Synthesis of ring-Aand -Bsubstituted 17α-acetoxypregnan-20-one derivatives with potential activity on the digitalis receptor in cardiac muscle

The synthesis of C-6 substituted (methyl, hydroxy, acetoxy, methoxy, ethoxy, methoxycarbonyloxy, ethoxycarbonyloxy, fluoro, chloro, bromo) 5α,5β,C-4 unsaturated and C-4,6 unsaturated derivatives of 17α-acetoxypregn-4-ene-3,20-dione (17α-acetoxyprogesterone) are reported. A convenient synthesis of 6α-hydroxy derivatives by selective reduction of the 4-ene-3,6-dione system is described as is the formation of 6α-alkoxycarbonyl derivatives. Synthesis of a 5α-hydroxy-6-ketone via the 5β,6β-epoxide with N-bromosuccinimide is reported. A new preparation of 3α-hydroxy-5α-derivatives from the 4-en-3-one group has been carried out. 1H n.m.r. spectra are recorded. These compounds were synthesized to test for ouabain displacement activity on the digitalis receptor in cardiac muscle.