Experimental. Crystal data. C 30 H 48 ClN 3 O M r = Orthorhombic, P a = (2) Å b = (3) Å c = 26.

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1 organic compounds Acta Crystallographica Section E Structure Reports Online ISSN b-Chloro-6-[2-(2-cyanoacetyl)hydrazin- 1-ylidene]-5a-cholestane Samina Khan Yusufzai, a Hasnah Osman, a Aisyah Saad Abdul Rahim, b Suhana Arshad c and Ibrahim Abdul Razak c * a School of Chemical Sciences, Universiti Sains Malaysia, USM, Penang, Malaysia, b School of Pharmaceutical Sciences, Universiti Sains Malaysia, USM, Penang, Malaysia, and c School of Physics, Universiti Sains Malaysia, USM, Penang, Malaysia Correspondence arazaki@usm.my Received 27 February 2012; accepted 2 March 2012 Key indicators: single-crystal X-ray study; T = 100 K; mean (C C) = Å; disorder in main residue; R factor = 0.104; wr factor = 0.221; data-to-parameter ratio = The asymmetric unit of the title compound, C 30 H 48 ClN 3 O, contains two molecules, A and B. In both molecules, the three cyclohexane rings in the steroid fused ring systems adopt chair conformations, while the cyclopentane rings adopt envelope and twist conformations in molecules A and B, respectively. In molecule B, the cyano group is disordered over two orientations with refined site-occupancies of (8) and (8). An intramolecular C HN interaction forms an S(10) ring in both molecules. In the crystal, molecules are linked by N HO, C HO and C HN interactions, resulting is chains propagating along the a-axis direction. Experimental Crystal data C 30 H 48 ClN 3 O M r = Orthorhombic, P a = (2) Å b = (3) Å c = (4) Å Data collection Bruker SMART APEXII CCD diffractometer Absorption correction: multi-scan (SADABS; Bruker, 2009) T min = 0.951, T max = Refinement R[F 2 >2(F 2 )] = wr(f 2 ) = S = reflections 655 parameters H-atom parameters constrained V = (16) Å 3 Z =8 Mo K radiation = 0.16 mm 1 T = 100 K mm measured reflections independent reflections reflections with I > 2(I) R int = max = 0.50 e Å 3 min = 0.52 e Å 3 Absolute structure: Flack (1983), 5882 Friedel pairs Flack parameter: 0.05 (11) Related literature For related structures, see: Yusufzai et al. (2012); Ketuly et al. (2011). For ring conformations, see: Cremer & Pople (1975). For hydrogen-bond motifs, see: Bernstein et al. (1995). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986). Table 1 Hydrogen-bond geometry (Å, ). D HA D H HA DA D HA C4B H4BAN3B (10) 149 N2A H1NAO1B i (6) 168 N2B H1NBO1A ii (6) 171 C1A H1ABO1B i (7) 162 C1B H1BBO1A ii (6) 153 C4A H4ABN3B iii (9) 173 C19A H19AN3B iii (11) 160 Symmetry codes: (i) x þ 1; y þ 1 2 ; z þ 1 2 ; (ii) x þ 1; y 1 2 ; z þ 1 2 ; (iii) x; y þ 1 2 ; z þ 1 2. Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009). Additional correspondence ohasnah@usm.my. Thomson Reuters ResearcherID: A The authors thank the Malaysian Government and Universiti Sains Malaysia (USM) for the FRGS grant (203/ PKIMIA/ ), MOSTI grant (No lfn-meb-004) o1056 Yusufzai et al. doi: /s

2 organic compounds and Research University grant (No.1001/PFIZIK/811151) to conduct this work. SKY also thanks USM for providing Graduate Assistance financial support. Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: HB6661). References Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, Bruker (2009). SADABS, APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Cosier, J. & Glazer, A. M. (1986). J. Appl. Cryst. 19, Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, Flack, H. D. (1983). Acta Cryst. A39, Ketuly, K. A., Hadi, A. H. A., Ng, S. W. & Tiekink, E. R. T. (2011). Acta Cryst. E67, o773 o774. Sheldrick, G. M. (2008). Acta Cryst. A64, Spek, A. L. (2009). Acta Cryst. D65, Yusufzai, S. K., Osman, H., Sulaiman, O., Arshad, S. & Razak, I. A. (2012). Acta Cryst. E68, o473 o474. Yusufzai et al. C 30 H 48 ClN 3 O o1057

