organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 69| Part 12| December 2013| Pages o1734-o1735

13-(Imidazol-1-yl)-11,13-di­hydro­melampomagnolide B monohydrate

aDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA, and bDepartment of Chemistry, University of Kentucky, Lexington KY 40506, USA
*Correspondence e-mail: pacrooks@uams.edu

(Received 22 October 2013; accepted 23 October 2013; online 6 November 2013)

The title compound, C18H24N2O4·H2O {systematic name: (1aR,7aS,8R,10aS,10bS,E)-5-hy­droxy­methyl-8-[(1H-imidazol-1-yl)meth­yl]-1a-methyl-2,3,6,7,7a,8,10a,10b-octa­hydro­oxireno[2′,3′:9,10]cyclo­deca­[1,2-b]furan-9(1aH)-one monohydrate}, an imidazole derivative of melampomagnolide B was synthesized under Michael addition conditions. The mol­ecule is built up from fused ten-, five- (lactone) and three-membered (epoxide) rings. The inter­nal double bond of the ten-membered ring identifies it as the cis or E isomer. The lactone ring has an envelope-type conformation, with the (chiral) C atom opposite the lactone O atoms as the flap atom. In the crystal, O—H⋯O, O—H⋯N and weak C—H⋯O hydrogen bonds link the mol­ecules (along with water) into sheets parallel to the bc plane.

Related literature

For the biological activity of similar compounds, see: El-Feraly (1984[El-Feraly, F. S. (1984). Phytochemistry, 23, 2372-2374.]); Macias et al. (1992[Macias, F. A., Galindo, J. C. G. & Massanet, G. M. (1992). Phytochemistry, 31, 1969-1977.]); Nasim et al. (2011[Nasim, S., Pei, S. S., Hagan, F. K., Jordan, C. T. & Crooks, P. A. (2011). Bioorg. Med. Chem. 19, 1515-1519.]); Nasim & Crooks (2008[Nasim, S. & Crooks, P. A. (2008). Bioorg. Med. Chem. Lett. 18, 3870-3873.]). For the structures of similar compounds, see; Neelakantan et al. (2009[Neelakantan, S., Nasim, S., Guzman, M. L., Jordan, C. T. & Crooks, P. A. (2009). Bioorg. Med. Chem. Lett. 19, 4346-4349.]); Woods et al. (2011[Woods, J. R., Mo, H., Bieberich, A. A., Alavanja, T. & Colby, D. A. (2011). J. Med. Chem. 54, 7934-7941.]); Neukirch et al. (2003[Neukirch, H., Guerriero, A. & Ambrosio, M. D. (2003). Eur. J. Org. Chem. pp. 3969-3975.]); Gonzalez et al. (1988[Gonzalez, A. G., Galindo, A., Mar Afonso, M., Mansilla, H. & Lopez, M. (1988). Tetrahedron, 44, 4585-4589.]).

[Scheme 1]

Experimental

Crystal data
  • C18H24N2O4·H2O

  • Mr = 350.41

  • Monoclinic, P 21

  • a = 9.8073 (2) Å

  • b = 8.2784 (1) Å

  • c = 10.7741 (2) Å

  • β = 95.015 (1)°

  • V = 871.39 (3) Å3

  • Z = 2

  • Cu Kα radiation

  • μ = 0.80 mm−1

  • T = 90 K

  • 0.25 × 0.20 × 0.04 mm

Data collection
  • Bruker X8 Proteum diffractometer

  • Absorption correction: multi-scan (SADABS; Sheldrick, 2008a[Sheldrick, G. M. (2008a). SADABS. University of Göttingen, Germany.]) Tmin = 0.836, Tmax = 0.942

  • 10767 measured reflections

  • 2437 independent reflections

  • 2425 reflections with I > 2σ(I)

  • Rint = 0.030

Refinement
  • R[F2 > 2σ(F2)] = 0.024

  • wR(F2) = 0.061

  • S = 1.04

  • 2437 reflections

  • 235 parameters

  • 1 restraint

  • H atoms treated by a mixture of independent and constrained refinement

  • Δρmax = 0.16 e Å−3

  • Δρmin = −0.15 e Å−3

  • Absolute structure: Flack parameter determined using 747 quotients [(I+)−(I)]/[(I+)+(I)] (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.])

