合成路线1

1) The reduction of the Corey lactone (I) with diisobutylaluminum hydride (DIBAL) in hexane/toluene gives the lactol (II), which is condensed with 4-carboxybutyltriphenylphosphonium bromide (III) by means of t-BuOK in THF yielding the pentenoic ester (IV). The oxidation of the free hydroxy group of (IV) with pyridinium chlorochromate (PCC) in dichloromethane affords the cyclopentanone (V), which is methylenated with Zn/CH2Br2/TiCl4 in dichloromethane giving compound (VI). The THP ether group of (VI) was selectively eliminated with dimethylaluminum chloride in dichloromethane and protected again with tert-butyldimethylsilyl chloride (TBDMS-Cl) and imidazole in DMF yielding the disilylated compound (VII). The hydrolytic cleavage of the exocyclic double bond of (VII) with 9-borabicyclo[3.3.1]nonane (9-BBN) in THF affords compound (VIII), which is oxidized with Collins reagent (CrO3/Pyr) to the corresponding aldehyde (IX). The cyclization of (IX) by heating at 180 C in toluene in a sealed tube gives the bicyclo[3.3.0]octane (X), still with the double bond in the pentenoic side chain, which is reduced with H2 over Pd/C in methanol yielding the saturated compound (XI). The dehydration of (XI) by mesylation with mesyl chloride and reaction with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in refluxing methanol affords the bicyclo[3.3.0]-2-octene (XII), which is selectively deprotected with pyridinium para-toluenesulfonate (PPTS) in ethanol giving the hydroxymethyl derivative (XIII). The oxidation of (XIII) with SO3/Pyr in DMSO yields the corresponding aldehyde (XIV), which is condensed with dimethyl 2-oxoheptylphosphonate (XV) in THF giving the oxidized isocarbacyclin derivative (XVI). The reduction of the keto group of (XVI) with NaBH4 in methanol yields the corresponding secondary alcohol (XVII) as a mixture of diastereomers. Finally, this compound is deprotected with tetrabutylammonium fluoride (TBAF) in THF and submitted to column chromatography over silicagel in ether/hexane in order to isolate the pure enantiomer.