De Novo Synthesis of Possible Candidates for the Inagami–Tamura Endogenous Digitalis-like Factor

De novo synthesis of possible candidates for the Inagami–Tamura endogenous digitalis-like factor (EDLF) was achieved to validate a previously proposed structure. Our synthetic approach involves a highly regio- and diastereoselective Mizoroki–Heck reaction and a Friedel–Crafts-type cyclodehydration to construct steroidal tetracycle 14 as a versatile common intermediate leading to seven 2,14β-dihydroxyestradiol analogues 1a–c, 2a–c, and 3 as possible candidates. By comparing the potency of inhibitory activity against Na+/K+-ATPase between the synthesized candidates and the EDLF, it was found that the proposed structure is not likely to be a true structure of the Inagami–Tamura EDLF.