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

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 70| Part 3| March 2014| Pages o251-o252

(E)-13-(2-Bromo­phen­yl)micheliolide

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 20 November 2013; accepted 29 January 2014; online 5 February 2014)

The title compound, C21H23BrO3 [systematic name: (3E,3aS,6Z,9R,9aS,9bS)-3-(2-bromo­benzyl­idene)-9-hy­droxy-6,9-dimethyl-3,3a,4,5,7,8,9,9a-octa­hydro­azuleno[4,5-b]furan-2(9bH)-one] was prepared by the reaction of 1-bromo-2-iodo­benzene with micheliolide [systematic name: (3aS,R,9aS,9bS,Z)-9-hy­droxy-6,9-dimethyl-3-methyl­ene-3,3a,4,5,7,8,9,9a-octa­hydro­azuleno[4,5-b]furan-2(9bH)-one] under Heck reaction conditions. The title compound exhibits intra­molecular O—H⋯O hydrogen bonding between the hy­droxy group and the lactone ring O atom, forming a ring of graph-set motif S(6). The 2-bromo­phenyl group is trans to the lactone ring, indicating that this is the E isomer (geometry of the exocyclic C=C bond). The dihedral angle between the benzene ring of the 2-bromo­phenyl moiety and the mean plane of the lactone ring is 51.68 (7)°.

Related literature

For the biological activity of micheliolide Michael addition compounds, see: Rodriguez et al. (1976[Rodriguez, E., Towers, G. H. N. & Mitchell, J. C. (1976). Phytochemistry, 15, 1573-1580.]); Sethi et al. (1984[Sethi, V. K., Thappat, R. K., Dhar, K. L. & Atal, C. K. (1984). Planta Med. 50, 364-?.]); 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.]); Zhang et al. (2012[Zhang, Q., Lu, Y., Ding, Y., Zhai, J., Ji, Q., Ma, W., Yang, M., Fan, H., Long, J., Tong, Z., Shi, Y., Jia, Y., Han, B., Zhang, W., Qiu, C., Ma, X., Li, Q., Shi, Q., Zhang, H., Li, D., Zhang, J., Lin, J., Li, L. Y., Gao, Y. & Chen, Y. (2012). J. Med. Chem. 55, 8757-8769.]). For details of the Heck chemistry, see: Han et al. (2009[Han, C., Barrios, F. J., Riofski, M. V. & Colby, D. A. (2009). J. Org. Chem. 74, 7176-7179.]). For the crystal structure of micheliolide, see: Acosta et al. (1991[Acosta, J. C., Fronczek, F. R. & Fischer, N. H. (1991). Acta Cryst. C47, 2702-2704.]). For the crystal structure of a similar compound, see: Penthala et al. (2013[Penthala, N. R., Janganati, V., Parkin, S., Varughese, K. I. & Crooks, P. A. (2013). Acta Cryst. E69, o1709-o1710.]).

[Scheme 1]

Experimental

Crystal data
  • C21H23BrO3

  • Mr = 403.30

  • Orthorhombic, P 21 21 21

  • a = 7.1617 (1) Å

  • b = 13.1615 (2) Å

  • c = 19.2306 (3) Å

  • V = 1812.65 (5) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 2.29 mm−1

  • T = 90 K

  • 0.20 × 0.20 × 0.15 mm

Data collection
  • Nonius KappaCCD diffractometer

  • Absorption correction: multi-scan (SADABS; Sheldrick, 2008a[Sheldrick, G. M. (2008a). SADABS University of Göttingen, Germany.]) Tmin = 0.550, Tmax = 0.714

  • 48139 measured reflections

  • 4148 independent reflections

  • 3871 reflections with I > 2σ(I)

  • Rint = 0.047

Refinement
  • R[F2 > 2σ(F2)] = 0.025

  • wR(F2) = 0.064

  • S = 1.04

  • 4148 reflections

  • 231 parameters

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

  • Δρmax = 0.41 e Å−3

  • Δρmin = −0.34 e Å−3

  • Absolute structure: Flack parameter determined using 1569 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: 0.032 (3)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
O3—H3⋯O2 0.77 (4) 2.26 (4) 2.883 (3) 139 (4)

Data collection: COLLECT (Nonius, 1998[Nonius (1998). COLLECT. Nonius BV, Delft, The Netherlands.]); cell refinement: SCALEPACK (Otwinowski & Minor, 2006[Otwinowski, Z. & Minor, W. (2006). International Tables for Crystallography, Vol. F, ch. 11.4, pp. 226-235. Dordrecht: Kluwer Academic Publishers.]); data reduction: DENZO-SMN (Otwinowski & Minor, 2006[Otwinowski, Z. & Minor, W. (2006). International Tables for Crystallography, Vol. F, ch. 11.4, pp. 226-235. Dordrecht: Kluwer Academic Publishers.]); 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: SHELXL97 (Sheldrick, 2008b[Sheldrick, G. M. (2008b). Acta Cryst. A64, 112-122.]).

