Steroids and related studies, part 75: The crystal and molecular structure of 17a-(2-hydroxyethyl)-17a-aza-D-homo-5-androsten-3βol (HS407)

Abstract

The crystal structure of 17a-(2 hydroxyethyl)-17a-aza-D-homo-5-androsten-3βol, C₂₂ NO₂ H₃₃ (HS407), an intermediate in the formation of azasteroidal neuromuscular blocking agents, has been determined by Vector Verification and refined by full-matrix least-squares toR=0.058 for 1805 reflections, Cu Kα radiation,θ≦65.49°. The space group is P2₁2₁2,a=25.537(5),b=9.847(4),c=7.545(5) Å,Z=4. The rings in the modified steroid nucleus are alltrans connected, with A and C in distorted chair conformations, D a symmetrical chair, and B a half-chair. The hydroxyethyl side-chain in position N (17a) adopts two distinct conformations with approximately equal statistical occupancies: the first, having a coiled conformation, forms a close intramolecular contact with N(17a) in the enlarged ring D of the steroid nucleus, while the alternative side chain position, which is extended, participates in tail-to-tail intermolecular hydrogen bonding. A switch mechanism is thus formed which could influence the mode of binding of this type of drug moleculein vivo.