Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270106009048/ln1194sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270106009048/ln1194Isup2.hkl |
CCDC reference: 609426
The title compound has been prepared according to a procedure in the literature (Posner et al., 1997). To a solution of dihydroartemisinin (599 mg, 2.11 mmol) in toluene (60 ml) at 293–298 K was added triethylene glycol (0.144 ml, 1.06 mmol) followed by BF3·Et2O (0.064 ml, 0.53 mmol). The reaction was stirred at the same temperature for 3 h. The mixture was then diluted with methylene chloride and washed twice with water. The organic portions were collected, dried over MgSO4 and concentrated. The crude product was purified by column chromatography (flash, 5–50% ethyl acetate/hexane) to produce compound (I) (203 mg, 0.368 mmol, yield 35%). Crystals were obtained from hexane by slow evaporation at room temperature. Analysis calculated for C30H46O9: C 65.43, H 8.42%; found: C 65.40, H 8.38%.
The methyl H atoms were constrained to an ideal geometry [C—H = 0.96 Å, with Uiso(H) = 1.5Ueq(C)] but were allowed to rotate freely about the C—C bonds. All other H atoms were placed in geometrically idealized positions and constrained to ride on their parent C atoms at distances of 0.97 or 0.98 Å for methylene or methine groups, respectively [Uiso(H) = 1.2Ueq(C)]. As there are no significant anomalous scatterers in the molecule, attempts to confirm the absolute structure by refinement of the Flack parameter (Flack & Bernardinelli, 2000) in the presence of 2761 sets of Friedel equivalents led to an inconclusive value for the parameter. Therefore, Friedel pairs were merged before the final refinement and the absolute configuration was assigned to correspond to that determined for artemisinin (Qinghaosu Research Group, 1980).
Data collection: RAPID-AUTO (Rigaku Corporation, 1998); cell refinement: RAPID-AUTO; data reduction: CrystalStructure (Rigaku/MSC, 2002); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97.
Fig. 1. A view of the title compound, showing the atom-labelling scheme and with displacement ellipsoids drawn at the 30% probability level. |
C30H46O9 | F(000) = 596 |
Mr = 550.67 | Dx = 1.223 Mg m−3 |
Monoclinic, P21 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2yb | Cell parameters from 13709 reflections |
a = 10.338 (2) Å | θ = 3.0–27.5° |
b = 12.012 (2) Å | µ = 0.09 mm−1 |
c = 12.065 (2) Å | T = 295 K |
β = 93.39 (3)° | Block, colorless |
V = 1495.6 (5) Å3 | 0.42 × 0.30 × 0.23 mm |
Z = 2 |
Rigaku R-AXIS RAPID diffractometer | 3576 independent reflections |
Radiation source: fine-focus sealed tube | 2877 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.069 |
Detector resolution: 10 pixels mm-1 | θmax = 27.5°, θmin = 3.0° |
ω scan | h = −13→13 |
Absorption correction: multi-scan (ABSCOR; Higashi, 1995) | k = −14→15 |
Tmin = 0.935, Tmax = 0.972 | l = −15→15 |
14678 measured reflections |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.058 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.156 | H-atom parameters constrained |
S = 1.10 | w = 1/[σ2(Fo2) + (0.0947P)2] where P = (Fo2 + 2Fc2)/3 |
3576 reflections | (Δ/σ)max < 0.001 |