Supporting information


Comment top

Micheliolide (MCL) belongs to the class of guaianolide sesquiterpene lactones, which are being developed for the treatment of cancer (Sethi et al., 1984 and Zhang et al., 2012). The exocyclic double bond in such sesquiterpenes is believed to be responsible for their biological properties because of its exceptional chemical reactivity with nucleophilic groups (Rodriguez et al., 1976). The MCL crystal structure was described by Acosta et al. (1991). Recently, micheliolide Michael addition analogs were reported as potent anti-leukemic agents (Zhang et al., 2012). In a recent communication we reported the crystal structure of (E)-13-(4-aminophenyl)parthenolide, a Heck reaction derivative of parthenolide (Penthala et al., 2013). Now, in continuation of our research on sesquiterpene lactones as anti-leukemic agents (Neelakantan et al., 2009), we are focusing on the synthesis of the title E-olefinic analogue of micheliolide, which was obtained from the reaction of micheliolide with 1-bromo-2-iodobenzene utilizing Heck chemistry (Han et al., 2009). In order to obtain detailed information on the structural conformation of the title compound and to establish the geometry of the exocyclic double bond, a single-crystal X-ray structure determination has been carried out.

Recrystallization of the title compound from hexanes gave colorless needles that were suitable for X-ray analysis. The title molecule, Fig. 1, contains a central seven-membered carbocyclic ring fused to a 5-membered carbocylic ring and a trans lactone ring. The two five-membered rings are in half-chair conformations, as reported in the literature for the parent compound, micheliolide (Acosta et al., 1991). The X-ray studies revealed that the title compound exhibits intramolecular O—H···O hydrogen bonding to form a ring of graph-set motif S(6). The 2-bromophenyl group is oriented trans to the lactone ring to form the E isomer (geometry of the exocyclic CC bond). The H atom of the hydroxy group in the molecule forms an intramolecular hydrogen bond with the lactone ring oxygen atom. The dihedral angle between the benzene ring of the 2-bromophenyl group and the mean plane of the lactone ring is 51.68 (7)°.

Related literature top

For the biological activity of micheliolide Michael addition compounds, see: Rodriguez et al. (1976); Sethi et al. (1984); Neelakantan et al. (2009); Zhang et al. (2012). For details of the Heck chemistry, see: Han et al. (2009). For the crystal structure of micheliolide, see: Acosta et al. (1991). For the crystal structure of a similar compound, see: Penthala et al. (2013).

Experimental top

A mixture of micheliolide (prepared from parthenolide, Zhang et al., 2012) (50 mg, 0.20 mmol), triethylamine (60 mg, 0.61 mmol), and 1-bromo-2-iodobenzene (63 mg, 0.22 mmol) in dimethylformamide (1 ml) was treated with palladium(II) acetate (0.5 mg, 0.002 mmol) and then stirred at 353 K for 24 h. The reaction mixture was cooled to room temperature, water (8 ml) was added, and the mixture was extracted with ethyl acetate (10 ml x 3). The separated organics were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude residue was purified using silica flash chromatography (7:3, hexanes/EtOAc) to afford the title compound, which was recrystallized from hexanes as colorless needles suitable for X-ray analysis (65 mg, 80% yield; M·P: 421–423 K); 1H NMR (400 MHz, CDCl3): δ 7.70–7.70 (d, J=2.8 Hz, 1H), 7.62–7.64 (d, J=8.0 Hz, 1H), 7.22–7.35 (m, 3H, Ar—H and =CH), 3.89–3.94 (t, J=10 Hz, 20.4 Hz, 1H), 3.01–3.06 (t, J=8.8 Hz, 19.6 Hz, 1H), 2.73–2.76 (d, J=11.2 Hz, 1H), 2.71 (s, 1H), 2.35–2.41 (m, 1H), 2.01–2.21 (m, 1H), 1.76–1.89 (m, 3H), 1.61 (s, 3H), 1.32 (s, 3H), 1.00–1.04 (m, 1H) p.p.m.. 13C NMR (100 MHz, CDCl3): δ 22.57, 23.69, 24.91, 29.86, 35.36, 38.23, 48.93, 58.99, 80.79, 124.14, 126.93, 129.86, 130.47, 130.55, 131.03, 131.50, 132.86, 134.54, 136.70, 170.68 p.p.m..

