Experimental. Crystal data. C 23 H 34 O 4 M r = Orthorhombic, P a = (6) Å b = (4) Å c = 18.

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1 organic compounds Acta Crystallographica Section E Structure Reports Online ISSN b-Acetoxy-19-hydroxy-D 5 -pregnen-20- one Aike Meier zu Greffen, Darius P. Kranz, Jörg-M. Neudörfl and Hans-Günther Schmalz* Department für Chemie der Universität zu Köln, Greinstrasse 4, Köln, Germany Correspondence schmalz@uni-koeln.de Received 9 July 2012; accepted 24 January 2013 Key indicators: single-crystal X-ray study; T = 100 K; mean (C C) = Å; R factor = 0.037; wr factor = 0.079; data-to-parameter ratio = 9.9. Experimental Crystal data C 23 H 34 O 4 M r = Orthorhombic, P a = (6) Å b = (4) Å c = (10) Å Data collection Nonius KappaCCD diffractometer 9889 measured reflections 2457 independent reflections Refinement R[F 2 >2(F 2 )] = wr(f 2 ) = S = reflections Table 1 Hydrogen-bond geometry (Å, ). V = (18) Å 3 Z =4 Mo K radiation = 0.08 mm 1 T = 100 K mm 1943 reflections with I > 2(I) R int = parameters H-atom parameters constrained max = 0.23 e Å 3 min = 0.23 e Å 3 In the title compound, C 23 H 34 O 4, the C/D and D/E rings are trans fused and the A/B ring possesses an anti fusion. The two cyclohexane rings adopt a chair conformation while the cyclohexene ring exhibits a half-chair conformation. The cyclopentane ring displays an envelope conformation with the C atom bearing the methyl group as the flap. In the crystal, the molecules are linked by O HO hydrogen bonds, forming chains along the b axis. Related literature For an overview of steroids as biologically important molecules, see: Fieser & Fieser (1961); Hanson (2010). For examples of steroids possessing a rearranged A/B-ring system, see: Du et al. (2008); Aoki et al. (2006); Flyer et al. (2010). For related C-19-functionalized steroids, see: El Sheikh et al. (2007); Shenvi et al. (2008). For an overview of remote functionalization, see: Reese (2001); Heusler & Kalvoda (1964). For the first synthesis of the title compound, see: Halpern et al. (1963). For examples of the title compound as an intermediate for rearranged A/B-ring systems, see: Knox et al. (1965); Kranz et al. (2011). For a description of the Cambridge Structural Database, see: Allen (2002). D HA D H HA DA D HA O3 H3AO2 i (19) 147 Symmetry code: (i) x; y 1 2 ; z þ 3 2. Data collection: COLLECT (Hooft 1998); cell refinement: DENZO (Otwinowski & Minor, 1997); data reduction: DENZO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SCHAKAL99 (Keller, 1999); software used to prepare material for publication: PLATON (Spek, 2009). Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: LR2076). References Allen, F. H. (2002). Acta Cryst. B58, Aoki, S., Watanabe, Y., Sanagawa, M., Setiawan, A., Kotoku, N. & Kobayashi, M. (2006). J. Am. Chem. Soc. 128, Du, L., Zhu, T., Fang, Y., Gu, Q. & Zhu, W. (2008). J. Nat. Prod. 71, El Sheikh, S., Meier zu Greffen, A., Lex, J., Neudörfl, J. M. & Schmalz, H. G. (2007). Synlett, pp Fieser & Fieser (1961). Please supply full reference. Flyer, A. N., Si, C. & Myers, A. G. (2010). Nat. Chem. 2, Halpern, O., Villotti, W. & Bowers, A. (1963). Chem. Ind. (London), 116, Hanson, J. R. (2010). Nat. Prod. Rep. 27, Heusler, K. & Kalvoda, J. (1964). Angew. Chem. Int. Ed. Engl. 3, Hooft, R. W. W. (1998). COLLECT. Nonius BV, Delft, The Netherlands. Keller, E. (1999). SCHAKAL99. University of Freiburg, Germany. Knox, L. H., Velarde, E., Berger, S., Delfin, I. & Grezemkovsky, R. (1965). J. Org. Chem. 30, Kranz, D. P., Meier zu Greffen, A., El Sheikh, S., Neudörfl, J. M. & Schmalz, H. G. (2011). Eur. J. Org. Chem. pp Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp New York: Academic Press. Reese, P. B. (2001). Steroids, 66, Sheldrick, G. M. (2008). Acta Cryst. A64, Shenvi, R. A., Guerrero, C. A., Shi, J., Li, C. C. & Baran, P. S. (2008). J. Am. Chem. Soc. 130, Spek, A. L. (2009). Acta Cryst. D65, doi: /s Meier zu Greffen et al. o313

