Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807041712/hg2279sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807041712/hg2279Isup2.hkl |
CCDC reference: 660377
Key indicators
- Single-crystal X-ray study
- T = 90 K
- Mean (C-C) = 0.002 Å
- R factor = 0.036
- wR factor = 0.096
- Data-to-parameter ratio = 14.7
checkCIF/PLATON results
No syntax errors found
Alert level C PLAT720_ALERT_4_C Number of Unusual/Non-Standard Label(s) ........ 2
Alert level G REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is correct. If it is not, please give the correct count in the _publ_section_exptl_refinement section of the submitted CIF. From the CIF: _diffrn_reflns_theta_max 68.01 From the CIF: _reflns_number_total 3531 Count of symmetry unique reflns 2050 Completeness (_total/calc) 172.24% TEST3: Check Friedels for noncentro structure Estimate of Friedel pairs measured 1481 Fraction of Friedel pairs measured 0.722 Are heavy atom types Z>Si present no PLAT791_ALERT_1_G Confirm the Absolute Configuration of C4 = . R PLAT791_ALERT_1_G Confirm the Absolute Configuration of C5 = . R PLAT791_ALERT_1_G Confirm the Absolute Configuration of C6 = . S PLAT791_ALERT_1_G Confirm the Absolute Configuration of C7 = . S PLAT791_ALERT_1_G Confirm the Absolute Configuration of C11 = . R PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints ....... 1
0 ALERT level A = In general: serious problem 0 ALERT level B = Potentially serious problem 1 ALERT level C = Check and explain 7 ALERT level G = General alerts; check 5 ALERT type 1 CIF construction/syntax error, inconsistent or missing data 0 ALERT type 2 Indicator that the structure model may be wrong or deficient 1 ALERT type 3 Indicator that the structure quality may be low 2 ALERT type 4 Improvement, methodology, query or suggestion 0 ALERT type 5 Informative message, check
For related literature, see: Allen et al. (1987); Crooks et al. (2005); Desiraju & Steiner (1999); Guzman et al. (2005); de Kraker et al. (2002); Parsons & Flack (2004).
The title compound was prepared by dissolving parthenolide (100 mg, 0.403 mmol) in MeOH (10 ml) and adding benzylamine (43.1 mg, 0.403 mmol) to the solution. The mixture was stirred at room temperature for 18 h. The solvent was evaporated and the title compound was purified by column chromatography over silica gel by eluting with 15% acetone in hexane. Crystals suitable for X-ray diffraction were obtained by slow evaporation of a solution of the title compound in chloroform/hexane at room temperature. The title compound was obtained as white crystals. 1H NMR (CDCl3, p.p.m.): δ 7.35–7.26 (m, 5H), 5.19 (app. d, 1H, J = 10.2), 3.92–3.75 (m, 3H), 3.02 (dd, 1H, J = 3.6 and 12.3 Hz), 2.74 (m, 2H), 2.44–1.78 (m, 11 H), 1.69 (s, 3H), 1.29 (s, 3H); 13C NMR (CDCl3, δ, p.p.m.): 176.7, 140.0, 134.6, 128.5, 128.1, 127.1, 125.2, 82.7, 66.5, 61.7, 54.1, 48.4, 46.7, 46.2, 41.2, 36.8, 30.2, 24.3, 17.5, 17.2.
H atoms were found in difference Fourier maps and those attached to carbon atoms were subsequently placed in idealized positions with constrained C—H distances of 0.98Å (RCH3), 0.99 Å (R2CH2), 1.00 Å (R3CH) and 0.95 Å (CArH) with Uiso(H) values set to either 1.5Ueq(methyl) or 1.2Ueq of the attached C atom respectively. Since the NH hydrogen was clearly not planar, and there being no suitable riding model available, the coordinates of this H atom were refined but its Uiso was set to 1.5Ueq of the attached N atom.
