Crystallographic Characterization of Trilostane and Derivatives

Abstract Trilostane, 2 α ‐cyano‐4 α ,5 α ‐epoxy‐17 β ‐hydroxyandrostan‐3‐one, as a synthetic steroid analogue, competitively inhibits the synthesis of several steroids, including cortisol and aldosterone. In veterinary medicine, trilostane has been used successfully to treat hypercortisolism. Trilostane is metabolized by the liver, producing the major metabolite ketotrilostane, 2 α ‐cyano‐4 α ,5 α ‐epoxyandrostane‐3,17‐dione, which is excreted by the liver. The parent compound and the major metabolite undergo metabolic interconversion. Pyridinium chlorochromate oxidation gave the α,β ‐unsaturated cyanoketone, which was hydrogenated to yield ketotrilostane. For the first time, all steroids were structurally characterized by X‐ray crystallography. Furthermore, a new derivative of trilostane could be synthesized and was structurally characterized.