3 supporting information [ 3β-Chloro-6-[2-(2-cyanoacetyl)hydrazin-1-ylidene]-5α-cholestane Samina Khan Yusufzai, Hasnah Osman, Aisyah Saad Abdul Rahim, Suhana Arshad and Ibrahim Abdul Razak S1. Comment The study being reported in this paper is a part of our on going effort towards the synthesis of modified steroids, which may be biologically active. In continuation of our previous work (Yusufzai et al., 2012) we report the synthesis of 3βchloro-6-[2-(2-cyanoacetyl)hydrazin-1-ylidene]-5α-cholestane which corresponds to the molecular formula, C 30 H 48 N 3 OCl. The asymmetric unit of the title compound (Fig. 1), consists of two crystallographically independent molecules A and B. The bond lengths are comparable to those in related structures (Yusufzai et al., 2012; Ketuly et al., 2011). In molecule B, the nitrile group is disordered over two positions with refined site-occupancies of (8): (8) ratio. The cyclopentane ring of the steroid fused ring system in both molecules adopts a different ring conformation (Cremer & Pople, 1975). In molecule A, it is in twist conformation where the cyclopentane (C12A C16A) ring is twisted about C16A C12A bonds, with puckering parameters Q= (6) Å and φ= (8). Meanwhile, the cyclopentane (C12B C16B) ring of molecule B is in envelope conformation with puckering parameters Q= (5) Å and φ= (7) with atom C12B at the flap. In addition, the three cyclohexane rings in the steroid fused ring system for both molecules adopt a chair conformation [Molecule A (C1A C3A/C8A/C9A/C17A):(C3A C8A):(C9A C12A/C16A/C17A); Q= (6):0.562 (3):0.588 (6) Å, Θ= (6):178.7 (3):175.7 (6) and Φ= 305 (4):232 (10):120 (8) ; Molecule B (C1B C3B/C8B/C9B/C17B): (C3B C8B):(C9B C12B/C16B/C17B); Q= (6):0.595 (6):0.568 (5) Å, Θ= (6):178.9 (6):174.7 (5) and Φ= 30 (4):258 (23):31 (6) ]. Furthermore, an intramolecular C4B H4BA N3B hydrogen bond is observed in B and forms an S(10) ring motif (Bernstein et al., 1995). There are nine chiral centres presented in molecule A and B. In each molecules, the centers exhibit the following relative chiralities: C3A/C3B = S; C5A/C5B = S; C8A/C8B = R; C9A/C9B = S; C12A/C12B = R; C13A/C13B = R; C16A/C16B = S; C17A/C17B = S and C24A/C24B = R. The crystal packing is shown in Fig. 2. N H O (Table 1) hydrogen bonds generate R 2 2(8) ring motifs, sandwiched by two R 1 2(7) ring motifs when combined with C H O (Table 1) hydrogen bonds. In addition, C H N (Table 1) interactions form R 1 2(10) ring motifs. These ring motifs link the molecules into chains along a-axis. S2. Experimental To a solution of steroidal ketone 3β-chloro-5α-cholestan-6-one (5 mmol), in absolute ethanol (10 ml) was added cyanoacetohydrazide (10 mmol) followed by few drops of triethylamine. The reaction mixture was refluxed for 24 hrs. The progress of reaction was monitored by thin layer chromatography. After completion of reaction, reaction mixture was concentrated under reduce pressure. The obtained solid, was extracted with ether and ethereal layer was washed with water, NaHCO 3 solution (5%), again with water and dried over anhydrous sodium sulfate. The solvent was evaporated and the product was recrystallized from ethanol to give compound as colourless blocks. sup-1

4 S3. Refinement The nitrile group of molecule B was disordered over two positions with refined site-occupancies of (8): (8) ratio. N-bound H atoms was located from the difference fourier map and was fixed at its found location using riding model with U iso (H) = 1.5 U eq (N) [N H = and Å]. The remaining H atoms were positioned geometrically [C H = Å] and refined using a riding model with U iso (H) = 1.2 or 1.5 U eq (C). A rotating group model was applied to the methyl groups. The same U ij parameters were used for atoms pair C28A and C29A Friedel pairs were used to determine the absolute configuration. Figure 1 The molecular structure of the title compound, showing 30% probability displacement ellipsoids. H-atoms are omitted for clarity. Disordered components are shown. sup-2

5 Figure 2 The crystal packing of the title compound. Only major disordered components is shown. 3β-Chloro-6-[2-(2-cyanoacetyl)hydrazin-1-ylidene]-5α-cholestane Crystal data C 30 H 48 ClN 3 O M r = Orthorhombic, P Hall symbol: P 2ac 2ab a = (2) Å b = (3) Å c = (4) Å V = (16) Å 3 Z = 8 F(000) = 2192 D x = Mg m 3 Mo Kα radiation, λ = Å Cell parameters from 9967 reflections θ = µ = 0.16 mm 1 T = 100 K Block, colourless mm sup-3

