The title molecule, 2(
R)-[(1
E,3
E,7
S,8
S,11
E,13
R)-13-hydroxy-4,8,12-trimethyl-7,8-epoxycyclotetradeca-1,3,11-trien-1-yl]propane-1,2-diol, C
20H
32O
4, is a semi-synthetic analog of sarcophine, the natural cembranoid of marine origin, isolated from the soft coral
Sarcophyton glaucum. The conformation of the 14-membered ring differs substantially from that of sarcophine. The two OH groups of the propane-1,2-diol moiety form an unusual weak intramolecular hydrogen bond with an O
O distance of 2.788 (2) Å, and the molecules are linked into double chains by intermolecular hydrogen bonds with O
O distances of 2.772 (2) and 2.849 (2) Å.
Supporting information
CCDC reference: 205314
The preparation of the title compound from sarcophine has been described by Katsuyama et al. (2002). Crystals of (I) were grown from hexane-acetone (1:1).
H atoms were placed in calculated positions, guided by difference maps, with C—H distances of 0.95–1.00 Å and Uiso(H) = 1.2Ueq(C) (1.5 for methyl), and thereafter treated as riding. Coordinates for the OH H atoms were refined. A torsional parameter was refined for each methyl group. The absolute configuration could not be established from the X-ray data, but was assigned based on the known configuration of sarcophine (Kashman, 1977). Friedel pairs were averaged.
Data collection: COLLECT (Nonius, 2000); cell refinement: HKL SCALEPACK (Otwinowski & Minor 1997); data reduction: HKL DENZO (Otwinowski & Minor 1997) and SCALEPACK; program(s) used to solve structure: SIR97 (Altomare, et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: SHELXL97.
2(
R)-[(1E,3E,7
S,8S,11E,13
R)-13-hydroxy-4,8,12-trimethyl- 7,8-epoxycyclotetradeca-1,3,11-trien-1-yl]propane-1,2-diol
top
Crystal data top
C20H32O4 | F(000) = 368 |
Mr = 336.46 | Dx = 1.205 Mg m−3 |
Monoclinic, P21 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2yb | Cell parameters from 2443 reflections |
a = 5.858 (2) Å | θ = 2.5–30.0° |
b = 8.232 (2) Å | µ = 0.08 mm−1 |
c = 19.241 (6) Å | T = 100 K |
β = 91.315 (10)° | Plate, pale yellow |
V = 927.6 (5) Å3 | 0.32 × 0.22 × 0.05 mm |
Z = 2 | |
Data collection top
Nonius KappaCCD area-detector (with Oxford Cryostream cooler) diffractometer | 2647 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.021 |
Graphite monochromator | θmax = 30.0°, θmin = 3.2° |
ω scans with κ offsets | h = −8→8 |
8313 measured reflections | k = −11→11 |
2875 independent reflections | l = −26→27 |
Refinement top
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)] = 0.036 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.089 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.04 | w = 1/[σ2(Fo2) + (0.0385P)2 + 0.2001P] where P = (Fo2 + 2Fc2)/3 |
