Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807026487/lh2400sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807026487/lh2400Isup2.hkl |
CCDC reference: 654906
Key indicators
- Single-crystal X-ray study
- T = 150 K
- Mean (C-C) = 0.003 Å
- R factor = 0.038
- wR factor = 0.096
- Data-to-parameter ratio = 14.2
checkCIF/PLATON results
No syntax errors found
Alert level C PLAT431_ALERT_2_C Short Inter HL..A Contact Cl1 .. O4 .. 3.24 Ang.
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 25.00 From the CIF: _reflns_number_total 4302 Count of symmetry unique reflns 2387 Completeness (_total/calc) 180.23% TEST3: Check Friedels for noncentro structure Estimate of Friedel pairs measured 1915 Fraction of Friedel pairs measured 0.802 Are heavy atom types Z>Si present yes PLAT791_ALERT_1_G Confirm the Absolute Configuration of C3 = . S PLAT791_ALERT_1_G Confirm the Absolute Configuration of C5 = . R PLAT791_ALERT_1_G Confirm the Absolute Configuration of C8 = . R PLAT791_ALERT_1_G Confirm the Absolute Configuration of C9 = . R PLAT791_ALERT_1_G Confirm the Absolute Configuration of C10 = . R PLAT791_ALERT_1_G Confirm the Absolute Configuration of C13 = . S PLAT791_ALERT_1_G Confirm the Absolute Configuration of C14 = . R PLAT791_ALERT_1_G Confirm the Absolute Configuration of C17 = . S 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 10 ALERT level G = General alerts; check 8 ALERT type 1 CIF construction/syntax error, inconsistent or missing data 1 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 1 ALERT type 4 Improvement, methodology, query or suggestion 0 ALERT type 5 Informative message, check
A mixture of diketone (2) (Fig. 3) (0.93 mmol) and AcOOH (20 ml of a 32%aq soln) and Ru(IV)O2.H2O (0.15 mmol) in CHCL3 (55 mL) was stirred at room temperature for one day. The extract was washed and evaporated. The resulting pale-yellow oil crystalization from CHCl3/MeOH afforded chloroketone I as a colourless crystals. Yield 52%,
All H atoms were positioned geometrically and refined as riding on their parent C atoms, with C—H = 0.98 Å, for CH, C—H = 0.97Å for –CH2 and Uiso(H) = 1.2Ueq(C) or C—H = 0.96Å and Uiso(H) = 1.5Ueq(C) for methyl H atoms. The absolute configuration was assigned from the known absolute structure of parent compound and was confirmed by the Flack (1983) parameter. Optical rotation [α]D +105o. m.p. 495–498 K.
Efforts have recently been exerted in order to synthesize new derivatives of natural compounds, especially terpenoides (Dzubak et al., 2006; Kim et al., 1998) with large number of functional groups (Kim et al., 1998; Biedermann et al., 2005; Urban et al., 2005). Several years ago a group of new compounds called betulinines (Šarek et al., 2003), was described. Betulinines have significant cytotoxic activity on broad scale of tumor lines including multidrug resistance. Among the most effective belulinines are β-ketoacids (1, Fig. 3) (Šarek et al., 2003). The search for new degradable analogs of 1 with similar high cytotoxity resulted in a hexanorlupane derivatives (I) (Fig. 3) with cytotoxicity two times higher than 1. The structure of I has been determined as a part of large study of structure-activity relationships.
The bond lengths and angles in I are unexceptional and very close to the pertinent ones in the parent molecule 1. In both molecules the oxygen atom of the carbonyl substituent on D ring is slightly bend towards adjoining carboxyl moiety as follows from comparison of the angle around C18 (see Table I). All rings adopts chair conformations (Cremer & Pople, 1975) (Fig. 1), the deviation from ideal geometry (τ = 0, 180 °) can be discerned on ring D due its carbonyl substituent (τ = 164.6 (2) °). Without the possibility of classical hydrogen bonds, the role of weak C—H···O contacts in crystal packing is clearly revealed. Molecules are packed by C(methyl)-H···O(acetyl) hydrogen bonds forming columns along the b axis. Second parallel column related by operation of a 21 screw is attached to the first one in a zip-like way via a CH2···O(carbonyl) interaction (see Fig. 2).
For general background, see: Kim et al. (1998); Biedermann et al. (2005); Urban et al. (2005). For a related structure, see: Šarek et al. (2003).
For related literature, see: Cremer & Pople (1975); Dzubak et al. (2006).
Data collection: COLLECT (Nonius, 1998) and DENZO (Otwinowski & Minor, 1997); cell refinement: COLLECT and DENZO; data reduction: COLLECT and DENZO; program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97.