Since this crystal structure was known to be of an all light-atom chiral compound, Cu Kα x-rays were used so that the absolute configuration could be determined from the anomalous scattering of the oxygen atoms. The value of the Flack parameter (Flack, 1983) based on refinement with unmerged Friedel pairs, as determined by the Parsons' quotient method (Parsons & Flack, 2004) was x(u) = 0.13 (6).
Parthenolide, is a germacrene sesquiterpene lactone. It has been isolated from several different species of plant in the Asteraceae (Compositae) family, feverfew (Tanacetum parthenium) being one of them (de Kraker et al., 2002). Its remarkable cytotoxic, antitumor, antiviral and antileishmanic properties have made it the focus of a large number of investigations. Its ability to induce tumor apoptosis through the inhibition of NF-kappaB make it a potential therapeutic for the treatment of leukemia (Guzman et al., 2005). Its development in this regard has been impeded by its low polarity and low water solubility. We saw a potential solution to this problem in the formation of a conjugate adduct of an amine species at the C-13, α-methylene group of the γ-butyrolactone function of parthenolide (Crooks et al., 2005). The title compound was synthesized as part of an ongoing drug discovery effort by reaction of benzylamine with parthenolide. The benzylamine adduct obtained was shown to be a single diastereomer by NMR analysis. The crystal structure of the title compound was determined to obtain the configuration of the newly formed stereocenter at C-11. An R absolute configuration was found. Bond distances and angles within the molecule are quite regular with average normal bonds (Allen et al., 1987). A hydrogen bond is observed between N-1H and O3 (2.30 (17) A°, 2.97 (17) A°, 130.2 (8) °) (Table 1) of the carbonyl oxygen of the 5-membered lactone ring, which can be considered as a weak hydrogen bond (Desiraju & Steiner, 1999).
For related literature, see: Allen et al. (1987); Crooks et al. (2005); Desiraju & Steiner (1999); Guzman et al. (2005); de Kraker et al. (2002); Parsons & Flack (2004).
Data collection: APEX2 (Bruker–Nonius, 2004); cell refinement: APEX2; data reduction: APEX2; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP in SHELXTL/PC (Sheldrick, 1995); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997) and local procedures.
C22H29NO3 | F(000) = 768 |
Mr = 355.46 | Dx = 1.208 Mg m−3 |
Orthorhombic, P212121 | Cu Kα radiation, λ = 1.54178 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 7188 reflections |
a = 8.3772 (6) Å | θ = 4.1–68.0° |
