Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807046983/hg2301sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807046983/hg2301Isup2.hkl |
CCDC reference: 667322
The title compound was prepared acording to the previously reported procedure of Nasim et al. (2007). Crystals suitable for X-ray diffraction were obtained by slow evaporation of a chloroform/hexane solution at room temperature. The title compound was obtained as white crystals. 1H NMR (CDCl3, p.p.m.): δ 8.29 (d, 1H, J = 8.4 Hz), 7.83 (m, 2H), 7.57 (m, 4H), 4.66 (app. d, 1H, J = 10.2 Hz), 4.45 (d, 1H, J = 13.2 Hz) 4.10 (d, 1H, J = 13.2 Hz), 3.73 (t, 1H, J = 9.0 Hz), 3.24 (dd, 1H, J = 3.6, 12.6 Hz), 2.70 (dd, 1H, J = 12.6, 4.8 Hz), 2.51 (d, 1H, J = 9.0 Hz), 2.40–2.24 (m, 2H), 2.11–1.86 (m, 7H), 1.58 (s, 3H), 1.53–1.09 (m, 2H), 1.22 (s, 3H); 13C NMR (CDCl3, δ, p.p.m.): 176.7, 135.0, 134.3, 134.1, 132.1, 128.8, 128.2, 126.9, 126.0, 125.8, 125.3, 124.9, 124.6, 82.7, 66.4, 61.6, 51.9, 48.8, 45.8, 45.1, 40.7, 36.7, 30.2, 24.2, 17.4, 17.0.
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 0.98 Å (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).
The title compound was synthesized as part of our ongoing drug discovery effort (Crooks et al., 2005), by the reaction of 1-naphthylmethylamine with parthenolide, and was shown to be a single diastereomer by NMR spectroscopic analysis. The crystal structure of the title compound was determined to obtain the configuration of the newly formed chiral center at C-11. An R absolute configuration was found.
The naphthalene ring of the amino side-chain is stacked against the cyclodecene ring of the parthenolide backbone. We believe that such a stacked structure is also consistent with the conformation of the title compound in the solution state (CDCl3), due to the unusual upfield resonance (4.66 p.p.m.) of the C-1 olefinic hydrogen as opposed to the usual value (ca 5.1–5.2 p.p.m.), in the NMR spectrum. This upfield shift is likely to be a result of anisotropic shielding of the C-1 hydrogen by the Pi cloud of the naphthalene ring. An intramolecular H-bonding is observed between N-1H and O3 (2.70 (17) A°, 3.07 (17) A°, 104.9 (12)°) of the carbonyl oxygen of the 5-membered lactone ring (Desiraju & Steiner, 1999). Other bond distances and angles within the molecule are quite regular (Allen et al., 1987).
For related literature, see: Allen et al. (1987); Crooks et al. (2005); Desiraju & Steiner (1999); Nasim et al. (2007); Parsons & Flack (2004).
Data collection: APEX2 (Bruker, 2006); cell refinement: APEX2 (Bruker, 2006); data reduction: APEX2 (Bruker, 2006); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP in SHELXTL (Sheldrick, 1995); software used to prepare material for publication: SHELX97 (Sheldrick, 1997) and local procedures.