2875 reflections | (Δ/σ)max < 0.001 |
230 parameters | Δρmax = 0.22 e Å−3 |
1 restraint | Δρmin = −0.21 e Å−3 |
Crystal data top
C20H32O4 | V = 927.6 (5) Å3 |
Mr = 336.46 | Z = 2 |
Monoclinic, P21 | Mo Kα radiation |
a = 5.858 (2) Å | µ = 0.08 mm−1 |
b = 8.232 (2) Å | T = 100 K |
c = 19.241 (6) Å | 0.32 × 0.22 × 0.05 mm |
β = 91.315 (10)° | |
Data collection top
Nonius KappaCCD area-detector (with Oxford Cryostream cooler) diffractometer | 2647 reflections with I > 2σ(I) |
8313 measured reflections | Rint = 0.021 |
2875 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.036 | 1 restraint |
wR(F2) = 0.089 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.04 | Δρmax = 0.22 e Å−3 |
2875 reflections | Δρmin = −0.21 e Å−3 |
230 parameters | |
Special details top
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. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
O1 | 0.1484 (2) | 1.16959 (16) | 0.46428 (7) | 0.0216 (3) | |
H10 | 0.107 (4) | 1.127 (4) | 0.5039 (13) | 0.032* | |
O2 | 0.4888 (2) | 1.04091 (18) | 0.38159 (7) | 0.0277 (3) | |
H20 | 0.501 (4) | 1.105 (4) | 0.4158 (14) | 0.042* | |
O3 | 0.4902 (2) | 0.21273 (16) | 0.08076 (7) | 0.0222 (3) | |
O4 | 0.0500 (2) | 0.49855 (16) | 0.42867 (7) | 0.0232 (3) | |
H40 | 0.081 (4) | 0.409 (4) | 0.4366 (14) | 0.035* | |
C1 | 0.2426 (3) | 0.8281 (2) | 0.33828 (8) | 0.0164 (3) | |
C2 | 0.3698 (3) | 0.8305 (2) | 0.28077 (9) | 0.0178 (3) | |
H2 | 0.5034 | 0.8960 | 0.2818 | 0.021* | |
C3 | 0.3179 (3) | 0.7407 (2) | 0.21742 (9) | 0.0178 (3) | |
H3 | 0.1845 | 0.6751 | 0.2172 | 0.021* | |
C4 | 0.4400 (3) | 0.7410 (2) | 0.15896 (9) | 0.0179 (3) | |
C5 | 0.3452 (3) | 0.6643 (2) | 0.09330 (9) | 0.0207 (3) | |
H5A | 0.3434 | 0.7474 | 0.0561 | 0.025* | |
H5B | 0.1848 | 0.6328 | 0.1012 | 0.025* | |
C6 | 0.4730 (3) | 0.5147 (2) | 0.06692 (9) | 0.0225 (4) | |
H6A | 0.4165 | 0.4884 | 0.0194 | 0.027* | |
H6B | 0.6376 | 0.5407 | 0.0643 | 0.027* | |
C7 | 0.4439 (3) | 0.3682 (2) | 0.11278 (9) | 0.0193 (3) | |
H7 | 0.5050 | 0.3807 | 0.1614 | 0.023* | |
C8 | 0.2604 (3) | 0.2469 (2) | 0.10389 (9) | 0.0188 (3) | |
C9 | 0.1944 (3) | 0.1413 (2) | 0.16450 (9) | 0.0202 (3) | |
H9A | 0.3331 | 0.1198 | 0.1934 | 0.024* | |
H9B | 0.1397 | 0.0356 | 0.1460 | 0.024* | |
C10 | 0.0102 (3) | 0.2110 (2) | 0.21152 (9) | 0.0213 (3) | |
H10A | −0.1105 | 0.2623 | 0.1821 | 0.026* | |
H10B | −0.0607 | 0.1209 | 0.2374 | 0.026* | |
C11 | 0.1021 (3) | 0.3347 (2) | 0.26265 (8) | 0.0176 (3) | |
H11 | 0.2620 | 0.3538 | 0.2625 | 0.021* | |