b = 13.7441 (10) Å | µ = 0.63 mm−1 |
c = 16.9684 (12) Å | T = 90 K |
V = 1953.7 (2) Å3 | Rod, colourless |
Z = 4 | 0.35 × 0.08 × 0.08 mm |
X8 Proteum diffractometer | 3446 reflections with I > 2σ(I) |
Radiation source: fine-focus rotating anode | Rint = 0.043 |
Helios multilayer optics monochromator | θmax = 68.0°, θmin = 4.1° |
Detector resolution: 18 pixels mm-1 | h = −10→10 |
ω and φ scans | k = −16→16 |
21942 measured reflections | l = −20→20 |
3531 independent reflections |
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H atoms treated by a mixture of independent and constrained refinement |
R[F2 > 2σ(F2)] = 0.036 | w = 1/[σ2(Fo2) + (0.0636P)2 + 0.2363P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.096 | (Δ/σ)max = 0.001 |
S = 1.08 | Δρmax = 0.26 e Å−3 |
3531 reflections | Δρmin = −0.19 e Å−3 |
241 parameters | Extinction correction: SHELXL97 (Sheldrick, 1997), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
1 restraint | Extinction coefficient: 0.0055 (5) |
Primary atom site location: structure-invariant direct methods | Absolute structure: Flack (1983), with 0000 Friedel pairs |
Secondary atom site location: difference Fourier map | Absolute structure parameter: 0.13 (6) |
C22H29NO3 | V = 1953.7 (2) Å3 |
Mr = 355.46 | Z = 4 |
Orthorhombic, P212121 | Cu Kα radiation |
a = 8.3772 (6) Å | µ = 0.63 mm−1 |
b = 13.7441 (10) Å | T = 90 K |
c = 16.9684 (12) Å | 0.35 × 0.08 × 0.08 mm |
X8 Proteum diffractometer | 3446 reflections with I > 2σ(I) |
21942 measured reflections | Rint = 0.043 |
3531 independent reflections |
R[F2 > 2σ(F2)] = 0.036 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.096 | Δρmax = 0.26 e Å−3 |
S = 1.08 | Δρmin = −0.19 e Å−3 |
3531 reflections | Absolute structure: Flack (1983), with 0000 Friedel pairs |
241 parameters | Absolute structure parameter: 0.13 (6) |
1 restraint |
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. Flack parameter from normal least-squares (unmerged data): is x = 0.09232; su = 0.07777 Flack parameter from Parson's quotients: CC = 15.45, GooF 1.2789, Flack x = 0.1327; su = 0.0656 Result from Parsons quotients given in this CIF. |
x | y | z | Uiso*/Ueq | ||
N1 | 0.48723 (15) | 0.32099 (8) | 0.46644 (9) | 0.0325 (3) | |
H1N | 0.422 (3) | 0.3350 (9) | 0.4245 (12) | 0.049* | |
O1 | 0.24522 (12) | 0.80545 (7) | 0.50257 (5) | 0.0269 (2) | |
O2 | 0.26117 (12) | 0.60530 (7) | 0.47005 (6) | 0.0282 (2) | |
O3 | 0.28650 (15) | 0.47566 (7) | 0.39368 (6) | 0.0397 (3) | |
C1 | 0.54615 (17) | 0.79131 (10) | 0.68316 (8) | 0.0260 (3) | |
H1 | 0.6343 | 0.7856 | 0.6482 | 0.031* | |
