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

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Abstract

Graphical abstract

The efficient synthesis of some 17E-(2-aryl-2-oxo-1-ethylidene)-5α-androstan-3β-ols was investigated. The synthesized compounds showed significant anticancer activity against A549, SKOV3, MKN-45 and MDA-MB-435 cell lines.

Highlights

▸ 17-Alkynyl-3,17-androstanediols were from epiandrosterone and the corresponding 1-alkynes. ▸ Meyer–Schuster rearrangement of 17-alkynyl-3,17-androstanediols gave 17E-(2-aryl-2-oxo-1-ethylidene)-5α-androstan-3β-ols. ▸ 17E-(2-aryl-2-oxo-1-ethylidene)-5α-androstan-3β-ols showed cytotoxicity against cancer cell lines.

The efficient synthesis of some 17E-(2-aryl-2-oxo-1-ethylidene)-5α-androstan-3β-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 α,β-unsaturated ketone 17E,5α-androstan-3β-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)-5α-androstanes possessing a hydroxyl groups at C-3 and fluoro-substituted group of aromatic ring in the side chain have significant inhibition activity.

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