6 Data collection Bruker SMART APEXII CCD diffractometer Radiation source: fine-focus sealed tube Graphite monochromator φ and ω scans Absorption correction: multi-scan (SADABS; Bruker, 2009) T min = 0.951, T max = Refinement Refinement on F 2 Least-squares matrix: full R[F 2 > 2σ(F 2 )] = wr(f 2 ) = S = reflections 655 parameters 0 restraints Primary atom site location: structure-invariant direct methods Secondary atom site location: difference Fourier map measured reflections independent reflections reflections with I > 2σ(I) R int = θ max = 27.5, θ min = 1.3 h = k = l = Hydrogen site location: inferred from neighbouring sites H-atom parameters constrained w = 1/[σ 2 (F o2 ) + (0.P) P] where P = (F o 2 + 2F c2 )/3 (Δ/σ) max < Δρ max = 0.50 e Å 3 Δρ min = 0.52 e Å 3 Extinction correction: SHELXL, Fc * =kfc[ xfc 2 λ 3 /sin(2θ)] -1/4 Extinction coefficient: (14) Absolute structure: Flack (1983), 5882 Friedel pairs Absolute structure parameter: 0.05 (11) Special details Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at (1) K. 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 Occ. (<1) Cl1A (13) (7) (6) (3) O1A (3) (17) (15) (8) N1A (4) (2) (15) (8) N2A (4) (2) (16) (9) H1NA * N3A (5) (3) (2) (15) C1A (5) (3) (18) (11) H1AA * H1AB * C2A (5) (2) (17) (10) C3A (5) (2) (18) (10) sup-4

7 H3AA * C4A (5) (2) (18) (10) H4AA * H4AB * C5A (5) (3) (2) (12) H5AA * C6A (6) (3) (2) (13) H6AA * H6AB * C7A (5) (3) (2) (13) H7AA * H7AB * C8A (5) (3) (18) (12) C9A (5) (3) (2) (12) H9AA * C10A (6) (3) (2) (16) H10A * H10B * C11A (6) (3) (2) (17) H11A * H11B * C12A (5) (2) (17) (11) C13A (7) (3) (2) (16) H13A * C14A (6) (3) (2) (14) H14A * H14B * C15A (6) (3) (2) (13) H15A * H15B * C16A (6) (2) (19) (12) H16A * C17A (5) (2) (18) (10) H17A * C18A (5) (2) (19) (10) C19A (5) (3) (2) (13) H19A * H19B * C20A (5) (3) (2) (13) C21A (5) (3) (18) (12) H21A * H21B * H21C * C22A (5) (3) (19) (12) H22A * H22B * H22C * C23A (7) (3) (2) (17) sup-5

8 H23A * H23B * H23C * C24A (6) (3) (19) (12) H24A * C25A (7) (3) (2) (15) H25A * H25B * C26A (6) (3) (2) (13) H26A * H26B * C27A (7) (3) (2) (16) H27A * H27B * C28A (6) (3) (3) (12) H28A * C29A (6) (3) (3) (12) H29A * H29B * H29C * C30A (7) (3) (2) (16) H30A * H30B * H30C * Cl1B (14) (10) (10) (7) O1B (4) (19) (17) (9) N1B (4) (2) (19) (10) N2B (4) (2) (18) (9) H1NB * N3B (8) (4) (3) (2) (8) C20B (9) (4) (4) (2) (8) N3X (11) (6) (4) (3) (8) C20X (12) (6) (5) (3) (8) C1B (4) (2) (2) (11) H1BA * H1BB * C2B (4) (3) (2) (11) C3B (5) (3) (2) (13) H3BA * C4B (5) (3) (3) (15) H4BA * H4BB * C5B (6) (3) (3) (19) H5BA * C6B (5) (3) (2) (15) H6BA * H6BB * C7B (5) (3) (2) (12) sup-6

9 H7BA * H7BB * C8B (5) (3) (2) (11) C9B (5) (2) (2) (11) H9BA * C10B (5) (2) (2) (10) H10C * H10D * C11B (5) (2) (2) (11) H11C * H11D * C12B (5) (2) (18) (10) C13B (5) (2) (19) (11) H13B * C14B (5) (3) (2) (11) H14C * H14D * C15B (5) (3) (2) (11) H15C * H15D * C16B (5) (2) (18) (10) H16B * C17B (5) (2) (19) (10) H17B * C18B (5) (3) (2) (11) C19B (5) (3) (3) (15) H19C * (8) H19D * (8) H19E * (8) H19F * (8) C21B (6) (3) (2) (15) H21D * H21E * H21F * C22B (5) (3) (19) (12) H22D * H22E * H22F * C23B (6) (3) (3) (14) H23D * H23E * H23F * C24B (5) (3) (2) (11) H24B * C25B (5) (3) (2) (12) H25C * H25D * C26B (5) (3) (2) (12) sup-7