C26H31NO3 | F(000) = 872 |
Mr = 405.52 | Dx = 1.294 Mg m−3 |
Orthorhombic, P212121 | Cu Kα radiation, λ = 1.54178 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 7441 reflections |
a = 9.3842 (6) Å | θ = 4.4–67.0° |
b = 11.9025 (7) Å | µ = 0.66 mm−1 |
c = 18.6386 (13) Å | T = 90 K |
V = 2081.8 (2) Å3 | Cut block, colourless |
Z = 4 | 0.30 × 0.28 × 0.25 mm |
Bruker X8 Proteum diffractometer | 3576 independent reflections |
Radiation source: fine-focus rotating anode | 3503 reflections with I > 2σ(I) |
Graded multilayer optics monochromator | Rint = 0.034 |
Detector resolution: 18 pixels mm-1 | θmax = 67.3°, θmin = 4.4° |
φ and ω scans | h = −11→10 |
Absorption correction: multi-scan (SADABS in APEX2; Bruker, 2006) | k = −14→14 |
Tmin = 0.826, Tmax = 0.852 | l = −20→22 |
16527 measured 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)] = 0.034 | w = 1/[σ2(Fo2) + (0.0495P)2 + 0.31P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.081 | (Δ/σ)max = 0.003 |
S = 1.11 | Δρmax = 0.28 e Å−3 |
3576 reflections | Δρmin = −0.33 e Å−3 |
276 parameters | Extinction correction: SHELXL97 (Sheldrick, 1997), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
0 restraints | Extinction coefficient: 0.0179 (7) |
Primary atom site location: structure-invariant direct methods | Absolute structure: Flack (1983), with 1490 Friedel pairs |
Secondary atom site location: difference Fourier map | Absolute structure parameter: 0.09 (5) |
C26H31NO3 | V = 2081.8 (2) Å3 |
Mr = 405.52 | Z = 4 |
Orthorhombic, P212121 | Cu Kα radiation |
a = 9.3842 (6) Å | µ = 0.66 mm−1 |
b = 11.9025 (7) Å | T = 90 K |
c = 18.6386 (13) Å | 0.30 × 0.28 × 0.25 mm |
Bruker X8 Proteum diffractometer | 3576 independent reflections |
Absorption correction: multi-scan (SADABS in APEX2; Bruker, 2006) | 3503 reflections with I > 2σ(I) |
Tmin = 0.826, Tmax = 0.852 | Rint = 0.034 |
16527 measured reflections |
R[F2 > 2σ(F2)] = 0.034 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.081 | Δρmax = 0.28 e Å−3 |
S = 1.11 | Δρmin = −0.33 e Å−3 |
3576 reflections | Absolute structure: Flack (1983), with 1490 Friedel pairs |
276 parameters | Absolute structure parameter: 0.09 (5) |
0 restraints |
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 > 2σ(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. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.73981 (11) | 0.85246 (8) | 0.94404 (6) | 0.0238 (2) | |
