STUDIES OF SYNTHETIC CONTRACEPTIVES Ⅲ.STEREOSPECIFIC TOTAL SYNTHESIS OF RACEMIC PROSTAGLADIN F_2α

In this paper, the stereospecific total synthesis of PGF_2αis reported. Starting from cyclopentadiene, the dl-diol (Ⅸ) was synthesized in 4 steps. The latter was epoxidized stereospecifically by 40% peracetic acid or monoperphthalic acid to the epoxide (Ⅹ). Reaction of compound (Ⅹ) with dl-3-t-butyloxy-1-octynyl diethylalane(Ⅺc) produced a racemic mixture of triol (Ⅻ). The position of the side chain on the five membered ring was verified by correlation with the intermediate ⅩⅩⅤ in Corey's PG synthetic route.Oxidation of the triol (Ⅻ) with MnO₂ furnished the lactone (ⅩⅢ). Reduction of ⅩⅢ with (i-Bu)₂ AIH followed by Wittig reaction to introduce the carboxylic side chain and then hydrolysis of the t-butyl group with trifluoroacetic acid gave 13-dehydro PGF_2α (ⅩⅦ). The acetylene bond in ⅩⅦ was selectively reduced with sodium in liquid ammonia and t-butyl alcohol to yield a mixture of PGF_2α and its 15-epimer, which could be separated by column chromatography.The triple bond of Ⅻ was reduced with Li-NH₃-EtOH to yield the trans substituted C_13,14-double bond of ⅩⅨ, but not with LAH in absolute ether. After oxidation of the reduction product (ⅩⅨ) with CrO₃-pyridine complex followed by introduction of the carboxylic side chain with Wittig reagent(ⅩⅫ), the 15-t-butyl ether of PGF_2α (ⅩⅪ) was synthesized. Attempted removal of the t-butyl group of compound(ⅩⅪ) into PGF_2α with trifluoracetic acid was not successful.