Synthesis of 3β,14-dihydroxy-5β,14β-pregnan-20-one C-3 derivatives: ozonolysis of digitoxin and digitoxigenin and their derivatives followed by zinc–acetic acid reduction to the C-21 methyl ketone

Abstract

Ozonolysis of digitoxin, digitoxin tetraacetate, digitoxin tetrakis-(2,2,2-trichloroethyl carbonate), digitoxigenin, digitoxigenin acetate, digitoxigenin hemisuccinate and digitoxigenin 2,2,2-trichloroethyl carbonate followed by treatment with excess of zinc in acetic acid gave either the corresponding 21-hydroxy ester after 5 min or the 21-methyl ketone after 20 h. This procedure is more efficient than methods previously reported for the conversion of the α,β-unsaturated γ-lactone into an acetyl group and is applicable to the cardiac glycosides directly to give 14β-hydroxypregnan-20-one derivatives. Acidic hydrolysis of 14,21-dihydroxy-and 14-hydroxy-3β-tris(digitoxosyloxy)-5β,14β-pregnan-20-one is reported. Structures are based on ¹H and ¹²C NMR assignments.