C1 | 0.81331 (16) | 0.62589 (13) | 0.78893 (8) | 0.0243 (3) | |
H1A | 0.7323 | 0.5806 | 0.7989 | 0.029* | |
O2 | 0.82549 (12) | 0.70644 (8) | 1.05639 (5) | 0.0245 (2) | |
C2 | 0.78375 (17) | 0.73806 (13) | 0.75591 (8) | 0.0261 (3) | |
H2A | 0.7151 | 0.7293 | 0.7160 | 0.031* | |
H2B | 0.8730 | 0.7698 | 0.7362 | 0.031* | |
O3 | 0.82066 (12) | 0.62291 (9) | 1.16246 (6) | 0.0294 (3) | |
C3 | 0.72219 (16) | 0.81826 (12) | 0.81239 (8) | 0.0241 (3) | |
H3A | 0.7175 | 0.8952 | 0.7923 | 0.029* | |
H3B | 0.6241 | 0.7946 | 0.8247 | 0.029* | |
C4 | 0.81190 (15) | 0.81904 (11) | 0.87883 (8) | 0.0203 (3) | |
C5 | 0.77511 (15) | 0.73593 (11) | 0.93375 (8) | 0.0205 (3) | |
H5A | 0.6921 | 0.6871 | 0.9212 | 0.025* | |
C6 | 0.87838 (15) | 0.68344 (12) | 0.98458 (8) | 0.0205 (3) | |
H6A | 0.9752 | 0.7169 | 0.9781 | 0.025* | |
C7 | 0.88646 (15) | 0.55483 (11) | 0.98032 (8) | 0.0199 (3) | |
H7A | 0.7902 | 0.5255 | 0.9670 | 0.024* | |
C8 | 0.99634 (16) | 0.50330 (13) | 0.92968 (8) | 0.0269 (3) | |
H8A | 1.0292 | 0.4316 | 0.9509 | 0.032* | |
H8B | 1.0796 | 0.5542 | 0.9277 | 0.032* | |
C9 | 0.94802 (17) | 0.48003 (12) | 0.85268 (8) | 0.0273 (3) | |
H9A | 1.0153 | 0.4262 | 0.8305 | 0.033* | |
H9B | 0.8532 | 0.4437 | 0.8542 | 0.033* | |
C10 | 0.93891 (16) | 0.58185 (12) | 0.80601 (8) | 0.0228 (3) | |
C11 | 0.91569 (15) | 0.52442 (12) | 1.05852 (8) | 0.0208 (3) | |
H11A | 1.0210 | 0.5256 | 1.0666 | 0.025* | |
C12 | 0.85036 (15) | 0.61909 (12) | 1.09992 (8) | 0.0219 (3) | |
C13 | 0.85856 (15) | 0.41104 (12) | 1.08246 (8) | 0.0217 (3) | |
H13A | 0.8896 | 0.3522 | 1.0483 | 0.026* | |
H13B | 0.8975 | 0.3923 | 1.1303 | 0.026* | |
C14 | 1.08003 (16) | 0.62865 (13) | 0.78347 (9) | 0.0280 (3) | |
H14A | 1.0650 | 0.6952 | 0.7534 | 0.042* | |
H14B | 1.1325 | 0.5718 | 0.7561 | 0.042* | |
H14C | 1.1351 | 0.6496 | 0.8261 | 0.042* | |
C15 | 0.95707 (16) | 0.86843 (12) | 0.87159 (8) | 0.0237 (3) | |
H15A | 1.0067 | 0.8638 | 0.9177 | 0.036* | |
H15B | 0.9491 | 0.9473 | 0.8570 | 0.036* | |
H15C | 1.0109 | 0.8267 | 0.8353 | 0.036* | |
N1' | 0.70323 (13) | 0.41347 (10) | 1.08575 (7) | 0.0206 (3) | |
H1N' | 0.6721 (18) | 0.4342 (14) | 1.1307 (11) | 0.028 (4)* | |
C2' | 0.63519 (15) | 0.30803 (12) | 1.06522 (8) | 0.0216 (3) | |
H2'A | 0.5347 | 0.3087 | 1.0814 | 0.026* | |
H2'B | 0.6841 | 0.2449 | 1.0895 | 0.026* | |
C3' | 0.63980 (15) | 0.28988 (11) | 0.98538 (8) | 0.0193 (3) | |
C4' | 0.56993 (14) | 0.36495 (11) | 0.93748 (8) | 0.0183 (3) | |