10 H26C * H26D * C27B (5) (2) (2) (11) H27C * H27D * C28B (5) (2) (2) (12) H28B * C29B (5) (3) (3) (14) H29D * H29E * H29F * C30B (5) (3) (2) (13) H30D * H30E * H30F * Atomic displacement parameters (Å 2 ) U 11 U 22 U 33 U 12 U 13 U 23 Cl1A (7) (7) (7) (6) (6) (6) O1A (18) (17) (2) (15) (17) (16) N1A (2) (19) (19) (17) (17) (15) N2A (2) (19) (2) (17) (18) (16) N3A (3) (3) (4) (2) (3) (3) C1A (3) (2) (2) (2) (2) (18) C2A (3) (2) (2) (2) (19) (17) C3A (3) (2) (2) (2) (2) (18) C4A (3) (2) (2) (2) (2) (18) C5A (3) (2) (3) (2) (2) (2) C6A (3) (3) (3) (3) (3) (2) C7A (3) (3) (3) (2) (3) (2) C8A (3) (3) (2) (2) (2) (2) C9A (3) (2) (3) (2) (2) (2) C10A (3) (4) (3) (3) (3) (3) C11A (4) (3) (3) (3) (3) (3) C12A (3) (2) (2) (2) (2) (18) C13A (5) (3) (3) (3) (3) (2) C14A (4) (3) (3) (3) (3) (2) C15A (3) (3) (3) (3) (3) (2) C16A (4) (2) (2) (2) (2) (19) C17A (3) (2) (2) (2) (2) (18) C18A (3) (2) (2) (2) (2) (18) C19A (3) (2) (3) (2) (3) (2) C20A (3) (3) (3) (2) (3) (2) C21A (3) (3) (2) (2) (2) (2) C22A (3) (3) (3) (2) (2) (2) C23A (5) (3) (3) (3) (3) (3) C24A (4) (3) (2) (3) (2) (2) sup-8

11 C25A (4) (3) (3) (3) (3) (2) C26A (4) (3) (2) (3) (3) (2) C27A (5) (3) (3) (3) (3) (2) C28A (3) (2) (3) (2) (2) (2) C29A (3) (2) (3) (2) (2) (2) C30A (5) (3) (3) (3) (3) (3) Cl1B (7) (10) (19) (8) (10) (12) O1B (2) (18) (3) (16) (19) (17) N1B (2) (2) (3) (18) (2) (2) N2B (2) (2) (2) (17) (19) (18) N3B (5) (4) (5) (4) (4) (4) C20B (5) (4) (5) (4) (4) (4) N3X (7) (7) (5) (6) (5) (5) C20X (7) (6) (6) (5) (5) (5) C1B (2) (2) (3) (18) (2) (2) C2B (2) (2) (3) (2) (2) (2) C3B (3) (2) (4) (2) (3) (2) C4B (3) (3) (4) (2) (3) (3) C5B (3) (3) (5) (3) (3) (3) C6B (3) (3) (3) (3) (3) (3) C7B (3) (3) (3) (2) (2) (2) C8B (3) (3) (3) (2) (2) (2) C9B (3) (2) (2) (2) (2) (19) C10B (3) (2) (2) (2) (2) (2) C11B (3) (2) (2) (2) (2) (19) C12B (3) (2) (2) (2) (2) (18) C13B (3) (2) (2) (2) (2) (18) C14B (3) (3) (2) (2) (2) (2) C15B (3) (2) (3) (2) (2) (2) C16B (3) (2) (2) (19) (2) (17) C17B (2) (2) (2) (2) (2) (19) C18B (2) (2) (3) (2) (2) (2) C19B (3) (3) (4) (2) (3) (3) C21B (3) (4) (3) (3) (3) (3) C22B (3) (3) (2) (2) (2) (2) C23B (3) (3) (4) (3) (3) (3) C24B (3) (2) (3) (2) (2) (2) C25B (3) (3) (3) (2) (2) (2) C26B (3) (3) (3) (2) (2) (2) C27B (3) (2) (3) (2) (2) (19) C28B (3) (2) (3) (2) (2) (2) C29B (3) (3) (4) (3) (3) (3) C30B (3) (2) (4) (2) (3) (2) Geometric parameters (Å, º) Cl1A C5A (6) N1B C2B (7) O1A C18A (6) N1B N2B (6) sup-9

