Adamczyk M, Johnson D D, Reddy R E
Division Organic Chemistry Research (9NM, AP20), Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
Steroids. 1997 Dec;62(12):771-5. doi: 10.1016/s0039-128x(97)00088-3.
Alkylation of 3,17 beta-bis(2-trimethylsilyl)ethoxymethyl-1,3,5(10) estratriene-6-one (2) with 5-bromo-1-pentene using NaHMDS in THF afforded 3,17 beta-bis(2-trimethylsilyl)ethoxymethyl-7-alpha-(4'pentenyl)-1,3,5(10) estratriene-6-one (3) in excellent stereoselectivity (> 95% epimeric excess). Functionalization of the side chain in compound 3 was accomplished via ozonolysis, oxidation and esterification to give 5 in 72% yield. The reduction of ester (5) using NaBH4 in MeOH afforded the corresponding 6 alpha-hydroxy compound (6) as a single isomer in 72% yield. The hydroxyl group in 6 was removed by converting to the corresponding xanthate (7) followed by reduction using n-Bu3SnH to afford 8 in good yield. Finally, the SEM protective groups in 8 were removed, after which the ester function was hydrolyzed with LiOH to give 7 alpha-(3'-carboxypropyl)estradiol (10), in 10.6% overall yield from 3.
在四氢呋喃中使用六甲基二硅基氨基钠（NaHMDS），使3,17β - 双（2 - 三甲基硅基）乙氧基甲基 - 1,3,5（10）雌甾三烯 - 6 - 酮（2）与5 - 溴 - 1 - 戊烯发生烷基化反应，以优异的立体选择性（>95%的差向异构体过量）得到3,17β - 双（2 - 三甲基硅基）乙氧基甲基 - 7 - α - （4'-戊烯基） - 1,3,5（10）雌甾三烯 - 6 - 酮（3）。化合物3侧链的官能化通过臭氧分解、氧化和酯化反应完成，以72%的产率得到5。在甲醇中使用硼氢化钠（NaBH4）还原酯（5），以72%的产率得到相应的单一异构体6α - 羟基化合物（6）。通过将6中的羟基转化为相应的黄原酸酯（7），然后用三丁基氢化锡（n - Bu3SnH）还原，以良好的产率得到8，从而去除6中的羟基。最后，去除8中的SEM保护基团，然后用氢氧化锂（LiOH）水解酯官能团，从3开始以10.6%的总产率得到7α - （3'-羧丙基）雌二醇（10）。