C2 | 0.46528 (19) | 0.88816 (10) | 0.68533 (8) | 0.0309 (3) | |
H2A | 0.5454 | 0.9401 | 0.6938 | 0.037* | |
H2B | 0.3883 | 0.8901 | 0.7296 | 0.037* | |
C3 | 0.37714 (17) | 0.90558 (10) | 0.60700 (8) | 0.0292 (3) | |
H3A | 0.3096 | 0.9644 | 0.6116 | 0.035* | |
H3B | 0.4560 | 0.9170 | 0.5645 | 0.035* | |
C4 | 0.27459 (16) | 0.81977 (10) | 0.58600 (8) | 0.0266 (3) | |
C5 | 0.35340 (15) | 0.74075 (9) | 0.54297 (7) | 0.0211 (3) | |
H5 | 0.4688 | 0.7525 | 0.5313 | 0.025* | |
C6 | 0.30846 (16) | 0.63576 (10) | 0.54922 (7) | 0.0233 (3) | |
H6 | 0.2174 | 0.6275 | 0.5868 | 0.028* | |
C7 | 0.44529 (16) | 0.56754 (10) | 0.57132 (8) | 0.0247 (3) | |
H7 | 0.5462 | 0.5941 | 0.5484 | 0.030* | |
C8 | 0.4736 (2) | 0.54673 (11) | 0.65905 (9) | 0.0349 (4) | |
H8A | 0.3689 | 0.5472 | 0.6861 | 0.042* | |
H8B | 0.5178 | 0.4802 | 0.6640 | 0.042* | |
C9 | 0.58504 (19) | 0.61685 (10) | 0.70247 (9) | 0.0331 (3) | |
H9A | 0.6238 | 0.5848 | 0.7511 | 0.040* | |
H9B | 0.6789 | 0.6300 | 0.6687 | 0.040* | |
C10 | 0.50933 (17) | 0.71205 (11) | 0.72440 (8) | 0.0305 (3) | |
C11 | 0.40039 (16) | 0.47539 (10) | 0.52589 (8) | 0.0263 (3) | |
H11 | 0.3246 | 0.4365 | 0.5587 | 0.032* | |
C12 | 0.31212 (17) | 0.51417 (10) | 0.45586 (9) | 0.0277 (3) | |
C13 | 0.53912 (17) | 0.41115 (11) | 0.50311 (10) | 0.0335 (3) | |
H13A | 0.6091 | 0.4469 | 0.4661 | 0.040* | |
H13B | 0.6025 | 0.3958 | 0.5508 | 0.040* | |
C14 | 0.3954 (3) | 0.70842 (16) | 0.79204 (11) | 0.0502 (5) | |
H14A | 0.3438 | 0.7720 | 0.7981 | 0.075* | |
H14B | 0.4536 | 0.6922 | 0.8404 | 0.075* | |
H14C | 0.3141 | 0.6587 | 0.7820 | 0.075* | |
C15 | 0.13073 (18) | 0.80289 (13) | 0.63629 (10) | 0.0369 (4) | |
H15A | 0.0642 | 0.8615 | 0.6366 | 0.055* | |
H15B | 0.1645 | 0.7878 | 0.6902 | 0.055* | |
H15C | 0.0692 | 0.7482 | 0.6150 | 0.055* | |
C2' | 0.62254 (18) | 0.26381 (12) | 0.44003 (13) | 0.0444 (4) | |
H2'1 | 0.6892 | 0.2464 | 0.4861 | 0.053* | |
H2'2 | 0.6885 | 0.3036 | 0.4039 | 0.053* | |
C3' | 0.57217 (17) | 0.17232 (10) | 0.39836 (10) | 0.0329 (3) | |
C4' | 0.62586 (19) | 0.15239 (12) | 0.32291 (10) | 0.0389 (4) | |
H4' | 0.6913 | 0.1983 | 0.2964 | 0.047* | |
C5' | 0.58531 (19) | 0.06646 (13) | 0.28581 (9) | 0.0391 (4) | |
H5' | 0.6237 | 0.0532 | 0.2342 | 0.047* | |
C6' | 0.48934 (19) | 0.00007 (12) | 0.32352 (9) | 0.0351 (3) | |
H6' | 0.4614 | −0.0590 | 0.2980 | 0.042* | |
C7' | 0.43343 (18) | 0.01924 (11) | 0.39868 (9) | 0.0329 (3) | |
H7' | 0.3664 | −0.0264 | 0.4247 | 0.039* | |
C8' | 0.47545 (17) | 0.10493 (10) | 0.43568 (9) | 0.0307 (3) | |
