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目的研究口服避孕药左炔诺孕酮原料药中的有关物质,就欧洲药典中给出的5个已知有关物质中的3个进行合成。方法分别以化合物3-甲氧基-13-乙基-1,3,5(10),8,14-雌甾五烯-17β-羟基(4)、18-甲基-3-甲氧基-2,5(10)-雌甾二烯-17-酮(8)和13-乙基-甾体-4-烯-3,17-双酮(10)经还原、炔化、水解等反应得到3个目标化合物13-乙基-17-羟基-18,19-双去甲基-17α-孕甾-4,8(14)-双烯-20-乙炔基-3-酮(1)、13-乙基-17-羟基-18,19-双去甲基-17α-孕甾-5(10)-烯-20-乙炔基-3-酮(2)和13-乙基-3-乙炔基-18,19-双去甲基-17α-孕甾-3,5-双烯-20-乙炔基-17-醇(3)。结果与结论以化合物4、8、10经8步反应合成了3个目标化合物,总收率分别为9.5%、36.9%和31.3%。结构经IR、NMR和M S进行了确证,并与欧洲药典公布的数据一致。
Objective To study the related substances in the oral contraceptive levonorgestrel drug substance and to synthesize three of the five known related substances given in the European Pharmacopoeia. Methods The compounds were synthesized by the methods described in the literature. Compounds 3-methoxy-13-ethyl-1,3,5 (10), 8,14-estratriene-17β-hydroxy -2, 5 (10) -estradien-17-one (8) and 13-ethyl-steroid-4-ene-3,17-dione (10) The target compound 13-ethyl-17-hydroxy-18,19-didemethyl-17α-pregna-4,8 (14) -diene-20-ethynyl- 13-Ethyl-17-hydroxy-18,19-didemethyl-17α-pregna-5 (10) -ene- 20-ethynyl-3-one (2) and 13-ethyl- -18,19-didemethyl-17α-pregna-3,5-diene-20-ethynyl-17-ol (3). Results and Conclusion Three target compounds were synthesized by 4, 8, and 10 reactions in 8 steps. The total yields were 9.5%, 36.9% and 31.3%, respectively. The structure was confirmed by IR, NMR and MS, and was consistent with the data published by the European Pharmacopoeia.