C12 | −0.0174 (3) | 0.4200 (2) | 0.30802 (8) | 0.0161 (3) | |
C13 | 0.1040 (3) | 0.5352 (2) | 0.35744 (8) | 0.0159 (3) | |
H13 | 0.2724 | 0.5229 | 0.3518 | 0.019* | |
C14 | 0.0387 (3) | 0.7159 (2) | 0.34457 (8) | 0.0166 (3) | |
H14A | −0.0557 | 0.7231 | 0.3013 | 0.020* | |
H14B | −0.0557 | 0.7539 | 0.3834 | 0.020* | |
C15 | 0.2993 (3) | 0.9387 (2) | 0.39965 (9) | 0.0174 (3) | |
C16 | 0.0945 (3) | 1.0506 (2) | 0.41186 (9) | 0.0196 (3) | |
H16A | 0.0511 | 1.1062 | 0.3679 | 0.023* | |
H16B | −0.0374 | 0.9849 | 0.4265 | 0.023* | |
C17 | 0.3673 (3) | 0.8410 (2) | 0.46431 (9) | 0.0234 (4) | |
H17A | 0.5037 | 0.7764 | 0.4549 | 0.035* | |
H17B | 0.2418 | 0.7685 | 0.4766 | 0.035* | |
H17C | 0.4002 | 0.9154 | 0.5030 | 0.035* | |
C18 | 0.6652 (3) | 0.8263 (3) | 0.15228 (10) | 0.0242 (4) | |
H18A | 0.6443 | 0.9244 | 0.1239 | 0.036* | |
H18B | 0.7740 | 0.7537 | 0.1300 | 0.036* | |
H18C | 0.7243 | 0.8566 | 0.1986 | 0.036* | |
C19 | 0.0816 (3) | 0.2589 (3) | 0.04604 (10) | 0.0264 (4) | |
H19A | 0.1381 | 0.3289 | 0.0090 | 0.040* | |
H19B | −0.0589 | 0.3053 | 0.0644 | 0.040* | |
H19C | 0.0498 | 0.1503 | 0.0273 | 0.040* | |
C20 | −0.2726 (3) | 0.4094 (3) | 0.31326 (10) | 0.0249 (4) | |
H20A | −0.3441 | 0.4950 | 0.2849 | 0.037* | |
H20B | −0.3154 | 0.4232 | 0.3619 | 0.037* | |
H20C | −0.3249 | 0.3030 | 0.2965 | 0.037* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
O1 | 0.0304 (6) | 0.0163 (6) | 0.0183 (6) | −0.0022 (5) | 0.0031 (5) | −0.0026 (5) |
O2 | 0.0275 (6) | 0.0277 (7) | 0.0281 (7) | −0.0116 (6) | 0.0086 (5) | −0.0081 (6) |
O3 | 0.0232 (6) | 0.0194 (6) | 0.0243 (6) | 0.0033 (5) | 0.0056 (5) | −0.0034 (5) |
O4 | 0.0397 (7) | 0.0151 (6) | 0.0148 (6) | 0.0024 (6) | 0.0044 (5) | 0.0008 (5) |
C1 | 0.0190 (7) | 0.0134 (7) | 0.0168 (7) | 0.0014 (6) | 0.0015 (6) | 0.0006 (6) |
C2 | 0.0198 (7) | 0.0143 (7) | 0.0194 (8) | −0.0003 (6) | 0.0020 (6) | 0.0011 (6) |
C3 | 0.0216 (7) | 0.0133 (7) | 0.0185 (7) | −0.0006 (6) | 0.0030 (6) | 0.0020 (6) |
C4 | 0.0222 (7) | 0.0134 (7) | 0.0182 (8) | 0.0025 (6) | 0.0027 (6) | 0.0016 (6) |
C5 | 0.0263 (8) | 0.0198 (8) | 0.0163 (7) | 0.0013 (7) | 0.0025 (6) | 0.0009 (6) |
C6 | 0.0298 (9) | 0.0195 (8) | 0.0186 (8) | −0.0001 (7) | 0.0078 (6) | −0.0016 (6) |
C7 | 0.0227 (7) | 0.0179 (8) | 0.0175 (8) | 0.0025 (7) | 0.0025 (6) | −0.0011 (6) |
C8 | 0.0209 (7) | 0.0184 (8) | 0.0173 (7) | 0.0019 (6) | 0.0024 (6) | −0.0030 (6) |
C9 | 0.0271 (8) | 0.0152 (7) | 0.0183 (8) | −0.0003 (7) | 0.0021 (6) | −0.0017 (6) |
C10 | 0.0232 (7) | 0.0220 (8) | 0.0189 (8) | −0.0055 (7) | 0.0039 (6) | −0.0049 (7) |
