Molecular dynamics of 17a- and 21-hydroxy progesterone studied by NMR. Relation between molecule conformation and height of the barrier for methyl group reorientations in steroid compounds

For the two steroid compounds 17aOH-progesterone and 21OH-progesterone, the activation energies of reorientations of the methyl groups have been determined. Their values together with results of the quantum chemical calculations permitted establishment of the sequence of the onset of the methyl group reorientations about the three-fold symmetry axis of the C–C bond. On the basis of the asymmetry parameters, the conformations of the hitherto studied pregnane derivatives and testosterone have been determined. It has been found that the conformation of ring A has dominant effect on the activation energies of the reorientation of C(19)H3. The reorientation of the methyl group C(18)H3 significantly depends on the conformation of the side chain 17b (torsional angle C(13)–C(17)–C(20)–O(20)) and the distance between C18 and O20. The study has proved that the 1H NMR method in combination with the quantum chemistry calculations and inelastic incoherent neutron scattering (IINS) are effective for prediction of the sequence of the methyl group reorientations about the three-fold symmetry axis. q 2004 Elsevier B.V. All rights reserved.