Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S2053229618013815/lf3081sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S2053229618013815/lf3081Isup2.hkl | |
Portable Document Format (PDF) file https://doi.org/10.1107/S2053229618013815/lf3081sup3.pdf |
CCDC reference: 1870837
Data collection: FRAMBO (Bruker, 2004); cell refinement: FRAMBO (Bruker, 2004); data reduction: SAINT (Bruker, 2004); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).
C15H28O3 | Dx = 1.164 Mg m−3 |
Mr = 256.37 | Cu Kα radiation, λ = 1.54178 Å |
Orthorhombic, P212121 | Cell parameters from 1647 reflections |
a = 6.4636 (6) Å | θ = 4.2–71.9° |
b = 12.9225 (12) Å | µ = 0.62 mm−1 |
c = 17.516 (2) Å | T = 293 K |
V = 1463.1 (3) Å3 | Block, colourless |
Z = 4 | 0.40 × 0.14 × 0.11 mm |
F(000) = 568 |
Bruker Xcalibur Eos Gemini diffractometer | 1969 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.053 |
CCD plate scans | θmax = 66.1°, θmin = 4.3° |
Absorption correction: multi-scan (SADABS; Bruker, 2004) | h = −7→4 |
Tmin = 0.789, Tmax = 0.935 | k = −15→14 |
8351 measured reflections | l = −20→19 |
2554 independent reflections |
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H-atom parameters constrained |
R[F2 > 2σ(F2)] = 0.049 | w = 1/[σ2(Fo2) + (0.0467P)2 + 0.1932P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.126 | (Δ/σ)max < 0.001 |
S = 1.08 | Δρmax = 0.12 e Å−3 |
2554 reflections | Δρmin = −0.16 e Å−3 |
170 parameters | Absolute structure: Flack x determined using 642 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013) |
0 restraints | Absolute structure parameter: 0.1 (3) |
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. |
x | y | z | Uiso*/Ueq | ||
C1 | 0.7838 (5) | 0.1931 (3) | 0.3122 (2) | 0.0393 (9) | |
C2 | 0.5989 (6) | 0.1540 (3) | 0.3597 (2) | 0.0466 (10) | |
H2A | 0.4856 | 0.1334 | 0.3268 | 0.056* | |
H2B | 0.6390 | 0.0952 | 0.3909 | 0.056* | |
C3 | 0.5367 (6) | 0.2444 (3) | 0.4094 (2) | 0.0486 (10) | |
H3A | 0.6317 | 0.2531 | 0.4517 | 0.058* | |
H3B | 0.3976 | 0.2355 | 0.4291 | 0.058* | |
C4 | 0.5483 (6) | 0.3369 (3) | 0.3540 (2) | 0.0415 (9) | |
H4 | 0.4165 | 0.3385 | 0.3263 | 0.050* | |
C5 | 0.7177 (5) | 0.3089 (3) | 0.2946 (2) | 0.0375 (8) | |
H5 | 0.8375 | 0.3539 | 0.3032 | 0.045* | |