C27H41ClO5 | F(000) = 520 |
Mr = 481.05 | Dx = 1.286 Mg m−3 |
Monoclinic, P21 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2yb | Cell parameters from 2233 reflections |
a = 11.331 (3) Å | θ = 1–25° |
b = 6.738 (1) Å | µ = 0.19 mm−1 |
c = 16.366 (3) Å | T = 150 K |
β = 96.275 (10)° | Bar, colourless |
V = 1242.0 (4) Å3 | 0.55 × 0.2 × 0.03 mm |
Z = 2 |
Bruker Nonius KappaCCD diffractometer | 3899 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.034 |
Graphite monochromator | θmax = 25.0°, θmin = 2.5° |
Detector resolution: 9.091 pixels mm-1 | h = −13→13 |
φ and ω scans to fill the Ewald sphere | k = −7→8 |
8942 measured reflections | l = −19→19 |
4320 independent reflections |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.038 | H-atom parameters constrained |
wR(F2) = 0.096 | w = 1/[σ2(Fo2) + (0.0449P)2 + 0.2905P] where P = (Fo2 + 2Fc2)/3 |
S = 1.10 | (Δ/σ)max = 0.001 |
4320 reflections | Δρmax = 0.20 e Å−3 |
305 parameters | Δρmin = −0.22 e Å−3 |
1 restraint | Absolute structure: Flack (1983), with 1923 Friedel pairs |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: −0.01 (6) |
C27H41ClO5 | V = 1242.0 (4) Å3 |
Mr = 481.05 | Z = 2 |
Monoclinic, P21 | Mo Kα radiation |
a = 11.331 (3) Å | µ = 0.19 mm−1 |
b = 6.738 (1) Å | T = 150 K |
c = 16.366 (3) Å | 0.55 × 0.2 × 0.03 mm |
β = 96.275 (10)° |
Bruker Nonius KappaCCD diffractometer | 3899 reflections with I > 2σ(I) |
8942 measured reflections | Rint = 0.034 |
4320 independent reflections |
R[F2 > 2σ(F2)] = 0.038 | H-atom parameters constrained |
wR(F2) = 0.096 | Δρmax = 0.20 e Å−3 |
S = 1.10 | Δρmin = −0.22 e Å−3 |
4320 reflections | Absolute structure: Flack (1983), with 1923 Friedel pairs |
305 parameters | Absolute structure parameter: −0.01 (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. |
x | y | z | Uiso*/Ueq | ||
C1 | 0.1096 (2) | 0.3185 (4) | 0.67922 (13) | 0.0296 (5) | |
H1A | 0.0379 | 0.2398 | 0.6790 | 0.035* | |
H1B | 0.0964 | 0.4435 | 0.7062 | 0.035* | |
C2 | 0.1329 (2) | 0.3596 (4) | 0.59006 (13) | 0.0315 (5) | |
H2A | 0.1415 | 0.2351 | 0.5615 | 0.038* | |
H2B | 0.0662 | 0.4310 | 0.5617 | 0.038* | |
C3 | 0.2446 (2) | 0.4811 (4) | 0.58938 (14) | 0.0296 (5) | |
H3 | 0.2335 | 0.6068 | 0.6177 | 0.036* | |
C4 | 0.3569 (2) | 0.3797 (4) | 0.63145 (13) | 0.0290 (5) | |
C5 | 0.32918 (19) | 0.3257 (4) | 0.72020 (13) | 0.0247 (5) | |
H5 | 0.3168 | 0.4540 | 0.7461 | 0.030* | |
C6 | 0.4344 (2) | 0.2339 (4) | 0.77348 (14) | 0.0292 (5) | |
H6A | 0.4432 | 0.0960 | 0.7582 | 0.035* | |
H6B | 0.5067 | 0.3036 | 0.7644 | 0.035* | |
C7 | 0.4148 (2) | 0.2469 (4) | 0.86420 (14) | 0.0299 (6) | |
H7A | 0.4130 | 0.3856 | 0.8799 | 0.036* | |
H7B | 0.4816 | 0.1854 | 0.8968 | 0.036* | |
C8 | 0.29946 (19) | 0.1467 (3) | 0.88479 (13) | 0.0235 (5) | |
C9 | 0.19388 (19) | 0.2178 (3) | 0.82254 (13) | 0.0228 (5) | |
