计划生育药物的合成——Ⅲ.dl-前列腺素F2α的定向合成

本文报告dl-PGF_2α的定向合成。从环戊二烯出发,经四步反应先合成得环戊烯二醇(Ⅸ),然后用40%过醋酸立体选择性地引入一个环氧而得双羟环氧物(Ⅹ),此物用辛炔-1-叔丁醚-3的二乙基铝(Ⅺ_c)开裂氧环,即可一步引入前列腺素分子中所需的一个C₁₂-八碳醇侧链,得开环物(Ⅻ),侧链在五元环上的位置通过与Corey合成路线中的中问体(ⅩⅩⅤ)相联系得到证明。开环物(Ⅻ)用MnO₂氧化时,主要得内酯(ⅩⅢ),然后经(i-Bu)₂AlH还原、Wittig反应引入羧酸侧链、再用三氟乙酸水解15-叔丁醚基,即得13-去氢PGF_2α,后者用Na-NH₃-t-BuOH进行炔键的选择性还原,用硅胶柱进行分离,可得dl-PGF_2α和dl-15-epi-PGF_2α。

STUDIES OF SYNTHETIC CONTRACEPTIVES Ⅲ.STEREOSPECIFIC TOTAL SYNTHESIS OF RACEMIC PROSTAGLADIN F2α

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.