12 N1A C2A (6) N2B C18B (6) N1A N2A (6) N2B H1NB N2A C18A (6) N3B C20B (13) N2A H1NA C20B C19B (11) N3A C20A (7) N3X C20X (17) C1A C2A (7) C20X C19B (14) C1A C17A (7) C1B C2B (7) C1A H1AA C1B C17B (7) C1A H1AB C1B H1BA C2A C3A (7) C1B H1BB C3A C4A (7) C2B C3B (7) C3A C8A (6) C3B C4B (7) C3A H3AA C3B C8B (8) C4A C5A (7) C3B H3BA C4A H4AA C4B C5B (7) C4A H4AB C4B H4BA C5A C6A (7) C4B H4BB C5A H5AA C5B C6B (10) C6A C7A (8) C5B H5BA C6A H6AA C6B C7B (8) C6A H6AB C6B H6BA C7A C8A (7) C6B H6BB C7A H7AA C7B C8B (7) C7A H7AB C7B H7BA C8A C21A (8) C7B H7BB C8A C9A (8) C8B C21B (8) C9A C17A (7) C8B C9B (7) C9A C10A (7) C9B C17B (7) C9A H9AA C9B C10B (7) C10A C11A (9) C9B H9BA C10A H10A C10B C11B (7) C10A H10B C10B H10C C11A C12A (8) C10B H10D C11A H11A C11B C12B (7) C11A H11B C11B H11C C12A C16A (6) C11B H11D C12A C13A (8) C12B C16B (6) C12A C22A (7) C12B C22B (7) C13A C24A (7) C12B C13B (7) C13A C14A (9) C13B C24B (7) C13A H13A C13B C14B (7) C14A C15A (7) C13B H13B C14A H14A C14B C15B (7) C14A H14B C14B H14C C15A C16A (9) C14B H14D C15A H15A C15B C16B (7) C15A H15B C15B H15C C16A C17A (8) C15B H15D sup-10

13 C16A H16A C16B C17B (7) C17A H17A C16B H16B C18A C19A (7) C17B H17B C19A C20A (7) C18B C19B (8) C19A H19A C19B H19C C19A H19B C19B H19D C21A H21A C19B H19E C21A H21B C19B H19F C21A H21C C21B H21D C22A H22A C21B H21E C22A H22B C21B H21F C22A H22C C22B H22D C23A C24A (8) C22B H22E C23A H23A C22B H22F C23A H23B C23B C24B (8) C23A H23C C23B H23D C24A C25A (9) C23B H23E C24A H24A C23B H23F C25A C26A (8) C24B C25B (7) C25A H25A C24B H24B C25A H25B C25B C26B (8) C26A C27A (9) C25B H25C C26A H26A C25B H25D C26A H26B C26B C27B (7) C27A C28A (9) C26B H26C C27A H27A C26B H26D C27A H27B C27B C28B (7) C28A C29A (9) C27B H27C C28A C30A (9) C27B H27D C28A H28A C28B C30B (8) C29A H29A C28B C29B (8) C29A H29B C28B H28B C29A H29C C29B H29D C30A H30A C29B H29E C30A H30B C29B H29F C30A H30C C30B H30D Cl1B C5B (6) C30B H30E O1B C18B (6) C30B H30F C2A N1A N2A (4) N3B C20B C19B (10) C18A N2A N1A (4) N3X C20X C19B (13) C18A N2A H1NA C2B C1B C17B (4) N1A N2A H1NA C2B C1B H1BA C2A C1A C17A (4) C17B C1B H1BA C2A C1A H1AA C2B C1B H1BB C17A C1A H1AA C17B C1B H1BB C2A C1A H1AB H1BA C1B H1BB C17A C1A H1AB N1B C2B C1B (4) sup-11

14 H1AA C1A H1AB N1B C2B C3B (4) N1A C2A C1A (5) C1B C2B C3B (4) N1A C2A C3A (5) C2B C3B C4B (4) C1A C2A C3A (4) C2B C3B C8B (5) C2A C3A C4A (4) C4B C3B C8B (5) C2A C3A C8A (4) C2B C3B H3BA C4A C3A C8A (4) C4B C3B H3BA C2A C3A H3AA C8B C3B H3BA C4A C3A H3AA C5B C4B C3B (5) C8A C3A H3AA C5B C4B H4BA C5A C4A C3A (4) C3B C4B H4BA C5A C4A H4AA C5B C4B H4BB C3A C4A H4AA C3B C4B H4BB C5A C4A H4AB H4BA C4B H4BB C3A C4A H4AB C6B C5B C4B (6) H4AA C4A H4AB C6B C5B Cl1B (5) C4A C5A C6A (4) C4B C5B Cl1B (4) C4A C5A Cl1A (4) C6B C5B H5BA C6A C5A Cl1A (4) C4B C5B H5BA C4A C5A H5AA Cl1B C5B H5BA C6A C5A H5AA C5B C6B C7B (5) Cl1A C5A H5AA C5B C6B H6BA C5A C6A C7A (5) C7B C6B H6BA C5A C6A H6AA C5B C6B H6BB C7A C6A H6AA C7B C6B H6BB C5A C6A H6AB H6BA C6B H6BB C7A C6A H6AB C8B C7B C6B (4) H6AA C6A H6AB C8B C7B H7BA C8A C7A C6A (4) C6B C7B H7BA C8A C7A H7AA C8B C7B H7BB C6A C7A H7AA C6B C7B H7BB C8A C7A H7AB H7BA C7B H7BB C6A C7A H7AB C7B C8B C3B (5) H7AA C7A H7AB C7B C8B C21B (5) C7A C8A C21A (5) C3B C8B C21B (5) C7A C8A C9A (4) C7B C8B C9B (4) C21A C8A C9A (4) C3B C8B C9B (4) C7A C8A C3A (4) C21B C8B C9B (5) C21A C8A C3A (4) C17B C9B C10B (4) C9A C8A C3A (5) C17B C9B C8B (4) C17A C9A C10A (4) C10B C9B C8B (4) C17A C9A C8A (4) C17B C9B H9BA C10A C9A C8A (5) C10B C9B H9BA C17A C9A H9AA C8B C9B H9BA C10A C9A H9AA C11B C10B C9B (4) C8A C9A H9AA C11B C10B H10C C9A C10A C11A (6) C9B C10B H10C C9A C10A H10A C11B C10B H10D sup-12

