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Acta Cryst. (2008). E64, o978-o979    [ doi:10.1107/S1600536808009410 ]

N-{3-[Bis(2-hydroxyethyl)aminomethyl]-5-nitrophenyl}benzamide

A. Mai, G. S. Khan, G. R. Clark and D. Barker

Abstract top

The title compound, C18H21N3O5, was prepared by the reaction of 3-benzamido-5-nitrobenzyl methanesulfonate with diethanolamine and is an intermediate in the synthesis of DNA minor-groove-binding polybenzamide agents capable of being conjugated to additional biologically active species. The asymmetric unit contains two independent molecules, which differ only in the orientations of the hydroxyethyl groups. In the crystal structure, intermolecular N-H...O and O-H...O hydrogen bonds link molecules into one-dimensional chains.

Comment top

The naturally occurring antibiotic oligopeptides distamycin A, isolated from Streptomyces Distallicus, and netropsin, from Streptomyces netropsis, are powerful DNA minor groove-binding agents but their cytotoxity precludes their use as medicines (Arcamone et al., 1964, Baraldi et al., 2004, Wemmer et al., 2000, Storl et al., 1993). In order to increase the DNA binding affinity and sequence specificity along with minimizing the unwanted physiological activities associated with these natural DNA binders, many synthetic oligopeptides have been prepared (Baraldi et al., 2007). In addition, numerous biologically active species have been conjugated to natural and synthetic DNA binding oligopeptides with the purpose of increasing the concentration of these species near DNA (Kumar et al., 2004, Stafford et al., 2007). The title compound is a key intermediate required in the synthesis of a novel polybenzamide DNA minor groove-binding agent.

Related literature top

For related literature on the biological activity of polybenzamide DNA binding agents, see: Storl et al. (1993). For related literature on natural and synthetic minor-groove binding agents, including agents containing conjugates, see: Arcamone et al. (1964); Atwell et al. (1995); Baraldi et al. (1999, 2004, 2007); Kumar et al. (2004); Sengupta et al. (1996); Stafford et al. (2007); Turner et al. (1999); Wemmer (2000); Yan et al. (1997). For related literature, see: Barker et al. (2008).

Experimental top

N,N-Bis(2-hydroxyethyl)-3-benzamido-5-nitrobenzylamine was prepared using the method of Barker et al.(2008). To a solution of 3-benzamido-5-nitrobenzyl methanesulfonate (0.129 g, 0.368 mmol) in dry THF (1 ml) was added dropwise to a stirred suspension of diethanolamine (0.387 g, 3.68 mmol) in dry THF (2 ml) at 273 K. The mixture was then stirred under an atmosphere of nitrogen overnight before being concentrated in vacuo to give a crude residue. This residue was diluted with ethyl acetate (10 ml) and extracted with 2M HCl (2 x 10 ml). The combined acidic extracts were neutralized with 4M NaOH and then extracted with ethyl acetate (2 x 15 ml). The combined organic extracts were dried (MgSO4), filtered and the solvent removed in vacuo, to afford the title compound (0.128 g, 97%), as a yellow solid, which was recrystallized from ethyl acetate to give yellow crystals (m.p. 385–387 K) suitable for X-ray crystallography. Spectroscopic analysis: IR (νmax, thin film, cm-1) 2906, 1680, 1527, 1377. 1H NMR (300 MHz, CDCl3, δ, p.p.m.) 2.60 (4H, m, N(CH2CH2OH)2, 3.61 (2H, s, Ar—CH2N), 3.68 (4H, m, N(CH2CH2OH)2), 7.32 (3H, m, Ar—H), 7.46 (1H, m, Ar—H), 7.59 (1H, s, Ar—H), 7.67 (1H, m, Ar—H), 8.10 (1H, br s, Ar—H), 8.35 (1H, m, Ar—H) and 9.03 (NH). 13C NMR (75 MHz, CDCl3, δ, p.p.m.) 55.9 (CH2, N(CH2CH2OH)2), 58.4 (CH2, Ar—CH2N), 59.2 (CH2, N(CH2CH2OH)2), 114.5 (CH, Ar—C), 118.6 (CH, Ar—C), 125.9 (CH, Ar—C), 127.2 (CH, Ar—C), 128.4 (CH, Ar—C), 132.3 (CH, Ar—C), 133.2 (quat. Ar—C), 139.2 (quat. Ar—C), 142.3 (quat. Ar—C), 148.1 (quat. Ar—C) and 166.4 (C=O) MS m/z (FAB) 360 (M+, 9%), 219 (4), 154 (100), and 120 (NHCOC6H5, 8). HRMS (FAB), found: MH+ 360.15572. C18H22N3O5 requires: 360.15595.