C5' | 0.48953 (15) | 0.45765 (11) | 0.96127 (8) | 0.0195 (3) | |
H5'A | 0.4802 | 0.4711 | 1.0113 | 0.023* | |
C6' | 0.42482 (15) | 0.52852 (12) | 0.91389 (8) | 0.0222 (3) | |
H6'A | 0.3694 | 0.5896 | 0.9311 | 0.027* | |
C7' | 0.43983 (15) | 0.51149 (13) | 0.83983 (8) | 0.0243 (3) | |
H7'A | 0.3969 | 0.5623 | 0.8070 | 0.029* | |
C8' | 0.51576 (15) | 0.42240 (12) | 0.81488 (8) | 0.0230 (3) | |
H8'A | 0.5251 | 0.4112 | 0.7646 | 0.028* | |
C9' | 0.58078 (14) | 0.34651 (11) | 0.86271 (8) | 0.0194 (3) | |
C10' | 0.65761 (15) | 0.25253 (13) | 0.83713 (8) | 0.0228 (3) | |
H10A | 0.6650 | 0.2397 | 0.7870 | 0.027* | |
C11' | 0.72056 (16) | 0.18102 (12) | 0.88348 (9) | 0.0252 (3) | |
H11B | 0.7710 | 0.1176 | 0.8659 | 0.030* | |
C12' | 0.71158 (15) | 0.20023 (12) | 0.95787 (8) | 0.0235 (3) | |
H12A | 0.7569 | 0.1492 | 0.9898 | 0.028* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0280 (5) | 0.0214 (5) | 0.0221 (5) | 0.0066 (4) | 0.0010 (4) | 0.0003 (4) |
C1 | 0.0242 (7) | 0.0244 (7) | 0.0243 (7) | −0.0060 (6) | 0.0018 (6) | −0.0065 (6) |
O2 | 0.0343 (6) | 0.0183 (5) | 0.0208 (5) | −0.0004 (4) | −0.0029 (4) | −0.0007 (4) |
C2 | 0.0270 (8) | 0.0314 (8) | 0.0198 (7) | −0.0012 (7) | −0.0046 (6) | −0.0013 (6) |
O3 | 0.0378 (6) | 0.0303 (5) | 0.0203 (5) | −0.0011 (5) | −0.0039 (5) | −0.0004 (4) |
C3 | 0.0247 (8) | 0.0238 (7) | 0.0239 (7) | 0.0020 (6) | −0.0028 (6) | 0.0024 (6) |
C4 | 0.0222 (7) | 0.0170 (6) | 0.0218 (7) | 0.0035 (5) | −0.0001 (6) | −0.0022 (6) |
C5 | 0.0199 (6) | 0.0194 (7) | 0.0222 (7) | 0.0011 (6) | −0.0003 (6) | −0.0011 (5) |
C6 | 0.0194 (7) | 0.0204 (7) | 0.0216 (7) | −0.0012 (5) | 0.0002 (6) | 0.0012 (6) |
C7 | 0.0185 (7) | 0.0187 (6) | 0.0224 (8) | 0.0007 (5) | 0.0003 (6) | 0.0014 (5) |
C8 | 0.0260 (7) | 0.0267 (7) | 0.0280 (8) | 0.0064 (6) | 0.0044 (6) | 0.0044 (6) |
C9 | 0.0316 (8) | 0.0201 (7) | 0.0302 (8) | 0.0024 (6) | 0.0087 (7) | −0.0038 (6) |
C10 | 0.0262 (8) | 0.0227 (7) | 0.0197 (7) | −0.0026 (6) | 0.0039 (6) | −0.0060 (6) |
C11 | 0.0187 (6) | 0.0210 (7) | 0.0227 (7) | −0.0006 (6) | −0.0033 (6) | 0.0014 (6) |
C12 | 0.0226 (7) | 0.0206 (7) | 0.0223 (8) | −0.0053 (6) | −0.0055 (6) | 0.0007 (6) |
C13 | 0.0189 (7) | 0.0207 (6) | 0.0257 (7) | −0.0002 (5) | −0.0033 (6) | 0.0047 (6) |
C14 | 0.0250 (7) | 0.0279 (7) | 0.0312 (8) | 0.0001 (6) | 0.0061 (7) | 0.0002 (7) |
C15 | 0.0281 (8) | 0.0195 (6) | 0.0236 (7) | −0.0019 (6) | −0.0018 (6) | 0.0002 (6) |
N1' | 0.0191 (6) | 0.0217 (6) | 0.0212 (6) | −0.0008 (5) | 0.0006 (5) | −0.0008 (5) |
