CRYSTAL AND MOLECULAR-STRUCTURES OF 3 MODIFICATIONS OF THE ANDROGEN DEHYDROEPIANDROSTERONE (DHEA)

The crystal and molecular structures of three forms of the androgen DHEA (dehydroepiandrosterone) have been determined by single crystal X-ray diffraction. They are: Form I, a polymorph crystallizing in space group P2(1) with Z = 4; Form S1, a hydrate with composition DHEA.(1/4)H2O, space group C2, Z = 8; and Form S4, a methanol half-solvate, DHEA.(1/2)CH3OH, space group C222(1), Z = 8. The A, B, and C steroid ring conformations adopted in the five crystallographically independent DHEA molecules are invariably: chair, 8 beta, 9 alpha-half-chair, and chair, respectively, while the D ring conformation ranges from a 14 alpha-envelope to a 13 beta, 14 alpha-half-chair. In Forms I and S1, intermolecular hydrogen bonding is of the head-to-tail type with water molecules participating as donors in Form S1. In Form S4, DHEA molecules pack in head-to-head fashion, their hydroxyl groups being linked by hydrogen bonding to the solvent hydroxyl group. The hydroxyl H atoms of both DHEA and the included methanol are disordered, giving rise to an unusual linearly-propagating 'flip-flop' hydrogen bonding scheme.