C6 | 0.6398 (6) | 0.3258 (3) | 0.2130 (2) | 0.0414 (9) | |
H6 | 0.5439 | 0.2695 | 0.2006 | 0.050* | |
C7 | 0.8138 (6) | 0.3275 (3) | 0.1501 (2) | 0.0452 (9) | |
C8 | 1.0105 (6) | 0.2697 (3) | 0.1724 (3) | 0.0502 (10) | |
H8A | 1.0676 | 0.3028 | 0.2174 | 0.060* | |
H8B | 1.1102 | 0.2783 | 0.1315 | 0.060* | |
C9 | 0.9903 (6) | 0.1542 (3) | 0.1890 (2) | 0.0499 (10) | |
H9A | 0.9740 | 0.1178 | 0.1410 | 0.060* | |
H9B | 1.1181 | 0.1303 | 0.2122 | 0.060* | |
C10 | 0.8120 (6) | 0.1249 (3) | 0.2410 (2) | 0.0425 (9) | |
H10 | 0.6841 | 0.1281 | 0.2111 | 0.051* | |
C11 | 0.5718 (6) | 0.4429 (3) | 0.3931 (2) | 0.0482 (10) | |
H11 | 0.5858 | 0.4947 | 0.3526 | 0.058* | |
C12 | 0.3774 (7) | 0.4700 (4) | 0.4380 (3) | 0.0700 (14) | |
H12A | 0.3566 | 0.4197 | 0.4776 | 0.105* | |
H12B | 0.2602 | 0.4698 | 0.4043 | 0.105* | |
H12C | 0.3927 | 0.5374 | 0.4603 | 0.105* | |
C13 | 0.7628 (7) | 0.4518 (3) | 0.4435 (3) | 0.0653 (13) | |
H13A | 0.7477 | 0.4075 | 0.4871 | 0.098* | |
H13B | 0.7785 | 0.5222 | 0.4602 | 0.098* | |
H13C | 0.8829 | 0.4314 | 0.4150 | 0.098* | |
C14 | 0.9815 (6) | 0.1934 (3) | 0.3611 (2) | 0.0505 (10) | |
H14A | 0.9584 | 0.2332 | 0.4065 | 0.076* | |
H14B | 1.0930 | 0.2235 | 0.3324 | 0.076* | |
H14C | 1.0166 | 0.1236 | 0.3748 | 0.076* | |
C15 | 0.7238 (8) | 0.2886 (4) | 0.0750 (2) | 0.0639 (13) | |
H15A | 0.6026 | 0.3280 | 0.0625 | 0.096* | |
H15B | 0.6875 | 0.2169 | 0.0800 | 0.096* | |
H15C | 0.8247 | 0.2964 | 0.0352 | 0.096* | |
O1 | 0.5287 (5) | 0.4215 (2) | 0.20694 (18) | 0.0571 (8) | |
H1 | 0.6020 | 0.4649 | 0.1860 | 0.086* | |
O2 | 0.8668 (5) | 0.4339 (2) | 0.13613 (17) | 0.0552 (8) | |
H2 | 0.9526 | 0.4530 | 0.1676 | 0.083* | |
O3 | 0.8466 (4) | 0.01860 (19) | 0.26237 (18) | 0.0514 (8) | |
H3 | 0.7350 | −0.0110 | 0.2669 | 0.077* |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0374 (19) | 0.0289 (18) | 0.052 (2) | −0.0012 (15) | −0.0026 (17) | 0.0012 (16) |
C2 | 0.047 (2) | 0.0355 (19) | 0.057 (2) | −0.0028 (17) | 0.0002 (19) | 0.0069 (19) |
C3 | 0.052 (2) | 0.040 (2) | 0.054 (2) | −0.0037 (19) | 0.006 (2) | 0.0045 (18) |
C4 | 0.0363 (18) | 0.0366 (19) | 0.052 (2) | 0.0022 (16) | 0.0005 (17) | 0.0038 (17) |
C5 | 0.0295 (17) | 0.0314 (18) | 0.051 (2) | −0.0034 (15) | −0.0017 (16) | 0.0007 (16) |