Refinement top

Most hydrogen atoms were placed in calculated positions and refined using the riding model with C—H 0.93–0.97 Å and N—H = 0.86 Å, with Uiso(H) = 1.2 or 1.5 times Ueq(C). H atoms bonded to O atoms were located in a difference map and refined independently with isotropic displacement parameters.

Computing details top

Data collection: SMART (Bruker, 1995); cell refinement: SAINT (Bruker, 1995); data reduction: SAINT (Bruker, 1995); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPIII (Burnett & Johnson, 1996); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. Molecular structure of one of the independent molecules showing 50% probability displacement ellipsoids for non-hydrogen atoms and hydrogen atoms as arbitary spheres (Burnett & Johnson, 1996).
N-{3-[Bis(2-hydroxyethyl)aminomethyl]-5-nitrophenyl}benzamide top
Crystal data top
C18H21N3O5F000 = 1520
Mr = 359.38Dx = 1.399 Mg m−3
Monoclinic, P21/cMo Kα radiation
λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 8192 reflections
a = 22.7867 (3) Åθ = 0.9–26.4º
b = 11.0879 (1) ŵ = 0.10 mm−1
c = 13.5106 (1) ÅT = 90 (2) K
β = 90.114 (1)ºNeedle, yellow
V = 3413.54 (6) Å30.34 × 0.22 × 0.20 mm
Z = 8
Data collection top
Bruker SMART CCD
diffractometer		6944 independent reflections
Radiation source: fine-focus sealed tube5142 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.039
T = 90(2) Kθmax = 26.4º
area–detector ω scansθmin = 0.9º
Absorption correction: multi-scan
(SADABS; Sheldrick, 1997)		h = −28→25
Tmin = 0.858, Tmax = 0.978k = −12→13
20279 measured reflectionsl = −16→16
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.058H atoms treated by a mixture of
independent and constrained refinement
wR(F2) = 0.134  w = 1/[σ2(Fo2) + (0.0471P)2 + 3.1255P]
where P = (Fo2 + 2Fc2)/3
S = 1.04(Δ/σ)max < 0.001
6944 reflectionsΔρmax = 0.25 e Å−3
485 parametersΔρmin = −0.29 e Å−3
Primary atom site location: structure-invariant direct methodsExtinction correction: none
Crystal data top
C18H21N3O5V = 3413.54 (6) Å3
Mr = 359.38Z = 8
Monoclinic, P21/cMo Kα
a = 22.7867 (3) ŵ = 0.10 mm−1
b = 11.0879 (1) ÅT = 90 (2) K
c = 13.5106 (1) Å0.34 × 0.22 × 0.20 mm
β = 90.114 (1)º
Data collection top
Bruker SMART CCD
diffractometer		6944 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 1997)		5142 reflections with I > 2σ(I)
Tmin = 0.858, Tmax = 0.978Rint = 0.039
20279 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.058485 parameters
wR(F2) = 0.134H atoms treated by a mixture of
independent and constrained refinement
S = 1.04Δρmax = 0.25 e Å−3
6944 reflectionsΔρmin = −0.29 e Å−3
Special details top