15 C11A C10A H10A C9B C10B H10D C9A C10A H10B H10C C10B H10D C11A C10A H10B C12B C11B C10B (4) H10A C10A H10B C12B C11B H11C C12A C11A C10A (5) C10B C11B H11C C12A C11A H11A C12B C11B H11D C10A C11A H11A C10B C11B H11D C12A C11A H11B H11C C11B H11D C10A C11A H11B C11B C12B C16B (4) H11A C11A H11B C11B C12B C22B (4) C11A C12A C16A (4) C16B C12B C22B (4) C11A C12A C13A (5) C11B C12B C13B (4) C16A C12A C13A (4) C16B C12B C13B 99.8 (4) C11A C12A C22A (5) C22B C12B C13B (4) C16A C12A C22A (4) C24B C13B C12B (4) C13A C12A C22A (4) C24B C13B C14B (4) C24A C13A C12A (5) C12B C13B C14B (4) C24A C13A C14A (5) C24B C13B H13B C12A C13A C14A (4) C12B C13B H13B C24A C13A H13A C14B C13B H13B C12A C13A H13A C15B C14B C13B (4) C14A C13A H13A C15B C14B H14C C15A C14A C13A (5) C13B C14B H14C C15A C14A H14A C15B C14B H14D C13A C14A H14A C13B C14B H14D C15A C14A H14B H14C C14B H14D C13A C14A H14B C16B C15B C14B (4) H14A C14A H14B C16B C15B H15C C16A C15A C14A (5) C14B C15B H15C C16A C15A H15A C16B C15B H15D C14A C15A H15A C14B C15B H15D C16A C15A H15B H15C C15B H15D C14A C15A H15B C17B C16B C15B (4) H15A C15A H15B C17B C16B C12B (4) C15A C16A C17A (4) C15B C16B C12B (4) C15A C16A C12A (4) C17B C16B H16B C17A C16A C12A (5) C15B C16B H16B C15A C16A H16A C12B C16B H16B C17A C16A H16A C16B C17B C9B (4) C12A C16A H16A C16B C17B C1B (4) C9A C17A C16A (4) C9B C17B C1B (4) C9A C17A C1A (4) C16B C17B H17B C16A C17A C1A (4) C9B C17B H17B C9A C17A H17A C1B C17B H17B C16A C17A H17A O1B C18B N2B (5) C1A C17A H17A O1B C18B C19B (5) O1A C18A N2A (5) N2B C18B C19B (5) O1A C18A C19A (4) C20X C19B C18B (7) sup-13

16 N2A C18A C19A (4) C20B C19B C18B (6) C20A C19A C18A (4) C20B C19B H19C C20A C19A H19A C18B C19B H19C C18A C19A H19A C20B C19B H19D C20A C19A H19B C18B C19B H19D C18A C19A H19B H19C C19B H19D H19A C19A H19B C20X C19B H19E N3A C20A C19A (6) C18B C19B H19E C8A C21A H21A C20X C19B H19F C8A C21A H21B C18B C19B H19F H21A C21A H21B H19E C19B H19F C8A C21A H21C C8B C21B H21D H21A C21A H21C C8B C21B H21E H21B C21A H21C H21D C21B H21E C12A C22A H22A C8B C21B H21F C12A C22A H22B H21D C21B H21F H22A C22A H22B H21E C21B H21F C12A C22A H22C C12B C22B H22D H22A C22A H22C C12B C22B H22E H22B C22A H22C H22D C22B H22E C24A C23A H23A C12B C22B H22F C24A C23A H23B H22D C22B H22F H23A C23A H23B H22E C22B H22F C24A C23A H23C C24B C23B H23D H23A C23A H23C C24B C23B H23E H23B C23A H23C H23D C23B H23E C13A C24A C25A (5) C24B C23B H23F C13A C24A C23A (5) H23D C23B H23F C25A C24A C23A (5) H23E C23B H23F C13A C24A H24A C23B C24B C13B (5) C25A C24A H24A C23B C24B C25B (4) C23A C24A H24A C13B C24B C25B (4) C24A C25A C26A (5) C23B C24B H24B C24A C25A H25A C13B C24B H24B C26A C25A H25A C25B C24B H24B C24A C25A H25B C26B C25B C24B (4) C26A C25A H25B C26B C25B H25C H25A C25A H25B C24B C25B H25C C27A C26A C25A (5) C26B C25B H25D C27A C26A H26A C24B C25B H25D C25A C26A H26A H25C C25B H25D C27A C26A H26B C27B C26B C25B (4) C25A C26A H26B C27B C26B H26C H26A C26A H26B C25B C26B H26C C28A C27A C26A (5) C27B C26B H26D C28A C27A H27A C25B C26B H26D C26A C27A H27A H26C C26B H26D C28A C27A H27B C26B C27B C28B (5) sup-14