2 [doi: /s ] 3β-Acetoxy-19-hydroxy-Δ 5 -pregnen-20-one Aike Meier zu Greffen, Darius P. Kranz, Jörg-M. Neudörfl and Hans-Günther Schmalz S1. Comment The structural diversity of steroids as well as their unsurpassed biological potential qualify them as challenging targets for chemical synthesis and as lead structures for pharmacological research (Fieser & Fieser, 1961; Hanson, 2010). In recent years, some unusual steroids displaying a rearranged A/B-ring system with promising biological properties have been reported (Du et al., 2008; Aoki et al., 2006; Flyer et al., 2010). Important intermediates for the synthesis of such rearranged derivatives are C-19 functionalized steroids (El Sheikh et al., 2007; Shenvi et al., 2008). The functionalization of the unactivated angular C-10 methyl group is achieved by remote functionalization (Heusler et al., 1964; Reese, 2001). During our synthesis of diverse B-homo-steroids the C-19-hydroxy-steroid (I) was isolated as an intermediate (Kranz et al., 2011). The C/D and D/E rings in C 23 H 34 O 4 are trans fused and the A/B ring possesses an anti fusion. The A ring and the C ring adopt a chair conformation, while the other six membered B ring displays a half chair conformation (Fig. 1). In the five membered ring, the atoms show an envelope conformation and C14/C15/C16/C17 are nearly coplanar while the C13 deviates from the plane by (2) Å. The C(5) C(10) C(19) O(3) torsion angle is (16) and the torsion angles C(4) C(5) C(10) C(1) with (2), C(1) C(10) C(9) C(11) with 68.3 (2) and C(8) C(14) C(13) C(12) with (2) are within the average range (Allen, 2002). The molecules are linked by O H O hydrogen bonds between the C19 hydroxy group of one steroid to the ester carbonyl oxygen of the next steroid, forming chain networks along the b axis. These chain networks generate layer structures parallel to the c axis (Fig. 2). S2. Experimental The title compound C 23 H 34 O 4 was prepared in 3 steps starting from commercial pregnenolone-acetate (Kranz et al., 2011). S3. Refinement All hydrogen atoms were placed in geometrically idealized positions and refined with using riding model with C H = 0.95 Å and U iso (H) = 1.2U eq (C) for CH, C H = 0.99 Å and U iso (H) = 1.2U eq (C) for CH 2, C H = 0.98 Å and U iso (H) = 1.5U eq (C) for CH 3 and OH. sup-1

3 Figure 1 Molecular structure of the title compound. Displacement ellipsoids are drawn at the 50% probability level. sup-2

4 Figure 2 Plot of the unit cell; the b axis is perpendicular to the plane of the paper and the a and c axes are horizontal and vertical, respectively. 3β-Acetoxy-19-hydroxy-Δ 5 -pregnen-20-one Crystal data C 23 H 34 O 4 M r = Orthorhombic, P Hall symbol: P 2ac 2ab a = (6) Å b = (4) Å c = (10) Å V = (18) Å 3 Z = 4 F(000) = 816 D x = Mg m 3 Mo Kα radiation, λ = Å Cell parameters from 9889 reflections θ = µ = 0.08 mm 1 T = 100 K Prism, colourless mm sup-3

5 Data collection Nonius KappaCCD diffractometer Radiation source: fine-focus sealed tube Graphite monochromator Phi/ω Scans scans 9889 measured reflections 2457 independent reflections Refinement Refinement on F 2 Least-squares matrix: full R[F 2 > 2σ(F 2 )] = wr(f 2 ) = S = reflections 247 parameters 0 restraints Primary atom site location: structure-invariant direct methods 1943 reflections with I > 2σ(I) R int = θ max = 27.0, θ min = 2.0 h = 6 11 k = l = Secondary atom site location: difference Fourier map Hydrogen site location: inferred from neighbouring sites H-atom parameters constrained w = 1/[σ 2 (F o2 ) + (0.0425P) 2 ] where P = (F o 2 + 2F c2 )/3 (Δ/σ) max < Δρ max = 0.23 e Å 3 Δρ min = 0.23 e Å 3 Special details Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wr and goodness of fit S are based on F 2, conventional R-factors R are based on F, with F set to zero for negative F 2. The threshold expression of F 2 > σ(f 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 ) x y z U iso */U eq O (17) (10) (8) (3) O (19) (11) (8) (4) O (19) (10) (8) (4) H3A * O (2) (11) (9) (5) C (2) (15) (11) (5) H1A * H1B * C (3) (14) (11) (5) H2A * H2B * C (3) (14) (11) (5) H * C (3) (15) (11) (5) H4A * H4B * C (2) (15) (11) (5) sup-4

