Synthesis of 20α- and 20β-acetamido, amino, nitro and hydroxy derivatives of 14-hydroxy-5β,14β-pregnane 3β-glycosides: pregnanes that bind to the digitalis receptor

Abstract

Synthesis of 20α- and 20β-acetamido-, amino-, nitro- and hydroxy-3β-glycoside (α-L-rhamnopyranoside and tris-β-D-digitoxoside) and genin derivatives of 14-hydroxy-5β,14β-pregnane together with the C-20 oxime, hydrazone and amidinohydrazone is described from digitoxin. Ortho esters were also isolated. Structures were established by NMR measurements. These compounds have been shown to bind to the digitalis receptor of heart muscle. The 20β derivatives were consistently more potent than are the corresponding 20α compounds. The 20β-nitro α-L-rhamnoside derivative proved to be the most potent. Receptor binding data are given and structure-activity relationships are presented.