Conformational equilibria in amino steroids. 1. A ¹H and ¹³C NMR spectroscopy and molecular mechanics study of 3α-Hydroxy-2β-(4-morpholinyl)-5βH-androstan-17-one

The A ring conformational equilibrium of the title steroid has been investigated using high-field NMR spectroscopy. At 600 MHz the spectral dispersion is such that resolved signals can be seen for most protons. We present a complete analysis of the ¹H and ¹³C spectra of the title compound in CDC1₃ and DMSO solutions and show that the conformation of ring A is determined by the medium: a chair is found in polar solvent, but in an apolar solvent a twist-boat is preferred. The drug design and drug transport implications of this equilibrium are discussed with regard to the neuromuscular blocking agent ORG 9426, whose A ring is modeled here. Molecular mechanics calculations are used to provide reasonable geometries for the two conformations.