C11 | 0.0186 (7) | 0.0168 (7) | 0.0176 (7) | −0.0019 (6) | 0.0018 (6) | −0.0001 (6) |
C12 | 0.0169 (7) | 0.0152 (7) | 0.0163 (7) | −0.0005 (6) | 0.0019 (5) | 0.0017 (6) |
C13 | 0.0188 (7) | 0.0149 (7) | 0.0142 (7) | 0.0002 (6) | 0.0028 (5) | 0.0009 (6) |
C14 | 0.0183 (7) | 0.0140 (7) | 0.0175 (7) | 0.0005 (6) | 0.0030 (6) | 0.0006 (6) |
C15 | 0.0179 (7) | 0.0168 (8) | 0.0177 (7) | −0.0018 (6) | 0.0023 (6) | −0.0007 (6) |
C16 | 0.0262 (8) | 0.0149 (7) | 0.0175 (7) | 0.0014 (7) | −0.0004 (6) | −0.0014 (6) |
C17 | 0.0243 (8) | 0.0246 (9) | 0.0210 (8) | 0.0030 (7) | −0.0027 (6) | 0.0002 (7) |
C18 | 0.0253 (8) | 0.0261 (9) | 0.0215 (8) | −0.0014 (8) | 0.0080 (6) | −0.0003 (7) |
C19 | 0.0267 (8) | 0.0326 (10) | 0.0198 (8) | −0.0014 (8) | −0.0014 (7) | −0.0008 (8) |
C20 | 0.0194 (8) | 0.0263 (9) | 0.0291 (9) | −0.0020 (7) | 0.0043 (7) | −0.0047 (8) |
Geometric parameters (Å, º) top
O1—C16 | 1.436 (2) | C9—H9B | 0.9900 |
O1—H10 | 0.88 (3) | C10—C11 | 1.506 (2) |
O2—C15 | 1.442 (2) | C10—H10A | 0.9900 |
O2—H20 | 0.85 (3) | C10—H10B | 0.9900 |
O3—C7 | 1.449 (2) | C11—C12 | 1.332 (2) |
O3—C8 | 1.455 (2) | C11—H11 | 0.9500 |
O4—C13 | 1.446 (2) | C12—C20 | 1.503 (2) |
O4—H40 | 0.77 (3) | C12—C13 | 1.509 (2) |
C1—C2 | 1.348 (2) | C13—C14 | 1.554 (2) |
C1—C14 | 1.517 (2) | C13—H13 | 1.0000 |
C1—C15 | 1.522 (2) | C14—H14A | 0.9900 |
C2—C3 | 1.452 (2) | C14—H14B | 0.9900 |
C2—H2 | 0.9500 | C15—C17 | 1.527 (2) |
C3—C4 | 1.347 (2) | C15—C16 | 1.535 (2) |
C3—H3 | 0.9500 | C16—H16A | 0.9900 |
C4—C18 | 1.503 (2) | C16—H16B | 0.9900 |
C4—C5 | 1.507 (2) | C17—H17A | 0.9800 |
C5—C6 | 1.534 (3) | C17—H17B | 0.9800 |
C5—H5A | 0.9900 | C17—H17C | 0.9800 |
C5—H5B | 0.9900 | C18—H18A | 0.9800 |
C6—C7 | 1.506 (3) | C18—H18B | 0.9800 |
C6—H6A | 0.9900 | C18—H18C | 0.9800 |
C6—H6B | 0.9900 | C19—H19A | 0.9800 |
C7—C8 | 1.474 (2) | C19—H19B | 0.9800 |
C7—H7 | 1.0000 | C19—H19C | 0.9800 |
C8—C9 | 1.512 (2) | C20—H20A | 0.9800 |
C8—C19 | 1.514 (2) | C20—H20B | 0.9800 |
C9—C10 | 1.535 (2) | C20—H20C | 0.9800 |
C9—H9A | 0.9900 | | |
| | | |
C16—O1—H10 | 106.3 (18) | C12—C11—H11 | 116.6 |
C15—O2—H20 | 103.2 (19) | C10—C11—H11 | 116.6 |
C7—O3—C8 | 61.03 (11) | C11—C12—C20 | 123.48 (16) |
C13—O4—H40 | 109 (2) | C11—C12—C13 | 119.81 (14) |
C2—C1—C14 | 121.70 (15) | C20—C12—C13 | 116.71 (14) |
C2—C1—C15 | 120.87 (15) | O4—C13—C12 | 110.85 (13) |
C14—C1—C15 | 117.42 (13) | O4—C13—C14 | 107.00 (13) |
C1—C2—C3 | 124.93 (16) | C12—C13—C14 | 112.95 (13) |
C1—C2—H2 | 117.5 | O4—C13—H13 | 108.6 |
C3—C2—H2 | 117.5 | C12—C13—H13 | 108.6 |
C4—C3—C2 | 126.54 (15) | C14—C13—H13 | 108.6 |
C4—C3—H3 | 116.7 | C1—C14—C13 | 113.82 (13) |
