An NMR Study of the Conformational Mobility of Steroid Estrogen 7α-Methyl-8α Analogues

S. I. Selivanov^1 #, A. Yu. Solov’ev¹, S. N. Morozkina¹ and A. G. Shavva¹

^#Phone: (812) 428-43-25; fax: (812) 428-69-39; e-mail: nmr@paloma.spbu.ru

¹Faculty of Chemistry, St. Petersburg State University, Universitetskii pr. 26, Staryi Petergof, St. Petersburg, 198504, Russia

Received: August  15, 2006; in final form: November  27, 2006

Abstract.  All the signals in the ¹H and ¹³C NMR spectra of some analogues of 7α-methyl-8α-and 6-oxa-8α-steroid estrogens were completely assigned. Considering the values of nuclear Overhauser effect and vicinal coupling constants, these steroids were shown to exhibit a fast, on the NMR time scale, conformational equilibrium arising due to the inversion of ring B. The conformer populations were obtained from a comparison of the experimental and theoretical values of the dihedral angles and the interproton distances. This conformational equilibrium was shown to depend on the nature of atom in position 6: for the 7α-methyl-6-oxa-8α analogues of the steroid estrogens, the population of the conformer with the pseudoaxial orientation of the 7α-methyl group was observed to be decreased compared with the 7α-methyl-8α analogue.

Key words:  conformational analysis, fast conformational exchange, 7α-methyl-8α analogues, NMR spectroscopy, nuclear Overhauser effect (NOE), steroid estrogens, vicinal constants

Russian Journal of Bioorganic Chemistry 2007, 33 (3): 302-309