A Synthesis of 3/3-Hydroxy-5/3,14a-bufa-20,22-dienolide from Deoxycorticosterone

A new procedure for the synthesis of γ-hydroxy-α,β-unsaturated thiol esters from ketones employed 1-(phenylthio)-l-(trimethylsilyl)-2-propene as an unsaturated homoenolate anion equivalent, and this procedure served as a key step in a synthesis of the α-pyrone ring characteristic of bufadienolides. In particular, the regio-and stereoselective trapping of various pregnan-20-ones by the anion of l-(phenylthio)-l-(tiimethylsilyl)-2-propene furnished (20S,23Z)-20-hydroxy-24-(phenylthio)-24-(trimethylsilyl)-23-cholenes and subsequent regioselective oxygenation of the dianions of these adducts provided S-phenyl (20S,22E)-20-hydroxychol-22-ene-24-thioates. Application of this procedure to 3β-hydroxy-21-methoxy-50,14a-pregnan-20-one furnished S-phenyl (20S,22£)-3β,20-dihydroxy-21-methoxy-5β-chol-22-ene-24-thioate, which was subsequently cyclized to 3β-hydroxy-5/3,14a-bufa-20,22-dienolide.