17 C26A C27A H27B C26B C27B H27C H27A C27A H27B C28B C27B H27C C29A C28A C27A (5) C26B C27B H27D C29A C28A C30A (5) C28B C27B H27D C27A C28A C30A (6) H27C C27B H27D C29A C28A H28A C30B C28B C29B (5) C27A C28A H28A C30B C28B C27B (5) C30A C28A H28A C29B C28B C27B (4) C28A C29A H29A C30B C28B H28B C28A C29A H29B C29B C28B H28B H29A C29A H29B C27B C28B H28B C28A C29A H29C C28B C29B H29D H29A C29A H29C C28B C29B H29E H29B C29A H29C H29D C29B H29E C28A C30A H30A C28B C29B H29F C28A C30A H30B H29D C29B H29F H30A C30A H30B H29E C29B H29F C28A C30A H30C C28B C30B H30D H30A C30A H30C C28B C30B H30E H30B C30A H30C H30D C30B H30E C2B N1B N2B (4) C28B C30B H30F C18B N2B N1B (4) H30D C30B H30F C18B N2B H1NB H30E C30B H30F N1B N2B H1NB C2A N1A N2A C18A (5) N2B N1B C2B C1B 1.2 (9) N2A N1A C2A C1A 0.2 (8) N2B N1B C2B C3B (5) N2A N1A C2A C3A (4) C17B C1B C2B N1B (6) C17A C1A C2A N1A (6) C17B C1B C2B C3B 48.2 (7) C17A C1A C2A C3A 57.3 (5) N1B C2B C3B C4B 0.6 (8) N1A C2A C3A C4A 11.8 (6) C1B C2B C3B C4B (5) C1A C2A C3A C4A (4) N1B C2B C3B C8B (5) N1A C2A C3A C8A (5) C1B C2B C3B C8B 51.9 (7) C1A C2A C3A C8A 62.5 (5) C2B C3B C4B C5B (6) C2A C3A C4A C5A (4) C8B C3B C4B C5B 57.0 (7) C8A C3A C4A C5A 59.2 (5) C3B C4B C5B C6B 56.1 (7) C3A C4A C5A C6A 58.9 (6) C3B C4B C5B Cl1B (5) C3A C4A C5A Cl1A (3) C4B C5B C6B C7B 55.3 (7) C4A C5A C6A C7A 57.8 (6) Cl1B C5B C6B C7B (4) Cl1A C5A C6A C7A (4) C5B C6B C7B C8B 54.3 (7) C5A C6A C7A C8A 58.2 (6) C6B C7B C8B C3B 53.3 (6) C6A C7A C8A C21A 64.5 (6) C6B C7B C8B C21B 66.8 (7) C6A C7A C8A C9A (5) C6B C7B C8B C9B (5) C6A C7A C8A C3A 55.3 (6) C2B C3B C8B C7B (4) C2A C3A C8A C7A (4) C4B C3B C8B C7B 55.7 (6) C4A C3A C8A C7A 55.5 (6) C2B C3B C8B C21B 66.3 (6) C2A C3A C8A C21A 63.3 (6) C4B C3B C8B C21B 63.1 (6) C4A C3A C8A C21A 63.4 (5) C2B C3B C8B C9B 54.9 (6) sup-15

