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

被引：17

作者：

Li, Yan ^{[1
]}

Huang, Jie ^{[1
]}

Liu, Jinliang ^{[1
]}

Yan, Peiyun ^{[1
]}

Liu, Hui ^{[1
]}

Sun, Qian ^{[1
]}

Wang, Xingbin ^{[1
]}

Wang, Cunde ^{[1
]}

机构：

[1] Yangzhou Univ, Sch Chem & Chem Engn, Yangzhou 225002, Peoples R China

来源：

STEROIDS | 2011年 / 76卷 / 14期

基金：

中国国家自然科学基金;

关键词：

Epiandrosterone; 17E-(2-aryl-2-oxo-1-ethylidene)-5 alpha-androstane; Meyer-Schuster rearrangement; Mercury sulfate; Anticancer activity; PROPARGYLIC ALCOHOLS; ANTICANCER AGENTS; ISOMERIZATION; STEROIDS; ELUCIDATION;

D O I：

10.1016/j.steroids.2011.10.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The efficient synthesis of some 17E-(2-aryl-2-oxo-1-ethylidene)-5 alpha-androstan-3 beta-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-Schuster 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 alpha,beta-unsaturated ketone 17E,5 alpha-androstan-3 beta-ols from the 17-alkyny1-3,17-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 alpha-androstanes possessing a hydroxyl groups at C-3 and fluoro-substituted group of aromatic ring in the side chain have significant inhibition activity. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：1615 / 1620

页数：6

共 26 条

[21] The reaction of azoles with 17-chloro-16-formylandrosta-5, 16-dien-3β-yl-acetate: Synthesis and structural elucidation of novel 16-azolylmethylene-17-oxoandrostanes [J].

Moreira, Vania M. ;

Salvador, Jorge A. R. ;

Beja, Ana Matos ;

Paixao, Jose A. .

STEROIDS, 2011, 76 (06) :582-587

[22] Enantioselective production of 3-hydroxy metabolites of tibolone by yeast reduction [J].

Romano, Diego ;

Ferrario, Valerio ;

Mora, Diego ;

Lenna, Roberto ;

Molinari, Francesco .

STEROIDS, 2008, 73 (01) :112-115

[23] Cationic rhodium(I)/bisphosphane complex-catalyzed isomerization of secondary propargylic alcohols to α,β-enones [J].

Tanaka, Ken ;

Shoji, Takeaki ;

Hirano, Masao .

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2007, 2007 (16) :2687-2699

[24] Novel and efficient synthesis of 22-alkynyl-13,24(23)-cyclo-18,21-dinorchol-22-en-20(23)-one analogues [J].

Wang, Cunde ;

Liu, Lanhai ;

Xu, Hangxian ;

Zhang, Zonglei ;

Wang, Xingbin ;

Liu, Hui .

STEROIDS, 2011, 76 (05) :491-496

[25] Synthesis of some novel androstanes as potential aromatase inhibitors [J].

Yadav, Mange Ram ;

Sabale, Prafulla M. ;

Giridhar, Rajani ;

Zimmer, Christina ;

Haupenthal, Jorg ;

Hartmann, Rolf W. .

STEROIDS, 2011, 76 (05) :464-470

[26] Methyl spongoate, a cytotoxic steroid from the Sanya soft coral Spongodes sp. [J].

Yan, Xiao-Hong ;

Lin, Li-Ping ;

Ding, Han ;

Guo, Yue-Wei .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (09) :2661-2663

← 1 2 3 →