C6 | 0.0420 (19) | 0.0282 (18) | 0.054 (2) | 0.0003 (16) | −0.0043 (17) | 0.0016 (17) |
C7 | 0.051 (2) | 0.034 (2) | 0.051 (2) | −0.0061 (17) | 0.0018 (19) | 0.0005 (17) |
C8 | 0.046 (2) | 0.043 (2) | 0.062 (2) | −0.0048 (18) | 0.007 (2) | 0.0006 (19) |
C9 | 0.047 (2) | 0.039 (2) | 0.064 (3) | 0.0015 (18) | 0.003 (2) | −0.0049 (19) |
C10 | 0.039 (2) | 0.0286 (17) | 0.060 (2) | 0.0001 (15) | −0.0035 (19) | −0.0002 (17) |
C11 | 0.057 (2) | 0.034 (2) | 0.054 (2) | 0.0072 (18) | 0.006 (2) | 0.0025 (17) |
C12 | 0.076 (3) | 0.060 (3) | 0.074 (3) | 0.021 (3) | 0.017 (3) | −0.003 (3) |
C13 | 0.075 (3) | 0.050 (3) | 0.071 (3) | −0.010 (2) | −0.004 (3) | −0.015 (2) |
C14 | 0.050 (2) | 0.038 (2) | 0.063 (3) | 0.0055 (18) | −0.011 (2) | 0.0007 (19) |
C15 | 0.077 (3) | 0.060 (3) | 0.055 (3) | −0.010 (2) | −0.007 (2) | −0.006 (2) |
O1 | 0.0601 (18) | 0.0451 (16) | 0.066 (2) | 0.0151 (14) | 0.0018 (16) | 0.0118 (14) |
O2 | 0.0659 (19) | 0.0384 (15) | 0.0613 (19) | −0.0081 (14) | 0.0002 (16) | 0.0068 (14) |
O3 | 0.0474 (15) | 0.0297 (13) | 0.077 (2) | 0.0022 (12) | −0.0027 (16) | 0.0018 (13) |
C1—C10 | 1.538 (5) | C9—C10 | 1.517 (5) |
C1—C14 | 1.538 (5) | C9—H9A | 0.9700 |
C1—C2 | 1.542 (5) | C9—H9B | 0.9700 |
C1—C5 | 1.586 (5) | C10—O3 | 1.441 (4) |
C2—C3 | 1.511 (5) | C10—H10 | 0.9800 |
C2—H2A | 0.9700 | C11—C13 | 1.522 (5) |
C2—H2B | 0.9700 | C11—C12 | 1.523 (5) |
C3—C4 | 1.541 (5) | C11—H11 | 0.9800 |
C3—H3A | 0.9700 | C12—H12A | 0.9600 |
C3—H3B | 0.9700 | C12—H12B | 0.9600 |
C4—C11 | 1.540 (5) | C12—H12C | 0.9600 |
C4—C5 | 1.553 (5) | C13—H13A | 0.9600 |
C4—H4 | 0.9800 | C13—H13B | 0.9600 |
C5—C6 | 1.532 (5) | C13—H13C | 0.9600 |
C5—H5 | 0.9800 | C14—H14A | 0.9600 |
C6—O1 | 1.434 (4) | C14—H14B | 0.9600 |
C6—C7 | 1.574 (5) | C14—H14C | 0.9600 |
C6—H6 | 0.9800 | C15—H15A | 0.9600 |
C7—O2 | 1.439 (4) | C15—H15B | 0.9600 |
C7—C15 | 1.524 (6) | C15—H15C | 0.9600 |
C7—C8 | 1.525 (5) | O1—H1 | 0.8200 |
C8—C9 | 1.527 (5) | O2—H2 | 0.8200 |
C8—H8A | 0.9700 | O3—H3 | 0.8200 |
C8—H8B | 0.9700 | ||
C10—C1—C14 | 110.7 (3) | H8A—C8—H8B | 107.3 |
C10—C1—C2 | 110.0 (3) | C10—C9—C8 | 115.0 (3) |
C14—C1—C2 | 110.1 (3) | C10—C9—H9A | 108.5 |
C10—C1—C5 | 114.6 (3) | C8—C9—H9A | 108.5 |
C14—C1—C5 | 109.3 (3) | C10—C9—H9B | 108.5 |
C2—C1—C5 | 101.8 (3) | C8—C9—H9B | 108.5 |
C3—C2—C1 | 105.3 (3) | H9A—C9—H9B | 107.5 |