358 parameters | Δρmax = 0.29 e Å−3 |
1 restraint | Δρmin = −0.20 e Å−3 |
C30H46O9 | V = 1495.6 (5) Å3 |
Mr = 550.67 | Z = 2 |
Monoclinic, P21 | Mo Kα radiation |
a = 10.338 (2) Å | µ = 0.09 mm−1 |
b = 12.012 (2) Å | T = 295 K |
c = 12.065 (2) Å | 0.42 × 0.30 × 0.23 mm |
β = 93.39 (3)° |
Rigaku R-AXIS RAPID diffractometer | 3576 independent reflections |
Absorption correction: multi-scan (ABSCOR; Higashi, 1995) | 2877 reflections with I > 2σ(I) |
Tmin = 0.935, Tmax = 0.972 | Rint = 0.069 |
14678 measured reflections |
R[F2 > 2σ(F2)] = 0.058 | 1 restraint |
wR(F2) = 0.156 | H-atom parameters constrained |
S = 1.10 | Δρmax = 0.29 e Å−3 |
3576 reflections | Δρmin = −0.20 e Å−3 |
358 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.4600 (3) | 0.3854 (3) | 0.9329 (2) | 0.0854 (9) | |
O2 | 0.5988 (3) | 0.3790 (2) | 0.96535 (18) | 0.0710 (7) | |
O3 | 0.4652 (2) | 0.26089 (19) | 0.78733 (17) | 0.0616 (6) | |
O4 | 0.55764 (19) | 0.41631 (17) | 0.72608 (17) | 0.0551 (5) | |
O5 | 0.6227 (2) | 0.58392 (16) | 0.66367 (15) | 0.0528 (5) | |
O6 | 0.2279 (2) | 0.5537 (2) | 0.6012 (2) | 0.0668 (6) | |
O7 | 0.4346 (2) | 0.54336 (16) | 0.55256 (17) | 0.0539 (5) | |
O8 | 0.2229 (2) | 0.6279 (2) | 0.42423 (17) | 0.0647 (6) | |
O9 | 0.2875 (2) | 0.73203 (17) | 0.45671 (15) | 0.0521 (5) | |
C1 | 0.4169 (4) | 0.2806 (4) | 0.8943 (3) | 0.0820 (12) | |
C2 | 0.4600 (6) | 0.1880 (5) | 0.9731 (4) | 0.1043 (19) | |
H2A | 0.3919 | 0.1324 | 0.9732 | 0.125* | |
H2B | 0.4711 | 0.2183 | 1.0475 | 0.125* | |
C3 | 0.5860 (5) | 0.1310 (4) | 0.9446 (4) | 0.0913 (14) | |
H3A | 0.6078 | 0.0761 | 1.0016 | 0.110* | |
H3B | 0.5699 | 0.0910 | 0.8752 | 0.110* | |
C4 | 0.7033 (4) | 0.2051 (3) | 0.9332 (3) | 0.0721 (10) | |
H4 | 0.7393 | 0.2195 | 1.0088 | 0.087* | |
C5 | 0.8098 (5) | 0.1436 (4) | 0.8731 (4) | 0.0878 (12) | |
H5 | 0.7741 | 0.1259 | 0.7982 | 0.105* | |
C6 | 0.9260 (5) | 0.2175 (4) | 0.8611 (5) | 0.0949 (13) | |
H6A | 0.9884 | 0.1786 | 0.8182 | 0.114* | |
H6B | 0.9668 | 0.2325 | 0.9340 | 0.114* | |
C7 | 0.8907 (4) | 0.3269 (4) | 0.8045 (3) | 0.0729 (9) | |
H7A | 0.8575 | 0.3124 | 0.7290 | 0.088* | |
H7B | 0.9680 | 0.3722 | 0.8010 | 0.088* | |
C8 | 0.7889 (3) | 0.3915 (3) | 0.8655 (2) | 0.0554 (7) | |
H8 | 0.8277 | 0.4086 | 0.9396 | 0.066* | |
C9 | 0.7482 (3) | 0.5031 (3) | 0.8117 (2) | 0.0529 (6) | |
H9 | 0.6923 | 0.5409 | 0.8627 | 0.064* | |
C10 | 0.6676 (3) | 0.4821 (2) | 0.7047 (2) | 0.0471 (6) | |
H10 | 0.7199 | 0.4451 | 0.6504 | 0.056* | |
C11 | 0.5851 (3) | 0.3117 (2) | 0.7741 (2) | 0.0488 (6) | |
H11 | 0.6321 | 0.2674 | 0.7214 | 0.059* | |
C12 | 0.6685 (3) | 0.3196 (3) | 0.8823 (2) | 0.0526 (7) | |
C13 | 0.2716 (5) | 0.2941 (6) | 0.8745 (6) | 0.125 (2) | |
H13A | 0.2533 | 0.3620 | 0.8346 | 0.188* | |
H13B | 0.2322 | 0.2966 | 0.9446 | 0.188* | |
H13C | 0.2373 | 0.2322 | 0.8319 | 0.188* | |
C14 | 0.8491 (8) | 0.0338 (6) | 0.9294 (7) | 0.144 (3) | |
H14A | 0.8745 | 0.0472 | 1.0061 | 0.216* | |
H14B | 0.9206 | 0.0019 | 0.8932 | 0.216* | |
H14C | 0.7771 | −0.0168 | 0.9244 | 0.216* | |
C15 | 0.8623 (4) | 0.5803 (4) | 0.7939 (4) | 0.0825 (11) | |
H15A | 0.8305 | 0.6529 | 0.7730 | 0.124* | |
H15B | 0.9123 | 0.5510 | 0.7360 | 0.124* | |
H15C | 0.9159 | 0.5857 | 0.8614 | 0.124* | |
