Synthesis and Characterization of Hybrid Dimeric Steroid Spiroketals

The synthesis of six dimeric spiroketals bearing an estradiol half fused to the 5-or 5-epimers of androstane, cholestane and spirostane nuclei is described. The synthetic procedure comprises the Sonogashira coupling of different steroid alkynes with 2-iodoestradiol 17-monoacetate, followed by Pd-catalyzed spiroketalization. The structural characterization of the obtained hybrid dimers was performed using a combination of 1D and 2D NMR techniques, and was assisted by DFT calculations. Single crystal X-ray diffraction of one of the obtained compounds confirmed the proposed structures.