Abstract: Digitalis cardiac glycosides are well known drugs clinically used for treatment of congestive heart failure.1 Their action is mainly due to inhibition of Na+,K+-ATPase, an enzyme located in the cell membrane and promoting the outward transport of Na+ and the inward transport of K+.2 Recently the existence of endogenous digitalis-like factors that may be responsible for essential hypertension3 has opened a new field in the study of compounds acting on the Na+,K+-ATPase. The most potent inhibitors of Na+,K+-ATPase are cardenolides such as digitoxigenin (Figure 1) with the following structural characteristics: 17b-unsaturated lactone, 3b- and 14b-hydroxy substituents and A/B and C/D cis ring junctions. The 14b-hydroxy group is involved in a hydrogen bonding with the receptor and plays an important role in binding digitalis compounds to Na+,K+-ATPase receptor; in fact compounds in which this group is absent show very low binding affinity or no affinity at all.4 However the known derivatives with a 14b,15b-epoxy group (Figure 1) show high binding affinities although not as high as the 14b-hydroxy analogues