C2' | 0.0199 (7) | 0.0219 (7) | 0.0229 (7) | −0.0046 (6) | −0.0010 (6) | 0.0031 (6) |
C3' | 0.0153 (7) | 0.0193 (6) | 0.0231 (7) | −0.0044 (5) | 0.0007 (6) | 0.0009 (5) |
C4' | 0.0146 (6) | 0.0178 (6) | 0.0224 (7) | −0.0043 (5) | 0.0008 (5) | −0.0009 (6) |
C5' | 0.0171 (6) | 0.0198 (7) | 0.0217 (7) | −0.0028 (5) | 0.0007 (5) | −0.0029 (5) |
C6' | 0.0174 (7) | 0.0182 (6) | 0.0309 (8) | −0.0005 (5) | 0.0000 (6) | −0.0031 (6) |
C7' | 0.0186 (7) | 0.0265 (7) | 0.0279 (7) | −0.0014 (6) | −0.0041 (6) | 0.0053 (6) |
C8' | 0.0182 (7) | 0.0303 (7) | 0.0204 (7) | −0.0054 (6) | −0.0009 (6) | −0.0001 (6) |
C9' | 0.0144 (6) | 0.0217 (7) | 0.0220 (7) | −0.0038 (5) | 0.0002 (5) | −0.0026 (5) |
C10' | 0.0198 (7) | 0.0259 (7) | 0.0228 (7) | −0.0034 (6) | 0.0027 (6) | −0.0084 (6) |
C11' | 0.0218 (7) | 0.0207 (7) | 0.0332 (8) | 0.0012 (6) | 0.0028 (6) | −0.0061 (6) |
C12' | 0.0181 (7) | 0.0213 (7) | 0.0312 (8) | 0.0000 (6) | −0.0002 (6) | 0.0026 (6) |
O1—C5 | 1.4388 (16) | C13—N1' | 1.4592 (19) |
O1—C4 | 1.4467 (17) | C13—H13A | 0.9900 |
C1—C10 | 1.329 (2) | C13—H13B | 0.9900 |
C1—C2 | 1.496 (2) | C14—H14A | 0.9800 |
C1—H1A | 0.9500 | C14—H14B | 0.9800 |
O2—C12 | 1.3393 (18) | C14—H14C | 0.9800 |
O2—C6 | 1.4534 (17) | C15—H15A | 0.9800 |
C2—C3 | 1.534 (2) | C15—H15B | 0.9800 |
C2—H2A | 0.9900 | C15—H15C | 0.9800 |
C2—H2B | 0.9900 | N1'—C2' | 1.4591 (18) |
O3—C12 | 1.1994 (18) | N1'—H1N' | 0.92 (2) |
C3—C4 | 1.497 (2) | C2'—C3' | 1.504 (2) |
C3—H3A | 0.9900 | C2'—H2'A | 0.9900 |
C3—H3B | 0.9900 | C2'—H2'B | 0.9900 |
C4—C5 | 1.465 (2) | C3'—C12' | 1.362 (2) |
C4—C15 | 1.490 (2) | C3'—C4' | 1.423 (2) |
C5—C6 | 1.492 (2) | C4'—C5' | 1.408 (2) |
C5—H5A | 1.0000 | C4'—C9' | 1.414 (2) |
C6—C7 | 1.5348 (19) | C5'—C6' | 1.364 (2) |
C6—H6A | 1.0000 | C5'—H5'A | 0.9500 |
C7—C8 | 1.527 (2) | C6'—C7' | 1.402 (2) |
C7—C11 | 1.527 (2) | C6'—H6'A | 0.9500 |
C7—H7A | 1.0000 | C7'—C8' | 1.360 (2) |
C8—C9 | 1.530 (2) | C7'—H7'A | 0.9500 |
C8—H8A | 0.9900 | C8'—C9' | 1.408 (2) |
C8—H8B | 0.9900 | C8'—H8'A | 0.9500 |
C9—C10 | 1.494 (2) | C9'—C10' | 1.414 (2) |
C9—H9A | 0.9900 | C10'—C11' | 1.349 (2) |
C9—H9B | 0.9900 | C10'—H10A | 0.9500 |
C10—C14 | 1.497 (2) | C11'—C12' | 1.408 (2) |
C11—C12 | 1.497 (2) | C11'—H11B | 0.9500 |
C11—C13 | 1.5190 (19) | C12'—H12A | 0.9500 |
C11—H11A | 1.0000 | ||
C5—O1—C4 | 61.01 (9) | C7—C11—H11A | 108.5 |
C10—C1—C2 | 127.96 (14) | O3—C12—O2 | 121.26 (14) |