  • Absolute structure parameter: −0.03 (5)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
O4—H4⋯N2i 0.84 1.93 2.7491 (17) 164
C13—H13B⋯O1Wii 0.99 2.45 3.388 (2) 157
C15—H15B⋯O3iii 0.98 2.55 3.282 (2) 131
C16—H16A⋯O1Wiv 0.95 2.44 3.370 (2) 167
C17—H17A⋯O3v 0.95 2.54 3.377 (2) 147
C18—H18A⋯O1v 0.95 2.57 3.5016 (19) 167
O1W—H1W⋯O4 0.87 (3) 1.93 (3) 2.7928 (17) 173 (3)
O1W—H2W⋯O3vi 0.85 (3) 2.14 (3) 2.9534 (19) 162 (2)
Symmetry codes: (i) [-x+1, y+{\script{1\over 2}}, -z+1]; (ii) [-x+1, y-{\script{1\over 2}}, -z]; (iii) [-x+2, y+{\script{1\over 2}}, -z+1]; (iv) x, y, z+1; (v) x, y-1, z; (vi) x, y, z-1.

Data collection: APEX2 (Bruker, 2006[Bruker (2006). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2006[Bruker (2006). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008b[Sheldrick, G. M. (2008b). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008b[Sheldrick, G. M. (2008b). Acta Cryst. A64, 112-122.]); molecular graphics: XP in SHELXTL (Sheldrick, 2008b[Sheldrick, G. M. (2008b). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXL2013.

Supporting information


Comment top

Melampomagnolide B (MMB) was derived from parthenolide (PTL) via selenium oxide mediated oxidation of the C10 methyl group of PTL (Macias et al., 1992; Neukirch et al., 2003). MMB is a melampolide originally isolated from Magnolia grandiflora and characterized by X-ray diffraction analysis (El-Feraly, 1984; Gonzalez et al., 1988), and has been identified as a new anti-leukemic sesquiterpene with properties similar to PTL (Nasim et al., 2011).

Recently, Nasim et al. (2008) reported formation of amino-parthenolide derivatives under Michael addition reaction conditions. These compounds showed more potency as antileukemic agents and improved water solubility relative to PTL. To further improve water solubility of melampomagnolide B, we synthesized an imidazole derivative by the reaction of MMB with imidazole via Michael addition chemistry (Neelakantan et al., 2009; Woods et al., 2011) to afford the title compound, which was re-crystallized from chloroform.

To obtain detailed information on the structural conformation of this molecule, establish the geometry of the double bond (C9C10) and orientation of the imidazole moiety, a single-crystal X-ray structure determination has been carried out. This has revealed that the double bond of the title compound has the E-geometry. In the crystal, intermolecular O—H···O, O—H···N and weak C—H···O hydrogen bonds link the molecules (along with water) into sheets parallel to the bc-plane.

Related literature top

For the biological activity of similar compounds, see: El-Feraly (1984); Macias et al. (1992); Nasim et al. (2011); Nasim & Crooks (2008). For the structures of similar compounds, see; Neelakantan et al. (2009); Woods et al. (2011); Neukirch et al. (2003); Gonzalez et al. (1988).