H8' | 0.4375 | 0.1178 | 0.4874 | 0.037* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.0196 (6) | 0.0285 (6) | 0.0494 (7) | −0.0004 (5) | −0.0044 (6) | 0.0005 (5) |
O1 | 0.0237 (5) | 0.0322 (5) | 0.0248 (5) | 0.0057 (4) | −0.0060 (4) | 0.0004 (4) |
O2 | 0.0274 (5) | 0.0280 (5) | 0.0291 (5) | 0.0004 (4) | −0.0113 (4) | −0.0012 (4) |
O3 | 0.0516 (7) | 0.0332 (5) | 0.0345 (6) | 0.0028 (5) | −0.0147 (5) | −0.0036 (4) |
C1 | 0.0213 (7) | 0.0332 (7) | 0.0236 (6) | −0.0046 (5) | −0.0039 (5) | −0.0001 (5) |
C2 | 0.0319 (8) | 0.0324 (7) | 0.0284 (7) | −0.0029 (6) | −0.0016 (6) | −0.0044 (5) |
C3 | 0.0296 (7) | 0.0284 (6) | 0.0296 (7) | 0.0051 (6) | −0.0017 (6) | −0.0031 (6) |
C4 | 0.0207 (6) | 0.0351 (7) | 0.0238 (6) | 0.0069 (5) | −0.0025 (5) | −0.0024 (5) |
C5 | 0.0148 (6) | 0.0274 (6) | 0.0213 (6) | 0.0011 (5) | −0.0027 (5) | 0.0007 (5) |
C6 | 0.0182 (6) | 0.0300 (6) | 0.0215 (6) | −0.0040 (5) | −0.0026 (5) | −0.0002 (5) |
C7 | 0.0209 (6) | 0.0256 (6) | 0.0276 (7) | −0.0063 (5) | −0.0060 (5) | 0.0071 (5) |
C8 | 0.0408 (9) | 0.0327 (7) | 0.0311 (7) | −0.0118 (7) | −0.0147 (7) | 0.0110 (6) |
C9 | 0.0313 (8) | 0.0329 (7) | 0.0350 (7) | −0.0068 (6) | −0.0134 (6) | 0.0088 (6) |
C10 | 0.0266 (7) | 0.0373 (7) | 0.0277 (7) | −0.0061 (6) | −0.0065 (6) | 0.0044 (6) |
C11 | 0.0204 (6) | 0.0251 (6) | 0.0334 (7) | −0.0053 (5) | −0.0055 (5) | 0.0045 (6) |
C12 | 0.0238 (6) | 0.0261 (6) | 0.0331 (7) | −0.0016 (6) | −0.0048 (6) | 0.0006 (5) |
C13 | 0.0196 (7) | 0.0279 (7) | 0.0531 (9) | −0.0040 (6) | −0.0065 (6) | 0.0043 (6) |
C14 | 0.0538 (11) | 0.0618 (11) | 0.0350 (8) | −0.0059 (9) | 0.0059 (8) | 0.0136 (8) |
C15 | 0.0239 (7) | 0.0512 (9) | 0.0357 (8) | 0.0058 (7) | 0.0040 (6) | −0.0041 (6) |
C2' | 0.0202 (7) | 0.0344 (8) | 0.0784 (12) | 0.0009 (6) | 0.0010 (8) | −0.0026 (8) |
C3' | 0.0150 (6) | 0.0324 (7) | 0.0514 (9) | 0.0046 (5) | 0.0011 (6) | 0.0049 (7) |
C4' | 0.0224 (7) | 0.0471 (9) | 0.0473 (9) | 0.0084 (6) | 0.0067 (6) | 0.0191 (7) |
C5' | 0.0255 (7) | 0.0611 (10) | 0.0308 (7) | 0.0157 (7) | 0.0014 (6) | 0.0070 (7) |
C6' | 0.0260 (7) | 0.0422 (8) | 0.0371 (7) | 0.0095 (6) | −0.0029 (6) | −0.0046 (6) |
C7' | 0.0233 (7) | 0.0362 (7) | 0.0391 (8) | −0.0006 (6) | 0.0007 (6) | 0.0022 (6) |
C8' | 0.0194 (7) | 0.0364 (7) | 0.0361 (7) | 0.0028 (6) | 0.0043 (6) | −0.0005 (6) |
N1—C2' | 1.450 (2) | C9—C10 | 1.501 (2) |
N1—C13 | 1.4532 (19) | C9—H9A | 0.9900 |
N1—H1N | 0.92 (2) | C9—H9B | 0.9900 |
O1—C5 | 1.4429 (15) | C10—C14 | 1.494 (2) |
O1—C4 | 1.4502 (16) | C11—C12 | 1.4975 (19) |
O2—C12 | 1.3450 (17) | C11—C13 | 1.510 (2) |
O2—C6 | 1.4617 (15) | C11—H11 | 1.0000 |
O3—C12 | 1.1998 (18) | C13—H13A | 0.9900 |
