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以炔诺酮中间体面△~(5(10))-雌甾-3,17-二酮-3,3-双甲醚(4)和消旋18-甲基炔诺酮中间体dl-18-甲基-△~(2(3),5(10))-雌甾-二烯-17-酮-3-甲醚(5)为原料,在四甲基氟化铵催化下和三氟甲基三甲基硅烷(TMSCF_3)发生羰基亲核加成反应,硅醚中间体分别经多步反应合成含三氯甲基的甾体化合物1a,b,2a,b和3a,b.总产率分别为82%,76%,54%,62%和27%,25%.17位三氟甲基经X-单晶衍射证明处于α-位.化合物1a,2a和3a经初步药理测试显示具有良好的抗生育活性.特别是化合物1a,对大鼠子宫胞液孕酮受体的亲和力是米非司酮(RU 486)的3倍.化合物1b,2b和3b的药理测试正在进行之中.
(N (4)) and racemic 18-norgestrel intermediate dl-18 (5) as raw material, under the catalysis of tetramethylammonium fluoride and trifluoroacetic acid Methyltrimethylsilane (TMSCF_3) carbonyl nucleophilic addition reaction occurs, the silicone ether intermediates were synthesized by multiple reactions trichloromethyl-containing steroids 1a, b, 2a, b and 3a, b. Rates were 82%, 76%, 54%, 62% and 27%, 25%, respectively. Trifluoromethyl was shown to be in the α-position by X-ray diffraction of compound X. Compounds 1a, 2a and 3a were initially pharmacologically tested Has good anti-fertility activity, especially Compound 1a has 3-fold more affinity for uterine progesterone receptors than mifepristone (RU 486) Pharmacological testing of compounds 1b, 2b and 3b is underway .