C2—C3—H3 | 116.7 | C1—C14—H14A | 108.8 |
C3—C4—C18 | 123.81 (16) | C13—C14—H14A | 108.8 |
C3—C4—C5 | 120.45 (15) | C1—C14—H14B | 108.8 |
C18—C4—C5 | 115.58 (14) | C13—C14—H14B | 108.8 |
C4—C5—C6 | 116.15 (15) | H14A—C14—H14B | 107.7 |
C4—C5—H5A | 108.2 | O2—C15—C1 | 108.52 (13) |
C6—C5—H5A | 108.2 | O2—C15—C17 | 108.41 (14) |
C4—C5—H5B | 108.2 | C1—C15—C17 | 111.45 (14) |
C6—C5—H5B | 108.2 | O2—C15—C16 | 107.15 (14) |
H5A—C5—H5B | 107.4 | C1—C15—C16 | 108.70 (13) |
C7—C6—C5 | 112.72 (14) | C17—C15—C16 | 112.44 (14) |
C7—C6—H6A | 109.0 | O1—C16—C15 | 110.92 (14) |
C5—C6—H6A | 109.0 | O1—C16—H16A | 109.5 |
C7—C6—H6B | 109.0 | C15—C16—H16A | 109.5 |
C5—C6—H6B | 109.0 | O1—C16—H16B | 109.5 |
H6A—C6—H6B | 107.8 | C15—C16—H16B | 109.5 |
O3—C7—C8 | 59.69 (11) | H16A—C16—H16B | 108.0 |
O3—C7—C6 | 115.67 (14) | C15—C17—H17A | 109.5 |
C8—C7—C6 | 124.50 (16) | C15—C17—H17B | 109.5 |
O3—C7—H7 | 115.0 | H17A—C17—H17B | 109.5 |
C8—C7—H7 | 115.0 | C15—C17—H17C | 109.5 |
C6—C7—H7 | 115.0 | H17A—C17—H17C | 109.5 |
O3—C8—C7 | 59.28 (10) | H17B—C17—H17C | 109.5 |
O3—C8—C9 | 112.32 (14) | C4—C18—H18A | 109.5 |
C7—C8—C9 | 119.92 (15) | C4—C18—H18B | 109.5 |
O3—C8—C19 | 114.65 (14) | H18A—C18—H18B | 109.5 |
C7—C8—C19 | 122.09 (16) | C4—C18—H18C | 109.5 |
C9—C8—C19 | 114.81 (15) | H18A—C18—H18C | 109.5 |
C8—C9—C10 | 115.79 (15) | H18B—C18—H18C | 109.5 |
C8—C9—H9A | 108.3 | C8—C19—H19A | 109.5 |
C10—C9—H9A | 108.3 | C8—C19—H19B | 109.5 |
C8—C9—H9B | 108.3 | H19A—C19—H19B | 109.5 |
C10—C9—H9B | 108.3 | C8—C19—H19C | 109.5 |
H9A—C9—H9B | 107.4 | H19A—C19—H19C | 109.5 |
C11—C10—C9 | 113.10 (14) | H19B—C19—H19C | 109.5 |
C11—C10—H10A | 109.0 | C12—C20—H20A | 109.5 |
C9—C10—H10A | 109.0 | C12—C20—H20B | 109.5 |
C11—C10—H10B | 109.0 | H20A—C20—H20B | 109.5 |
C9—C10—H10B | 109.0 | C12—C20—H20C | 109.5 |
H10A—C10—H10B | 107.8 | H20A—C20—H20C | 109.5 |
C12—C11—C10 | 126.82 (15) | H20B—C20—H20C | 109.5 |
| | | |
C14—C1—C2—C3 | 5.8 (3) | C8—C9—C10—C11 | −79.6 (2) |
C15—C1—C2—C3 | −174.27 (16) | C9—C10—C11—C12 | 177.26 (17) |
C1—C2—C3—C4 | 179.55 (18) | C10—C11—C12—C20 | −2.4 (3) |
C2—C3—C4—C18 | 5.3 (3) | C10—C11—C12—C13 | 177.84 (16) |
C2—C3—C4—C5 | −169.72 (16) | C11—C12—C13—O4 | −124.92 (17) |
C3—C4—C5—C6 | −114.76 (18) | C20—C12—C13—O4 | 55.3 (2) |
C18—C4—C5—C6 | 69.8 (2) | C11—C12—C13—C14 | 115.01 (17) |
C4—C5—C6—C7 | 70.2 (2) | C20—C12—C13—C14 | −64.79 (19) |
C8—O3—C7—C6 | −116.54 (17) | C2—C1—C14—C13 | 74.7 (2) |
C5—C6—C7—O3 | 159.82 (14) | C15—C1—C14—C13 | −105.30 (16) |
C5—C6—C7—C8 | 90.3 (2) | O4—C13—C14—C1 | 108.29 (15) |
C7—O3—C8—C9 | −112.53 (16) | C12—C13—C14—C1 | −129.46 (14) |
