Conformational studies. Part 13. 1H N.m.r. and X-ray analyses of 2β-bromo-3α-hydroxy-5α-pregnane-11,20-dione, 3α-hydroxy-2β-methoxy-5α-pregnane-11,20-dione, and 3α-hydroxy-2α-methyl-5α-pregnane-11,20-dione

Abstract

To investigate the potential relationship between structure and anaesthetic activity, the title steroids have been analysed by ¹H n.m.r. spectroscopy, and by X-ray crystallography. The three compounds crystallise in the monoclinic space group P2₁ with two molecules per unit cell. Crystals of the 2β-bromo-derivative (2) have a= 10.288(4), b= 7.480(5), c= 13.646(4)Å, β= 107.78(2)°. The structure was solved by the heavy-atom method and refined by full-matrix least-squares calculations: R= 0.083 for 1 428 reflections. The 2β-methoxy-derivative (3) has a= 10.814(3), b= 7.207(2), c= 13.963(3)Å, β= 106.73(1)°. Structure solution was by direct methods and refinement as for (2) lowered R= 0.052 for 1 505 reflections. Crystals of the 2α-methyl derivative (4) are isomorphous with those of (2) with a= 10.183(8), b= 7.552(7), c= 13.772(9)Å, β= 106.73(4)°; refinement by full-matrix least-squares calculations lowered R to 0.072 for 698 reflections.

The torsion angles in ring A of (2) involving atom C(2) are smaller than standard values because of a slight flattening of the ring. In (3) this flattening is marginally less marked whereas in (4) the ring A conformation is close to a ‘normal’ chair. The ¹H n.m.r. (solution) data are compatible with these observations.