Experimental. Crystal data. C 26 H 36 O 7 M r = Orthorhombic, P a = (2) Å b = (3) Å c = (3) Å.

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1 organic compounds Acta Crystallographica Section E Structure Reports Online ISSN ,3,7-Trideacetylkhivorin Experimental Crystal data C 26 H 36 O 7 M r = Orthorhombic, P a = (2) Å b = (3) Å c = (3) Å V = (8) Å 3 Z =4 Mo K radiation = 0.10 mm 1 T = 153 (2) K mm Huaping Zhang, a * Don VanDerveer, b Xi Wang, c Feng Chen a and Michael J. Wargovich d * a Department of Food Science and Human Nutrition, Clemson University, Clemson, SC 29634, USA, b Department of Chemistry, Clemson University, Clemson, SC 29634, USA, c Department of Genetics and Biochemistry, Clemson University, Clemson, SC 29634, USA, and d Department of Cell and Molecular Pharmacology, Hollings Cancer Center, Charleston, SC 29425, USA Correspondence huapinz@clemson.edu, wargovic@musc.edu Received 19 October 2007; accepted 31 October 2007 Key indicators: single-crystal X-ray study; T = 153 K; mean (C C) = Å; disorder in main residue; R factor = 0.037; wr factor = 0.094; data-to-parameter ratio = 7.3. Data collection Riguka Mercury CCD diffractometer Absorption correction: multi-scan (REQAB; Rigaku/MSC, 2006) T min = 0.961, T max = Refinement R[F 2 >2(F 2 )] = wr(f 2 ) = S = reflections Table 1 Hydrogen-bond geometry (Å, ) measured reflections 2222 independent reflections 2133 reflections with I > 2(I) R int = parameters H-atom parameters constrained max = 0.19 e Å 3 min = 0.16 e Å 3 The title d-seco limonoid, named 1,3,7-trideacetylkhivorin (systematic name: 14,15:21,23-diepoxy-1,3,7-trihydroxy- 4,4,8-trimethyl-d-homo-24-nor-17-oxochola-20,22-diene-16- one), C 26 H 36 O 7, was isolated from the stem bark of African mahogany Khaya senegalensis (Meliaceae). The four fused six-membered rings adopt chair, chair, boat and half-chair conformations. The five-membered furan ring is disordered by a180 rotation about the bond linking it to the pyran ring. The crystal structure is stabilized by strong classical O HO hydrogen-bond interactions to form a network. Related literature For general background, see: Androulakis et al. (2006). Details of the chemical modification from the original chemical khivorin are given by Bevan et al. (1963). Isolation from Khaya ivorensis and the antifungal activity of the title compound are described by Abdelgaleil et al. (2005). Details of the similar d-seco limonoids gedunin and 3,7-dideacetyl khivorin and their in vitro antitumor activities are given by: Toscano et al. (1996); Uddin et al. (2007); Zhang, Wang et al. (2007); Zhang, VanDerveer et al. (2007). D HA D H HA DA D HA O1 H1AO7 i (3) 155 O4 H4O3 ii (2) 171 Symmetry codes: (i) x þ 1; y; z; (ii) x 1 2 ; y þ 3 2 ; z þ 1. Data collection: CrystalClear (Rigaku/MSC, 2006); cell refinement: CrystalClear; data reduction: SHELXTL (Bruker, 2000); program(s) used to solve structure: SHELXTL; program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: PLATON (Spek, 2003). The authors thank the National Institutes of Health (Bethedsa, Maryland, USA) and South Carolina Nutrition Research Consortium (Columbia, South Carolina, USA) for financial research support (grant No. NIH R21CA107138). Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: PK2059). References Abdelgaleil, S. A. M., Hashinaga, F. & Nakatani, M. (2005). Pest Manag. Sci. 61, Androulakis, X. M., Muga, S. J., Chen, F., Koita, Y., Toure, B. & Wargovich, M. J. (2006). Anticancer Res. 26, Bevan, C. W. L., Powell, J. W. & Taylor, D. A. H. (1963). J. Chem. Soc. pp Bruker (2000). SHELXTL. Version Bruker AXS Inc., Madison, Wisconsin, USA. Rigaku/MSC (2006). REQAB and CrystalClear. Rigaku/MSC, The Woodlands, Texas, USA. Spek, A. L. (2003). J. Appl. Cryst. 36, Toscano, R. A., Mata, R., Calderon, J. & Segura, R. (1996). J. Chem. Crystallogr. 26, Uddin, S. J., Nahar, L., Shilpi, J. A., Shoeb, M., Borkowski, T., Gibbons, S., Middleton, M., Byres, M. & Sarler. S. D. (2007). Phytother. Res. 21, Zhang, H., VanDerveer, D., Chen, F., Wang, X. & Wargovich, M. J. (2007). Acta Cryst. E63, o4162. Zhang, H. P., Wang, X., Chen, F., Androulakis, X. M. & Wargovich, M. J. (2007). Phytother. Res. 21, Acta Cryst. (2007). E63, o4599 doi: /s # 2007 International Union of Crystallography o4599