C16 | 0.1463 (3) | 0.5942 (3) | 0.5105 (3) | 0.0689 (8) | |
C17 | 0.0604 (3) | 0.6878 (4) | 0.5492 (3) | 0.0755 (10) | |
H17A | 0.0444 | 0.7400 | 0.4886 | 0.091* | |
H17B | −0.0224 | 0.6568 | 0.5671 | 0.091* | |
C18 | 0.1175 (3) | 0.7500 (3) | 0.6488 (3) | 0.0709 (9) | |
H18A | 0.1257 | 0.6987 | 0.7109 | 0.085* | |
H18B | 0.0568 | 0.8075 | 0.6678 | 0.085* | |
C19 | 0.2490 (3) | 0.8042 (3) | 0.6357 (2) | 0.0552 (7) | |
H19 | 0.2319 | 0.8698 | 0.5888 | 0.066* | |
C20 | 0.3082 (4) | 0.8489 (3) | 0.7469 (3) | 0.0700 (9) | |
H20A | 0.3187 | 0.7861 | 0.7985 | 0.084* | |
C21 | 0.4410 (4) | 0.8992 (3) | 0.7331 (3) | 0.0759 (10) | |
H21A | 0.4315 | 0.9655 | 0.6875 | 0.091* | |
H21B | 0.4786 | 0.9213 | 0.8053 | 0.091* | |
C22 | 0.5313 (4) | 0.8197 (3) | 0.6806 (3) | 0.0659 (8) | |
H22A | 0.5463 | 0.7559 | 0.7289 | 0.079* | |
H22B | 0.6139 | 0.8562 | 0.6724 | 0.079* | |
C23 | 0.4767 (3) | 0.7798 (2) | 0.5665 (2) | 0.0496 (6) | |
H23 | 0.4671 | 0.8463 | 0.5196 | 0.060* | |
C24 | 0.5643 (3) | 0.6992 (3) | 0.5061 (2) | 0.0543 (7) | |
H24 | 0.5251 | 0.6923 | 0.4304 | 0.065* | |
C25 | 0.5620 (3) | 0.5848 (3) | 0.5548 (2) | 0.0517 (6) | |
H25 | 0.6121 | 0.5360 | 0.5084 | 0.062* | |
C26 | 0.3478 (3) | 0.6090 (2) | 0.6125 (2) | 0.0501 (6) | |
H26 | 0.3777 | 0.6089 | 0.6911 | 0.060* | |
C27 | 0.3404 (3) | 0.7294 (2) | 0.57176 (19) | 0.0447 (5) | |
C28 | 0.0703 (5) | 0.4940 (4) | 0.4636 (5) | 0.1078 (17) | |
H28A | 0.1240 | 0.4516 | 0.4170 | 0.162* | |
H28B | −0.0052 | 0.5194 | 0.4207 | 0.162* | |
H28C | 0.0444 | 0.4481 | 0.5235 | 0.162* | |
C29 | 0.2196 (6) | 0.9343 (5) | 0.7978 (4) | 0.111 (2) | |
H29A | 0.2005 | 0.9931 | 0.7454 | 0.167* | |
H29B | 0.2621 | 0.9648 | 0.8639 | 0.167* | |
H29C | 0.1404 | 0.8988 | 0.8161 | 0.167* | |
C30 | 0.7010 (3) | 0.7427 (4) | 0.4938 (4) | 0.0806 (11) | |
H30A | 0.7466 | 0.6928 | 0.4477 | 0.121* | |
H30B | 0.7457 | 0.7475 | 0.5656 | 0.121* | |
H30C | 0.6968 | 0.8152 | 0.4603 | 0.121* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0555 (15) | 0.0947 (19) | 0.1094 (19) | −0.0204 (13) | 0.0322 (14) | −0.0381 (16) |
O2 | 0.0738 (17) | 0.0810 (15) | 0.0594 (11) | −0.0229 (13) | 0.0137 (10) | −0.0213 (11) |
O3 | 0.0445 (12) | 0.0684 (13) | 0.0722 (12) | −0.0178 (10) | 0.0056 (9) | −0.0110 (11) |
O4 | 0.0340 (10) | 0.0585 (11) | 0.0714 (11) | −0.0069 (8) | −0.0084 (8) | 0.0039 (9) |
O5 | 0.0445 (11) | 0.0512 (10) | 0.0610 (10) | 0.0000 (9) | −0.0101 (8) | −0.0007 (9) |
O6 | 0.0421 (12) | 0.0619 (12) | 0.0945 (15) | −0.0110 (10) | −0.0113 (10) | 0.0235 (11) |
O7 | 0.0418 (11) | 0.0446 (9) | 0.0736 (12) | 0.0012 (8) | −0.0109 (9) | −0.0037 (9) |
O8 | 0.0546 (13) | 0.0668 (13) | 0.0703 (12) | −0.0022 (10) | −0.0156 (10) | −0.0080 (10) |
O9 | 0.0473 (11) | 0.0580 (11) | 0.0499 (9) | −0.0010 (9) | −0.0059 (8) | 0.0060 (8) |
C1 | 0.062 (2) | 0.097 (3) | 0.090 (2) | −0.029 (2) | 0.0283 (18) | −0.026 (2) |
C2 | 0.119 (4) | 0.115 (4) | 0.082 (3) | −0.064 (3) | 0.033 (3) | −0.005 (3) |
C3 | 0.122 (4) | 0.070 (2) | 0.081 (2) | −0.036 (2) | −0.003 (2) | 0.017 (2) |
C4 | 0.093 (3) | 0.065 (2) | 0.0571 (16) | −0.0122 (19) | −0.0089 (16) | 0.0114 (15) |
C5 | 0.088 (3) | 0.070 (2) | 0.102 (3) | 0.012 (2) | −0.019 (2) | 0.011 (2) |