C10—C1—H1A | 116.0 | O3—C12—C11 | 128.65 (14) |
C2—C1—H1A | 116.0 | O2—C12—C11 | 110.08 (12) |
C12—O2—C6 | 110.62 (11) | N1'—C13—C11 | 110.32 (12) |
C1—C2—C3 | 110.05 (12) | N1'—C13—H13A | 109.6 |
C1—C2—H2A | 109.7 | C11—C13—H13A | 109.6 |
C3—C2—H2A | 109.7 | N1'—C13—H13B | 109.6 |
C1—C2—H2B | 109.7 | C11—C13—H13B | 109.6 |
C3—C2—H2B | 109.7 | H13A—C13—H13B | 108.1 |
H2A—C2—H2B | 108.2 | C10—C14—H14A | 109.5 |
C4—C3—C2 | 111.08 (12) | C10—C14—H14B | 109.5 |
C4—C3—H3A | 109.4 | H14A—C14—H14B | 109.5 |
C2—C3—H3A | 109.4 | C10—C14—H14C | 109.5 |
C4—C3—H3B | 109.4 | H14A—C14—H14C | 109.5 |
C2—C3—H3B | 109.4 | H14B—C14—H14C | 109.5 |
H3A—C3—H3B | 108.0 | C4—C15—H15A | 109.5 |
O1—C4—C5 | 59.23 (9) | C4—C15—H15B | 109.5 |
O1—C4—C15 | 113.28 (12) | H15A—C15—H15B | 109.5 |
C5—C4—C15 | 123.04 (13) | C4—C15—H15C | 109.5 |
O1—C4—C3 | 115.70 (12) | H15A—C15—H15C | 109.5 |
C5—C4—C3 | 116.19 (13) | H15B—C15—H15C | 109.5 |
C15—C4—C3 | 116.20 (13) | C2'—N1'—C13 | 114.15 (12) |
O1—C5—C4 | 59.76 (9) | C2'—N1'—H1N' | 109.3 (11) |
O1—C5—C6 | 117.93 (12) | C13—N1'—H1N' | 111.1 (11) |
C4—C5—C6 | 124.99 (13) | N1'—C2'—C3' | 111.73 (12) |
O1—C5—H5A | 114.3 | N1'—C2'—H2'A | 109.3 |
C4—C5—H5A | 114.3 | C3'—C2'—H2'A | 109.3 |
C6—C5—H5A | 114.3 | N1'—C2'—H2'B | 109.3 |
O2—C6—C5 | 106.50 (11) | C3'—C2'—H2'B | 109.3 |
O2—C6—C7 | 104.62 (11) | H2'A—C2'—H2'B | 107.9 |
C5—C6—C7 | 114.64 (12) | C12'—C3'—C4' | 118.91 (13) |
O2—C6—H6A | 110.3 | C12'—C3'—C2' | 119.94 (13) |
C5—C6—H6A | 110.3 | C4'—C3'—C2' | 121.14 (12) |
C7—C6—H6A | 110.3 | C5'—C4'—C9' | 118.05 (13) |
C8—C7—C11 | 111.95 (12) | C5'—C4'—C3' | 122.77 (13) |
C8—C7—C6 | 117.78 (12) | C9'—C4'—C3' | 119.18 (12) |
C11—C7—C6 | 101.30 (11) | C6'—C5'—C4' | 121.28 (13) |
C8—C7—H7A | 108.5 | C6'—C5'—H5'A | 119.4 |
C11—C7—H7A | 108.5 | C4'—C5'—H5'A | 119.4 |
C6—C7—H7A | 108.5 | C5'—C6'—C7' | 120.22 (13) |
C7—C8—C9 | 116.90 (13) | C5'—C6'—H6'A | 119.9 |
C7—C8—H8A | 108.1 | C7'—C6'—H6'A | 119.9 |
C9—C8—H8A | 108.1 | C8'—C7'—C6' | 120.13 (14) |
C7—C8—H8B | 108.1 | C8'—C7'—H7'A | 119.9 |
C9—C8—H8B | 108.1 | C6'—C7'—H7'A | 119.9 |
H8A—C8—H8B | 107.3 | C7'—C8'—C9' | 120.73 (14) |
C10—C9—C8 | 114.59 (13) | C7'—C8'—H8'A | 119.6 |
C10—C9—H9A | 108.6 | C9'—C8'—H8'A | 119.6 |
C8—C9—H9A | 108.6 | C8'—C9'—C10' | 121.00 (13) |
C10—C9—H9B | 108.6 | C8'—C9'—C4' | 119.54 (13) |
C8—C9—H9B | 108.6 | C10'—C9'—C4' | 119.46 (13) |
H9A—C9—H9B | 107.6 | C11'—C10'—C9' | 120.44 (13) |
C1—C10—C9 | 120.68 (14) | C11'—C10'—H10A | 119.8 |
