ON THE CONFORMATIONAL EQUILIBRIUM OF 16-ALPHA-ACETOXY-13, 17-SECO-5-ALPHA-ANDROSTAN-13-ZETA-HYDROXY-17-CARBOXYLIC ACID LACTONE MOLECULE IN THE CRYSTALLINE STATE - X-RAY STUDY AND MMX CALCULATIONS

The reaction of 13,17-seco-5-alpha-androstan-13-xi-hydroxy-17-carboxylic acid lactone with lead tetraacetate yields both alpha- and beta-epimers. The structure of the alpha-epimer was determined by X-ray diffraction substantiating the ambiguous conclusions inferred from spectroscopic studies. Crystals are monoclinic, space group C2 with a = 28.003(3) angstrom, b = 7.351(2) angstrom, c = 18.970(4) angstrom, beta = 90.75(2)-degrees, Z = 8 (two molecules in the asymmetric unit) and D(c) = 1.186 g cm-3. The structure determined by direct methods was refined to R = 0.049 for 2652 reflections. The conformational disorder of one of the symmetry independent molecules (A and B) was noticed at R = 0.16. and corrected at the end of the standard refinement. The shape of the disordered delta-lactone ring in molecules B1 and B2 has been substantially improved by molecular mechanical calculations (MMX). Altogether in the unit cell there are three conformers which differ in the puckering of the delta-lactone ring and the position of the 16-alpha-acetoxy group. The predominant lactone ring conformation T/S --> S related by a C2 mode of rotation, is altered towards an envelope shape (E). The adjoining 16-alpha-acetoxy group twice assumes pseudo-equatorial (conformer A (50%) and conformer B1 (25%)) and once the pseudo-axial (conformer B2 (25%)) orientation.