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 F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 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 (Å2) top
xyzUiso*/Ueq
O1A0.75115 (7)0.40282 (14)0.38171 (13)0.0273 (4)
O2A0.49791 (7)0.27802 (15)0.31865 (13)0.0281 (4)
O3A0.56436 (7)0.41672 (15)0.30441 (13)0.0313 (4)
O4A0.74524 (7)−0.35100 (16)0.37188 (13)0.0298 (4)
HO4A0.7493 (15)−0.433 (3)0.384 (2)0.066 (11)*
O5A0.67682 (7)−0.03575 (15)0.58394 (12)0.0220 (4)
HO5A0.7008 (14)−0.098 (3)0.574 (2)0.051 (9)*
N1A0.75628 (7)0.19893 (16)0.37317 (13)0.0169 (4)
H1A0.78000.13870.37340.020*
N2A0.54971 (8)0.31179 (18)0.31848 (14)0.0218 (4)
N3A0.63691 (8)−0.19644 (16)0.41918 (13)0.0186 (4)
C1A0.62210 (9)0.0133 (2)0.35151 (15)0.0185 (5)
C2A0.68029 (9)0.0499 (2)0.36241 (15)0.0176 (5)
H2A0.7094−0.00810.37080.021*
C3A0.69585 (9)0.1717 (2)0.36096 (15)0.0167 (5)
C4A0.65270 (9)0.2599 (2)0.34618 (15)0.0179 (5)
H4A0.66210.34150.34400.021*
C5A0.59536 (9)0.2201 (2)0.33495 (15)0.0186 (5)
C6A0.57860 (9)0.1005 (2)0.33811 (15)0.0179 (5)
H6A0.53940.07860.33150.022*
C7A0.60623 (9)−0.1185 (2)0.34772 (16)0.0199 (5)
H7A10.5643−0.12610.35870.024*
H7A20.6143−0.14820.28160.024*
C8A0.78069 (9)0.3098 (2)0.38447 (15)0.0178 (5)
C9A0.84602 (9)0.3155 (2)0.39933 (14)0.0170 (5)
C10A0.88212 (9)0.2143 (2)0.40848 (15)0.0188 (5)
H10A0.86590.13740.40610.023*
C11A0.94201 (10)0.2282 (2)0.42108 (16)0.0223 (5)
H11A0.96580.16030.42690.027*
C12A0.96711 (10)0.3422 (2)0.42520 (16)0.0234 (5)
H12A1.00740.35080.43320.028*
C13A0.93159 (10)0.4429 (2)0.41722 (17)0.0244 (5)
H13A0.94810.51950.42020.029*
C14A0.87147 (10)0.4300 (2)0.40483 (16)0.0222 (5)
H14A0.84790.49820.40010.027*
C15A0.63902 (10)−0.3212 (2)0.38016 (16)0.0217 (5)
H15A0.6036−0.33710.34240.026*
H15B0.6402−0.37750.43510.026*
C16A0.69204 (10)−0.3417 (2)0.31475 (17)0.0250 (5)
H16A0.6865−0.41520.27690.030*
H16B0.6956−0.27530.26840.030*
C17A0.61045 (10)−0.1931 (2)0.51788 (16)0.0222 (5)
H17A0.6280−0.25640.55780.027*
H17B0.5689−0.21100.51160.027*
C18A0.61714 (10)−0.0742 (2)0.57241 (17)0.0225 (5)
H18A0.5957−0.01240.53670.027*
H18B0.5995−0.08190.63740.027*
O1B0.75199 (7)0.42678 (15)0.63678 (14)0.0322 (4)
O2B1.00570 (7)0.29674 (15)0.68363 (12)0.0273 (4)
O3B0.93973 (7)0.43732 (15)0.69510 (13)0.0297 (4)
O4B0.75112 (7)−0.22469 (16)0.54787 (15)0.0344 (4)
HO4B0.7437 (17)−0.269 (4)0.482 (3)0.097 (14)*
O5B0.81384 (7)−0.05141 (15)0.39894 (13)0.0241 (4)
HO5B0.7984 (15)−0.080 (3)0.455 (3)0.066 (11)*
N1B0.74752 (7)0.22275 (16)0.62409 (13)0.0172 (4)
H1B0.72400.16310.61500.021*
N2B0.95413 (8)0.33162 (17)0.68277 (13)0.0207 (4)
N3B0.87113 (8)−0.15414 (16)0.55811 (13)0.0189 (4)