Refinement top

H atoms were found in difference Fourier maps. Carbon-bound H atoms were subsequently placed at idealized positions with constrained distances of 0.98 Å (RCH3), 0.99 Å (R2CH2), 1.00 Å (R3CH) and 0.95 Å (Csp2H). The hydroxy 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: COLLECT (Nonius, 1998); cell refinement: SCALEPACK (Otwinowski & Minor, 2006); data reduction: DENZO-SMN (Otwinowski & Minor, 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: SHELXL97 (Sheldrick, 2008b).

Figures top
[Figure 1] Fig. 1. A view of the molecule with displacement ellipsoids drawn at the 50% probability level.
(3E,3aS,6Z,9R,9aS,9bS)-3-(2-Bromobenzylidene)-9-hydroxy-6,9-dimethyl-3,3a,4,5,7,8,9,9a-octahydroazuleno[4,5-b]furan-2(9bH)-one top
Crystal data top
C21H23BrO3Dx = 1.478 Mg m3
Mr = 403.30Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121Cell parameters from 127083 reflections
a = 7.1617 (1) Åθ = 1.0–27.5°
b = 13.1615 (2) ŵ = 2.29 mm1
c = 19.2306 (3) ÅT = 90 K
V = 1812.65 (5) Å3Block, cut from needle, colourless
Z = 40.20 × 0.20 × 0.15 mm
F(000) = 832
Data collection top
Nonius KappaCCD
diffractometer
4148 independent reflections
Radiation source: fine-focus sealed-tube3871 reflections with I > 2σ(I)
Detector resolution: 9.1 pixels mm-1Rint = 0.047
φ and ω scans at fixed χ = 55°θmax = 27.5°, θmin = 1.9°
Absorption correction: multi-scan
(SADABS; Sheldrick, 2008a)
h = 99
Tmin = 0.550, Tmax = 0.714k = 1717
48139 measured reflectionsl = 2424
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.025H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.064 w = 1/[σ2(Fo2) + (0.0352P)2 + 0.4253P]
where P = (Fo2 + 2Fc2)/3
S = 1.04(Δ/σ)max = 0.001
4148 reflectionsΔρmax = 0.41 e Å3
231 parametersΔρmin = 0.34 e Å3
0 restraintsAbsolute structure: Flack parameter determined using 1569 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
Primary atom site location: structure-invariant direct methodsAbsolute structure parameter: 0.032 (3)
Crystal data top
C21H23BrO3V = 1812.65 (5) Å3
Mr = 403.30Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 7.1617 (1) ŵ = 2.29 mm1
b = 13.1615 (2) ÅT = 90 K
c = 19.2306 (3) Å0.20 × 0.20 × 0.15 mm
Data collection top
Nonius KappaCCD
diffractometer
4148 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 2008a)
3871 reflections with I > 2σ(I)
Tmin = 0.550, Tmax = 0.714Rint = 0.047
48139 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.025H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.064Δρmax = 0.41 e Å3
S = 1.04Δρmin = 0.34 e Å3
4148 reflectionsAbsolute structure: Flack parameter determined using 1569 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
231 parametersAbsolute structure parameter: 0.032 (3)
0 restraints
Special details top

Experimental. The crystal was mounted with polyisobutene oil on the tip of a fine glass fibre, fastened in a copper mounting pin with electrical solder. It was placed directly into the cold stream of a liquid nitrogen based cryostat.

Diffraction data were collected with the crystal at 90 K, which is standard practice in this laboratory for the majority of flash-cooled crystals.

