Mechanistic studies of the rearrangements of steroidal 16,17-ketols and syntheses of 20→16- cis-γ-carbolactones

Utilization of 17-keto-androstanes as starting materials for the synthesis of α- or β-oriented steroidal 20→16-γ-carbolactones has been explored following two different strategies. A highly efficient, stereospecific protocol has been developed for the β-oriented cis-γ-lactone. A different approach, involving prior attachment of a 3-carbon side chain on C-17 of a 17-oxo-16β-acetoxy-androstane led to the epimeric, α-oriented lactone. The mechanism of the rearrangement of epimeric 16β- or 16α-hydroxy-17-keto-androstanes to 17β-hydroxy-16-keto-androstanes was studied by 13C NMR spectroscopy. The former occurs through a 1,2-sigmatropic H-shift, while the latter is likely to take place by simple enolization–reprotonation.