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3 Acta Cryst. (2007). E63, o4599 [ doi: /s ] 1,3,7-Trideacetylkhivorin H. Zhang, D. VanDerveer, X. Wang, F. Chen and M. J. Wargovich Comment 1,3,7-trideacetylkhivorin, a D-seco limonoid, has been isolated by trichloromethane extract of the stem bark of African mahogany Khaya senegalensis belonging to the Meliaceae family. Our previous study showed the stem bark extract displayed anti-proliferative effects on HT-29, HCT-15, and HCA-7 cells (Androulakis et al., 2006). In addition, a major D-seco tetranortriterpenoid, 3,7-dideacetylkhivorin, isolated from the same extract, exhibited growth inhibitory activities against MCF-7, SiHa, and Caco-2 cells with IC 50 values in the range of µg/ml (Zhang, Wang et al., 2007). In our furthur investigations of the anti-tumor constituents of this African mahogany, another minor tetranortriterpenoid, the title compound, named 14,15β:21,23-diepoxy-1α,3α,7α-trihydroxy-4,4,8-trimethyl-D-homo-24-nor-17-oxochola-20,22-diene-16-one, was purified from the plant extract for the first time. It was reported as a synthetic derivative by basic hydrolysis of khivorin (Bevan et al., 1963) and isolated as a natural product from Khaya ivorensis recently (Abdelgaleil et al., 2005). In our preliminary in vitro anti-cancer bioassay, the title compound showed similar bioactivies to those of two other D-seco limonoids, 3,7-dideacetyl khivorin and gedunin (Uddin et al., 2007). Herein, the X-ray crystal analysis of the title compound was undertaken to establish its structure and relative stereochemistry, which will benefit further work on structure activity relationships of anti-tumor bioactivities of D-seco limonoids. Fig. 1 is a thermal ellipsoid plot with atomic labeling of the title compound. The structure contains four six-membered rings A D, one three-membered ring E, and one furan ring F linked to ring D through a C C bond in an equatorial position, known as a D-seco limonoid. The ring junctions A/B, B/C and C/D are all trans, while D/E is cis. The six-membered rings A D adopt chair, chair, twist boat and half-chair conformations, while rings E and F are essentially planar. The fivemembered furan ring is disordered by a 180 rotation about the C17 C20 bond. All the bond lengths and angles are close to their expected values and the data are comparable with the corresponding values in those of gedunin (Toscano et al., 1996) and 3,7-dideacetylkhivorin (Zhang, VanDerveer et al., 2007). The title compound exhibits strong classical intermolecular O1 H1A O7, O4 H4 O3 hydrogen bond interactions (Table 1), which link the molecules together to form a stablized network. Experimental Air-dried and powdered barks of Khaya senegalensis (3.8 kg) were extracted with 95% alcohol at room temperature. The EtOH extract was dried under reduced pressure to yield a crude extract (310 g). The crude extract was suspended in 1000 ml water and partitioned with 2000 ml trichloromethane to yield a CHCl 3 fraction (45 g). This part was separated by chromatography on silica gel, eluting with mixtures of hexane and acetone (increasing polarity). The purified powder (30 mg) of the title compound was obtained from the hexane:acetone (3:1) fractions. Transparent rod shaped crystals of the title compound were obtained by recrystallization from 5% CHCl 3 in MeOH by slow evaporation at room temperature. sup-1

4 Refinement Since the most electron-rich atom is oxygen it was not possible to determine the absolute configuation using MoKα radiation. Therefore, Friedel pairs were merged before the final refinement because of the absence of significant anomalous scattering. All H atoms were placed geometrically and allowed to ride on the corresponding non-h atom with C H = 0.96 Å, O H = 0.83 Å, and U iso (H) = 1.5U eq of the attached atom for methyl and hydroxyl H atoms and 1.2U eq (C) for other H atoms. Figures Fig. 1. view of the title compound, showing 50% probability displacement and the atom-numbering scheme 14,15β:21,23-diepoxy-1α,3α,7α-trihydroxy-4,4,8-trimethyl-D-homo-24- nor-17-oxochola-20,22-diene-16-one Crystal data C 26 H 36 O 7 F 000 = 992 M r = Orthorhombic, P Hall symbol: P 2ac 2ab D x = Mg m 3 Mo Kα radiation λ = Å a = (2) Å θ = º b = (3) Å c = (3) Å V = (8) Å 3 Z = 4 Cell parameters from 8564 reflections µ = 0.10 mm 1 T = 153 (2) K Block, colourless mm Data collection Riguka Mercury CCD diffractometer Radiation source: sealed tube Monochromator: graphite R int = T = 153(2) K θ max = 25.1º ω scans θ min = 3.3º 2222 independent reflections 2133 reflections with I > 2σ(I) sup-2