C1B0.88035 (9)0.0342 (2)0.65113 (15)0.0171 (5)
C2B0.82249 (9)0.0722 (2)0.63819 (15)0.0175 (4)
H2B0.79330.01470.62860.021*
C3B0.80713 (9)0.1941 (2)0.63923 (14)0.0164 (4)
C4B0.85090 (9)0.2812 (2)0.65427 (15)0.0182 (5)
H4B0.84210.36310.65550.022*
C5B0.90790 (9)0.2400 (2)0.66727 (15)0.0181 (5)
C6B0.92402 (9)0.1200 (2)0.66600 (15)0.0182 (5)
H6B0.96300.09720.67480.022*
C7B0.89400 (10)−0.0993 (2)0.64869 (16)0.0201 (5)
H7B10.9361−0.11110.65200.024*
H7B20.8765−0.13830.70580.024*
C8B0.72308 (9)0.3357 (2)0.62235 (16)0.0183 (5)
C9B0.65804 (9)0.3421 (2)0.60460 (15)0.0174 (5)
C10B0.62171 (9)0.2426 (2)0.59274 (16)0.0211 (5)
H10B0.63760.16530.59350.025*
C11B0.56166 (10)0.2582 (2)0.57970 (17)0.0230 (5)
H11B0.53750.19120.57180.028*
C12B0.53755 (10)0.3727 (2)0.57847 (16)0.0230 (5)
H12B0.49730.38260.56990.028*
C13B0.57351 (10)0.4725 (2)0.59003 (17)0.0244 (5)
H13B0.55740.54960.58940.029*
C14B0.63358 (10)0.4578 (2)0.60249 (16)0.0217 (5)
H14B0.65760.52510.60950.026*
C15B0.85390 (10)−0.2800 (2)0.56934 (18)0.0241 (5)
H15C0.8810−0.32050.61380.029*
H15D0.8556−0.32020.50560.029*
C16B0.79190 (10)−0.2881 (2)0.6105 (2)0.0295 (6)
H16C0.7803−0.37210.61520.035*
H16D0.7910−0.25370.67650.035*
C17B0.90493 (9)−0.1255 (2)0.46962 (16)0.0219 (5)
H17C0.9354−0.18560.46030.026*
H17D0.9237−0.04760.47770.026*
C18B0.86478 (10)−0.1229 (2)0.37859 (17)0.0256 (5)
H18C0.8858−0.08910.32270.031*
H18D0.8530−0.20440.36160.031*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O1A0.0197 (8)0.0177 (9)0.0446 (10)0.0000 (7)−0.0021 (7)−0.0027 (7)
O2A0.0161 (8)0.0301 (10)0.0381 (10)0.0037 (7)−0.0001 (7)0.0003 (8)
O3A0.0264 (9)0.0175 (9)0.0500 (11)0.0047 (7)−0.0008 (8)0.0038 (8)
O4A0.0260 (9)0.0202 (10)0.0433 (10)0.0004 (7)−0.0023 (8)−0.0025 (8)
O5A0.0189 (8)0.0200 (9)0.0269 (9)−0.0015 (7)−0.0029 (6)−0.0022 (7)
N1A0.0124 (9)0.0179 (10)0.0203 (9)0.0004 (7)0.0003 (7)0.0007 (7)
N2A0.0177 (10)0.0245 (11)0.0231 (10)0.0042 (8)0.0009 (7)−0.0007 (8)
N3A0.0184 (9)0.0159 (10)0.0216 (9)−0.0025 (7)−0.0008 (7)0.0015 (7)
C1A0.0160 (11)0.0223 (12)0.0172 (11)−0.0010 (9)−0.0012 (8)0.0007 (9)
C2A0.0165 (11)0.0197 (12)0.0166 (10)0.0022 (9)−0.0004 (8)0.0013 (8)
C3A0.0140 (10)0.0212 (12)0.0148 (10)−0.0024 (9)0.0008 (8)0.0000 (8)
C4A0.0172 (11)0.0184 (12)0.0180 (11)−0.0006 (9)0.0019 (8)0.0009 (8)
C5A0.0162 (11)0.0225 (12)0.0171 (10)0.0037 (9)0.0016 (8)0.0010 (9)
C6A0.0134 (10)0.0231 (12)0.0174 (10)−0.0027 (9)0.0019 (8)0.0011 (9)
C7A0.0151 (10)0.0193 (12)0.0252 (12)−0.0027 (9)−0.0041 (9)0.0002 (9)
C8A0.0195 (11)0.0184 (12)0.0156 (10)0.0003 (9)0.0014 (8)0.0006 (8)
C9A0.0145 (10)0.0248 (12)0.0116 (10)−0.0020 (9)0.0011 (8)−0.0003 (8)
C10A0.0176 (11)0.0198 (12)0.0188 (11)−0.0031 (9)0.0007 (8)0.0002 (9)