C6 | 0.062 (3) | 0.096 (3) | 0.124 (3) | 0.016 (2) | −0.019 (2) | 0.016 (3) |
C7 | 0.0418 (18) | 0.087 (2) | 0.089 (2) | 0.0054 (16) | −0.0034 (15) | 0.0125 (19) |
C8 | 0.0451 (16) | 0.0664 (17) | 0.0534 (13) | −0.0092 (13) | −0.0077 (11) | 0.0033 (13) |
C9 | 0.0409 (16) | 0.0575 (16) | 0.0594 (14) | −0.0092 (12) | −0.0055 (11) | 0.0006 (13) |
C10 | 0.0353 (14) | 0.0476 (13) | 0.0577 (13) | −0.0065 (10) | −0.0024 (10) | −0.0002 (11) |
C11 | 0.0392 (14) | 0.0543 (14) | 0.0531 (13) | −0.0078 (11) | 0.0043 (10) | −0.0043 (12) |
C12 | 0.0516 (17) | 0.0592 (15) | 0.0471 (13) | −0.0091 (13) | 0.0045 (11) | −0.0057 (12) |
C13 | 0.055 (3) | 0.148 (5) | 0.177 (5) | −0.035 (3) | 0.040 (3) | −0.053 (4) |
C14 | 0.146 (6) | 0.090 (4) | 0.192 (6) | 0.020 (4) | −0.034 (5) | 0.041 (4) |
C15 | 0.053 (2) | 0.090 (3) | 0.101 (2) | −0.0313 (19) | −0.0251 (17) | 0.022 (2) |
C16 | 0.0413 (17) | 0.0687 (19) | 0.095 (2) | −0.0078 (15) | −0.0135 (15) | 0.0146 (17) |
C17 | 0.0393 (18) | 0.093 (3) | 0.094 (2) | 0.0018 (17) | 0.0000 (16) | 0.022 (2) |
C18 | 0.0514 (19) | 0.087 (2) | 0.0749 (18) | 0.0152 (17) | 0.0129 (15) | 0.0133 (18) |
C19 | 0.0521 (18) | 0.0588 (15) | 0.0545 (13) | 0.0125 (13) | 0.0021 (12) | 0.0068 (12) |
C20 | 0.082 (3) | 0.072 (2) | 0.0549 (15) | 0.0260 (19) | −0.0022 (15) | −0.0004 (14) |
C21 | 0.099 (3) | 0.0533 (17) | 0.0721 (19) | 0.0066 (18) | −0.0199 (18) | −0.0121 (15) |
C22 | 0.062 (2) | 0.0555 (16) | 0.0781 (18) | −0.0058 (14) | −0.0158 (15) | −0.0053 (15) |
C23 | 0.0474 (16) | 0.0429 (13) | 0.0577 (14) | −0.0042 (11) | −0.0047 (11) | 0.0076 (11) |
C24 | 0.0394 (15) | 0.0670 (17) | 0.0564 (14) | 0.0008 (13) | 0.0015 (11) | 0.0091 (13) |
C25 | 0.0408 (15) | 0.0597 (15) | 0.0536 (13) | 0.0032 (13) | −0.0046 (10) | −0.0060 (13) |
C26 | 0.0401 (15) | 0.0504 (15) | 0.0587 (14) | −0.0037 (11) | −0.0060 (11) | 0.0074 (11) |
C27 | 0.0430 (14) | 0.0488 (13) | 0.0418 (11) | 0.0018 (11) | −0.0012 (9) | 0.0041 (10) |
C28 | 0.062 (3) | 0.092 (3) | 0.164 (4) | −0.020 (2) | −0.042 (3) | 0.005 (3) |
C29 | 0.122 (4) | 0.134 (4) | 0.077 (2) | 0.061 (4) | −0.011 (2) | −0.032 (3) |
C30 | 0.0431 (18) | 0.102 (3) | 0.098 (2) | −0.0029 (18) | 0.0076 (17) | 0.027 (2) |
O1—C1 | 1.405 (5) | C13—H13B | 0.9600 |
O1—O2 | 1.467 (4) | C13—H13C | 0.9600 |
O2—C12 | 1.455 (4) | C14—H14A | 0.9600 |
O3—C11 | 1.399 (3) | C14—H14B | 0.9600 |
O3—C1 | 1.430 (4) | C14—H14C | 0.9600 |
O4—C11 | 1.406 (4) | C15—H15A | 0.9600 |
O4—C10 | 1.421 (3) | C15—H15B | 0.9600 |
O5—C10 | 1.389 (3) | C15—H15C | 0.9600 |
O5—C25 | 1.421 (3) | C16—C17 | 1.524 (6) |
O6—C26 | 1.406 (3) | C16—C28 | 1.527 (6) |
O6—C16 | 1.428 (4) | C17—C18 | 1.506 (6) |
O7—C25 | 1.407 (4) | C17—H17A | 0.9700 |
O7—C26 | 1.423 (4) | C17—H17B | 0.9700 |
O8—C16 | 1.404 (4) | C18—C19 | 1.524 (5) |
O8—O9 | 1.461 (3) | C18—H18A | 0.9700 |
O9—C27 | 1.462 (3) | C18—H18B | 0.9700 |
C1—C2 | 1.513 (8) | C19—C20 | 1.538 (5) |
C1—C13 | 1.516 (7) | C19—C27 | 1.544 (4) |
C2—C3 | 1.529 (8) | C19—H19 | 0.9800 |
C2—H2A | 0.9700 | C20—C21 | 1.518 (6) |
C2—H2B | 0.9700 | C20—C29 | 1.528 (5) |
C3—C4 | 1.517 (6) | C20—H20A | 0.9800 |
C3—H3A | 0.9700 | C21—C22 | 1.502 (5) |
C3—H3B | 0.9700 | C21—H21A | 0.9700 |