5 Absorption correction: multi-scan (Rigaku/MSC, 2006) T min = 0.961, T max = h = 8 11 k = measured reflections l = Refinement Refinement on F 2 H-atom parameters constrained Least-squares matrix: full w = 1/[σ 2 (F o 2 ) + (0.063P) P] where P = (F o 2 + 2F c 2 )/3 R[F 2 > 2σ(F 2 )] = (Δ/σ) max < wr(f 2 ) = S = 1.07 Δρ max = 0.19 e Å 3 Δρ min = 0.16 e Å reflections Extinction correction: none 306 parameters Primary atom site location: structure-invariant direct methods Secondary atom site location: difference Fourier map Hydrogen site location: inferred from neighbouring sites 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 > 2σ(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 Occ. (<1) O (19) (11) (11) (4) H1A * O (2) (12) (10) (4) H3A * O (19) (12) (10) (4) H * O (18) (11) (11) (4) O (17) (12) (11) (4) O (19) (13) (13) (4) O (2) (16) (13) (5) 0.50 C23' (2) (16) (13) (5) 0.50 H23' * 0.50 sup-3

6 C (3) (16) (15) (5) H * C (3) (19) (15) (5) H2A * H2B * C (3) (17) (15) (5) H * C (3) (16) (15) (5) C (2) (15) (14) (5) H * C (3) (16) (15) (5) H6A * H6B * C (2) (16) (15) (5) H * C (2) (15) (14) (5) C (2) (16) (14) (5) H * C (2) (16) (14) (5) C (3) (18) (15) (5) H11A * H11B * C (3) (17) (14) (5) H12A * H12B * C (2) (15) (14) (5) C (2) (16) (14) (5) C (2) (17) (15) (5) H * C (3) (17) (16) (5) C (2) (16) (15) (5) H * C (3) (16) (15) (5) H18A * H18B * H18C * C (3) (16) (15) (5) H19A * H19B * H19C * C (3) (16) (15) (5) C (3) (18) (16) (6) H * C (3) (18) (17) (6) H * C (3) (17) (17) (6) 0.50 H * 0.50 O8' (3) (17) (17) (6) 0.50 C (3) (17) (17) (6) sup-4

7 H28A * H28B * H28C * C (3) (18) (14) (5) H29A * H29B * H29C * C (3) (16) (16) (5) H30A * H30B * H30C * Atomic displacement parameters (Å 2 ) U 11 U 22 U 33 U 12 U 13 U 23 O (9) (8) (9) (7) (8) (7) O (11) (9) (8) (9) (8) (8) O (9) (8) (8) (8) (8) (7) O (9) (8) (9) (7) (8) (7) O (9) (9) (9) (7) (8) (7) O (9) (10) (11) (8) (9) (9) O (11) (12) (11) (10) (9) (10) C23' (11) (12) (11) (10) (9) (10) C (12) (12) (11) (10) (10) (10) C (12) (13) (13) (11) (10) (10) C (12) (12) (11) (11) (10) (10) C (12) (11) (11) (10) (10) (9) C (11) (10) (10) (9) (9) (9) C (12) (11) (11) (10) (10) (10) C (11) (11) (11) (10) (10) (9) C (11) (10) (11) (10) (9) (9) C (12) (10) (11) (10) (9) (9) C (12) (11) (11) (10) (9) (9) C (12) (12) (12) (11) (10) (10) C (12) (12) (11) (10) (10) (9) C (12) (11) (11) (9) (10) (9) C (11) (11) (11) (10) (9) (9) C (12) (12) (11) (10) (10) (10) C (12) (12) (12) (10) (11) (10) C (12) (11) (11) (10) (10) (10) C (13) (11) (11) (10) (10) (9) C (13) (12) (11) (11) (11) (10) C (12) (12) (12) (10) (10) (10) C (14) (13) (12) (11) (11) (10) C (14) (12) (13) (11) (11) (11) C (14) (13) (14) (11) (13) (12) O8' (14) (13) (14) (11) (13) (12) C (13) (13) (13) (11) (11) (11) sup-5