C1—C10 | 1.331 (2) | C13—H13B | 0.9900 |
C1—C2 | 1.494 (2) | C14—H14A | 0.9800 |
C1—H1 | 0.9500 | C14—H14B | 0.9800 |
C2—C3 | 1.539 (2) | C14—H14C | 0.9800 |
C2—H2A | 0.9900 | C15—H15A | 0.9800 |
C2—H2B | 0.9900 | C15—H15B | 0.9800 |
C3—C4 | 1.502 (2) | C15—H15C | 0.9800 |
C3—H3A | 0.9900 | C2'—C3' | 1.503 (2) |
C3—H3B | 0.9900 | C2'—H2'1 | 0.9900 |
C4—C5 | 1.4658 (18) | C2'—H2'2 | 0.9900 |
C4—C15 | 1.495 (2) | C3'—C8' | 1.384 (2) |
C5—C6 | 1.4950 (18) | C3'—C4' | 1.384 (2) |
C5—H5 | 1.0000 | C4'—C5' | 1.381 (3) |
C6—C7 | 1.5277 (19) | C4'—H4' | 0.9500 |
C6—H6 | 1.0000 | C5'—C6' | 1.374 (2) |
C7—C11 | 1.5297 (18) | C5'—H5' | 0.9500 |
C7—C8 | 1.5343 (18) | C6'—C7' | 1.384 (2) |
C7—H7 | 1.0000 | C6'—H6' | 0.9500 |
C8—C9 | 1.531 (2) | C7'—C8' | 1.380 (2) |
C8—H8A | 0.9900 | C7'—H7' | 0.9500 |
C8—H8B | 0.9900 | C8'—H8' | 0.9500 |
C2'—N1—C13 | 111.13 (12) | H9A—C9—H9B | 107.6 |
C2'—N1—H1N | 109.8 (8) | C1—C10—C14 | 125.41 (16) |
C13—N1—H1N | 109.4 (8) | C1—C10—C9 | 119.03 (13) |
C5—O1—C4 | 60.88 (8) | C14—C10—C9 | 115.56 (14) |
C12—O2—C6 | 110.20 (10) | C12—C11—C13 | 112.65 (12) |
C10—C1—C2 | 127.67 (14) | C12—C11—C7 | 103.10 (10) |
C10—C1—H1 | 116.2 | C13—C11—C7 | 115.08 (11) |
C2—C1—H1 | 116.2 | C12—C11—H11 | 108.6 |
C1—C2—C3 | 109.56 (11) | C13—C11—H11 | 108.6 |
C1—C2—H2A | 109.8 | C7—C11—H11 | 108.6 |
C3—C2—H2A | 109.8 | O3—C12—O2 | 120.76 (13) |
C1—C2—H2B | 109.8 | O3—C12—C11 | 128.99 (13) |
C3—C2—H2B | 109.8 | O2—C12—C11 | 110.25 (11) |
H2A—C2—H2B | 108.2 | N1—C13—C11 | 112.21 (11) |
C4—C3—C2 | 110.92 (11) | N1—C13—H13A | 109.2 |
C4—C3—H3A | 109.5 | C11—C13—H13A | 109.2 |
C2—C3—H3A | 109.5 | N1—C13—H13B | 109.2 |
C4—C3—H3B | 109.5 | C11—C13—H13B | 109.2 |
C2—C3—H3B | 109.5 | H13A—C13—H13B | 107.9 |
H3A—C3—H3B | 108.0 | C10—C14—H14A | 109.5 |
O1—C4—C5 | 59.32 (8) | C10—C14—H14B | 109.5 |
O1—C4—C15 | 113.54 (12) | H14A—C14—H14B | 109.5 |
C5—C4—C15 | 122.17 (13) | C10—C14—H14C | 109.5 |
O1—C4—C3 | 115.80 (12) | H14A—C14—H14C | 109.5 |
C5—C4—C3 | 116.26 (12) | H14B—C14—H14C | 109.5 |
C15—C4—C3 | 116.59 (13) | C4—C15—H15A | 109.5 |
O1—C5—C4 | 59.80 (8) | C4—C15—H15B | 109.5 |
O1—C5—C6 | 118.06 (10) | H15A—C15—H15B | 109.5 |
C4—C5—C6 | 124.50 (11) | C4—C15—H15C | 109.5 |
O1—C5—H5 | 114.4 | H15A—C15—H15C | 109.5 |
C4—C5—H5 | 114.4 | H15B—C15—H15C | 109.5 |
C6—C5—H5 | 114.4 | N1—C2'—C3' | 112.29 (12) |
O2—C6—C5 | 106.23 (10) | N1—C2'—H2'1 | 109.1 |
O2—C6—C7 | 104.67 (10) | C3'—C2'—H2'1 | 109.1 |
C5—C6—C7 | 114.89 (11) | N1—C2'—H2'2 | 109.1 |
O2—C6—H6 | 110.3 | C3'—C2'—H2'2 | 109.1 |
C5—C6—H6 | 110.3 | H2'1—C2'—H2'2 | 107.9 |
