Cardiac Glycosides. 1.¹ A Systematic Study of Digitoxigenin d-Glycosides

A series of digitoxigenin glycosides was studied: five with β-D-sugars varying stepwise in sugar structure from β-D-digitoxose to β-D-galactose, including one β-D/α-D pair. I₅₀ values for these glycosides and digitoxigenin were determined with hog kidney Na⁺,K⁺-ATPase. These data suggest a major and unexpected role for 4'-OH conformation in the sugar. All the glycosides with an equatorial 4'-OH were more active than the two with the 4'-OH axial [digitoxigenin β-D-galactoside (6) I₅₀ = 6.45 X 10^-8 M; digitoxigenin 2'-deoxy-α-D-rtbo-hexopyranoside (α-3a) I₅₀ = 9.33 X 10^-8M; digitoxigenin I₅₀ = 1.17 X 10^-7 M], Stereochemistry of the 3'-OH had much less of an activity role than that of the 4^',-OH, in contrast to existing models of “sugar-site”binding.