H9 | 0.1862 | 0.3597 | 0.8340 | 0.027* | |
C10 | 0.2134 (2) | 0.2076 (3) | 0.72883 (14) | 0.0243 (5) | |
C11 | 0.0761 (2) | 0.1264 (4) | 0.84232 (13) | 0.0276 (5) | |
H11A | 0.0118 | 0.1778 | 0.8042 | 0.033* | |
H11B | 0.0789 | −0.0163 | 0.8351 | 0.033* | |
C12 | 0.05115 (19) | 0.1728 (4) | 0.93012 (13) | 0.0256 (5) | |
H12A | 0.0371 | 0.3141 | 0.9352 | 0.031* | |
H12B | −0.0202 | 0.1036 | 0.9417 | 0.031* | |
C13 | 0.15378 (19) | 0.1115 (3) | 0.99265 (13) | 0.0230 (5) | |
H13 | 0.1629 | −0.0325 | 0.9877 | 0.028* | |
C14 | 0.2738 (2) | 0.2072 (3) | 0.97524 (14) | 0.0243 (5) | |
C15 | 0.3710 (2) | 0.1300 (4) | 1.04065 (14) | 0.0285 (5) | |
H15A | 0.3748 | −0.0135 | 1.0370 | 0.034* | |
H15B | 0.4472 | 0.1826 | 1.0291 | 0.034* | |
C16 | 0.3494 (2) | 0.1879 (4) | 1.12772 (14) | 0.0316 (6) | |
H16A | 0.3541 | 0.3311 | 1.1332 | 0.038* | |
H16B | 0.4113 | 0.1307 | 1.1662 | 0.038* | |
C17 | 0.2285 (2) | 0.1178 (4) | 1.14980 (14) | 0.0288 (5) | |
C18 | 0.1275 (2) | 0.1525 (3) | 1.07962 (14) | 0.0259 (5) | |
C22 | 0.1959 (2) | 0.2277 (4) | 1.22574 (15) | 0.0335 (6) | |
C23 | 0.3937 (2) | 0.2028 (4) | 0.58118 (15) | 0.0379 (6) | |
H23A | 0.4212 | 0.2498 | 0.5312 | 0.057* | |
H23B | 0.3268 | 0.1167 | 0.5682 | 0.057* | |
H23C | 0.4563 | 0.1309 | 0.6126 | 0.057* | |
C24 | 0.4572 (2) | 0.5360 (4) | 0.63727 (16) | 0.0383 (6) | |
H24A | 0.5303 | 0.4758 | 0.6602 | 0.057* | |
H24B | 0.4376 | 0.6434 | 0.6719 | 0.057* | |
H24C | 0.4662 | 0.5859 | 0.5834 | 0.057* | |
C25 | 0.2135 (2) | −0.0073 (4) | 0.69583 (14) | 0.0321 (6) | |
H25A | 0.1617 | −0.0878 | 0.7247 | 0.048* | |
H25B | 0.2926 | −0.0600 | 0.7041 | 0.048* | |
H25C | 0.1862 | −0.0077 | 0.6382 | 0.048* | |
C26 | 0.3176 (2) | −0.0803 (4) | 0.88048 (15) | 0.0338 (6) | |
H26A | 0.3440 | −0.1144 | 0.8285 | 0.051* | |
H26B | 0.2439 | −0.1464 | 0.8862 | 0.051* | |
H26C | 0.3762 | −0.1210 | 0.9241 | 0.051* | |
C27 | 0.2652 (2) | 0.4347 (3) | 0.98586 (15) | 0.0290 (5) | |
H27A | 0.2295 | 0.4637 | 1.0351 | 0.044* | |
H27B | 0.2175 | 0.4901 | 0.9393 | 0.044* | |
H27C | 0.3433 | 0.4914 | 0.9898 | 0.044* | |
C28 | 0.2175 (2) | 0.6906 (4) | 0.47046 (16) | 0.0355 (6) | |
C29 | 0.2527 (3) | 0.7223 (5) | 0.38621 (16) | 0.0434 (7) | |
H29A | 0.1834 | 0.7170 | 0.3469 | 0.065* | |
H29B | 0.3074 | 0.6204 | 0.3740 | 0.065* | |
H29C | 0.2899 | 0.8498 | 0.3835 | 0.065* | |
C30 | 0.1176 (3) | 0.2194 (5) | 1.35275 (17) | 0.0531 (8) | |
H30A | 0.1875 | 0.2789 | 1.3809 | 0.080* | |
H30B | 0.0847 | 0.1267 | 1.3886 | 0.080* | |
H30C | 0.0602 | 0.3209 | 1.3367 | 0.080* | |
Cl1 | 0.23243 (5) | −0.14730 (8) | 1.16448 (3) | 0.03141 (15) | |
O1 | 0.26597 (15) | 0.5253 (3) | 0.50489 (9) | 0.0340 (4) | |
O2 | 0.15200 (19) | 0.7987 (3) | 0.50365 (12) | 0.0512 (5) | |
O3 | 0.03047 (15) | 0.2038 (3) | 1.09674 (10) | 0.0339 (4) | |