C7—C6—H6 | 110.3 | C8'—C3'—C4' | 118.74 (15) |
C6—C7—C11 | 101.53 (10) | C8'—C3'—C2' | 120.59 (15) |
C6—C7—C8 | 117.94 (12) | C4'—C3'—C2' | 120.63 (15) |
C11—C7—C8 | 111.88 (11) | C5'—C4'—C3' | 120.73 (15) |
C6—C7—H7 | 108.3 | C5'—C4'—H4' | 119.6 |
C11—C7—H7 | 108.3 | C3'—C4'—H4' | 119.6 |
C8—C7—H7 | 108.3 | C6'—C5'—C4' | 119.98 (15) |
C9—C8—C7 | 116.34 (12) | C6'—C5'—H5' | 120.0 |
C9—C8—H8A | 108.2 | C4'—C5'—H5' | 120.0 |
C7—C8—H8A | 108.2 | C5'—C6'—C7' | 120.04 (15) |
C9—C8—H8B | 108.2 | C5'—C6'—H6' | 120.0 |
C7—C8—H8B | 108.2 | C7'—C6'—H6' | 120.0 |
H8A—C8—H8B | 107.4 | C8'—C7'—C6' | 119.70 (14) |
C10—C9—C8 | 114.22 (13) | C8'—C7'—H7' | 120.2 |
C10—C9—H9A | 108.7 | C6'—C7'—H7' | 120.2 |
C8—C9—H9A | 108.7 | C7'—C8'—C3' | 120.81 (14) |
C10—C9—H9B | 108.7 | C7'—C8'—H8' | 119.6 |
C8—C9—H9B | 108.7 | C3'—C8'—H8' | 119.6 |
C10—C1—C2—C3 | −110.86 (17) | C2—C1—C10—C9 | 168.37 (13) |
C1—C2—C3—C4 | 50.01 (16) | C8—C9—C10—C1 | −104.86 (16) |
C5—O1—C4—C15 | −114.63 (14) | C8—C9—C10—C14 | 74.63 (17) |
C5—O1—C4—C3 | 106.53 (13) | C6—C7—C11—C12 | 29.69 (13) |
C2—C3—C4—O1 | −152.77 (11) | C8—C7—C11—C12 | 156.36 (12) |
C2—C3—C4—C5 | −85.95 (15) | C6—C7—C11—C13 | 152.74 (12) |
C2—C3—C4—C15 | 69.67 (16) | C8—C7—C11—C13 | −80.59 (16) |
C4—O1—C5—C6 | 115.63 (13) | C6—O2—C12—O3 | −179.43 (13) |
C15—C4—C5—O1 | 100.10 (14) | C6—O2—C12—C11 | −0.25 (15) |
C3—C4—C5—O1 | −105.76 (13) | C13—C11—C12—O3 | 35.0 (2) |
O1—C4—C5—C6 | −105.09 (13) | C7—C11—C12—O3 | 159.65 (16) |
C15—C4—C5—C6 | −5.0 (2) | C13—C11—C12—O2 | −144.11 (12) |
C3—C4—C5—C6 | 149.15 (12) | C7—C11—C12—O2 | −19.44 (15) |
C12—O2—C6—C5 | 141.96 (11) | C2'—N1—C13—C11 | 175.89 (14) |
C12—O2—C6—C7 | 20.01 (14) | C12—C11—C13—N1 | −67.32 (15) |
O1—C5—C6—O2 | 48.47 (14) | C7—C11—C13—N1 | 174.88 (12) |
C4—C5—C6—O2 | 119.49 (13) | C13—N1—C2'—C3' | −177.25 (14) |
O1—C5—C6—C7 | 163.67 (11) | N1—C2'—C3'—C8' | −57.4 (2) |
C4—C5—C6—C7 | −125.31 (13) | N1—C2'—C3'—C4' | 124.74 (16) |
O2—C6—C7—C11 | −30.40 (13) | C8'—C3'—C4'—C5' | −0.7 (2) |
C5—C6—C7—C11 | −146.50 (11) | C2'—C3'—C4'—C5' | 177.20 (14) |
O2—C6—C7—C8 | −152.99 (11) | C3'—C4'—C5'—C6' | 0.7 (2) |
C5—C6—C7—C8 | 90.90 (14) | C4'—C5'—C6'—C7' | −0.1 (2) |
C6—C7—C8—C9 | −88.67 (17) | C5'—C6'—C7'—C8' | −0.5 (2) |
C11—C7—C8—C9 | 154.15 (14) | C6'—C7'—C8'—C3' | 0.4 (2) |
C7—C8—C9—C10 | 78.04 (18) | C4'—C3'—C8'—C7' | 0.2 (2) |
C2—C1—C10—C14 | −11.1 (2) | C2'—C3'—C8'—C7' | −177.73 (14) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1N···O3 | 0.92 (2) | 2.30 (2) | 2.9784 (17) | 130 (1) |
Experimental details
Crystal data | |
Chemical formula | C22H29NO3 |
