Steroidal analogues of unnatural configuration. Part 12. RingAreactions of 9-methyl-5β,9β,10α- and 9-methyl-5α,9β,10α-estran-3-ones: conformational analysis and X-ray crystallography of products

Abstract

Bromination of 17β-acetoxy-9-methyl-5β- and 17β-acetoxy-9-methyl-5α,9β,10α-estran-3-one, obtained through stereoselective reductions of the olefinic bond of the corresponding testosterone analogue, leads to complex mixtures of α-bromo-ketones. In both cases, bromination at C(2) is favoured, and the distributions of positional isomers are rationalised in terms of conformational transmission effects. It is shown that the respective epimeric pairs are readily interconverted. The crystal structures of 17β-acetoxy-9-methyl-5α,9β,10α-estran-3-one (3b) and its 2α- and 2β-bromo-derivatives (11) and (12) have been determined by X-ray analysis. Ring A of (3b) and (11) suffers slight deformation from a chair conformation, whereas that of (12) adopts a twist-boat conformation in response to the severe steric interaction between the 2β-bromo- and 9β-methyl groups. The solid-state conformations of the three compounds clarify anomalies in their spectroscopic properties.