C11A0.0191 (11)0.0266 (13)0.0213 (11)0.0031 (10)0.0001 (9)0.0023 (9)
C12A0.0152 (11)0.0326 (14)0.0223 (12)−0.0056 (10)−0.0007 (9)0.0000 (10)
C13A0.0216 (12)0.0227 (13)0.0290 (12)−0.0079 (10)0.0007 (10)−0.0021 (10)
C14A0.0205 (12)0.0219 (12)0.0242 (12)−0.0008 (9)−0.0004 (9)−0.0022 (9)
C15A0.0234 (12)0.0193 (12)0.0226 (11)−0.0049 (9)−0.0001 (9)−0.0001 (9)
C16A0.0262 (12)0.0216 (13)0.0271 (12)0.0016 (10)0.0019 (10)−0.0004 (9)
C17A0.0201 (11)0.0217 (12)0.0250 (12)−0.0027 (9)0.0020 (9)−0.0009 (9)
C18A0.0195 (11)0.0245 (13)0.0233 (12)−0.0001 (10)0.0031 (9)−0.0017 (9)
O1B0.0197 (9)0.0183 (9)0.0585 (12)−0.0010 (7)−0.0027 (8)−0.0001 (8)
O2B0.0166 (8)0.0315 (10)0.0340 (9)−0.0032 (7)0.0004 (7)−0.0044 (8)
O3B0.0248 (9)0.0210 (10)0.0432 (10)−0.0052 (7)0.0037 (8)−0.0076 (7)
O4B0.0218 (9)0.0294 (10)0.0519 (12)0.0049 (8)−0.0131 (8)−0.0103 (9)
O5B0.0194 (8)0.0239 (9)0.0289 (9)0.0039 (7)−0.0015 (7)0.0039 (7)
N1B0.0120 (9)0.0178 (10)0.0217 (9)−0.0008 (7)−0.0002 (7)−0.0017 (7)
N2B0.0178 (10)0.0248 (11)0.0195 (9)−0.0052 (8)0.0029 (7)−0.0023 (8)
N3B0.0186 (9)0.0159 (10)0.0223 (10)0.0001 (7)0.0000 (7)−0.0012 (7)
C1B0.0164 (11)0.0211 (12)0.0136 (10)0.0001 (9)−0.0007 (8)0.0007 (8)
C2B0.0171 (11)0.0183 (11)0.0170 (10)−0.0029 (9)−0.0002 (8)−0.0019 (8)
C3B0.0154 (10)0.0214 (12)0.0124 (10)−0.0005 (9)0.0017 (8)−0.0020 (8)
C4B0.0188 (11)0.0191 (12)0.0168 (10)0.0013 (9)0.0031 (8)−0.0018 (8)
C5B0.0174 (11)0.0234 (12)0.0134 (10)−0.0053 (9)0.0032 (8)−0.0020 (8)
C6B0.0142 (10)0.0251 (12)0.0154 (10)0.0009 (9)0.0005 (8)−0.0023 (9)
C7B0.0170 (11)0.0194 (12)0.0238 (11)0.0026 (9)−0.0029 (9)0.0016 (9)
C8B0.0190 (11)0.0170 (12)0.0189 (11)0.0001 (9)0.0012 (8)0.0012 (8)
C9B0.0168 (11)0.0209 (12)0.0145 (10)0.0019 (9)0.0018 (8)0.0011 (8)
C10B0.0187 (11)0.0185 (12)0.0260 (12)0.0020 (9)0.0003 (9)−0.0020 (9)
C11B0.0184 (11)0.0246 (13)0.0262 (12)−0.0016 (10)0.0007 (9)−0.0012 (9)
C12B0.0169 (11)0.0306 (14)0.0216 (11)0.0041 (10)−0.0006 (9)0.0006 (10)
C13B0.0255 (12)0.0209 (13)0.0267 (12)0.0086 (10)−0.0011 (10)0.0016 (9)
C14B0.0228 (12)0.0191 (12)0.0232 (11)−0.0002 (9)0.0003 (9)0.0022 (9)
C15B0.0229 (12)0.0172 (12)0.0322 (13)0.0012 (10)−0.0023 (10)−0.0003 (9)
C16B0.0217 (12)0.0218 (13)0.0449 (15)0.0001 (10)−0.0013 (11)0.0010 (11)
C17B0.0169 (11)0.0228 (12)0.0259 (12)0.0029 (9)0.0018 (9)−0.0008 (9)
C18B0.0261 (12)0.0266 (13)0.0243 (12)0.0027 (10)−0.0003 (10)−0.0021 (10)
Geometric parameters (Å, °) top
O1A—C8A1.232 (3)O1B—C8B1.221 (3)
O2A—N2A1.238 (2)O2B—N2B1.237 (2)
O3A—N2A1.225 (3)O3B—N2B1.229 (2)
O4A—C16A1.440 (3)O4B—C16B1.439 (3)
O4A—HO4A0.93 (4)O4B—HO4B1.03 (4)
O5A—C18A1.433 (3)O5B—C18B1.433 (3)
O5A—HO5A0.89 (3)O5B—HO5B0.90 (4)