Experimental top

To a solution of MMB (50 mg, 0.189 m mol) in methanol, was added imidazole (19.31 mg, 0.284 m mol). The reaction mixture was stirred at ambient temperature for 24 h. After completion of the reaction (monitored by thin-layer chromatography), the reaction mixture was dissolved in dichloromethane. The organic layer was separated, washed with water, dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford the crude product. The crude compound was recrystallized from chloroform to obtain the title compound as colorless crystals (56 mg, yield: 89%). Melting point 398-399°K. 1H NMR (400 MHz, CDCl3): δ 7.60 (s, 1H), 7.10 (s, 1H), 7.01 (s, 1H), 5.55 (t, J=8Hz, 1H), 4.48 (dd, J=14.4 Hz, 1H), 4.32 (dd, J=14.8, 1H),3.93 (s, 2H), 3.89(t, J=9.6Hz, 1H), 2.68 (d, J=9.2 Hz, 2H), 2.34-1.90 (m, 11H), 1.88-1.53 (m, 3H), 1.04 (t, J=9.6 Hz, 1H). 13C NMR (CDCl3, 100 MHz): δ 174.9, 139.1, 138.0, 130.3, 126.8, 119.4, 81.2, 65.2, 62.5, 60.3, 48.4, 43.8, 41.6, 36.7, 26.9, 24.6, 23.4, 17.9 ppm.

Refinement top

H atoms were found in difference Fourier maps and subsequently placed at idealized positions with constrained distances of 0.98 Å (RCH3), 0.99 Å (R2CH2), 1.00 Å (R3CH), 0.95 Å (Csp2H). Water hydrogen coordinates were refined. Uiso(H) values were set to either 1.2Ueq or 1.5Ueq (RCH3, OH) of the attached atom.

Computing details top

Data collection: APEX2 (Bruker, 2006); cell refinement: SAINT (Bruker, 2006); data reduction: SAINT (Bruker, 2006); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008b); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008b); molecular graphics: XP in SHELXTL (Sheldrick, 2008b); software used to prepare material for publication: SHELXL2013 (Sheldrick, 2008b).

