A full conformational characterization of 13-ethylprogestogens through theoretical calculations and nuclear magnetic resonance spectroscopy.
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.
Colombo
Diego
D
Dipartimento di Chimica, Biochimica e Biotecnologie per la Medicina, Università di Milano, Via Saldini 50, 20133 Milano, Italy. diego.colombo@unimi.it
Ferraboschi
Patrizia
P
Legnani
Laura
L
Prestileo
Paolo
P
Toma
Lucio
L
D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D008958:Models, Molecular; D008962:Models, Theoretical; D008968:Molecular Conformation; D045167:Progesterone Congeners / Q000737:chemistry*
D045167:Progesterone Congeners