O4 | 0.2100 (2) | 0.4038 (3) | 1.23222 (11) | 0.0525 (6) | |
O5 | 0.14850 (17) | 0.1160 (3) | 1.27991 (10) | 0.0406 (5) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0247 (11) | 0.0379 (15) | 0.0257 (11) | 0.0015 (11) | 0.0013 (9) | 0.0014 (11) |
C2 | 0.0314 (12) | 0.0386 (14) | 0.0243 (11) | 0.0007 (13) | 0.0028 (9) | 0.0019 (12) |
C3 | 0.0366 (13) | 0.0333 (13) | 0.0197 (11) | 0.0025 (12) | 0.0066 (10) | 0.0007 (10) |
C4 | 0.0279 (12) | 0.0330 (14) | 0.0271 (11) | −0.0006 (11) | 0.0069 (9) | 0.0020 (11) |
C5 | 0.0255 (11) | 0.0250 (12) | 0.0239 (11) | −0.0013 (10) | 0.0046 (9) | −0.0020 (10) |
C6 | 0.0251 (12) | 0.0330 (13) | 0.0301 (12) | −0.0004 (10) | 0.0062 (10) | 0.0019 (11) |
C7 | 0.0225 (12) | 0.0384 (14) | 0.0284 (12) | 0.0004 (11) | 0.0015 (10) | 0.0054 (11) |
C8 | 0.0222 (11) | 0.0234 (12) | 0.0248 (11) | −0.0015 (10) | 0.0018 (9) | 0.0021 (10) |
C9 | 0.0243 (11) | 0.0193 (11) | 0.0246 (11) | −0.0012 (9) | 0.0020 (9) | −0.0003 (9) |
C10 | 0.0255 (11) | 0.0254 (12) | 0.0225 (11) | −0.0012 (10) | 0.0044 (9) | −0.0007 (10) |
C11 | 0.0250 (12) | 0.0316 (13) | 0.0255 (11) | −0.0046 (10) | −0.0001 (9) | 0.0034 (10) |
C12 | 0.0243 (11) | 0.0258 (12) | 0.0265 (11) | 0.0010 (10) | 0.0024 (9) | 0.0035 (10) |
C13 | 0.0238 (11) | 0.0210 (11) | 0.0242 (11) | −0.0002 (9) | 0.0023 (9) | 0.0021 (9) |
C14 | 0.0250 (12) | 0.0233 (12) | 0.0240 (11) | −0.0006 (10) | 0.0009 (9) | 0.0030 (10) |
C15 | 0.0251 (12) | 0.0309 (12) | 0.0288 (12) | −0.0019 (11) | −0.0007 (10) | 0.0037 (10) |
C16 | 0.0345 (13) | 0.0310 (13) | 0.0279 (12) | −0.0044 (11) | −0.0023 (10) | 0.0060 (10) |
C17 | 0.0350 (13) | 0.0237 (12) | 0.0269 (12) | −0.0015 (11) | −0.0003 (10) | 0.0042 (10) |
C18 | 0.0334 (13) | 0.0165 (11) | 0.0280 (12) | −0.0002 (10) | 0.0044 (10) | 0.0034 (9) |
C22 | 0.0420 (15) | 0.0326 (15) | 0.0256 (13) | −0.0030 (12) | 0.0020 (11) | 0.0029 (11) |
C23 | 0.0407 (15) | 0.0422 (16) | 0.0329 (13) | 0.0077 (13) | 0.0135 (11) | −0.0021 (12) |
C24 | 0.0361 (14) | 0.0447 (16) | 0.0351 (14) | −0.0056 (12) | 0.0078 (12) | 0.0064 (12) |
C25 | 0.0375 (14) | 0.0309 (14) | 0.0283 (12) | −0.0038 (12) | 0.0049 (11) | −0.0053 (11) |
C26 | 0.0402 (15) | 0.0277 (13) | 0.0338 (13) | 0.0071 (11) | 0.0052 (11) | 0.0010 (10) |
C27 | 0.0365 (14) | 0.0231 (12) | 0.0275 (12) | −0.0045 (10) | 0.0031 (10) | −0.0006 (10) |
C28 | 0.0418 (14) | 0.0331 (14) | 0.0301 (13) | −0.0047 (13) | −0.0022 (11) | 0.0005 (11) |
C29 | 0.0464 (16) | 0.0484 (17) | 0.0358 (15) | −0.0052 (14) | 0.0061 (12) | 0.0093 (13) |
C30 | 0.072 (2) | 0.0530 (18) | 0.0378 (15) | −0.0152 (17) | 0.0215 (15) | −0.0093 (14) |
Cl1 | 0.0375 (3) | 0.0236 (3) | 0.0324 (3) | 0.0000 (3) | 0.0006 (2) | 0.0054 (2) |
O1 | 0.0445 (10) | 0.0351 (10) | 0.0236 (8) | 0.0032 (8) | 0.0099 (8) | 0.0034 (7) |
O2 | 0.0684 (13) | 0.0474 (13) | 0.0364 (10) | 0.0190 (11) | −0.0002 (10) | −0.0016 (9) |