C7—O3—C8—C19 | 114.04 (18) | C2—C1—C15—O2 | 3.3 (2) |
C6—C7—C8—O3 | 101.96 (17) | C14—C1—C15—O2 | −176.73 (14) |
O3—C7—C8—C9 | 99.66 (16) | C2—C1—C15—C17 | −116.01 (17) |
C6—C7—C8—C9 | −158.39 (16) | C14—C1—C15—C17 | 63.96 (18) |
O3—C7—C8—C19 | −101.55 (17) | C2—C1—C15—C16 | 119.52 (17) |
C6—C7—C8—C19 | 0.4 (3) | C14—C1—C15—C16 | −60.51 (18) |
O3—C8—C9—C10 | 155.00 (14) | O2—C15—C16—O1 | −56.53 (17) |
C7—C8—C9—C10 | 88.63 (19) | C1—C15—C16—O1 | −173.63 (13) |
C19—C8—C9—C10 | −71.6 (2) | C17—C15—C16—O1 | 62.49 (19) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H10···O4i | 0.88 (3) | 1.92 (3) | 2.772 (2) | 162 (2) |
O2—H20···O1 | 0.85 (3) | 2.35 (3) | 2.788 (2) | 113 (2) |
O4—H40···O1ii | 0.77 (3) | 2.08 (3) | 2.849 (2) | 176 (3) |
Symmetry codes: (i) −x, y+1/2, −z+1; (ii) x, y−1, z. |
Experimental details
Crystal data |
Chemical formula | C20H32O4 |
Mr | 336.46 |
Crystal system, space group | Monoclinic, P21 |
Temperature (K) | 100 |
a, b, c (Å) | 5.858 (2), 8.232 (2), 19.241 (6) |
β (°) | 91.315 (10) |
V (Å3) | 927.6 (5) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.08 |
Crystal size (mm) | 0.32 × 0.22 × 0.05 |
|
Data collection |
Diffractometer | Nonius KappaCCD area-detector (with Oxford Cryostream cooler) diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 8313, 2875, 2647 |
Rint | 0.021 |
(sin θ/λ)max (Å−1) | 0.703 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.036, 0.089, 1.04 |
No. of reflections | 2875 |
No. of parameters | 230 |
No. of restraints | 1 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.22, −0.21 |
Selected geometric parameters (Å, º) topO1—C16 | 1.436 (2) | C1—C2 | 1.348 (2) |
O2—C15 | 1.442 (2) | C2—C3 | 1.452 (2) |
O3—C7 | 1.449 (2) | C3—C4 | 1.347 (2) |
O3—C8 | 1.455 (2) | C7—C8 | 1.474 (2) |
O4—C13 | 1.446 (2) | C11—C12 | 1.332 (2) |
| | | |
C7—O3—C8 | 61.03 (11) | | |
| | | |
C14—C1—C2—C3 | 5.8 (3) | C8—C9—C10—C11 | −79.6 (2) |
C1—C2—C3—C4 | 179.55 (18) | C10—C11—C12—C13 | 177.84 (16) |
C2—C3—C4—C5 | −169.72 (16) | C11—C12—C13—C14 | 115.01 (17) |
C3—C4—C5—C6 | −114.76 (18) | C2—C1—C14—C13 | 74.7 (2) |
C4—C5—C6—C7 | 70.2 (2) | C12—C13—C14—C1 | −129.46 (14) |
C5—C6—C7—C8 | 90.3 (2) | C2—C1—C15—O2 | 3.3 (2) |
C6—C7—C8—C9 | −158.39 (16) | O2—C15—C16—O1 | −56.53 (17) |
C7—C8—C9—C10 | 88.63 (19) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H10···O4i | 0.88 (3) | 1.92 (3) | 2.772 (2) | 162 (2) |
O2—H20···O1 | 0.85 (3) | 2.35 (3) | 2.788 (2) | 113 (2) |
O4—H40···O1ii | 0.77 (3) | 2.08 (3) | 2.849 (2) | 176 (3) |
Symmetry codes: (i) −x, y+1/2, −z+1; (ii) x, y−1, z. |