C1—C10—C14 | 124.80 (14) | C9'—C10'—H10A | 119.8 |
C9—C10—C14 | 114.50 (13) | C10'—C11'—C12' | 120.13 (13) |
C12—C11—C13 | 111.88 (12) | C10'—C11'—H11B | 119.9 |
C12—C11—C7 | 103.89 (11) | C12'—C11'—H11B | 119.9 |
C13—C11—C7 | 115.32 (12) | C3'—C12'—C11' | 121.85 (14) |
C12—C11—H11A | 108.5 | C3'—C12'—H12A | 119.1 |
C13—C11—H11A | 108.5 | C11'—C12'—H12A | 119.1 |
C10—C1—C2—C3 | −106.01 (18) | C6—O2—C12—O3 | 176.63 (13) |
C1—C2—C3—C4 | 50.10 (16) | C6—O2—C12—C11 | −3.70 (16) |
C5—O1—C4—C15 | −115.77 (13) | C13—C11—C12—O3 | 38.6 (2) |
C5—O1—C4—C3 | 106.47 (14) | C7—C11—C12—O3 | 163.59 (15) |
C2—C3—C4—O1 | −155.94 (12) | C13—C11—C12—O2 | −141.08 (12) |
C2—C3—C4—C5 | −89.27 (15) | C7—C11—C12—O2 | −16.04 (15) |
C2—C3—C4—C15 | 67.55 (16) | C12—C11—C13—N1' | 48.63 (16) |
C4—O1—C5—C6 | 116.24 (15) | C7—C11—C13—N1' | −69.81 (16) |
C15—C4—C5—O1 | 99.28 (15) | C11—C13—N1'—C2' | 144.82 (13) |
C3—C4—C5—O1 | −105.64 (13) | C13—N1'—C2'—C3' | −74.63 (16) |
O1—C4—C5—C6 | −104.71 (15) | N1'—C2'—C3'—C12' | 117.47 (15) |
C15—C4—C5—C6 | −5.4 (2) | N1'—C2'—C3'—C4' | −62.64 (17) |
C3—C4—C5—C6 | 149.66 (13) | C12'—C3'—C4'—C5' | 177.91 (13) |
C12—O2—C6—C5 | 143.65 (12) | C2'—C3'—C4'—C5' | −2.0 (2) |
C12—O2—C6—C7 | 21.87 (15) | C12'—C3'—C4'—C9' | −2.02 (19) |
O1—C5—C6—O2 | 52.48 (16) | C2'—C3'—C4'—C9' | 178.08 (12) |
C4—C5—C6—O2 | 123.53 (14) | C9'—C4'—C5'—C6' | −0.60 (19) |
O1—C5—C6—C7 | 167.65 (12) | C3'—C4'—C5'—C6' | 179.47 (13) |
C4—C5—C6—C7 | −121.30 (15) | C4'—C5'—C6'—C7' | −1.3 (2) |
O2—C6—C7—C8 | −152.32 (12) | C5'—C6'—C7'—C8' | 1.8 (2) |
C5—C6—C7—C8 | 91.42 (16) | C6'—C7'—C8'—C9' | −0.3 (2) |
O2—C6—C7—C11 | −29.90 (14) | C7'—C8'—C9'—C10' | 178.80 (13) |
C5—C6—C7—C11 | −146.16 (12) | C7'—C8'—C9'—C4' | −1.6 (2) |
C11—C7—C8—C9 | 152.93 (13) | C5'—C4'—C9'—C8' | 2.07 (19) |
C6—C7—C8—C9 | −90.25 (17) | C3'—C4'—C9'—C8' | −177.99 (13) |
C7—C8—C9—C10 | 76.25 (17) | C5'—C4'—C9'—C10' | −178.36 (12) |
C2—C1—C10—C9 | 166.76 (14) | C3'—C4'—C9'—C10' | 1.57 (19) |
C2—C1—C10—C14 | −11.4 (2) | C8'—C9'—C10'—C11' | 179.37 (14) |
C8—C9—C10—C1 | −105.11 (17) | C4'—C9'—C10'—C11' | −0.2 (2) |
C8—C9—C10—C14 | 73.23 (16) | C9'—C10'—C11'—C12' | −0.8 (2) |
C8—C7—C11—C12 | 153.82 (12) | C4'—C3'—C12'—C11' | 1.1 (2) |
C6—C7—C11—C12 | 27.45 (14) | C2'—C3'—C12'—C11' | −178.98 (13) |
C8—C7—C11—C13 | −83.38 (15) | C10'—C11'—C12'—C3' | 0.3 (2) |
C6—C7—C11—C13 | 150.25 (12) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1′—H1N′···O3 | 0.92 (2) | 2.709 (17) | 3.0778 (17) | 104.9 (12) |
