合成路线1

2) The methylenation of the disilylated 5,6-didehydroprostaglandin E2 (XVIII) with Zn/CH2Br2/TiCl4 as before gives the methylene derivative (XIX), which is converted into the hydroxymethyl derivative (XX) with 9-BBN also as before. The oxidation of (XX) with CrO3/Pyr in dichloromethane yields the corresponding aldehyde (XXI), which is treated with [Ph(Me)2Si]2CuCNLi2 [(PDMS)2CuCNLi2] affording the trisilylated compound (XXII). The esterification of the hydroxy group of (XXII) with 3-(trifluoromethyl)benzoyl chloride (XXIII) by means of DMAP in acetonitrile gives the benzoate (XXIV), which is cyclized by means of N-methylcarbazol (NMC) and magnesium perchlorate in THF/water and irradiation with a 500 W UV-lamp giving the bicyclo[3.3.0]octan-3-ylidene derivative (XXV). The selective desilylation of (XXV) with HClO4 in ether/methanol gives the dihydroxycarbacyclin (XXVI), which is finally desilylated and simultaneously isomerized by a treatment with trifluoroacetic acid in dichloromethane affording the expected clinprost. 3) The cyclization of (XXII) to (XXV) can also be performed by treatment of (XXII) with CS2, CH3I and lithium diisopropylamide in THF to give (XXVII), which is then cyclized to (XXV) by means of Bu3SnH and di-tert-butyl peroxide in hot benzene.