Cembranoids, diterpenoids with a 14-membered ring, have been isolated from terrestrial and marine sources (Wahlberg & Eklund 1992). Some cembranoids from soft corals have a remarkably wide spectrum of biological activities, including inhibitory activity against tumor promoters (Suganuma et al., 1996; Tius, 1988). In order to obtain new compounds with chemopreventive activity, the marine natural product sarcophine, isolated from the soft coral Sarcophyton glaucum, was subjected to series of chemical modifications (Katsuyama et al., 2002). One of the products obtained as a result of such modifications was the title analog, (I). This compound displayed significant inhibitory activity against the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) in an Epstein-Barr virus early-antigen activation assay (Katsuyama et al., 2002). We have undertaken the crystal structure analysis of (I) to confirm the structure and to establish the configuration of the stereogenic centers at atoms C13 and C15. The relative configuration of (I) compared with sarcophine allowed determination of the configuration of these stereogenic centers on atoms C13 and C15 as R, R. This is the first case of the determination of the configuration of the stereogenic center in a propane-1,2-diol side chain attached to a Csp2 atom, which is otherwise difficult to elucidate by spectroscopic methods. \sch
The configuration and conformation of cembranoid (I) are illustrated in Fig. 1. The conformation of the 14-membered ring, described by the torsion angles in Table 1, differs substantially from that of sarcophine (Bernstein et al., 1974; El Sayed et al., 1998). Sarcophine lacks the OH group at C13 and has a γ-lactone at C1—C2 (i.e. a C1═C15 double bond), rather than the propane-1,2-diol substituent here. The differences are small in the portion of the ring carrying the epoxide, with the three endocyclic torsion angles in the C6—C7—C8—C9—C10—C11 sequence exhibiting a mean deviation of only 9.1°. However, in sarcophine, methyl group C18 is β-oriented (up in Fig. 1), while in (I), C18 points outward and the H atom at C3 points into the 14-membered ring. Likewise, the torsion angle about C10—C11, which determines the orientation of methyl group C20, is 177.26 (17)° in (I) and −95.7 (4)° in sarcophine. Thus, the 14-membered ring of (I) lies roughly in a plane, with an r.m.s. deviation of 0.37 Å and a maximum deviation of only 0.758 (2) Å for atom C5. The ring in sarcophine is slightly less planar, with an r.m.s. deviation of 0.49 Å and a maximum deviation of 0.825 (4) Å for atom C13.