C4—C12 | 1.541 (5) | C21—H21B | 0.9700 |
C4—C5 | 1.542 (6) | C22—C23 | 1.533 (4) |
C4—H4 | 0.9800 | C22—H22A | 0.9700 |
C5—C6 | 1.507 (7) | C22—H22B | 0.9700 |
C5—C14 | 1.529 (7) | C23—C27 | 1.539 (4) |
C5—H5 | 0.9800 | C23—C24 | 1.538 (4) |
C6—C7 | 1.517 (6) | C23—H23 | 0.9800 |
C6—H6A | 0.9700 | C24—C25 | 1.496 (4) |
C6—H6B | 0.9700 | C24—C30 | 1.522 (4) |
C7—C8 | 1.531 (5) | C24—H24 | 0.9800 |
C7—H7A | 0.9700 | C25—H25 | 0.9800 |
C7—H7B | 0.9700 | C26—C27 | 1.528 (4) |
C8—C9 | 1.537 (4) | C26—H26 | 0.9800 |
C8—C12 | 1.537 (4) | C28—H28A | 0.9600 |
C8—H8 | 0.9800 | C28—H28B | 0.9600 |
C9—C10 | 1.516 (4) | C28—H28C | 0.9600 |
C9—C15 | 1.526 (4) | C29—H29A | 0.9600 |
C9—H9 | 0.9800 | C29—H29B | 0.9600 |
C10—H10 | 0.9800 | C29—H29C | 0.9600 |
C11—C12 | 1.524 (4) | C30—H30A | 0.9600 |
C11—H11 | 0.9800 | C30—H30B | 0.9600 |
C13—H13A | 0.9600 | C30—H30C | 0.9600 |
C1—O1—O2 | 109.1 (3) | H15A—C15—H15B | 109.5 |
C12—O2—O1 | 111.0 (2) | C9—C15—H15C | 109.5 |
C11—O3—C1 | 112.9 (2) | H15A—C15—H15C | 109.5 |
C11—O4—C10 | 115.3 (2) | H15B—C15—H15C | 109.5 |
C10—O5—C25 | 117.1 (2) | O8—C16—O6 | 109.4 (3) |
C26—O6—C16 | 113.0 (2) | O8—C16—C17 | 112.3 (3) |
C25—O7—C26 | 114.3 (2) | O6—C16—C17 | 110.2 (3) |
C16—O8—O9 | 108.5 (2) | O8—C16—C28 | 104.6 (4) |
O8—O9—C27 | 112.07 (18) | O6—C16—C28 | 106.5 (3) |
O1—C1—O3 | 109.1 (3) | C17—C16—C28 | 113.5 (3) |
O1—C1—C2 | 112.0 (4) | C18—C17—C16 | 113.8 (3) |
O3—C1—C2 | 109.8 (4) | C18—C17—H17A | 108.8 |
O1—C1—C13 | 104.4 (4) | C16—C17—H17A | 108.8 |
O3—C1—C13 | 105.7 (4) | C18—C17—H17B | 108.8 |
C2—C1—C13 | 115.4 (4) | C16—C17—H17B | 108.8 |
C1—C2—C3 | 114.3 (3) | H17A—C17—H17B | 107.7 |
C1—C2—H2A | 108.7 | C17—C18—C19 | 116.1 (3) |
C3—C2—H2A | 108.7 | C17—C18—H18A | 108.3 |
C1—C2—H2B | 108.7 | C19—C18—H18A | 108.3 |
C3—C2—H2B | 108.7 | C17—C18—H18B | 108.3 |
H2A—C2—H2B | 107.6 | C19—C18—H18B | 108.3 |
C4—C3—C2 | 117.0 (4) | H18A—C18—H18B | 107.4 |
C4—C3—H3A | 108.1 | C18—C19—C20 | 111.7 (3) |
C2—C3—H3A | 108.1 | C18—C19—C27 | 112.3 (3) |
C4—C3—H3B | 108.1 | C20—C19—C27 | 114.5 (3) |
C2—C3—H3B | 108.1 | C18—C19—H19 | 105.8 |
H3A—C3—H3B | 107.3 | C20—C19—H19 | 105.8 |
C3—C4—C12 | 113.0 (3) | C27—C19—H19 | 105.8 |
C3—C4—C5 | 111.0 (4) | C21—C20—C29 | 110.1 (4) |
C12—C4—C5 | 113.4 (3) | C21—C20—C19 | 111.0 (3) |
C3—C4—H4 | 106.3 | C29—C20—C19 | 111.6 (3) |
C12—C4—H4 | 106.3 | C21—C20—H20A | 108.0 |
C5—C4—H4 | 106.3 | C29—C20—H20A | 108.0 |
C6—C5—C14 | 111.0 (5) | C19—C20—H20A | 108.0 |
C6—C5—C4 | 111.1 (4) | C22—C21—C20 | 112.5 (3) |
C14—C5—C4 | 112.5 (5) | C22—C21—H21A | 109.1 |
C6—C5—H5 | 107.3 | C20—C21—H21A | 109.1 |
C14—C5—H5 | 107.3 | C22—C21—H21B | 109.1 |
C4—C5—H5 | 107.3 | C20—C21—H21B | 109.1 |
C5—C6—C7 | 112.4 (4) | H21A—C21—H21B | 107.8 |
C5—C6—H6A | 109.1 | C21—C22—C23 | 111.9 (3) |
C7—C6—H6A | 109.1 | C21—C22—H22A | 109.2 |
C5—C6—H6B | 109.1 | C23—C22—H22A | 109.2 |
C7—C6—H6B | 109.1 | C21—C22—H22B | 109.2 |
H6A—C6—H6B | 107.9 | C23—C22—H22B | 109.2 |
C6—C7—C8 | 112.2 (3) | H22A—C22—H22B | 107.9 |
C6—C7—H7A | 109.2 | C22—C23—C27 | 112.0 (2) |
C8—C7—H7A | 109.2 | C22—C23—C24 | 115.3 (2) |
C6—C7—H7B | 109.2 | C27—C23—C24 | 109.7 (2) |
C8—C7—H7B | 109.2 | C22—C23—H23 | 106.4 |