C3—C2—H2A | 110.7 | O3—C10—C9 | 106.0 (3) |
C1—C2—H2A | 110.7 | O3—C10—C1 | 110.8 (3) |
C3—C2—H2B | 110.7 | C9—C10—C1 | 115.7 (3) |
C1—C2—H2B | 110.7 | O3—C10—H10 | 108.0 |
H2A—C2—H2B | 108.8 | C9—C10—H10 | 108.0 |
C2—C3—C4 | 103.0 (3) | C1—C10—H10 | 108.0 |
C2—C3—H3A | 111.2 | C13—C11—C12 | 110.7 (4) |
C4—C3—H3A | 111.2 | C13—C11—C4 | 113.9 (3) |
C2—C3—H3B | 111.2 | C12—C11—C4 | 110.6 (3) |
C4—C3—H3B | 111.2 | C13—C11—H11 | 107.1 |
H3A—C3—H3B | 109.1 | C12—C11—H11 | 107.1 |
C11—C4—C3 | 114.5 (3) | C4—C11—H11 | 107.1 |
C11—C4—C5 | 115.8 (3) | C11—C12—H12A | 109.5 |
C3—C4—C5 | 106.0 (3) | C11—C12—H12B | 109.5 |
C11—C4—H4 | 106.6 | H12A—C12—H12B | 109.5 |
C3—C4—H4 | 106.6 | C11—C12—H12C | 109.5 |
C5—C4—H4 | 106.6 | H12A—C12—H12C | 109.5 |
C6—C5—C4 | 111.1 (3) | H12B—C12—H12C | 109.5 |
C6—C5—C1 | 113.9 (3) | C11—C13—H13A | 109.5 |
C4—C5—C1 | 106.2 (3) | C11—C13—H13B | 109.5 |
C6—C5—H5 | 108.5 | H13A—C13—H13B | 109.5 |
C4—C5—H5 | 108.5 | C11—C13—H13C | 109.5 |
C1—C5—H5 | 108.5 | H13A—C13—H13C | 109.5 |
O1—C6—C5 | 110.9 (3) | H13B—C13—H13C | 109.5 |
O1—C6—C7 | 107.1 (3) | C1—C14—H14A | 109.5 |
C5—C6—C7 | 114.9 (3) | C1—C14—H14B | 109.5 |
O1—C6—H6 | 107.9 | H14A—C14—H14B | 109.5 |
C5—C6—H6 | 107.9 | C1—C14—H14C | 109.5 |
C7—C6—H6 | 107.9 | H14A—C14—H14C | 109.5 |
O2—C7—C15 | 105.0 (3) | H14B—C14—H14C | 109.5 |
O2—C7—C8 | 108.2 (3) | C7—C15—H15A | 109.5 |
C15—C7—C8 | 112.2 (4) | C7—C15—H15B | 109.5 |
O2—C7—C6 | 107.6 (3) | H15A—C15—H15B | 109.5 |
C15—C7—C6 | 109.1 (3) | C7—C15—H15C | 109.5 |
C8—C7—C6 | 114.2 (3) | H15A—C15—H15C | 109.5 |
C7—C8—C9 | 117.2 (3) | H15B—C15—H15C | 109.5 |
C7—C8—H8A | 108.0 | C6—O1—H1 | 109.5 |
C9—C8—H8A | 108.0 | C7—O2—H2 | 109.5 |
C7—C8—H8B | 108.0 | C10—O3—H3 | 109.5 |
C9—C8—H8B | 108.0 | ||
C10—C1—C2—C3 | −159.9 (3) | C5—C6—C7—O2 | −96.0 (4) |
C14—C1—C2—C3 | 77.8 (4) | O1—C6—C7—C15 | −85.8 (4) |
C5—C1—C2—C3 | −38.0 (4) | C5—C6—C7—C15 | 150.6 (3) |
C1—C2—C3—C4 | 42.7 (4) | O1—C6—C7—C8 | 147.8 (3) |
C2—C3—C4—C11 | −158.5 (3) | C5—C6—C7—C8 | 24.2 (4) |
C2—C3—C4—C5 | −29.5 (4) | O2—C7—C8—C9 | −179.3 (3) |
C11—C4—C5—C6 | −101.2 (4) | C15—C7—C8—C9 | −63.9 (5) |
C3—C4—C5—C6 | 130.6 (3) | C6—C7—C8—C9 | 60.9 (5) |
C11—C4—C5—C1 | 134.4 (3) | C7—C8—C9—C10 | −46.9 (5) |
C3—C4—C5—C1 | 6.2 (4) | C8—C9—C10—O3 | −168.0 (3) |