Figures top
[Figure 1] Fig. 1. The title molecule with the atom numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
(1aR,7aS,8R,10aS,10bS,E)-5-Hydroxymethyl-8-[(1H-imidazol-1-yl)methyl]-1a-methyl-2,3,6,7,7a,8,10a,10b-octahydrooxireno[2',3':9,10]cyclodeca[1,2-b]furan-9(1aH)-one monohydrate top
Crystal data top
C18H24N2O4·H2OF(000) = 376
Mr = 350.41Dx = 1.335 Mg m3
Monoclinic, P21Cu Kα radiation, λ = 1.54178 Å
a = 9.8073 (2) ÅCell parameters from 9966 reflections
b = 8.2784 (1) Åθ = 4.1–68.1°
c = 10.7741 (2) ŵ = 0.80 mm1
β = 95.015 (1)°T = 90 K
V = 871.39 (3) Å3Tablet, colourless
Z = 20.25 × 0.20 × 0.04 mm
Data collection top
Bruker X8 Proteum
diffractometer
2437 independent reflections
Radiation source: fine-focus rotating anode2425 reflections with I > 2σ(I)
Detector resolution: 5.6 pixels mm-1Rint = 0.030
ϕ and ω scansθmax = 68.1°, θmin = 4.5°
Absorption correction: multi-scan
(SADABS; Sheldrick, 2008a)
h = 1111
Tmin = 0.836, Tmax = 0.942k = 97
10767 measured reflectionsl = 1211
Refinement top
Refinement on F2Hydrogen site location: difference Fourier map
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.024 w = 1/[σ2(Fo2) + (0.0332P)2 + 0.170P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.061(Δ/σ)max < 0.001
S = 1.04Δρmax = 0.16 e Å3
2437 reflectionsΔρmin = 0.15 e Å3
235 parametersExtinction correction: SHELXL2013 (Sheldrick, 2008a), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
1 restraintExtinction coefficient: 0.0090 (15)
Primary atom site location: structure-invariant direct methodsAbsolute structure: Flack parameter determined using 747 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
Secondary atom site location: difference Fourier mapAbsolute structure parameter: 0.03 (5)
Crystal data top
C18H24N2O4·H2OV = 871.39 (3) Å3
Mr = 350.41Z = 2
Monoclinic, P21Cu Kα radiation
a = 9.8073 (2) ŵ = 0.80 mm1
b = 8.2784 (1) ÅT = 90 K
c = 10.7741 (2) Å0.25 × 0.20 × 0.04 mm
β = 95.015 (1)°
Data collection top
Bruker X8 Proteum
diffractometer
2437 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 2008a)
2425 reflections with I > 2σ(I)
Tmin = 0.836, Tmax = 0.942Rint = 0.030
10767 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.024H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.061Δρmax = 0.16 e Å3
S = 1.04Δρmin = 0.15 e Å3
2437 reflectionsAbsolute structure: Flack parameter determined using 747 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
235 parametersAbsolute structure parameter: 0.03 (5)
1 restraint
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
N10.63838 (13)0.11358 (19)0.56147 (12)0.0159 (3)
N20.61292 (14)0.0075 (2)0.74068 (12)0.0197 (3)
O10.92738 (12)0.85603 (16)0.33577 (10)0.0183 (3)
O20.83645 (12)0.60393 (16)0.51264 (9)0.0185 (3)
O30.71648 (13)0.48872 (17)0.65518 (10)0.0221 (3)