H7A—C7—H7B | 107.9 | C27—C23—H23 | 106.4 |
C7—C8—C9 | 114.7 (3) | C24—C23—H23 | 106.4 |
C7—C8—C12 | 111.3 (3) | C25—C24—C30 | 112.9 (3) |
C9—C8—C12 | 110.0 (2) | C25—C24—C23 | 111.6 (2) |
C7—C8—H8 | 106.8 | C30—C24—C23 | 113.9 (3) |
C9—C8—H8 | 106.8 | C25—C24—H24 | 105.8 |
C12—C8—H8 | 106.8 | C30—C24—H24 | 105.8 |
C10—C9—C15 | 111.8 (2) | C23—C24—H24 | 105.8 |
C10—C9—C8 | 109.7 (2) | O7—C25—O5 | 112.2 (2) |
C15—C9—C8 | 113.3 (3) | O7—C25—C24 | 110.7 (2) |
C10—C9—H9 | 107.2 | O5—C25—C24 | 110.7 (2) |
C15—C9—H9 | 107.2 | O7—C25—H25 | 107.7 |
C8—C9—H9 | 107.2 | O5—C25—H25 | 107.7 |
O5—C10—O4 | 107.4 (2) | C24—C25—H25 | 107.7 |
O5—C10—C9 | 108.2 (2) | O6—C26—O7 | 105.5 (2) |
O4—C10—C9 | 110.1 (2) | O6—C26—C27 | 112.9 (2) |
O5—C10—H10 | 110.3 | O7—C26—C27 | 112.5 (2) |
O4—C10—H10 | 110.3 | O6—C26—H26 | 108.6 |
C9—C10—H10 | 110.3 | O7—C26—H26 | 108.6 |
O3—C11—O4 | 106.1 (2) | C27—C26—H26 | 108.6 |
O3—C11—C12 | 113.0 (2) | O9—C27—C26 | 109.5 (2) |
O4—C11—C12 | 112.8 (2) | O9—C27—C23 | 104.13 (19) |
O3—C11—H11 | 108.3 | C26—C27—C23 | 110.9 (2) |
O4—C11—H11 | 108.3 | O9—C27—C19 | 104.9 (2) |
C12—C11—H11 | 108.3 | C26—C27—C19 | 114.3 (2) |
O2—C12—C11 | 110.0 (3) | C23—C27—C19 | 112.4 (2) |
O2—C12—C4 | 106.0 (2) | C16—C28—H28A | 109.5 |
C11—C12—C4 | 113.1 (2) | C16—C28—H28B | 109.5 |
O2—C12—C8 | 104.6 (2) | H28A—C28—H28B | 109.5 |
C11—C12—C8 | 110.1 (2) | C16—C28—H28C | 109.5 |
C4—C12—C8 | 112.5 (3) | H28A—C28—H28C | 109.5 |
C1—C13—H13A | 109.5 | H28B—C28—H28C | 109.5 |
C1—C13—H13B | 109.5 | C20—C29—H29A | 109.5 |
H13A—C13—H13B | 109.5 | C20—C29—H29B | 109.5 |
C1—C13—H13C | 109.5 | H29A—C29—H29B | 109.5 |
H13A—C13—H13C | 109.5 | C20—C29—H29C | 109.5 |
H13B—C13—H13C | 109.5 | H29A—C29—H29C | 109.5 |
C5—C14—H14A | 109.5 | H29B—C29—H29C | 109.5 |
C5—C14—H14B | 109.5 | C24—C30—H30A | 109.5 |
H14A—C14—H14B | 109.5 | C24—C30—H30B | 109.5 |
C5—C14—H14C | 109.5 | H30A—C30—H30B | 109.5 |
H14A—C14—H14C | 109.5 | C24—C30—H30C | 109.5 |
H14B—C14—H14C | 109.5 | H30A—C30—H30C | 109.5 |
C9—C15—H15A | 109.5 | H30B—C30—H30C | 109.5 |
C9—C15—H15B | 109.5 | ||
C1—O1—O2—C12 | 45.0 (3) | C9—C8—C12—C4 | 178.5 (2) |
C16—O8—O9—C27 | 43.9 (3) | O9—O8—C16—O6 | −73.1 (3) |
O2—O1—C1—O3 | −72.9 (4) | O9—O8—C16—C17 | 49.6 (3) |
O2—O1—C1—C2 | 48.9 (4) | O9—O8—C16—C28 | 173.1 (3) |
O2—O1—C1—C13 | 174.5 (4) | C26—O6—C16—O8 | 33.0 (4) |
C11—O3—C1—O1 | 31.1 (4) | C26—O6—C16—C17 | −90.9 (3) |
C11—O3—C1—C2 | −92.0 (4) | C26—O6—C16—C28 | 145.6 (4) |
C11—O3—C1—C13 | 142.8 (4) | O8—C16—C17—C18 | −95.7 (4) |
O1—C1—C2—C3 | −94.4 (4) | O6—C16—C17—C18 | 26.5 (4) |
O3—C1—C2—C3 | 27.0 (5) | C28—C16—C17—C18 | 145.9 (4) |
C13—C1—C2—C3 | 146.4 (4) | C16—C17—C18—C19 | 58.2 (4) |
C1—C2—C3—C4 | 54.8 (5) | C17—C18—C19—C20 | −170.8 (3) |
C2—C3—C4—C12 | −35.3 (5) | C17—C18—C19—C27 | −40.5 (4) |
C2—C3—C4—C5 | −163.9 (4) | C18—C19—C20—C21 | 178.1 (3) |
C3—C4—C5—C6 | 179.6 (3) | C27—C19—C20—C21 | 49.0 (4) |
C12—C4—C5—C6 | 51.1 (4) | C18—C19—C20—C29 | −58.6 (5) |
C3—C4—C5—C14 | −55.3 (5) | C27—C19—C20—C29 | 172.3 (4) |
C12—C4—C5—C14 | 176.3 (4) | C29—C20—C21—C22 | −178.5 (3) |
C14—C5—C6—C7 | 179.5 (5) | C19—C20—C21—C22 | −54.4 (4) |
C4—C5—C6—C7 | −54.5 (5) | C20—C21—C22—C23 | 57.9 (4) |