18 C2A C3A C8A C9A 58.7 (5) C4B C3B C8B C9B (4) C4A C3A C8A C9A (4) C7B C8B C9B C17B (5) C7A C8A C9A C17A (5) C3B C8B C9B C17B 57.8 (6) C21A C8A C9A C17A 65.7 (6) C21B C8B C9B C17B 63.6 (6) C3A C8A C9A C17A 56.0 (6) C7B C8B C9B C10B 56.3 (6) C7A C8A C9A C10A 61.9 (6) C3B C8B C9B C10B (4) C21A C8A C9A C10A 60.5 (6) C21B C8B C9B C10B 63.9 (6) C3A C8A C9A C10A (4) C17B C9B C10B C11B 50.9 (6) C17A C9A C10A C11A 56.8 (7) C8B C9B C10B C11B (4) C8A C9A C10A C11A (5) C9B C10B C11B C12B 54.1 (6) C9A C10A C11A C12A 55.5 (7) C10B C11B C12B C16B 55.3 (5) C10A C11A C12A C16A 52.5 (7) C10B C11B C12B C22B 66.3 (6) C10A C11A C12A C13A (5) C10B C11B C12B C13B (4) C10A C11A C12A C22A 69.2 (6) C11B C12B C13B C24B 78.8 (6) C11A C12A C13A C24A 79.9 (7) C16B C12B C13B C24B (5) C16A C12A C13A C24A (5) C22B C12B C13B C24B 48.7 (6) C22A C12A C13A C24A 47.3 (7) C11B C12B C13B C14B (4) C11A C12A C13A C14A (5) C16B C12B C13B C14B 41.3 (5) C16A C12A C13A C14A 40.9 (5) C22B C12B C13B C14B 76.2 (5) C22A C12A C13A C14A 78.2 (5) C24B C13B C14B C15B (4) C24A C13A C14A C15A (5) C12B C13B C14B C15B 22.8 (5) C12A C13A C14A C15A 19.8 (6) C13B C14B C15B C16B 5.2 (6) C13A C14A C15A C16A 9.7 (6) C14B C15B C16B C17B (4) C14A C15A C16A C17A (5) C14B C15B C16B C12B 31.9 (5) C14A C15A C16A C12A 36.0 (6) C11B C12B C16B C17B 59.9 (5) C11A C12A C16A C15A (5) C22B C12B C16B C17B 60.9 (6) C13A C12A C16A C15A 48.8 (5) C13B C12B C16B C17B (4) C22A C12A C16A C15A 69.5 (6) C11B C12B C16B C15B (4) C11A C12A C16A C17A 57.0 (6) C22B C12B C16B C15B 70.3 (5) C13A C12A C16A C17A (4) C13B C12B C16B C15B 45.8 (5) C22A C12A C16A C17A 63.3 (6) C15B C16B C17B C9B (4) C10A C9A C17A C16A 58.3 (6) C12B C16B C17B C9B 58.9 (6) C8A C9A C17A C16A (4) C15B C16B C17B C1B 53.5 (6) C10A C9A C17A C1A (5) C12B C16B C17B C1B (4) C8A C9A C17A C1A 52.2 (6) C10B C9B C17B C16B 51.9 (5) C15A C16A C17A C9A (5) C8B C9B C17B C16B (4) C12A C16A C17A C9A 61.7 (5) C10B C9B C17B C1B (4) C15A C16A C17A C1A 50.6 (6) C8B C9B C17B C1B 55.9 (6) C12A C16A C17A C1A (4) C2B C1B C17B C16B (4) C2A C1A C17A C9A 50.5 (6) C2B C1B C17B C9B 49.8 (6) C2A C1A C17A C16A (4) N1B N2B C18B O1B (5) N1A N2A C18A O1A (5) N1B N2B C18B C19B 1.6 (8) N1A N2A C18A C19A 4.2 (7) O1B C18B C19B C20X 31.8 (10) O1A C18A C19A C20A 4.5 (8) N2B C18B C19B C20X (7) N2A C18A C19A C20A (5) O1B C18B C19B C20B (7) C12A C13A C24A C25A (5) N2B C18B C19B C20B 52.5 (9) C14A C13A C24A C25A 58.2 (6) C12B C13B C24B C23B 52.0 (7) C12A C13A C24A C23A 57.5 (7) C14B C13B C24B C23B (5) sup-16

19 C14A C13A C24A C23A (5) C12B C13B C24B C25B (5) C13A C24A C25A C26A (5) C14B C13B C24B C25B 64.0 (6) C23A C24A C25A C26A 61.9 (7) C23B C24B C25B C26B 72.1 (6) C24A C25A C26A C27A (6) C13B C24B C25B C26B (5) C25A C26A C27A C28A (6) C24B C25B C26B C27B (5) C26A C27A C28A C29A (6) C25B C26B C27B C28B (4) C26A C27A C28A C30A 63.6 (8) C26B C27B C28B C30B (5) C2B N1B N2B C18B (5) C26B C27B C28B C29B 67.3 (6) Hydrogen-bond geometry (Å, º) D H A D H H A D A D H A C4B H4BA N3B (10) 149 N2A H1NA O1B i (6) 168 N2B H1NB O1A ii (6) 171 C1A H1AB O1B i (7) 162 C1B H1BB O1A ii (6) 153 C4A H4AB N3B iii (9) 173 C19A H19A N3B iii (11) 160 Symmetry codes: (i) x+1, y+1/2, z+1/2; (ii) x+1, y 1/2, z+1/2; (iii) x, y+1/2, z+1/2. sup-17