Cardiac Glycosides. 6. Gitoxigenin C16 Acetates, Formates, Methoxycarbonates, and Digitoxosides. Synthesis and Na+, K+ -ATPase Inhibitory Activities

Article abstract of DOI:10.1021/jm00156a017

A series of 17 gitoxigenin 16β-formates, acetates, and methoxycarbonates was synthesized, including their 3β-acetates, formates, and digitoxosides.A 16β-formate group was generally found to increase activity 30 times, a 16β-acetate group 9-12 times, while a 16β-methoxycarbonate decreased activity by two-thirds. 3β-Formates and acetates had little effect on activity by themselves, but sometimes reduced the activity-increasing properties of 16β-formates and acetates.A 3β-digitoxoside increases the activity of ditoxigenin by 15 times, but the effect is less ifthe 16β-group is esterified.And finally, a 16-one decreases activity dramatically.These data suggest an important role for C16 esters and possibly the presence of a separate binding site on Na⁺, K⁺ -ATPase corresponding to the cardenolide C16 position.