Mr | 355.46 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 90 |
a, b, c (Å) | 8.3772 (6), 13.7441 (10), 16.9684 (12) |
V (Å3) | 1953.7 (2) |
Z | 4 |
Radiation type | Cu Kα |
µ (mm−1) | 0.63 |
Crystal size (mm) | 0.35 × 0.08 × 0.08 |
Data collection | |
Diffractometer | X8 Proteum |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 21942, 3531, 3446 |
Rint | 0.043 |
(sin θ/λ)max (Å−1) | 0.601 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.036, 0.096, 1.08 |
No. of reflections | 3531 |
No. of parameters | 241 |
No. of restraints | 1 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.26, −0.19 |
Absolute structure | Flack (1983), with 0000 Friedel pairs |
Absolute structure parameter | 0.13 (6) |
Computer programs: APEX2 (Bruker–Nonius, 2004), APEX2, SHELXS97 (Sheldrick, 1997), XP in SHELXTL/PC (Sheldrick, 1995), SHELXL97 (Sheldrick, 1997) and local procedures.
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1N···O3 | 0.92 (2) | 2.303 (17) | 2.9784 (17) | 130.2 (8) |
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Parthenolide, is a germacrene sesquiterpene lactone. It has been isolated from several different species of plant in the Asteraceae (Compositae) family, feverfew (Tanacetum parthenium) being one of them (de Kraker et al., 2002). Its remarkable cytotoxic, antitumor, antiviral and antileishmanic properties have made it the focus of a large number of investigations. Its ability to induce tumor apoptosis through the inhibition of NF-kappaB make it a potential therapeutic for the treatment of leukemia (Guzman et al., 2005). Its development in this regard has been impeded by its low polarity and low water solubility. We saw a potential solution to this problem in the formation of a conjugate adduct of an amine species at the C-13, α-methylene group of the γ-butyrolactone function of parthenolide (Crooks et al., 2005). The title compound was synthesized as part of an ongoing drug discovery effort by reaction of benzylamine with parthenolide. The benzylamine adduct obtained was shown to be a single diastereomer by NMR analysis. The crystal structure of the title compound was determined to obtain the configuration of the newly formed stereocenter at C-11. An R absolute configuration was found. Bond distances and angles within the molecule are quite regular with average normal bonds (Allen et al., 1987). A hydrogen bond is observed between N-1H and O3 (2.30 (17) A°, 2.97 (17) A°, 130.2 (8) °) (Table 1) of the carbonyl oxygen of the 5-membered lactone ring, which can be considered as a weak hydrogen bond (Desiraju & Steiner, 1999).