O3 | 0.0365 (10) | 0.0343 (10) | 0.0314 (9) | 0.0079 (8) | 0.0062 (7) | 0.0007 (8) |
O4 | 0.0908 (16) | 0.0313 (11) | 0.0377 (10) | −0.0103 (10) | 0.0169 (10) | −0.0042 (8) |
O5 | 0.0574 (12) | 0.0367 (10) | 0.0297 (9) | −0.0097 (9) | 0.0140 (8) | −0.0025 (8) |
C1—C2 | 1.536 (3) | C14—C27 | 1.547 (3) |
C1—C10 | 1.547 (3) | C15—C16 | 1.523 (3) |
C1—H1A | 0.9700 | C15—H15A | 0.9700 |
C1—H1B | 0.9700 | C15—H15B | 0.9700 |
C2—C3 | 1.508 (3) | C16—C17 | 1.529 (3) |
C2—H2A | 0.9700 | C16—H16A | 0.9700 |
C2—H2B | 0.9700 | C16—H16B | 0.9700 |
C3—O1 | 1.460 (3) | C17—C22 | 1.526 (4) |
C3—C4 | 1.539 (3) | C17—C18 | 1.549 (3) |
C3—H3 | 0.9800 | C17—Cl1 | 1.802 (2) |
C4—C23 | 1.532 (4) | C18—O3 | 1.214 (3) |
C4—C24 | 1.545 (4) | C22—O4 | 1.200 (3) |
C4—C5 | 1.562 (3) | C22—O5 | 1.321 (3) |
C5—C6 | 1.529 (3) | C23—H23A | 0.9600 |
C5—C10 | 1.554 (3) | C23—H23B | 0.9600 |
C5—H5 | 0.9800 | C23—H23C | 0.9600 |
C6—C7 | 1.528 (3) | C24—H24A | 0.9600 |
C6—H6A | 0.9700 | C24—H24B | 0.9600 |
C6—H6B | 0.9700 | C24—H24C | 0.9600 |
C7—C8 | 1.541 (3) | C25—H25A | 0.9600 |
C7—H7A | 0.9700 | C25—H25B | 0.9600 |
C7—H7B | 0.9700 | C25—H25C | 0.9600 |
C8—C26 | 1.546 (3) | C26—H26A | 0.9600 |
C8—C9 | 1.560 (3) | C26—H26B | 0.9600 |
C8—C14 | 1.593 (3) | C26—H26C | 0.9600 |
C9—C11 | 1.536 (3) | C27—H27A | 0.9600 |
C9—C10 | 1.575 (3) | C27—H27B | 0.9600 |
C9—H9 | 0.9800 | C27—H27C | 0.9600 |
C10—C25 | 1.546 (3) | C28—O2 | 1.210 (3) |
C11—C12 | 1.527 (3) | C28—O1 | 1.339 (3) |
C11—H11A | 0.9700 | C28—C29 | 1.492 (4) |
C11—H11B | 0.9700 | C29—H29A | 0.9600 |
C12—C13 | 1.520 (3) | C29—H29B | 0.9600 |
C12—H12A | 0.9700 | C29—H29C | 0.9600 |
C12—H12B | 0.9700 | C30—O5 | 1.456 (3) |
C13—C18 | 1.511 (3) | C30—H30A | 0.9600 |
C13—C14 | 1.559 (3) | C30—H30B | 0.9600 |
C13—H13 | 0.9800 | C30—H30C | 0.9600 |
C14—C15 | 1.540 (3) | ||
C2—C1—C10 | 112.70 (18) | C15—C14—C27 | 107.8 (2) |
C2—C1—H1A | 109.1 | C15—C14—C13 | 107.78 (18) |
C10—C1—H1A | 109.1 | C27—C14—C13 | 108.8 (2) |
C2—C1—H1B | 109.1 | C15—C14—C8 | 111.72 (18) |
C10—C1—H1B | 109.1 | C27—C14—C8 | 112.23 (19) |
H1A—C1—H1B | 107.8 | C13—C14—C8 | 108.40 (18) |
C3—C2—C1 | 109.66 (19) | C16—C15—C14 | 112.8 (2) |
C3—C2—H2A | 109.7 | C16—C15—H15A | 109.0 |
C1—C2—H2A | 109.7 | C14—C15—H15A | 109.0 |
C3—C2—H2B | 109.7 | C16—C15—H15B | 109.0 |
C1—C2—H2B | 109.7 | C14—C15—H15B | 109.0 |
H2A—C2—H2B | 108.2 | H15A—C15—H15B | 107.8 |
O1—C3—C2 | 110.11 (19) | C15—C16—C17 | 112.46 (19) |
O1—C3—C4 | 107.44 (17) | C15—C16—H16A | 109.1 |
C2—C3—C4 | 114.2 (2) | C17—C16—H16A | 109.1 |
O1—C3—H3 | 108.3 | C15—C16—H16B | 109.1 |
C2—C3—H3 | 108.3 | C17—C16—H16B | 109.1 |
C4—C3—H3 | 108.3 | H16A—C16—H16B | 107.8 |
C23—C4—C3 | 111.4 (2) | C22—C17—C16 | 110.2 (2) |
C23—C4—C24 | 108.74 (19) | C22—C17—C18 | 107.8 (2) |