N1A—C8A1.357 (3)N1B—C8B1.371 (3)
N1A—C3A1.419 (3)N1B—C3B1.410 (3)
N1A—H1A0.8600N1B—H1B0.8600
N2A—C5A1.471 (3)N2B—C5B1.478 (3)
N3A—C17A1.465 (3)N3B—C15B1.458 (3)
N3A—C7A1.472 (3)N3B—C17B1.458 (3)
N3A—C15A1.481 (3)N3B—C7B1.462 (3)
C1A—C2A1.394 (3)C1B—C6B1.391 (3)
C1A—C6A1.396 (3)C1B—C2B1.394 (3)
C1A—C7A1.506 (3)C1B—C7B1.514 (3)
C2A—C3A1.396 (3)C2B—C3B1.396 (3)
C2A—H2A0.9300C2B—H2B0.9300
C3A—C4A1.401 (3)C3B—C4B1.403 (3)
C4A—C5A1.387 (3)C4B—C5B1.388 (3)
C4A—H4A0.9300C4B—H4B0.9300
C5A—C6A1.381 (3)C5B—C6B1.380 (3)
C6A—H6A0.9300C6B—H6B0.9300
C7A—H7A10.9700C7B—H7B10.9700
C7A—H7A20.9700C7B—H7B20.9700
C8A—C9A1.503 (3)C8B—C9B1.503 (3)
C9A—C10A1.396 (3)C9B—C10B1.389 (3)
C9A—C14A1.398 (3)C9B—C14B1.399 (3)
C10A—C11A1.383 (3)C10B—C11B1.390 (3)
C10A—H10A0.9300C10B—H10B0.9300
C11A—C12A1.389 (3)C11B—C12B1.384 (3)
C11A—H11A0.9300C11B—H11B0.9300
C12A—C13A1.383 (3)C12B—C13B1.386 (3)
C12A—H12A0.9300C12B—H12B0.9300
C13A—C14A1.387 (3)C13B—C14B1.388 (3)
C13A—H13A0.9300C13B—H13B0.9300
C14A—H14A0.9300C14B—H14B0.9300
C15A—C16A1.515 (3)C15B—C16B1.522 (3)
C15A—H15A0.9700C15B—H15C0.9700
C15A—H15B0.9700C15B—H15D0.9700
C16A—H16A0.9700C16B—H16C0.9700
C16A—H16B0.9700C16B—H16D0.9700
C17A—C18A1.517 (3)C17B—C18B1.532 (3)
C17A—H17A0.9700C17B—H17C0.9700
C17A—H17B0.9700C17B—H17D0.9700
C18A—H18A0.9700C18B—H18C0.9700
C18A—H18B0.9700C18B—H18D0.9700
C16A—O4A—HO4A104 (2)C16B—O4B—HO4B112 (2)
C18A—O5A—HO5A110 (2)C18B—O5B—HO5B107 (2)
C8A—N1A—C3A127.10 (19)C8B—N1B—C3B126.87 (19)
C8A—N1A—H1A116.5C8B—N1B—H1B116.6
C3A—N1A—H1A116.5C3B—N1B—H1B116.6
O3A—N2A—O2A123.19 (19)O3B—N2B—O2B123.43 (19)
O3A—N2A—C5A119.14 (18)O3B—N2B—C5B118.97 (18)
O2A—N2A—C5A117.67 (19)O2B—N2B—C5B117.59 (19)
C17A—N3A—C7A112.73 (17)C15B—N3B—C17B115.88 (18)
C17A—N3A—C15A111.18 (17)C15B—N3B—C7B113.99 (18)
C7A—N3A—C15A109.31 (17)C17B—N3B—C7B114.08 (17)
C2A—C1A—C6A119.1 (2)C6B—C1B—C2B119.2 (2)
C2A—C1A—C7A120.9 (2)C6B—C1B—C7B121.68 (19)
C6A—C1A—C7A119.81 (19)C2B—C1B—C7B119.12 (19)
C1A—C2A—C3A121.4 (2)C1B—C2B—C3B121.9 (2)
C1A—C2A—H2A119.3C1B—C2B—H2B119.1
C3A—C2A—H2A119.3C3B—C2B—H2B119.1
C2A—C3A—C4A119.95 (19)C2B—C3B—C4B119.32 (19)
C2A—C3A—N1A116.78 (19)C2B—C3B—N1B117.30 (19)
C4A—C3A—N1A123.26 (19)C4B—C3B—N1B123.4 (2)
C5A—C4A—C3A117.0 (2)C5B—C4B—C3B117.2 (2)
C5A—C4A—H4A121.5C5B—C4B—H4B121.4
C3A—C4A—H4A121.5C3B—C4B—H4B121.4
C6A—C5A—C4A124.3 (2)C6B—C5B—C4B124.4 (2)
C6A—C5A—N2A118.23 (19)C6B—C5B—N2B118.33 (19)
C4A—C5A—N2A117.5 (2)C4B—C5B—N2B117.3 (2)
C5A—C6A—C1A118.21 (19)C5B—C6B—C1B118.1 (2)
C5A—C6A—H6A120.9C5B—C6B—H6B121.0
C1A—C6A—H6A120.9C1B—C6B—H6B121.0
N3A—C7A—C1A115.71 (17)N3B—C7B—C1B110.62 (17)
N3A—C7A—H7A1108.4N3B—C7B—H7B1109.5
C1A—C7A—H7A1108.4C1B—C7B—H7B1109.5