O40.47506 (11)0.43708 (16)0.02773 (10)0.0179 (3)
H40.43640.46480.09100.027*
C10.71890 (15)0.6089 (2)0.02275 (13)0.0161 (3)
H1A0.62930.64970.00170.019*
C20.83497 (16)0.7229 (2)0.00040 (14)0.0163 (3)
H2A0.81120.78030.07910.020*
H2B0.91780.65760.00990.020*
C30.87106 (16)0.8502 (2)0.10296 (14)0.0166 (4)
H3A0.93200.93300.07130.020*
H3B0.78640.90460.12450.020*
C40.94124 (16)0.7722 (2)0.21808 (14)0.0153 (3)
C50.85016 (16)0.7092 (2)0.30889 (14)0.0152 (3)
H5A0.75060.72740.28470.018*
C60.87955 (16)0.5643 (2)0.38885 (14)0.0152 (4)
H6A0.97900.53620.39400.018*
C70.79086 (15)0.4188 (2)0.34526 (13)0.0141 (3)
H7A0.70110.46030.30690.017*
C80.85003 (16)0.3049 (2)0.25191 (14)0.0165 (4)
H8A0.79470.20470.24650.020*
H8B0.94420.27500.28440.020*
C90.85478 (15)0.3742 (2)0.11888 (14)0.0164 (4)
H9A0.93220.45110.11930.020*
H9B0.87340.28470.06180.020*
C100.72548 (15)0.4597 (2)0.06786 (13)0.0147 (3)
C110.76625 (16)0.3373 (2)0.46888 (14)0.0153 (3)
H11A0.84570.26530.49420.018*
C120.76819 (16)0.4785 (2)0.55787 (14)0.0168 (3)
C130.63503 (16)0.2376 (2)0.46427 (14)0.0179 (4)
H13A0.55670.31070.47350.021*
H13B0.62010.18480.38170.021*
C140.59851 (15)0.3551 (2)0.06538 (14)0.0168 (4)
H14A0.60890.26340.00800.020*
H14B0.59180.30990.14970.020*
C151.08469 (16)0.7115 (2)0.20694 (15)0.0181 (4)
H15A1.11820.65630.28410.027*
H15B1.14480.80290.19250.027*
H15C1.08430.63580.13700.027*
C160.58471 (15)0.1233 (2)0.67287 (14)0.0178 (4)
H16A0.53340.21260.69890.021*
C170.68861 (16)0.1053 (2)0.66946 (15)0.0186 (4)
H17A0.72390.20840.69400.022*
C180.70535 (15)0.0320 (2)0.55829 (14)0.0167 (3)
H18A0.75340.07310.49230.020*
O1W0.45357 (13)0.47330 (19)0.23096 (12)0.0248 (3)
H1W0.458 (2)0.470 (4)0.150 (2)0.037*
H2W0.534 (3)0.492 (4)0.249 (2)0.037*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0161 (6)0.0167 (8)0.0149 (6)0.0029 (6)0.0018 (5)0.0004 (6)
N20.0210 (7)0.0198 (8)0.0187 (6)0.0055 (6)0.0036 (5)0.0015 (6)
O10.0228 (5)0.0157 (7)0.0168 (5)0.0042 (5)0.0042 (4)0.0020 (5)
O20.0261 (6)0.0167 (7)0.0131 (5)0.0028 (5)0.0043 (4)0.0003 (5)
O30.0317 (6)0.0194 (7)0.0163 (5)0.0021 (6)0.0088 (5)0.0018 (5)
O40.0141 (5)0.0227 (7)0.0170 (5)0.0000 (5)0.0021 (4)0.0003 (5)
C10.0143 (7)0.0191 (9)0.0149 (7)0.0006 (7)0.0003 (5)0.0004 (7)
C20.0173 (7)0.0167 (9)0.0147 (7)0.0001 (7)0.0005 (5)0.0041 (7)
C30.0163 (7)0.0151 (9)0.0186 (7)0.0016 (7)0.0022 (6)0.0021 (7)
C40.0175 (7)0.0134 (9)0.0150 (7)0.0018 (6)0.0014 (6)0.0012 (6)
C50.0161 (7)0.0138 (9)0.0157 (7)0.0000 (7)0.0022 (6)0.0008 (7)
C60.0161 (7)0.0168 (10)0.0130 (7)0.0004 (6)0.0031 (6)0.0003 (6)
C70.0157 (7)0.0130 (9)0.0139 (7)0.0004 (7)0.0019 (5)0.0019 (6)
C80.0185 (7)0.0144 (9)0.0166 (7)0.0023 (7)0.0016 (6)0.0006 (7)
C90.0170 (7)0.0172 (9)0.0154 (7)0.0014 (7)0.0038 (6)0.0005 (7)
C100.0160 (7)0.0174 (9)0.0109 (6)0.0005 (7)0.0021 (5)0.0018 (6)