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
Br10.79983 (4)0.11654 (2)0.35920 (2)0.03215 (9)
O10.7715 (3)0.26157 (14)0.45446 (10)0.0248 (4)
O20.5251 (3)0.34175 (14)0.40803 (9)0.0215 (4)
O30.3499 (3)0.53339 (15)0.43985 (11)0.0285 (5)
H30.434 (6)0.498 (3)0.444 (2)0.043*
C10.0338 (3)0.3743 (2)0.33548 (13)0.0202 (5)
C20.0575 (4)0.4794 (2)0.33076 (16)0.0252 (6)
H2A0.05530.50460.28230.030*
H2B0.18870.47650.34680.030*
C30.0577 (4)0.5486 (2)0.37792 (14)0.0243 (6)
H3A0.06330.61840.35890.029*
H3B0.00370.55120.42530.029*
C40.2513 (4)0.50008 (19)0.37900 (13)0.0208 (5)
C50.2022 (3)0.38520 (18)0.38337 (12)0.0185 (4)
H50.16020.37040.43190.022*
C60.3602 (3)0.31433 (18)0.36651 (14)0.0192 (5)
H60.39170.32110.31610.023*
C70.3212 (4)0.20208 (18)0.38266 (13)0.0198 (5)
H70.23140.19840.42240.024*
C80.2325 (4)0.1511 (2)0.31966 (14)0.0237 (6)
H8A0.24080.07640.32510.028*
H8B0.30310.17020.27740.028*
C90.0275 (4)0.1814 (2)0.31045 (16)0.0259 (6)
H9A0.04130.15380.35090.031*
H9B0.01930.14490.26900.031*
C100.0321 (4)0.2927 (2)0.30252 (14)0.0212 (5)
C110.5102 (4)0.1654 (2)0.40740 (13)0.0201 (5)
C120.6223 (4)0.2566 (2)0.42595 (13)0.0204 (5)
C130.5791 (4)0.07309 (19)0.42009 (13)0.0210 (5)
H130.70920.06970.42950.025*
C140.2025 (4)0.3016 (2)0.25629 (14)0.0257 (5)
H14A0.24710.37200.25650.039*
H14B0.30110.25670.27380.039*
H14C0.16950.28170.20870.039*
C150.3630 (4)0.5270 (2)0.31404 (15)0.0255 (6)
H15A0.37760.60100.31110.038*
H15B0.29690.50240.27270.038*
H15C0.48640.49510.31650.038*
C160.4774 (4)0.0247 (2)0.42131 (13)0.0204 (5)
C170.5616 (4)0.1163 (2)0.40254 (13)0.0220 (5)
C180.4756 (4)0.2095 (2)0.41364 (14)0.0252 (6)
H180.53560.27070.39990.030*
C190.3015 (5)0.21243 (19)0.44500 (14)0.0261 (6)
H190.24340.27590.45420.031*
C200.2116 (4)0.1224 (2)0.46308 (13)0.0251 (5)
H200.09090.12440.48350.030*
C210.2988 (4)0.02945 (19)0.45117 (13)0.0228 (5)
H210.23640.03170.46340.027*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Br10.03169 (14)0.02821 (14)0.03656 (15)0.00934 (12)0.00802 (12)0.00322 (13)
O10.0264 (10)0.0225 (9)0.0254 (9)0.0003 (8)0.0026 (8)0.0020 (8)
O20.0249 (9)0.0140 (8)0.0256 (9)0.0014 (7)0.0045 (7)0.0001 (7)
O30.0383 (12)0.0152 (9)0.0319 (11)0.0016 (8)0.0109 (9)0.0040 (8)
C10.0231 (11)0.0163 (12)0.0212 (11)0.0009 (10)0.0027 (9)0.0025 (10)
C20.0257 (13)0.0145 (12)0.0355 (15)0.0004 (10)0.0034 (11)0.0028 (11)
C30.0301 (13)0.0148 (12)0.0281 (14)0.0020 (10)0.0017 (11)0.0004 (10)
C40.0289 (12)0.0112 (11)0.0224 (13)0.0009 (9)0.0046 (10)0.0001 (9)
C50.0231 (11)0.0120 (10)0.0204 (10)0.0016 (12)0.0008 (9)0.0005 (9)
C60.0242 (11)0.0148 (11)0.0185 (12)0.0012 (9)0.0028 (10)0.0006 (10)