6 C (3) (15) (11) (5) H * C (3) (14) (11) (5) H7A * H7B * C (3) (14) (11) (5) H * C (2) (14) (11) (5) H * C (2) (14) (11) (5) C (3) (14) (11) (5) H20A * H20B * C (3) (15) (11) (5) H12A * H12B * C (2) (15) (11) (5) C (3) (14) (11) (5) H * C (3) (15) (11) (5) H15A * H15B * C (3) (14) (11) (5) H16A * H16B * C (3) (14) (11) (5) H * C (3) (16) (12) (5) H18A * H18B * H18C * C (2) (15) (12) (5) H19A * H19B * C (3) (16) (11) (5) C (3) (17) (11) (6) H21A * H21B * H21C * C (3) (17) (12) (5) C (3) (18) (12) (6) H23A * H23B * H23C * sup-5

7 Atomic displacement parameters (Å 2 ) U 11 U 22 U 33 U 12 U 13 U 23 O (9) (7) (8) (7) (7) (6) O (10) (8) (9) (7) (8) (7) O (10) (7) (9) (7) (8) (6) O (13) (8) (10) (9) (9) (6) C (11) (10) (11) (9) (9) (8) C (12) (10) (12) (9) (10) (8) C (12) (10) (11) (10) (10) (8) C (12) (10) (11) (9) (10) (9) C (11) (11) (12) (9) (9) (8) C (12) (10) (11) (9) (10) (8) C (12) (10) (11) (9) (10) (8) C (11) (10) (12) (9) (10) (8) C (12) (10) (11) (9) (9) (8) C (11) (10) (11) (9) (9) (8) C (13) (10) (12) (9) (9) (8) C (12) (10) (11) (9) (10) (9) C (11) (10) (11) (9) (9) (8) C (11) (10) (11) (9) (9) (8) C (12) (10) (12) (9) (10) (8) C (14) (10) (12) (10) (11) (8) C (12) (10) (11) (9) (10) (8) C (13) (11) (13) (10) (10) (10) C (12) (11) (12) (9) (10) (9) C (13) (11) (12) (10) (11) (9) C (17) (12) (13) (11) (12) (9) C (12) (12) (12) (10) (11) (9) C (17) (12) (13) (12) (12) (10) Geometric parameters (Å, º) O1 C (2) C11 C (3) O1 C (2) C11 H20A O2 C (2) C11 H20B O3 C (2) C12 C (3) O3 H3A C12 H12A O4 C (2) C12 H12B C1 C (3) C13 C (3) C1 C (3) C13 C (3) C1 H1A C13 C (3) C1 H1B C14 C (3) C2 C (3) C14 H C2 H2A C15 C (3) C2 H2B C15 H15A C3 C (3) C15 H15B C3 H C16 C (3) sup-6

8 C4 C (3) C16 H16A C4 H4A C16 H16B C4 H4B C17 C (3) C5 C (3) C17 H C5 C (3) C18 H18A C6 C (3) C18 H18B C6 H C18 H18C C7 C (2) C19 H19A C7 H7A C19 H19B C7 H7B C20 C (3) C8 C (3) C21 H21A C8 C (3) C21 H21B C8 H C21 H21C C9 C (3) C22 C (3) C9 C (3) C23 H23A C9 H C23 H23B C10 C (3) C23 H23C C22 O1 C (15) C11 C12 H12A C19 O3 H3A C13 C12 H12B C2 C1 C (17) C11 C12 H12B C2 C1 H1A H12A C12 H12B C10 C1 H1A C18 C13 C (16) C2 C1 H1B C18 C13 C (17) C10 C1 H1B C12 C13 C (16) H1A C1 H1B C18 C13 C (18) C3 C2 C (15) C12 C13 C (17) C3 C2 H2A C14 C13 C (14) C1 C2 H2A C8 C14 C (17) C3 C2 H2B C8 C14 C (15) C1 C2 H2B C15 C14 C (16) H2A C2 H2B C8 C14 H O1 C3 C (14) C15 C14 H O1 C3 C (16) C13 C14 H C2 C3 C (17) C14 C15 C (16) O1 C3 H C14 C15 H15A C2 C3 H C16 C15 H15A C4 C3 H C14 C15 H15B C5 C4 C (17) C16 C15 H15B C5 C4 H4A H15A C15 H15B C3 C4 H4A C15 C16 C (15) C5 C4 H4B C15 C16 H16A C3 C4 H4B C17 C16 H16A H4A C4 H4B C15 C16 H16B C6 C5 C (17) C17 C16 H16B C6 C5 C (18) H16A C16 H16B C4 C5 C (16) C20 C17 C (16) C5 C6 C (18) C20 C17 C (17) sup-7