8 C (13) (12) (11) (11) (10) (10) C (14) (11) (12) (11) (11) (10) Geometric parameters (Å, ) O1 C (3) C10 C (3) O1 H1A C11 C (3) O3 C (3) C11 H11A O3 H3A C11 H11B O4 C (3) C12 C (3) O4 H C12 H12A O5 C (3) C12 H12B O5 C (3) C13 C (3) O6 C (3) C13 C (3) O6 C (3) C13 C (3) O7 C (3) C14 C (3) O8 C (4) C15 C (3) C1 C (3) C15 H C1 C (3) C17 C (3) C1 H C17 H C2 C (3) C18 H18A C2 H2A C18 H18B C2 H2B C18 H18C C3 C (3) C19 H19A C3 H C19 H19B C4 C (3) C19 H19C C4 C (3) C20 C (4) C4 C (3) C20 C (4) C5 C (3) C21 H C5 C (3) C22 C (4) C5 H C22 H C6 C (3) C23 H C6 H6A C28 H28A C6 H6B C28 H28B C7 C (3) C28 H28C C7 H C29 H29A C8 C (3) C29 H29B C8 C (3) C29 H29C C8 C (3) C30 H30A C9 C (3) C30 H30B C9 C (3) C30 H30C C9 H C1 O1 H1A C13 C12 H12A C3 O3 H3A C11 C12 H12A C7 O4 H C13 C12 H12B C15 O5 C (15) C11 C12 H12B C16 O6 C (19) H12A C12 H12B O1 C1 C (2) C12 C13 C (19) O1 C1 C (19) C12 C13 C (19) sup-6

9 C2 C1 C (19) C14 C13 C (19) O1 C1 H C12 C13 C (2) C2 C1 H C14 C13 C (19) C10 C1 H C17 C13 C (19) C3 C2 C (2) O5 C14 C (15) C3 C2 H2A O5 C14 C (18) C1 C2 H2A C15 C14 C (2) C3 C2 H2B O5 C14 C (18) C1 C2 H2B C15 C14 C (2) H2A C2 H2B C13 C14 C (2) O3 C3 C (2) O5 C15 C (15) O3 C3 C (19) O5 C15 C (2) C2 C3 C (2) C14 C15 C (2) O3 C3 H O5 C15 H C2 C3 H C14 C15 H C4 C3 H C16 C15 H C28 C4 C (2) O7 C16 O (2) C28 C4 C (2) O7 C16 C (2) C3 C4 C (2) O6 C16 C (2) C28 C4 C (2) O6 C17 C (19) C3 C4 C (18) O6 C17 C (18) C29 C4 C (19) C20 C17 C (2) C6 C5 C (19) O6 C17 H C6 C5 C (19) C20 C17 H C4 C5 C (19) C13 C17 H C6 C5 H C13 C18 H18A C4 C5 H C13 C18 H18B C10 C5 H H18A C18 H18B C7 C6 C (19) C13 C18 H18C C7 C6 H6A H18A C18 H18C C5 C6 H6A H18B C18 H18C C7 C6 H6B C10 C19 H19A C5 C6 H6B C10 C19 H19B H6A C6 H6B H19A C19 H19B O4 C7 C (19) C10 C19 H19C O4 C7 C (18) H19A C19 H19C C6 C7 C (19) H19B C19 H19C O4 C7 H C21 C20 C (2) C6 C7 H C21 C20 C (2) C8 C7 H C22 C20 C (2) C30 C8 C (19) C20 C21 H C30 C8 C (19) C23 C22 C (3) C7 C8 C (18) C23 C22 H C30 C8 C (19) C20 C22 H C7 C8 C (19) C22 C23 O (2) C9 C8 C (18) C22 C23 H C11 C9 C (19) O8 C23 H C11 C9 C (19) C4 C28 H28A C8 C9 C (18) C4 C28 H28B sup-7

10 C11 C9 H H28A C28 H28B C8 C9 H C4 C28 H28C C10 C9 H H28A C28 H28C C19 C10 C (18) H28B C28 H28C C19 C10 C (18) C4 C29 H29A C1 C10 C (18) C4 C29 H29B C19 C10 C (18) H29A C29 H29B C1 C10 C (18) C4 C29 H29C C9 C10 C (18) H29A C29 H29C C9 C11 C (2) H29B C29 H29C C9 C11 H11A C8 C30 H30A C12 C11 H11A C8 C30 H30B C9 C11 H11B H30A C30 H30B C12 C11 H11B C8 C30 H30C H11A C11 H11B H30A C30 H30C C13 C12 C (19) H30B C30 H30C Hydrogen-bond geometry (Å, ) D H A D H H A D A D H A O1 H1A O7 i (3) 155 O4 H4 O3 ii (2) 171 Symmetry codes: (i) x+1, y, z; (ii) x 1/2, y+3/2, z+1. sup-8

11 Fig. 1 sup-9