C70.0258 (12)0.0119 (11)0.0218 (12)0.0010 (10)0.0007 (10)0.0009 (9)
C80.0304 (14)0.0162 (12)0.0246 (13)0.0016 (10)0.0023 (11)0.0038 (10)
C90.0290 (13)0.0172 (13)0.0316 (14)0.0001 (11)0.0044 (11)0.0055 (11)
C100.0229 (12)0.0187 (13)0.0221 (13)0.0003 (10)0.0010 (10)0.0000 (10)
C110.0261 (13)0.0175 (13)0.0168 (12)0.0002 (10)0.0008 (10)0.0004 (10)
C120.0254 (13)0.0176 (12)0.0182 (12)0.0011 (10)0.0006 (10)0.0013 (10)
C130.0255 (13)0.0184 (12)0.0191 (12)0.0010 (10)0.0022 (10)0.0006 (10)
C140.0236 (12)0.0222 (13)0.0312 (14)0.0014 (12)0.0005 (12)0.0016 (11)
C150.0262 (13)0.0179 (13)0.0323 (15)0.0013 (10)0.0030 (11)0.0043 (11)
C160.0277 (13)0.0157 (12)0.0179 (12)0.0002 (10)0.0028 (11)0.0009 (10)
C170.0243 (12)0.0205 (12)0.0211 (12)0.0033 (12)0.0017 (9)0.0009 (11)
C180.0360 (15)0.0148 (13)0.0247 (14)0.0045 (11)0.0032 (12)0.0021 (11)
C190.0361 (14)0.0163 (12)0.0259 (13)0.0040 (13)0.0051 (14)0.0014 (10)
C200.0275 (12)0.0214 (12)0.0264 (12)0.0042 (13)0.0001 (11)0.0025 (11)
C210.0279 (12)0.0155 (12)0.0251 (12)0.0024 (12)0.0004 (13)0.0019 (10)
Geometric parameters (Å, º) top
Br1—C171.899 (3)C8—H8B0.9900
O1—C121.203 (3)C9—C101.533 (4)
O2—C121.364 (3)C9—H9A0.9900
O2—C61.470 (3)C9—H9B0.9900
O3—C41.435 (3)C10—C141.514 (4)
O3—H30.77 (4)C11—C131.335 (4)
C1—C101.333 (4)C11—C121.487 (4)
C1—C51.525 (3)C13—C161.479 (4)
C1—C21.532 (4)C13—H130.9500
C2—C31.527 (4)C14—H14A0.9800
C2—H2A0.9900C14—H14B0.9800
C2—H2B0.9900C14—H14C0.9800
C3—C41.527 (4)C15—H15A0.9800
C3—H3A0.9900C15—H15B0.9800
C3—H3B0.9900C15—H15C0.9800
C4—C151.525 (4)C16—C171.396 (4)
C4—C51.555 (3)C16—C211.403 (4)
C5—C61.502 (3)C17—C181.389 (4)
C5—H51.0000C18—C191.386 (4)
C6—C71.535 (3)C18—H180.9500
C6—H61.0000C19—C201.393 (4)
C7—C111.514 (4)C19—H190.9500
C7—C81.524 (4)C20—C211.392 (4)
C7—H71.0000C20—H200.9500
C8—C91.532 (4)C21—H210.9500
C8—H8A0.9900
C12—O2—C6110.22 (19)C8—C9—H9A106.9
C4—O3—H3106 (3)C10—C9—H9A106.9
C10—C1—C5130.0 (2)C8—C9—H9B106.9
C10—C1—C2123.2 (2)C10—C9—H9B106.9
C5—C1—C2106.8 (2)H9A—C9—H9B106.7
C3—C2—C1105.8 (2)C1—C10—C14120.2 (2)
C3—C2—H2A110.6C1—C10—C9128.6 (2)
C1—C2—H2A110.6C14—C10—C9110.8 (2)
C3—C2—H2B110.6C13—C11—C12119.4 (2)
C1—C2—H2B110.6C13—C11—C7132.7 (2)
H2A—C2—H2B108.7C12—C11—C7107.5 (2)
C4—C3—C2104.4 (2)O1—C12—O2121.6 (2)
C4—C3—H3A110.9O1—C12—C11129.3 (2)
C2—C3—H3A110.9O2—C12—C11109.1 (2)
C4—C3—H3B110.9C11—C13—C16127.8 (2)
C2—C3—H3B110.9C11—C13—H13116.1
H3A—C3—H3B108.9C16—C13—H13116.1
O3—C4—C15109.8 (2)C10—C14—H14A109.5
O3—C4—C3109.3 (2)C10—C14—H14B109.5
C15—C4—C3111.6 (2)H14A—C14—H14B109.5
O3—C4—C5111.4 (2)C10—C14—H14C109.5
C15—C4—C5112.9 (2)H14A—C14—H14C109.5