C5—C6—C7—C8 | 56.9 (5) | C21—C22—C23—C27 | −54.3 (4) |
C6—C7—C8—C9 | −179.6 (3) | C21—C22—C23—C24 | 179.2 (3) |
C6—C7—C8—C12 | −53.9 (4) | C22—C23—C24—C25 | 75.6 (3) |
C7—C8—C9—C10 | 71.2 (3) | C27—C23—C24—C25 | −52.0 (3) |
C12—C8—C9—C10 | −55.2 (3) | C22—C23—C24—C30 | −53.9 (4) |
C7—C8—C9—C15 | −54.5 (4) | C27—C23—C24—C30 | 178.5 (2) |
C12—C8—C9—C15 | 179.1 (3) | C26—O7—C25—O5 | 64.5 (3) |
C25—O5—C10—O4 | −70.8 (3) | C26—O7—C25—C24 | −59.7 (3) |
C25—O5—C10—C9 | 170.4 (2) | C10—O5—C25—O7 | 77.2 (3) |
C11—O4—C10—O5 | −176.7 (2) | C10—O5—C25—C24 | −158.6 (2) |
C11—O4—C10—C9 | −59.0 (3) | C30—C24—C25—O7 | −173.2 (3) |
C15—C9—C10—O5 | −58.8 (3) | C23—C24—C25—O7 | 56.9 (3) |
C8—C9—C10—O5 | 174.6 (2) | C30—C24—C25—O5 | 61.8 (3) |
C15—C9—C10—O4 | −176.0 (3) | C23—C24—C25—O5 | −68.2 (3) |
C8—C9—C10—O4 | 57.4 (3) | C16—O6—C26—O7 | −93.6 (3) |
C1—O3—C11—O4 | −92.8 (3) | C16—O6—C26—C27 | 29.6 (4) |
C1—O3—C11—C12 | 31.3 (4) | C25—O7—C26—O6 | −179.3 (2) |
C10—O4—C11—O3 | −179.6 (2) | C25—O7—C26—C27 | 57.1 (3) |
C10—O4—C11—C12 | 56.2 (3) | O8—O9—C27—C26 | 16.7 (3) |
O1—O2—C12—C11 | 16.1 (3) | O8—O9—C27—C23 | 135.4 (2) |
O1—O2—C12—C4 | −106.6 (3) | O8—O9—C27—C19 | −106.4 (2) |
O1—O2—C12—C8 | 134.3 (2) | O6—C26—C27—O9 | −55.7 (3) |
O3—C11—C12—O2 | −56.6 (3) | O7—C26—C27—O9 | 63.6 (3) |
O4—C11—C12—O2 | 63.8 (3) | O6—C26—C27—C23 | −170.1 (2) |
O3—C11—C12—C4 | 61.8 (3) | O7—C26—C27—C23 | −50.8 (3) |
O4—C11—C12—C4 | −177.8 (3) | O6—C26—C27—C19 | 61.6 (3) |
O3—C11—C12—C8 | −171.4 (2) | O7—C26—C27—C19 | −179.1 (2) |
O4—C11—C12—C8 | −51.1 (3) | C22—C23—C27—O9 | 161.2 (2) |
C3—C4—C12—O2 | 69.3 (3) | C24—C23—C27—O9 | −69.4 (3) |
C5—C4—C12—O2 | −163.3 (3) | C22—C23—C27—C26 | −81.0 (3) |
C3—C4—C12—C11 | −51.4 (4) | C24—C23—C27—C26 | 48.4 (3) |
C5—C4—C12—C11 | 76.0 (4) | C22—C23—C27—C19 | 48.3 (3) |
C3—C4—C12—C8 | −177.0 (3) | C24—C23—C27—C19 | 177.7 (2) |
C5—C4—C12—C8 | −49.5 (4) | C18—C19—C27—O9 | 72.1 (3) |
C7—C8—C12—O2 | 164.9 (3) | C20—C19—C27—O9 | −159.1 (3) |
C9—C8—C12—O2 | −66.9 (3) | C18—C19—C27—C26 | −47.9 (3) |
C7—C8—C12—C11 | −76.9 (3) | C20—C19—C27—C26 | 80.9 (3) |
C9—C8—C12—C11 | 51.3 (3) | C18—C19—C27—C23 | −175.4 (2) |
C7—C8—C12—C4 | 50.2 (3) | C20—C19—C27—C23 | −46.6 (3) |
Experimental details
Crystal data | |
Chemical formula | C30H46O9 |
Mr | 550.67 |
Crystal system, space group | Monoclinic, P21 |
Temperature (K) | 295 |
a, b, c (Å) | 10.338 (2), 12.012 (2), 12.065 (2) |
β (°) | 93.39 (3) |
V (Å3) | 1495.6 (5) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.42 × 0.30 × 0.23 |
Data collection | |
Diffractometer | Rigaku R-AXIS RAPID diffractometer |
Absorption correction | Multi-scan (ABSCOR; Higashi, 1995) |
Tmin, Tmax | 0.935, 0.972 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 14678, 3576, 2877 |
Rint | 0.069 |
(sin θ/λ)max (Å−1) | 0.649 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.058, 0.156, 1.10 |
No. of reflections | 3576 |
No. of parameters | 358 |
No. of restraints | 1 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.29, −0.20 |
Computer programs: RAPID-AUTO (Rigaku Corporation, 1998), RAPID-AUTO, CrystalStructure (Rigaku/MSC, 2002), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), ORTEPII (Johnson, 1976), SHELXL97.