9 C5 C6 H C13 C17 C (16) C7 C6 H C20 C17 H C6 C7 C (16) C13 C17 H C6 C7 H7A C16 C17 H C8 C7 H7A C13 C18 H18A C6 C7 H7B C13 C18 H18B C8 C7 H7B H18A C18 H18B H7A C7 H7B C13 C18 H18C C14 C8 C (15) H18A C18 H18C C14 C8 C (17) H18B C18 H18C C7 C8 C (16) O3 C19 C (17) C14 C8 H O3 C19 H19A C7 C8 H C10 C19 H19A C9 C8 H O3 C19 H19B C8 C9 C (16) C10 C19 H19B C8 C9 C (16) H19A C19 H19B C11 C9 C (15) O4 C20 C (19) C8 C9 H O4 C20 C (19) C11 C9 H C17 C20 C (17) C10 C9 H C20 C21 H21A C5 C10 C (16) C20 C21 H21B C5 C10 C (16) H21A C21 H21B C1 C10 C (15) C20 C21 H21C C5 C10 C (15) H21A C21 H21C C1 C10 C (17) H21B C21 H21C C19 C10 C (17) O2 C22 O (2) C12 C11 C (15) O2 C22 C (2) C12 C11 H20A O1 C22 C (18) C9 C11 H20A C22 C23 H23A C12 C11 H20B C22 C23 H23B C9 C11 H20B H23A C23 H23B H20A C11 H20B C22 C23 H23C C13 C12 C (17) H23A C23 H23C C13 C12 H12A H23B C23 H23C C10 C1 C2 C (2) C9 C11 C12 C (2) C22 O1 C3 C (17) C11 C12 C13 C (2) C22 O1 C3 C (2) C11 C12 C13 C (2) C1 C2 C3 O (16) C11 C12 C13 C (16) C1 C2 C3 C (2) C7 C8 C14 C (2) O1 C3 C4 C (15) C9 C8 C14 C (17) C2 C3 C4 C (2) C7 C8 C14 C (17) C3 C4 C5 C (2) C9 C8 C14 C (2) C3 C4 C5 C (2) C18 C13 C14 C (2) C4 C5 C6 C (2) C12 C13 C14 C (2) C10 C5 C6 C7 2.3 (4) C17 C13 C14 C (18) C5 C6 C7 C (3) C18 C13 C14 C (2) C6 C7 C8 C (18) C12 C13 C14 C (17) sup-8

10 C6 C7 C8 C (3) C17 C13 C14 C (2) C14 C8 C9 C (2) C8 C14 C15 C (18) C7 C8 C9 C (18) C13 C14 C15 C (2) C14 C8 C9 C (16) C14 C15 C16 C (2) C7 C8 C9 C (2) C18 C13 C17 C (2) C6 C5 C10 C (2) C12 C13 C17 C (2) C4 C5 C10 C (2) C14 C13 C17 C (19) C6 C5 C10 C (2) C18 C13 C17 C (19) C4 C5 C10 C (2) C12 C13 C17 C (17) C6 C5 C10 C (3) C14 C13 C17 C (19) C4 C5 C10 C (18) C15 C16 C17 C (18) C2 C1 C10 C (2) C15 C16 C17 C (2) C2 C1 C10 C (2) C5 C10 C19 O (16) C2 C1 C10 C (16) C1 C10 C19 O (2) C8 C9 C10 C (2) C9 C10 C19 O (2) C11 C9 C10 C (17) C13 C17 C20 O (3) C8 C9 C10 C (15) C16 C17 C20 O (2) C11 C9 C10 C (2) C13 C17 C20 C (2) C8 C9 C10 C (19) C16 C17 C20 C (3) C11 C9 C10 C (2) C3 O1 C22 O2 5.2 (3) C8 C9 C11 C (2) C3 O1 C22 C (17) C10 C9 C11 C (18) Hydrogen-bond geometry (Å, º) D H A D H H A D A D H A O3 H3A O2 i (19) 147 Symmetry code: (i) x, y 1/2, z+3/2. sup-9