C3—C4—C24 | 107.0 (2) | C16—C17—C18 | 112.78 (19) |
C23—C4—C5 | 114.3 (2) | C22—C17—Cl1 | 112.13 (17) |
C3—C4—C5 | 106.22 (17) | C16—C17—Cl1 | 109.15 (18) |
C24—C4—C5 | 108.83 (19) | C18—C17—Cl1 | 104.69 (16) |
C6—C5—C10 | 110.76 (19) | O3—C18—C13 | 123.1 (2) |
C6—C5—C4 | 113.66 (17) | O3—C18—C17 | 119.1 (2) |
C10—C5—C4 | 117.46 (18) | C13—C18—C17 | 117.7 (2) |
C6—C5—H5 | 104.5 | O4—C22—O5 | 124.3 (2) |
C10—C5—H5 | 104.5 | O4—C22—C17 | 120.6 (2) |
C4—C5—H5 | 104.5 | O5—C22—C17 | 115.0 (2) |
C7—C6—C5 | 110.10 (18) | C4—C23—H23A | 109.5 |
C7—C6—H6A | 109.6 | C4—C23—H23B | 109.5 |
C5—C6—H6A | 109.6 | H23A—C23—H23B | 109.5 |
C7—C6—H6B | 109.6 | C4—C23—H23C | 109.5 |
C5—C6—H6B | 109.6 | H23A—C23—H23C | 109.5 |
H6A—C6—H6B | 108.2 | H23B—C23—H23C | 109.5 |
C6—C7—C8 | 113.9 (2) | C4—C24—H24A | 109.5 |
C6—C7—H7A | 108.8 | C4—C24—H24B | 109.5 |
C8—C7—H7A | 108.8 | H24A—C24—H24B | 109.5 |
C6—C7—H7B | 108.8 | C4—C24—H24C | 109.5 |
C8—C7—H7B | 108.8 | H24A—C24—H24C | 109.5 |
H7A—C7—H7B | 107.7 | H24B—C24—H24C | 109.5 |
C7—C8—C26 | 107.7 (2) | C10—C25—H25A | 109.5 |
C7—C8—C9 | 109.31 (18) | C10—C25—H25B | 109.5 |
C26—C8—C9 | 111.75 (19) | H25A—C25—H25B | 109.5 |
C7—C8—C14 | 109.66 (18) | C10—C25—H25C | 109.5 |
C26—C8—C14 | 109.55 (18) | H25A—C25—H25C | 109.5 |
C9—C8—C14 | 108.87 (17) | H25B—C25—H25C | 109.5 |
C11—C9—C8 | 111.18 (18) | C8—C26—H26A | 109.5 |
C11—C9—C10 | 113.93 (18) | C8—C26—H26B | 109.5 |
C8—C9—C10 | 116.33 (17) | H26A—C26—H26B | 109.5 |
C11—C9—H9 | 104.7 | C8—C26—H26C | 109.5 |
C8—C9—H9 | 104.7 | H26A—C26—H26C | 109.5 |
C10—C9—H9 | 104.7 | H26B—C26—H26C | 109.5 |
C25—C10—C1 | 107.38 (19) | C14—C27—H27A | 109.5 |
C25—C10—C5 | 114.52 (18) | C14—C27—H27B | 109.5 |
C1—C10—C5 | 107.82 (18) | H27A—C27—H27B | 109.5 |
C25—C10—C9 | 112.74 (19) | C14—C27—H27C | 109.5 |
C1—C10—C9 | 108.09 (17) | H27A—C27—H27C | 109.5 |
C5—C10—C9 | 106.03 (17) | H27B—C27—H27C | 109.5 |
C12—C11—C9 | 111.76 (19) | O2—C28—O1 | 123.7 (2) |
C12—C11—H11A | 109.3 | O2—C28—C29 | 124.6 (2) |
C9—C11—H11A | 109.3 | O1—C28—C29 | 111.7 (2) |
C12—C11—H11B | 109.3 | C28—C29—H29A | 109.5 |
C9—C11—H11B | 109.3 | C28—C29—H29B | 109.5 |
H11A—C11—H11B | 107.9 | H29A—C29—H29B | 109.5 |
C13—C12—C11 | 111.81 (18) | C28—C29—H29C | 109.5 |
C13—C12—H12A | 109.3 | H29A—C29—H29C | 109.5 |
C11—C12—H12A | 109.3 | H29B—C29—H29C | 109.5 |
C13—C12—H12B | 109.3 | O5—C30—H30A | 109.5 |
C11—C12—H12B | 109.3 | O5—C30—H30B | 109.5 |
H12A—C12—H12B | 107.9 | H30A—C30—H30B | 109.5 |
C18—C13—C12 | 111.67 (18) | O5—C30—H30C | 109.5 |
C18—C13—C14 | 111.25 (18) | H30A—C30—H30C | 109.5 |
C12—C13—C14 | 112.51 (18) | H30B—C30—H30C | 109.5 |
C18—C13—H13 | 107.0 | C28—O1—C3 | 117.74 (19) |
C12—C13—H13 | 107.0 | C22—O5—C30 | 115.4 (2) |
C14—C13—H13 | 107.0 | ||
C10—C1—C2—C3 | −58.5 (3) | C11—C12—C13—C14 | 55.6 (3) |
C1—C2—C3—O1 | −178.6 (2) | C18—C13—C14—C15 | 55.4 (2) |