C110.0171 (7)0.0152 (9)0.0135 (7)0.0000 (7)0.0012 (5)0.0023 (6)
C120.0186 (7)0.0159 (9)0.0156 (7)0.0002 (7)0.0008 (6)0.0030 (6)
C130.0182 (7)0.0188 (10)0.0165 (7)0.0015 (7)0.0001 (6)0.0045 (7)
C140.0184 (7)0.0157 (9)0.0164 (7)0.0006 (7)0.0019 (5)0.0001 (7)
C150.0152 (7)0.0223 (10)0.0168 (7)0.0015 (7)0.0006 (6)0.0013 (7)
C160.0162 (7)0.0190 (10)0.0187 (7)0.0020 (7)0.0044 (6)0.0017 (7)
C170.0194 (7)0.0144 (9)0.0216 (8)0.0017 (7)0.0005 (6)0.0009 (7)
C180.0174 (7)0.0141 (9)0.0186 (7)0.0012 (6)0.0014 (6)0.0039 (7)
O1W0.0252 (6)0.0304 (8)0.0190 (6)0.0031 (6)0.0024 (5)0.0011 (6)
Geometric parameters (Å, º) top
N1—C161.354 (2)C7—C81.529 (2)
N1—C181.374 (2)C7—C111.531 (2)
N1—C131.465 (2)C7—H7A1.0000
N2—C161.322 (2)C8—C91.549 (2)
N2—C171.377 (2)C8—H8A0.9900
O1—C51.448 (2)C8—H8B0.9900
O1—C41.4623 (19)C9—C101.513 (2)
O2—C121.350 (2)C9—H9A0.9900
O2—C61.4709 (18)C9—H9B0.9900
O3—C121.207 (2)C10—C141.515 (2)
O4—C141.416 (2)C11—C121.511 (2)
O4—H40.8400C11—C131.526 (2)
C1—C101.327 (3)C11—H11A1.0000
C1—C21.514 (2)C13—H13A0.9900
C1—H1A0.9500C13—H13B0.9900
C2—C31.545 (2)C14—H14A0.9900
C2—H2A0.9900C14—H14B0.9900
C2—H2B0.9900C15—H15A0.9800
C3—C41.510 (2)C15—H15B0.9800
C3—H3A0.9900C15—H15C0.9800
C3—H3B0.9900C16—H16A0.9500
C4—C51.477 (2)C17—C181.365 (2)
C4—C151.509 (2)C17—H17A0.9500
C5—C61.490 (2)C18—H18A0.9500
C5—H5A1.0000O1W—H1W0.87 (3)
C6—C71.536 (2)O1W—H2W0.85 (3)
C6—H6A1.0000
C16—N1—C18107.33 (15)C7—C8—H8B108.5
C16—N1—C13127.27 (16)C9—C8—H8B108.5
C18—N1—C13125.28 (14)H8A—C8—H8B107.5
C16—N2—C17105.71 (14)C10—C9—C8114.69 (13)
C5—O1—C460.97 (10)C10—C9—H9A108.6
C12—O2—C6110.30 (13)C8—C9—H9A108.6
C14—O4—H4109.5C10—C9—H9B108.6
C10—C1—C2128.70 (15)C8—C9—H9B108.6
C10—C1—H1A115.6H9A—C9—H9B107.6
C2—C1—H1A115.7C1—C10—C9125.51 (15)
C1—C2—C3116.07 (13)C1—C10—C14120.80 (14)
C1—C2—H2A108.3C9—C10—C14113.61 (15)
C3—C2—H2A108.3C12—C11—C13113.76 (13)
C1—C2—H2B108.3C12—C11—C7102.53 (14)
C3—C2—H2B108.3C13—C11—C7113.99 (12)
H2A—C2—H2B107.4C12—C11—H11A108.8
C4—C3—C2110.81 (14)C13—C11—H11A108.8
C4—C3—H3A109.5C7—C11—H11A108.8
C2—C3—H3A109.5O3—C12—O2121.27 (17)
C4—C3—H3B109.5O3—C12—C11128.51 (17)
C2—C3—H3B109.5O2—C12—C11110.21 (13)
H3A—C3—H3B108.1N1—C13—C11112.93 (12)
O1—C4—C559.05 (10)N1—C13—H13A109.0
O1—C4—C15112.65 (12)C11—C13—H13A109.0
C5—C4—C15123.88 (15)N1—C13—H13B109.0
O1—C4—C3116.05 (14)C11—C13—H13B109.0
C5—C4—C3115.89 (13)H13A—C13—H13B107.8
C15—C4—C3116.01 (13)O4—C14—C10114.33 (14)
O1—C5—C459.98 (10)O4—C14—H14A108.7
O1—C5—C6119.25 (12)C10—C14—H14A108.7
C4—C5—C6124.74 (15)O4—C14—H14B108.7
O1—C5—H5A114.0C10—C14—H14B108.7
C4—C5—H5A114.0H14A—C14—H14B107.6
C6—C5—H5A114.0C4—C15—H15A109.5
O2—C6—C5106.78 (14)C4—C15—H15B109.5
O2—C6—C7104.61 (12)H15A—C15—H15B109.5
C5—C6—C7112.27 (12)C4—C15—H15C109.5
O2—C6—H6A111.0H15A—C15—H15C109.5
C5—C6—H6A111.0H15B—C15—H15C109.5