Experimental details
Crystal data | |
Chemical formula | C26H31NO3 |
Mr | 405.52 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 90 |
a, b, c (Å) | 9.3842 (6), 11.9025 (7), 18.6386 (13) |
V (Å3) | 2081.8 (2) |
Z | 4 |
Radiation type | Cu Kα |
µ (mm−1) | 0.66 |
Crystal size (mm) | 0.30 × 0.28 × 0.25 |
Data collection | |
Diffractometer | Bruker X8 Proteum |
Absorption correction | Multi-scan (SADABS in APEX2; Bruker, 2006) |
Tmin, Tmax | 0.826, 0.852 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 16527, 3576, 3503 |
Rint | 0.034 |
(sin θ/λ)max (Å−1) | 0.598 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.034, 0.081, 1.11 |
No. of reflections | 3576 |
No. of parameters | 276 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.28, −0.33 |
Absolute structure | Flack (1983), with 1490 Friedel pairs |
Absolute structure parameter | 0.09 (5) |
Computer programs: APEX2 (Bruker, 2006), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), XP in SHELXTL (Sheldrick, 1995), SHELX97 (Sheldrick, 1997) and local procedures.
D—H···A | D—H | H···A | D···A | D—H···A |
N1'—H1N'···O3 | 0.92 (2) | 2.709 (17) | 3.0778 (17) | 104.9 (12) |
The title compound was synthesized as part of our ongoing drug discovery effort (Crooks et al., 2005), by the reaction of 1-naphthylmethylamine with parthenolide, and was shown to be a single diastereomer by NMR spectroscopic analysis. The crystal structure of the title compound was determined to obtain the configuration of the newly formed chiral center at C-11. An R absolute configuration was found.
The naphthalene ring of the amino side-chain is stacked against the cyclodecene ring of the parthenolide backbone. We believe that such a stacked structure is also consistent with the conformation of the title compound in the solution state (CDCl3), due to the unusual upfield resonance (4.66 p.p.m.) of the C-1 olefinic hydrogen as opposed to the usual value (ca 5.1–5.2 p.p.m.), in the NMR spectrum. This upfield shift is likely to be a result of anisotropic shielding of the C-1 hydrogen by the Pi cloud of the naphthalene ring. An intramolecular H-bonding is observed between N-1H and O3 (2.70 (17) A°, 3.07 (17) A°, 104.9 (12)°) of the carbonyl oxygen of the 5-membered lactone ring (Desiraju & Steiner, 1999). Other bond distances and angles within the molecule are quite regular (Allen et al., 1987).