C10—C1—C5—C6 | 14.8 (4) | C8—C9—C10—C1 | −44.8 (5) |
C14—C1—C5—C6 | 139.7 (3) | C14—C1—C10—O3 | 63.0 (4) |
C2—C1—C5—C6 | −103.8 (3) | C2—C1—C10—O3 | −58.9 (4) |
C10—C1—C5—C4 | 137.5 (3) | C5—C1—C10—O3 | −172.9 (3) |
C14—C1—C5—C4 | −97.6 (3) | C14—C1—C10—C9 | −57.6 (4) |
C2—C1—C5—C4 | 18.8 (4) | C2—C1—C10—C9 | −179.5 (3) |
C4—C5—C6—O1 | 43.4 (4) | C5—C1—C10—C9 | 66.5 (4) |
C1—C5—C6—O1 | 163.3 (3) | C3—C4—C11—C13 | 58.4 (4) |
C4—C5—C6—C7 | 165.0 (3) | C5—C4—C11—C13 | −65.4 (4) |
C1—C5—C6—C7 | −75.0 (4) | C3—C4—C11—C12 | −67.0 (4) |
O1—C6—C7—O2 | 27.6 (4) | C5—C4—C11—C12 | 169.2 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
O3—H3···O1i | 0.82 | 1.97 | 2.783 (4) | 172 |
O2—H2···O3ii | 0.82 | 1.98 | 2.791 (4) | 172 |
O1—H1···O2 | 0.82 | 1.96 | 2.518 (4) | 124 |
Symmetry codes: (i) −x+1, y−1/2, −z+1/2; (ii) −x+2, y+1/2, −z+1/2. |
Position | (1) | (2)b | (3) | |||
δ(H) | δ(C) | δ(H) | δ(C) | δ(H) | δ(C) | |
1 | 47.8 | 49.7 | 3.79 (dd) (11.6, 4.4) | 72.4 | ||
2 | 1.64 m; 1.41 m | 39.6 | 1.61 m | 40.7 | 1.90 m; 1.46 m | 27.2 |
3 | 1.57 m; 1.37 m | 23.6 | 1.69 m; 1.36 m | 27.3 | 2.04 m; 1.39 m | 35.5 |
4 | 2.03 m | 50.6 | 1.88 m | 51.2 | 74.0 | |
5 | 1.60 overlapped | 50.8 | 2.02 dd (7.8, 0.9) | 49.0 | 76.7 | |
6 | 3.27 d (11.4) | 75.6 | 3.44 d (5.7) | 82.2 | 1.72 t (12.9); 1.53 m | 29.9 |
7 | 73.0 | 72.9 | 1.62 m | 37.8 | ||
8 | 1.83 m; 1.56 m | 33.9 | 1.98 dt (13.5, 3.1); 1.41 m | 36.1 | 1.46 m; 1.28 m | 23.4 |
9 | 1.79 m; 1.63 m | 28.7 | 2.15 m; 1.31 m | 29.3 | 1.78 dt (4.2, 13.3); 1.54 m | 32.6 |
10 | 3.54 dd (10.2, 6.0) | 74.5 | 4.04 d (10.3) | 77.0 | 42.0 | |
11 | 1.80 m | 31.6 | 1.57 m | 33.0 | 1.44 m | 33.1 |
12 | 0.87 d (6.6) | 21.7 | 0.87 d (6.7) | 19.1 | 0.89 d (6.8) | 19.1 |
13 | 0.93 d (6.6) | 16.6 | 0.94 d (6.7) | 22.0 | 0.89 d (6.8) | 19.5 |
14 | 0.94 s | 18.8 | 0.94 s | 20.3 | 1.16 s | 14.9 |
15 | 1.22 s | 25.3 | 1.23 s | 30.6 | 1.15 s | 25.0 |
6-OH | 3.92 d (5.7) |
Notes: (a) data were measured in MeOH-d4 at 600 MHz for (1), in acetone–d6 at 500 MHz for (2) and (3); (b) C-9 of (2) was overlapped by signals of solvent, and data was obtained from the correlation in HMBC spectrum. |
Compound | IC50 (µM) | Compound | IC50 (µM) |
(1) | 5.7±0.22 | (3) | >50 |
(2) | >50 | Dexamethasone | 0.13±0.06 |