C1—C2—C3—C4 | 60.5 (3) | C12—C13—C14—C15 | −178.43 (18) |
O1—C3—C4—C23 | −52.4 (3) | C18—C13—C14—C27 | −61.2 (2) |
C2—C3—C4—C23 | 70.1 (2) | C12—C13—C14—C27 | 65.0 (2) |
O1—C3—C4—C24 | 66.4 (2) | C18—C13—C14—C8 | 176.50 (17) |
C2—C3—C4—C24 | −171.20 (19) | C12—C13—C14—C8 | −57.3 (2) |
O1—C3—C4—C5 | −177.48 (19) | C7—C8—C14—C15 | −64.0 (2) |
C2—C3—C4—C5 | −55.1 (3) | C26—C8—C14—C15 | 54.0 (3) |
C23—C4—C5—C6 | 60.1 (3) | C9—C8—C14—C15 | 176.47 (19) |
C3—C4—C5—C6 | −176.5 (2) | C7—C8—C14—C27 | 57.2 (3) |
C24—C4—C5—C6 | −61.6 (3) | C26—C8—C14—C27 | 175.2 (2) |
C23—C4—C5—C10 | −71.4 (3) | C9—C8—C14—C27 | −62.3 (3) |
C3—C4—C5—C10 | 51.9 (3) | C7—C8—C14—C13 | 177.42 (19) |
C24—C4—C5—C10 | 166.8 (2) | C26—C8—C14—C13 | −64.6 (2) |
C10—C5—C6—C7 | −63.3 (2) | C9—C8—C14—C13 | 57.9 (2) |
C4—C5—C6—C7 | 161.9 (2) | C27—C14—C15—C16 | 55.6 (3) |
C5—C6—C7—C8 | 57.3 (3) | C13—C14—C15—C16 | −61.7 (3) |
C6—C7—C8—C26 | 72.8 (2) | C8—C14—C15—C16 | 179.35 (18) |
C6—C7—C8—C9 | −48.8 (3) | C14—C15—C16—C17 | 56.4 (3) |
C6—C7—C8—C14 | −168.11 (19) | C15—C16—C17—C22 | −163.6 (2) |
C7—C8—C9—C11 | −178.25 (18) | C15—C16—C17—C18 | −43.1 (3) |
C26—C8—C9—C11 | 62.7 (2) | C15—C16—C17—Cl1 | 72.8 (2) |
C14—C8—C9—C11 | −58.5 (2) | C12—C13—C18—O3 | 8.8 (3) |
C7—C8—C9—C10 | 49.1 (3) | C14—C13—C18—O3 | 135.5 (2) |
C26—C8—C9—C10 | −70.0 (2) | C12—C13—C18—C17 | −173.91 (19) |
C14—C8—C9—C10 | 168.91 (18) | C14—C13—C18—C17 | −47.3 (3) |
C2—C1—C10—C25 | −71.1 (3) | C22—C17—C18—O3 | −20.2 (3) |
C2—C1—C10—C5 | 52.8 (3) | C16—C17—C18—O3 | −142.1 (2) |
C2—C1—C10—C9 | 167.0 (2) | Cl1—C17—C18—O3 | 99.4 (2) |
C6—C5—C10—C25 | −65.2 (2) | C22—C17—C18—C13 | 162.45 (19) |
C4—C5—C10—C25 | 67.7 (3) | C16—C17—C18—C13 | 40.5 (3) |
C6—C5—C10—C1 | 175.40 (18) | Cl1—C17—C18—C13 | −78.0 (2) |
C4—C5—C10—C1 | −51.7 (3) | C16—C17—C22—O4 | 44.6 (4) |
C6—C5—C10—C9 | 59.8 (2) | C18—C17—C22—O4 | −78.9 (3) |
C4—C5—C10—C9 | −167.29 (19) | Cl1—C17—C22—O4 | 166.4 (2) |
C11—C9—C10—C25 | −59.8 (2) | C16—C17—C22—O5 | −137.7 (2) |
C8—C9—C10—C25 | 71.6 (2) | C18—C17—C22—O5 | 98.8 (2) |
C11—C9—C10—C1 | 58.8 (2) | Cl1—C17—C22—O5 | −15.9 (3) |
C8—C9—C10—C1 | −169.87 (19) | O2—C28—O1—C3 | −4.3 (4) |
C11—C9—C10—C5 | 174.18 (18) | C29—C28—O1—C3 | 176.7 (2) |
C8—C9—C10—C5 | −54.5 (2) | C2—C3—O1—C28 | 89.2 (3) |
C8—C9—C11—C12 | 56.5 (2) | C4—C3—O1—C28 | −145.9 (2) |
C10—C9—C11—C12 | −169.71 (19) | O4—C22—O5—C30 | −2.7 (4) |
C9—C11—C12—C13 | −54.1 (3) | C17—C22—O5—C30 | 179.7 (2) |
C11—C12—C13—C18 | −178.44 (18) |
D—H···A | D—H | H···A | D···A | D—H···A |
C25—H25C···O2i | 0.96 | 2.55 | 3.407 (3) | 148 |
C11—H11B···O3ii | 0.97 | 2.58 | 3.290 (3) | 130 |
Symmetry codes: (i) x, y−1, z; (ii) −x, y−1/2, −z+2. |
Experimental details
Crystal data | |
Chemical formula | C27H41ClO5 |
Mr | 481.05 |
Crystal system, space group | Monoclinic, P21 |