Subscribe to Acta Crystallographica Section C: Structural Chemistry
The full text of this article is available to subscribers to the journal.
- Information on subscribing
- Sample issue
- Purchase subscription
- Reduced-price subscriptions
- If you have already subscribed, you may need to register
Dihydroartemisinin, (II), derived from artemisinin with retention of the endoperoxide bridge, is found to possess antimalarial activity (Posner & O'Neill, 2004). Their dimers have both antimalarial and antitumor activities (Beekman et al., 1997). The ether linkage itself can yield considerable cytotoxicity to EN2 tumor cells, particularly when the ether linkage is asymmetric (Beekman et al., 1997). The endoperoxide group is also an important determinant for cytotoxicity. In the endoperoxides tested, the asymmetric dimer was 22 times more cytotoxic than artemisinin and 60 times more than dihydroartemisinin (Woerdenbag et al., 1993). Hence, knowledge of the structure of the title compound, (I), is of interest.
The crystal structures of artemisinin (Qinghaosu) (III) (Qinghaosu Research Group, 1980) and its derivatives have been reported, including dihydroartemisinin, artemether, artesunic acid (Luo et al., 1984), both cis- (Brossi et al., 1988) and trans-deoxyarteether (Dominguez Gerpe et al., 1988), α-artesunate, β-artesunate (Haynes et al., 2002), and the symmetric form of the ether dimer of deoxydihydroartemisinin (Flippen-Anderson et al., 1989). Although the endoperoxide group is an important determinant for cytotoxicity, a crystal structure of an ether dimer of dihydroartemisinin with a peroxy unit has not been reported previously. We report here the crystal structure of the title compound, which is an ether dimer of dihydroartemisinin with a unique 1,2,4-trioxane peroxy bridge.
A view of the molecular structure of (I) with the atom numbering is provided in Fig. 1. A ttempts to determine the absolute configuration of the molecule were inconclusive, but the title compound can be placed into the illustrated configuration since the chirality of the starting materials is known (Qinghaosu Research Group, 1980). The overall conformation on each side of the ether linkage of (I) is essentially the same as that found in the crystal structure of dihydroartemisinin (Luo et al., 1984). The orientation of the two dihydroartemisinin groups about the ether linkage is such that the C10—H10 and C25—H25 bonds are almost parallel. This orientation gives the molecule almost pseudo-C2 symmetry. The only configurational difference in the two halves of the molecule is that atom C10 has the R configuration, which corresponds with the situation in α-dihydroartemisinin (the H atoms at atoms C9 and C10 are trans oriented), while atom C25 has the S configuration of β-dihydroartemisinin (the H atoms at atoms C24 and C25 are cis oriented).
The seven-membered rings A (C1–C4/C12/O2/O1) and A' (C16–C19/C27/O9/O8) include the key peroxy linkage [O1—O2 = 1.467 (4) Å and O8—O9 = 1.461 (3) Å]. The six-membered rings B (C4–C8/C12) and B' (C19–C23/C27) have very slightly distorted chair conformations, with Cremer & Pople (1975) puckering parameters of Q = 0.537 (5) Å, θ = 175.4 (4)° and ϕ = 327 (7)° for ring B, and Q = 0.528 (4) Å, θ = 173.4 (4)° and ϕ = 330 (3)° for ring B'. For an ideal chair, θ has a value of 0 or 180°. The six-membered rings C (C8–C10/O4/C11/C12) and C' (C23–C25/O7/C26/C27) have normal chair conformations, with puckering parameters Q, θ and ϕ of 0.550 (3) Å, 4.4 (3)° and 66 (4)°, and 0.536 (3) Å, 3.8 (3)° and 110 (5)°, respectively. The same conformations were found in the corresponding six-membered rings of dihydroartemisinin (Luo et al., 1984). The six-membered rings involving the endoperoxide bridges, D (C1/O1/O2/C12/C11/O3) and D' (C16/O8/O9/C27/C26/O6), are best described by a twist-boat conformation, for which the puckering parameters Q, θ and ϕ are 0.741 (4) Å, 85.6 (2)° and 36.7 (2)° for ring D, and 0.740 (3) Å, 85.5 (2)° and 35.5 (2)° for ring D'. For an ideal twist-boat conformation, θ and ϕ are 90° and 60n + 30°, respectively. In contrast, the six-membered ring formed by the endoperoxide bridge in dihydroartemisinin has a somewhat distorted boat conformation.