Epimer 20?-, 20?-hydroxy derivatives of pregnane of the 5?,14? series, substituted on the D ring:13C NMR spectra and theoretical conformational analysis by the molecular mechanics method

Abstract

We have obtained the high-resolution13C NMR spectra of a series of epimer 20α-,20β-hydroxy derivatives of pregnane, substituted on the D ring, and we have analyzed the effects of a change in the configuration of the C20 center on the13C chemical shifts observed for the C atoms of the entire steroid skeleton, including the A ring. For the first time, by the molecular mechanics method using the Ellinger MM2 program, we have carried out a conformational analysis of these epimer pairs; on the basis of the theoretical data obtained in the geometries and populations of the conformers, we have calculated the constants\({}^3J_{H^{17} }\), H20 for the 20α-, 20β-epimers of 20-hydroxypregnane and its 16α-Me-derivative; their values agree with the experimental values. We have found a qualitative functional relationship between the differences in the chemical shifts of the C atoms closest to the 17 β-CH(OH)Me group in the 20α- and 20β-epimers of 20-hydroxypregnanes and the van der Waals energies calculated using the MM2 program. We have demonstrated that it is necessary to take into account all four types of nonvalence interactions: C*-C, C*-H, H*-C and H*-H.