RESUMO
The conformational preferences of a group of 13-ethylsteroids and related estranes have been determined through theoretical calculations at the B3LYP/6-31G(*) level in order to ascertain differences and similarities in the conformational behavior which might, in principle, influence the activity. Attention was focussed on two geometrical features usually related to the progestational activity of this class of compounds, namely, the inversion of the A ring and the orientation of the 13-ethyl group. The present calculations show that the absence of the C10 methyl group, like in levonorgestrel, 3-ketodesogesterel, and gestodene, makes the inversion of the A ring easier than in norethisterone and ethisterone even if in any case the 1alpha,2beta-half-chair conformation remains preferred. The preference of the ethyl group for the trans orientation is maintained by all the 13-ethylprogestogens though in gestodene also the g(+)gauche conformation is significantly populated. This preference was experimentally supported through a high field NMR spectroscopy study of the ethylsteroids.
Assuntos
Modelos Teóricos , Congêneres da Progesterona/química , Espectroscopia de Ressonância Magnética , Modelos Biológicos , Modelos Moleculares , Conformação MolecularRESUMO
6-Dehydroretroprogesterone (dydrogesterone) and three other natural or synthetic progestins (progesterone, retroprogesterone, and 6-dehydroprogesterone) were submitted to a conformational study through theoretical calculations at the B3LYP/6-31G(*) level and high field NMR spectroscopy. The study allows to define the role of the two structural features which differentiate these steroids, i.e., the C9 and C10 configuration and the C6-C7 unsaturation. The combined effects of the conformational preference of A ring, determined by the configuration at C9 and C10, and the enhanced rigidity due to the C6-C7 double bond, could account both for the higher activity and selectivity of dydrogesterone with respect to the other three steroids.