C3—C4—C5101.7 (2)H14B—C14—H14C109.5
C6—C5—C1114.0 (2)C4—C15—H15A109.5
C6—C5—C4115.0 (2)C4—C15—H15B109.5
C1—C5—C4103.7 (2)H15A—C15—H15B109.5
C6—C5—H5107.9C4—C15—H15C109.5
C1—C5—H5107.9H15A—C15—H15C109.5
C4—C5—H5107.9H15B—C15—H15C109.5
O2—C6—C5109.59 (19)C17—C16—C21117.4 (2)
O2—C6—C7105.82 (19)C17—C16—C13122.3 (2)
C5—C6—C7114.6 (2)C21—C16—C13119.7 (2)
O2—C6—H6108.9C18—C17—C16122.1 (2)
C5—C6—H6108.9C18—C17—Br1117.7 (2)
C7—C6—H6108.9C16—C17—Br1120.2 (2)
C11—C7—C8118.8 (2)C19—C18—C17119.3 (3)
C11—C7—C6102.0 (2)C19—C18—H18120.3
C8—C7—C6109.8 (2)C17—C18—H18120.3
C11—C7—H7108.6C18—C19—C20120.1 (2)
C8—C7—H7108.6C18—C19—H19120.0
C6—C7—H7108.6C20—C19—H19120.0
C7—C8—C9112.1 (2)C21—C20—C19119.9 (2)
C7—C8—H8A109.2C21—C20—H20120.0
C9—C8—H8A109.2C19—C20—H20120.0
C7—C8—H8B109.2C20—C21—C16121.0 (3)
C9—C8—H8B109.2C20—C21—H21119.5
H8A—C8—H8B107.9C16—C21—H21119.5
C8—C9—C10121.8 (2)
C10—C1—C2—C3178.0 (2)C2—C1—C10—C141.5 (4)
C5—C1—C2—C31.5 (3)C5—C1—C10—C98.9 (5)
C1—C2—C3—C426.5 (3)C2—C1—C10—C9170.6 (3)
C2—C3—C4—O3158.4 (2)C8—C9—C10—C139.4 (4)
C2—C3—C4—C1580.0 (3)C8—C9—C10—C14147.9 (3)
C2—C3—C4—C540.6 (3)C8—C7—C11—C1348.2 (4)
C10—C1—C5—C631.2 (4)C6—C7—C11—C13169.0 (3)
C2—C1—C5—C6149.3 (2)C8—C7—C11—C12138.5 (2)
C10—C1—C5—C4157.0 (3)C6—C7—C11—C1217.7 (3)
C2—C1—C5—C423.5 (3)C6—O2—C12—O1173.0 (2)
O3—C4—C5—C679.2 (3)C6—O2—C12—C119.5 (3)
C15—C4—C5—C644.9 (3)C13—C11—C12—O13.0 (4)
C3—C4—C5—C6164.5 (2)C7—C11—C12—O1171.3 (3)
O3—C4—C5—C1155.6 (2)C13—C11—C12—O2179.7 (2)
C15—C4—C5—C180.3 (2)C7—C11—C12—O26.0 (3)
C3—C4—C5—C139.3 (2)C12—C11—C13—C16164.5 (2)
C12—O2—C6—C5145.0 (2)C7—C11—C13—C168.2 (5)
C12—O2—C6—C721.0 (3)C11—C13—C16—C17148.9 (3)
C1—C5—C6—O2171.08 (19)C11—C13—C16—C2140.2 (4)
C4—C5—C6—O251.4 (3)C21—C16—C17—C181.1 (4)
C1—C5—C6—C770.1 (3)C13—C16—C17—C18170.0 (3)
C4—C5—C6—C7170.2 (2)C21—C16—C17—Br1178.06 (18)
O2—C6—C7—C1122.9 (2)C13—C16—C17—Br110.8 (3)
C5—C6—C7—C11143.8 (2)C16—C17—C18—C190.7 (4)
O2—C6—C7—C8149.8 (2)Br1—C17—C18—C19179.9 (2)
C5—C6—C7—C889.3 (3)C17—C18—C19—C202.0 (4)
C11—C7—C8—C9168.4 (2)C18—C19—C20—C211.6 (4)
C6—C7—C8—C974.9 (3)C19—C20—C21—C160.3 (4)
C7—C8—C9—C1057.4 (4)C17—C16—C21—C201.6 (4)
C5—C1—C10—C14179.1 (2)C13—C16—C21—C20169.8 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3···O20.77 (4)2.26 (4)2.883 (3)139 (4)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3···O20.77 (4)2.26 (4)2.883 (3)139 (4)
 

Acknowledgements

This work was supported by the NIH/NCI [grant No. CA158275].

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Volume 70| Part 3| March 2014| Pages o251-o252
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