C7—C6—H6A111.0N2—C16—N1111.24 (16)
C8—C7—C11113.47 (14)N2—C16—H16A124.4
C8—C7—C6116.59 (13)N1—C16—H16A124.4
C11—C7—C6102.00 (12)C18—C17—N2109.84 (16)
C8—C7—H7A108.1C18—C17—H17A125.1
C11—C7—H7A108.1N2—C17—H17A125.1
C6—C7—H7A108.1C17—C18—N1105.87 (14)
C7—C8—C9115.08 (14)C17—C18—H18A127.1
C7—C8—H8A108.5N1—C18—H18A127.1
C9—C8—H8A108.5H1W—O1W—H2W106 (2)
C10—C1—C2—C398.0 (2)C2—C1—C10—C14170.69 (14)
C1—C2—C3—C472.09 (17)C8—C9—C10—C1126.24 (17)
C5—O1—C4—C15117.00 (17)C8—C9—C10—C1456.95 (19)
C5—O1—C4—C3105.88 (16)C8—C7—C11—C12156.85 (12)
C2—C3—C4—O1154.00 (13)C6—C7—C11—C1230.61 (15)
C2—C3—C4—C587.53 (18)C8—C7—C11—C1379.73 (17)
C2—C3—C4—C1570.32 (19)C6—C7—C11—C13154.03 (14)
C4—O1—C5—C6115.52 (17)C6—O2—C12—O3175.49 (14)
C15—C4—C5—O197.94 (17)C6—O2—C12—C113.08 (17)
C3—C4—C5—O1106.14 (16)C13—C11—C12—O332.8 (2)
O1—C4—C5—C6106.62 (16)C7—C11—C12—O3156.40 (16)
C15—C4—C5—C68.7 (3)C13—C11—C12—O2145.62 (13)
C3—C4—C5—C6147.24 (15)C7—C11—C12—O222.05 (16)
C12—O2—C6—C5136.46 (13)C16—N1—C13—C1197.44 (18)
C12—O2—C6—C717.28 (15)C18—N1—C13—C1178.22 (19)
O1—C5—C6—O267.27 (17)C12—C11—C13—N185.46 (18)
C4—C5—C6—O2139.25 (15)C7—C11—C13—N1157.44 (14)
O1—C5—C6—C7178.64 (13)C1—C10—C14—O48.0 (2)
C4—C5—C6—C7106.66 (17)C9—C10—C14—O4174.99 (12)
O2—C6—C7—C8153.79 (12)C17—N2—C16—N10.21 (18)
C5—C6—C7—C890.80 (17)C18—N1—C16—N20.26 (18)
O2—C6—C7—C1129.62 (15)C13—N1—C16—N2176.55 (14)
C5—C6—C7—C11145.03 (13)C16—N2—C17—C180.07 (17)
C11—C7—C8—C9170.63 (12)N2—C17—C18—N10.08 (17)
C6—C7—C8—C971.29 (17)C16—N1—C18—C170.20 (17)
C7—C8—C9—C1045.1 (2)C13—N1—C18—C17176.58 (13)
C2—C1—C10—C95.9 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O4—H4···N2i0.841.932.7491 (17)164
C13—H13B···O1Wii0.992.453.388 (2)157
C15—H15B···O3iii0.982.553.282 (2)131
C16—H16A···O1Wiv0.952.443.370 (2)167
C17—H17A···O3v0.952.543.377 (2)147
C18—H18A···O1v0.952.573.5016 (19)167
O1W—H1W···O40.87 (3)1.93 (3)2.7928 (17)173 (3)
O1W—H2W···O3vi0.85 (3)2.14 (3)2.9534 (19)162 (2)
Symmetry codes: (i) x+1, y+1/2, z+1; (ii) x+1, y1/2, z; (iii) x+2, y+1/2, z+1; (iv) x, y, z+1; (v) x, y1, z; (vi) x, y, z1.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O4—H4···N2i0.841.932.7491 (17)164.2
C13—H13B···O1Wii0.992.453.388 (2)157.1
C15—H15B···O3iii0.982.553.282 (2)131.1
C16—H16A···O1Wiv0.952.443.370 (2)166.6
C17—H17A···O3v0.952.543.377 (2)146.7
C18—H18A···O1v0.952.573.5016 (19)167.0
O1W—H1W···O40.87 (3)1.93 (3)2.7928 (17)173 (3)
O1W—H2W···O3vi0.85 (3)2.14 (3)2.9534 (19)162 (2)
Symmetry codes: (i) x+1, y+1/2, z+1; (ii) x+1, y1/2, z; (iii) x+2, y+1/2, z+1; (iv) x, y, z+1; (v) x, y1, z; (vi) x, y, z1.
 

Acknowledgements

This work was supported by NIH/NCI grant CA158275.

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Volume 69| Part 12| December 2013| Pages o1734-o1735
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