The hydrogen bonding in (I) is illustrated in Fig. 2. Hydrogen bonds donated by atoms O1 and O4 link the molecules into double chains, which extend in the 21 direction. The chain-linking hydrogen-bonding unit contains 12 atoms, and involves three molecules and three intermolecular hydrogen bonds. The two OH groups of the propane-1,2-diol moiety form a weak intramolecular hydrogen bond, with atom O1 as acceptor. Although the O···O distance is not long, the five-membered ring imposes poor geometry on the donor and acceptor. This type of weak intramolecular hydrogen bond in propanediol substituents is somewhat unusual. They appear to be present only when stronger intermolecular bonding possibilites are unfavorable (André et al., 1997), and are usually a component in bi- or trifurcated hydrogen bonds, where the other components are intermolecular (Kopf et al., 1990; Jeffrey & Maluszynska, 1990; Jeffrey, 1997). The unusual weak intramolecular interaction in (I), unsupported by an intermolecular component, is similar to that in galactonic acid hydrazide (André et al., 1997), in which the O···O distance is 2.748 (3) Å and the angle about H is 118 (4)°. Brock (2002) has recently examined crystal packing in vicinal diols, and has also noted the rarity of this type of intramolecular interaction. Yeh et al. (1994) and Dahlqvist et al. (1998) have calculated that, in the absence of intermolecular hydrogen bonding, the intramolecular hydrogen bond in vicinal diols causes the gauche conformer to be ca 2 kcal mol−1 (1 kcal mol−1 = 4.184 kJ mol−1) lower in energy than the anti conformer.
A search of the Cambridge Structural Database (CSD; Allen, 2002) for the propane-1,2-diol side chain with atoms C1, C2 and C14 produced no hits. The most similar fragment in the CSD has the sp2 atom C1 attached to two other Csp2 atoms in a phenyl ring, rather than to the sp2 C2 and the sp3 C14 atoms in (I). That fragment is found in only two compounds, two isomers of endo-2-{o-[(bicyclo[2.2.1]hept-5-en-2-yl)sulfinyl]phenyl}propane-1,2-diol, refcodes WOFXEU and WOFXIY (Abe et al., 1999), both of which are racemic. The conformations of the propane-1,2-diol side chain in WOFXEU and WOFXIY differ somewhat from that of (I), as they have C2—C1—C15—O2 torsion angles of −30.4 (4)° for WOFXEU and −38.4 (4)° for WOFXIY, while in (I), it is nearly eclipsed, at 3.3 (2)°. This torsion angle appears to be controlled by the steric demands of the H atoms on atoms C14, C16 and C17. In (I), the nearest such distance is between H14B and H16B, at 2.08 Å. The O2—C15—C16—O1 torsion angle magnitude is 14.7 (4)° larger in WOFXEU and 11.1 (4)° larger in WOFXIY than the gauche −56.53 (17)° in (I), probably as a result of the fact that, in both these compounds, atom O2 forms a normal intermolecular hydrogen bond rather than a weak intramolecular hydrogen bond. Thus, in (I), the conformation of the propane-1,2-diol side chain appears to result from two factors, the intramolecular H···H interactions and the intramolecular hydrogen bond.