The Crystal Structure and Molecular Conformation of Aldosterone

The structure of aldosterone (C₂₁O₅H₂₈) in a monohydrated crystalline form has been determined by X-ray analysis to be the 18-acetal-20-hemiketal structural isomer. The steroid crystallizes in the monoclinic space group P2_I with a = 12.199, b = 6.0345, and c = 13.181 Å, β = 107.31°, Z = 2. The structure was solved by application of direct methods, in particular the development of a technique for strong enantiomorph selection based upon the expected distribution of values of cosine invariants. With all atoms located the final R value for 1749 observed reflections measured with a diffractometer is 0.052. The addition of two five-membered rings to the four-ring steroid nucleus introduces considerable strain into the C ring as indicated by the C(11)–C(12)–C(13) valency angle of 97.6°. Despite this strain and the nearly total eclipsing of the bonds to C(17) and C(20) introduced by the hemiketal formation, the crystalline hydrate is very stable and the thermal motion is no greater than that generally observed in steroid structures. Both hydroxyl groups of the 17 side chain participate in strong hydrogen bonds in the solid. The hydroxyl of the C(21) atom is in the most extended conformation possible resulting in an intramolecular O(3)–O(21) distance of 12.64 Å.