Structure of methyl (4'S,16S)-3β-acetoxy-17-oxospiro[5-androstene-16,3'-(4,5-dihydropyrazole)]-4'-carboxylate

Abstract

C25H34N2Os, M r--442.54, monoclinic, P2~, a = 6 . 4 1 4 ( 1 ) , b=9 .729 (2 ) , c = 1 9 . 1 9 2 ( 3 ) A , f l= 91.09 (1) °, V = 1197.4 (4) A 3, Z = 2, Dx= 1.227 (1) Mg m -a, Mo Ka, 2 = 0.71069 fi,, g = 0.796 mm -~, F(000)=476, T = 293 K, final R = 0-035 for 1150 independent reflections. The configurations at chiral centers 4' and 16 (3')were found to be both S, assuming the S configuration at 13. The bowing of ring A relative to the remainder of the steroid nucleus is 17.03 (2) ° . The rings have the following conformations: A chair; B half chair; C slightly deformed chair; D slightly distorted envelope. Introduetion. In the course of investigations on steroidal lactones having cytostatic properties (Koc6r, Kabat, Wicha & Peczyfiska-Czoch, 1983), the title compound was synthesized by treatment of (E)-3fl,17fl-dihydroxy-5-androsten16-ylidenacetic acid with diazomethane followed by acetylation of the hydroxy group at C(3). The sequence of atoms in the dihydropyrazole ring thus formed was elucidated from the ~H NMR data. However, the configuration at the new chiral centers 16 (3') and 4' could not be established and therefore X-ray structural analysis of the title compound was necessary. Experimental. Crystal (0.25 x 0.36 x 0.67 mm) from methanol. CAD-4D diffractometer (Enraf-Nonius), MoKu radiation. Cell constants refined from 25 reflections (13.3 2tr I. Equivalent reflections averaged automatically by SDP system, Rln t not estimated. Lorentz and polarization, no absorption correction. Space group P2 r Structure solved by direct methods (MUL TAN80; Main et al., 1980). Mean atomic scattering factors taken from International Tables for X-ray Crystallography (1974). Non-H-atom parameters refined anisotropically for one enantio0108-2701/85/111630-03501.50 morph by a full-matrix procedure (XRAY70 system; Stewart, Kundell & Baldwin, 1970) for 1150 observed F's. H-atom positions found from Ap maps, added and refined (damping 0.3) in the last refinement step (B = Beq of adjacent atom + 1A 2, invariant). Final R = 0.035 (wR = 0.033, unit weights) at A/tr < O. 1. Max. and min. electron densities on final Ap map 0.3 and 0 . 2 e A -3, respectively. Programs used for calculations of secondary results were RING (Phrkfinyi, 1979) and PLALIN (Nardelli, Musatti, Domiano & Andreetti, 1978). Computations done on PDP8/I 1, Cyber-73 and MERA-400 computers. Discussion. Table 1 gives the fractional coordinates of non-hydrogen atoms.* The bond lengths and valence angles are given in Table 2. Fig. 1 presents a projection of the steroid molecule oriented at optimal viewing. In the description of the molecular structure of the steroid under investigation the conventions applied by Duax & Norton (1975) are followed. Fig. 2 shows a view of the steroid parallel to the least-squares plane through the atoms C(1) to C(17) (rings B, C and D). The bowing angle of ring A with respect to this plane (A/B-C-D) is 17.03 (2) °. The mean values of C C bond lengths and C C C angles in saturated rings A and C are 1.536 (8)/k and 111.0 (4) °, respectively. For the unsaturated ring B, the mean value for single C C bond lengths is 1.533 (7)/k with the mean angle of 111.6 (4) °. All bond lengths and angles in rings A, B and C are in agreement (within twice the e.s.d.) with the mean values for 13 AS-steroid structures quoted by Duax & Norton (1975) with two exceptions: bonds C(9)-C(11) and C(13)C(14) (ring C) deviate by more than 0.03 A, being longer and shorter, respectively. * Lists of structure factors, hydrogen-atom positions, anisotropic thermal parameters and torsion angles have been deposited with the British Library Lending Division as Supplementary Publication No. SUP 42348 (15 pp.). Copies may be obtained through The Executive Secretary, International Union of Crystallography, 5 Abbey Square, Chester CH 1 2HU, England. © 1985 International Union of Crystallography GLUZIlqSKI, KRAJEWSKI, URBAlqCZYK-LIPKOWSKA, ARGAY A N D P/~RK/~NYI 1631 Ring A of the steroid reported here may be characterized by a chair conformation ~°C 3 (4C 0. The asymmetry parameters are: AC] = 5.6 (6) ° and AC~z ,2 = 3.0 (6) °. Since the deviations of C(3) and C(10) from the least-squares plane of A [defined by C(1), C(2), C(4) and C(5)] are nearly symmetrical [+0.656 (6)/k], an almost ideal chair conformation with mean torsion angle of 54.6 (6) ° may be assumed. The O-acetyl substituent at C(3) is found in the equatorial position. The unsaturated ring B has the half-chair conformation 8H 9. The asymmetry parameter dCSz,6= 0.8 (7) °. The deviations of C(8) and C(9) from the Table 1. Fractional atomic coordinates (× 10 4) with e.s.d. 's in parentheses Origin along b specified by keeping y of O(1) fixed.