Synthesis and cytotoxicity of 17E-(2-aryl-2-oxo-1-ethylidene)-5¦Á-androstane derivatives

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• 作者：Yan Li ; Jie Huang ; Jinliang Liu ; Peiyun Yan ; Hui Liu ; Qian Sun ; Xingbin Wang ; Cunde Wang  ; ;   ; ^{wangcd@yzu.edu.cn}
• 关键词：Epiandrosterone ; 17E-(2-aryl-2-oxo-1-ethylidene)-5¦Á-androstane ; Meyer&ndash ; Schuster rearrangement ; Mercury sulfate ; Anticancer activity
• 刊名：Steroids
• 出版年：2011
• 出版时间：20 December 2011
• 年：2011
• 卷：76
• 期：14
• 页码：1615-1620
• 全文大小：304 K

文摘

The efficient synthesis of some 17E-(2-aryl-2-oxo-1-ethylidene)-5¦Á-androstan-3¦Â-ols was investigated. 17-Alkynyl-3,17-androstanediols were prepared through the nucleophilic addition of epiandrosterone using the corresponding 1-alkynes in the presence of a strong base n-BuLi firstly. The Meyer¨CSchuster rearrangement of 17-alkynyl-3,17-androstanediols was carried out efficiently catalyzed by 10 % H₂SO₄ and HgSO₄ in THF. This strategy offered a very straightforward and efficient method for access to conjugated ¦Á,¦Â-unsaturated ketone 17E,5¦Á-androstan-3¦Â-ols from the 17-alkynyl-3,17-androstanediols in good overall yields, which are key intermediates for the preparation of some biologically important modified 17-side chain steroids. Evaluation of the synthesized compounds for cytotoxicity against A549, SKOV3, MKN-45 and MDA-MB-435 cell lines showed that 17E-(2-aryl-2-oxo-1-ethylidene)-5¦Á-androstanes possessing a hydroxyl groups at C-3 and fluoro-substituted group of aromatic ring in the side chain have significant inhibition activity.