Temperature (K) | 150 |
a, b, c (Å) | 11.331 (3), 6.738 (1), 16.366 (3) |
β (°) | 96.275 (10) |
V (Å3) | 1242.0 (4) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.19 |
Crystal size (mm) | 0.55 × 0.2 × 0.03 |
Data collection | |
Diffractometer | Bruker Nonius KappaCCD |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 8942, 4320, 3899 |
Rint | 0.034 |
(sin θ/λ)max (Å−1) | 0.595 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.038, 0.096, 1.10 |
No. of reflections | 4320 |
No. of parameters | 305 |
No. of restraints | 1 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.20, −0.22 |
Absolute structure | Flack (1983), with 1923 Friedel pairs |
Absolute structure parameter | −0.01 (6) |
Computer programs: COLLECT (Nonius, 1998) and DENZO (Otwinowski & Minor, 1997), COLLECT and DENZO, SIR92 (Altomare et al., 1994), SHELXL97 (Sheldrick, 1997), PLATON (Spek, 2003), SHELXL97.
D—H···A | D—H | H···A | D···A | D—H···A |
C25—H25C···O2i | 0.96 | 2.55 | 3.407 (3) | 148.4 |
C11—H11B···O3ii | 0.97 | 2.58 | 3.290 (3) | 130.4 |
Symmetry codes: (i) x, y−1, z; (ii) −x, y−1/2, −z+2. |
Efforts have recently been exerted in order to synthesize new derivatives of natural compounds, especially terpenoides (Dzubak et al., 2006; Kim et al., 1998) with large number of functional groups (Kim et al., 1998; Biedermann et al., 2005; Urban et al., 2005). Several years ago a group of new compounds called betulinines (Šarek et al., 2003), was described. Betulinines have significant cytotoxic activity on broad scale of tumor lines including multidrug resistance. Among the most effective belulinines are β-ketoacids (1, Fig. 3) (Šarek et al., 2003). The search for new degradable analogs of 1 with similar high cytotoxity resulted in a hexanorlupane derivatives (I) (Fig. 3) with cytotoxicity two times higher than 1. The structure of I has been determined as a part of large study of structure-activity relationships.
The bond lengths and angles in I are unexceptional and very close to the pertinent ones in the parent molecule 1. In both molecules the oxygen atom of the carbonyl substituent on D ring is slightly bend towards adjoining carboxyl moiety as follows from comparison of the angle around C18 (see Table I). All rings adopts chair conformations (Cremer & Pople, 1975) (Fig. 1), the deviation from ideal geometry (τ = 0, 180 °) can be discerned on ring D due its carbonyl substituent (τ = 164.6 (2) °). Without the possibility of classical hydrogen bonds, the role of weak C—H···O contacts in crystal packing is clearly revealed. Molecules are packed by C(methyl)-H···O(acetyl) hydrogen bonds forming columns along the b axis. Second parallel column related by operation of a 21 screw is attached to the first one in a zip-like way via a CH2···O(carbonyl) interaction (see Fig. 2).