Crystal chemistry of some synthetic 2-oxa-steroids: Conformation, packing motifs and isostructurality

Abstract

The crystal structures of six synthetic 2-oxa-steroids (A-ring lactone steroids) have been determined by single-crystal X-ray diffraction. The conformation and hydrogen bonding in these oxa-steroids is compared with packing motifs in the natural steroids and the anabolic agent, Anavar®. O - H⋯O hydrogen bonding with lactone carbonyl O is the preferred arrangement in molecules with a C - OH group. The donor H atoms of A, B and D rings participate in C - H⋯O interactions with lactone carbonyl O and D-ring hydroxyl/ ketone O acceptor atoms. The conformation of the lactone ring in these analogues is different from the natural androgens because replacement of the C2-methylene group by an O atom changes the geometry of the A ring. Two structurally related lactone steroids provide the first example of O - H⋯O/C -H⋯O interaction mimicry and furthermore the two components form a binary solid solution. The O - H⋯O and C -H⋯O hydrogen bonds in 2-oxa-steroid crystal structures are analysed and the observed preferences discussed in terms of geometric and chemical factors.