl disulfide and lithium bis(trimethylsilyl)amide in THF/HMPT yielding the sulfenylated enol (CVIII). The oxidation of (CVIII) with m-chloroperbenzoic acid (MCPBA) affords the corresponding sulfonated enol (CIX), which is condensed with methyl 4-iodobutyrate (CX) by means of t-BuOK in DMSO giving the dialkylated bicyclic ketone (CXI). The reduction of (CXI) with NaBH4 in methanol, followed by mesylation with mesyl chloride yields the alpha-mesyloxy sulfone (CXII), which by a reductive elimination with Na-Hg in methanol is converted into the bisilylated clinprost (XCIII). Finally, this compound is desilyated with TBAF as usual.