N3A—C7A—H7A2108.4N3B—C7B—H7B2109.5
C1A—C7A—H7A2108.4C1B—C7B—H7B2109.5
H7A1—C7A—H7A2107.4H7B1—C7B—H7B2108.1
O1A—C8A—N1A122.1 (2)O1B—C8B—N1B122.3 (2)
O1A—C8A—C9A120.6 (2)O1B—C8B—C9B121.2 (2)
N1A—C8A—C9A117.29 (19)N1B—C8B—C9B116.54 (19)
C10A—C9A—C14A118.73 (19)C10B—C9B—C14B119.3 (2)
C10A—C9A—C8A124.1 (2)C10B—C9B—C8B124.6 (2)
C14A—C9A—C8A117.1 (2)C14B—C9B—C8B116.1 (2)
C11A—C10A—C9A120.1 (2)C11B—C10B—C9B120.1 (2)
C11A—C10A—H10A119.9C11B—C10B—H10B119.9
C9A—C10A—H10A119.9C9B—C10B—H10B119.9
C10A—C11A—C12A120.8 (2)C12B—C11B—C10B120.4 (2)
C10A—C11A—H11A119.6C12B—C11B—H11B119.8
C12A—C11A—H11A119.6C10B—C11B—H11B119.8
C13A—C12A—C11A119.4 (2)C11B—C12B—C13B119.8 (2)
C13A—C12A—H12A120.3C11B—C12B—H12B120.1
C11A—C12A—H12A120.3C13B—C12B—H12B120.1
C12A—C13A—C14A120.3 (2)C12B—C13B—C14B120.1 (2)
C12A—C13A—H13A119.9C12B—C13B—H13B119.9
C14A—C13A—H13A119.9C14B—C13B—H13B119.9
C13A—C14A—C9A120.6 (2)C13B—C14B—C9B120.2 (2)
C13A—C14A—H14A119.7C13B—C14B—H14B119.9
C9A—C14A—H14A119.7C9B—C14B—H14B119.9
N3A—C15A—C16A111.96 (18)N3B—C15B—C16B110.18 (19)
N3A—C15A—H15A109.2N3B—C15B—H15C109.6
C16A—C15A—H15A109.2C16B—C15B—H15C109.6
N3A—C15A—H15B109.2N3B—C15B—H15D109.6
C16A—C15A—H15B109.2C16B—C15B—H15D109.6
H15A—C15A—H15B107.9H15C—C15B—H15D108.1
O4A—C16A—C15A111.69 (19)O4B—C16B—C15B110.8 (2)
O4A—C16A—H16A109.3O4B—C16B—H16C109.5
C15A—C16A—H16A109.3C15B—C16B—H16C109.5
O4A—C16A—H16B109.3O4B—C16B—H16D109.5
C15A—C16A—H16B109.3C15B—C16B—H16D109.5
H16A—C16A—H16B107.9H16C—C16B—H16D108.1
N3A—C17A—C18A115.01 (19)N3B—C17B—C18B110.30 (18)
N3A—C17A—H17A108.5N3B—C17B—H17C109.6
C18A—C17A—H17A108.5C18B—C17B—H17C109.6
N3A—C17A—H17B108.5N3B—C17B—H17D109.6
C18A—C17A—H17B108.5C18B—C17B—H17D109.6
H17A—C17A—H17B107.5H17C—C17B—H17D108.1
O5A—C18A—C17A113.93 (18)O5B—C18B—C17B109.84 (18)
O5A—C18A—H18A108.8O5B—C18B—H18C109.7
C17A—C18A—H18A108.8C17B—C18B—H18C109.7
O5A—C18A—H18B108.8O5B—C18B—H18D109.7
C17A—C18A—H18B108.8C17B—C18B—H18D109.7
H18A—C18A—H18B107.7H18C—C18B—H18D108.2
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O4A—HO4A···O1Ai0.93 (4)1.82 (4)2.736 (2)168 (3)
O5A—HO5A···O4B0.89 (3)1.85 (3)2.738 (2)178 (3)
N1A—H1A···O5B0.862.273.089 (2)159
O5B—HO5B···O4B0.90 (4)2.30 (4)3.130 (3)153 (3)
O4B—HO4B···O4A1.03 (4)1.75 (4)2.762 (3)169 (3)
N1B—H1B···O5A0.862.493.332 (2)167
Symmetry codes: (i) x, y−1, z.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O4A—HO4A···O1Ai0.93 (4)1.82 (4)2.736 (2)168 (3)
O5A—HO5A···O4B0.89 (3)1.85 (3)2.738 (2)178 (3)
N1A—H1A···O5B0.862.273.089 (2)159
O5B—HO5B···O4B0.90 (4)2.30 (4)3.130 (3)153 (3)
O4B—HO4B···O4A1.03 (4)1.75 (4)2.762 (3)169 (3)
N1B—H1B···O5A0.862.493.332 (2)167
Symmetry codes: (i) x, y−1, z.
Acknowledgements top

