N-tert-Butyl-5α-androstane-17β-carboxamide

The title compound, C24H41NO, is a new derivative of the anti-HIV steroid 17β-(N-tert-butylaminocarbonyl)androst-4-en-3-one. There are four rings in the structure and these are trans-fused. The three six-membered rings exhibit chair conformations, while the five-membered ring adopts an envelope conformation.

The title compound, C 24 H 41 NO, is a new derivative of the anti-HIV steroid 17-(N-tert-butylaminocarbonyl)androst-4-en-3one. There are four rings in the structure and these are transfused. The three six-membered rings exhibit chair conformations, while the five-membered ring adopts an envelope conformation.
The molecular structure of (I), Fig.1, shows the A/B, B/C and C/D ring junctions to be all trans. The cyclohexane rings adopt chair conformations, and the cyclopentane ring adopts an envelope conformation. Based on the known configurations of the C10, C13-methyl groups, see Experimental, 5-H is assigned an α-configuration. The 17-N-tert-butylcarboxamide group is in a β-configuration. The stereogenic sites of (I) exhibit the following chirality: C5 = R, C8 = R, C9 = S, C10 = S, C13 = S, C14 = S and C17 = S.

Experimental
Compound (I) was prepared from the corresponding 4-ene-3-ol by catalytic hydrogenation with 5% palladium-on-charcoal in EtOH for 1 day. After filtration and removal of the solvent, the residue was crystallized from acetone to give colourless crystals.
The starting material, 17β-(N-tert-butylcarboxamide)-androst-4-ene-3-ol, was obtained from the reduction of 17β-(Ntert-butylcarboxamide)-androst-4-ene-3-one with NaBH 4 . It is an intermediate in the synthesis of Finasteride and derived initially from diosgenin, for which the absolute configurations of all chiral centers of the steroid skeleton have been determined (Fieser & Fieser, 1959;Marker et al., 1940). Recently, the absolute configurations of the chiral centres were confirmed by the X-ray crystal structure determination of a 3-Br substituted steroid substrate synthesized from diosgenin (Castro-Méndez et al., 2002). The hydrogenation of 4-en-3-one moiety did not cause inversion of the configurations at C8, C9, C10, C13 and C14 (Throop & Tokes, 1967;House, 1972). Thus, by comparing the orientation of 5-H to that of methyl groups at C10 and C13, the absolute configuration of (I) could be determined.

Refinement
All H atoms were placed in the idealized positions with N-H = 0.86 Å, methine C-H = 0.98 Å, methylene C-H = 0.97 Å and methyl C-H = 0.96 Å, and treated as riding with U iso (H) = 1.2 U eq (N-H, CH 2 and CH) and 1.5U eq (CH 3 ). In the absence of significant anomalous scattering effects, 1971 Friedel pairs were averaged in the final refinement. Fig. 1. The molecular structure of (I), with atom labels and 30% probability displacement ellipsoids for non-H atoms.