Crystalline Molecular Structures of Two Derivatives of 2β-Hydroxytestosterone Having an Unusual A-Ring Conformation

In the crystal structures of 2β-acetoxy-17β-chloroacetoxy-4-androsten-3-one-MeOH complex (1:1) and 2β,17β-diacetoxy-4-androsten-3-one-p-bromophenol complex (1:1), the A-rings of the steroids have been determined to be in an inverted half-chair conformation. This conformation is in sharp contrast to the normal half-chair conformation observed in the crystal structures of 14 other Δ⁴-3-one steroids including one with a 2β-C1 substituent. Steric interaction between the 19-Me substituent and the acetate group in the 2β position may be the cause of this surprising conformational difference. In the inverted half-chair arrangement, the conjugation of the α,β-unsaturated ketone system in the A-ringis disrupted, atoms O(2), C(2), C(3), and O(3) achieve a nearly coplanar arrangement, and atoms C(3), C(4), C(5), C(10), and C(l) also reside in nearly coplanar positions. This combination of the two coplanar arrangements of atoms may be an energetically favorable conformation and suggests that the inverted half-chair may also constitute a stable form of these molecules in solution.