The authors acknowledge financial support from the Higher Education Commission of Pakistan and the University of Auckland, New Zealand.

references
References top

Arcamone, F., Penco, S., Orezzi, P., Nicolella, V. & Pirelli, A. (1964). Nature (London), 203, 1064–1065.

Atwell, G. J., Yaghi, B. M., Turner, P. R., Boyd, M., O'Connor, C. J., Ferguson, L. R., Baguley, B. C. & Denny, W. A. (1995). Bioorg. Med. Chem. 3, 679–691.

Baraldi, P., Bovero, G., Fruttarolo, A., Preti, F., Tabrizi, D., Pavani, M. & Romagnoli, R. (2004). Med. Res. Rev. 24, 475–528.

Baraldi, P. G., Cozzi, P., Geroni, C., Mongelli, N., Romagnoli, R. & Spalluto, G. (1999). Bioorg. Med. Chem. 7, 251–262.

Baraldi, P., Preti, D., Fruttarolo, F., Tabrizi, M. & Romagnoli, R. (2007). Bioorg. Med. Chem. 15, 17–35.

Barker, D., Lehmann, A. L., Mai, A., Khan, G. S. & Ng, E. (2008). Tetrahedron Lett. 49, 1660–1664.

Bruker (1995). SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.

Burnett, M. N. & Johnson, C. K. (1996). ORTEPIII. Report ORNL-6895. Oak Ridge National Laboratory, Tennessee, USA.

Kumar, R., Rai, D., Marcus, S. L., Ko, S. C. C. & Lown, J. W. (2004). Lett. Org. Chem. 1, 154–158.

Sengupta, D., Blasko, A. & Bruice, T. C. (1996). Biorg. Med. Chem. 4, 803–813.

Sheldrick, G. M. (1997). SADABS. University of Göttingen, Germany.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.

Stafford, R. L., Arndt, H.-D., Brezinski, M. L., Ansari, A. Z. & Dervan, P. B. (2007). J. Am. Chem. Soc. 129, 2660–2668.

Storl, K., Storl, J., Zimmer, C. & Lown, J. (1993). FEBS Lett. 317, 157–161.

Turner, P., Fergusson, L. & Denny, W. (1999). Anti-Cancer Drug. Des. 14, 61–70.

Wemmer, D. E. (2000). Annu. Rev. Biophys. Biomol. Struct. 29, 439–461.

Yan, Y., Liu, M. & Gong, B. (1997). Bioorg. Med. Chem. Lett. 7, 1469–1474.