Palladium Catalyzed Synthesis of Benzannulated Steroid Spiroketals

Nine cytotoxic [5/7] and [6/6] benzannulated steroid spiroketals were synthesized by palladium catalyzed spiroketalization of 5α and 5β-alkynediols derived from testosterone, diosgenin and cholesterol. The regioselectivity of the spiroketalization reaction is decisively influenced by the α or β-orientation of the hydroxyl group at C-5. NMR and Single Crystal X-ray Diffraction corroborated the structure of the obtained compounds. Compounds bearing a cholestane skeleton exhibited the higher cytotoxicity against U251 and T47D cells, and the BrdU incorporation assay suggests that the synthesized spiroketals inhibit cell proliferation.