Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270113011852/gz3232sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270113011852/gz3232Isup2.hkl | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270113011852/gz3232IIsup3.hkl | |
Chemical Markup Language (CML) file https://doi.org/10.1107/S0108270113011852/gz3232Isup4.cml | |
Chemical Markup Language (CML) file https://doi.org/10.1107/S0108270113011852/gz3232IIsup5.cml |
CCDC references: 950444; 950445
Crystals were obtained as long needles for both compounds. For (II), they were very difficult to handle because they are easily bent and split along the longest dimension. No attempt was made to cut the specimen used for data collection. By mounting the crystals along the ϕ spindle axis, an approximately constant crystal volume was exposed to X-ray radiation upon ϕ and ω rotation during data collection, thus minimizing absorption effects.
The coordinates were refined for the hydroxy H atom. Other H atoms were positioned with idealized geometry and fixed C—H distances for CH3, CH2, CH (methine) and CH (sp2) groups of 0.98, 0.99, 1.00 and 0.95 Å, respectively, and with Uiso(H) = 1.5Ueq(C,O) for hydroxy and methyl groups or 1.2Ueq(C) otherwise. In the absence of significant anomalous scattering effects, 1020 and 1631 Friedel pairs were merged for (I) and (II), respectively.
For both compounds, data collection: APEX2 (Bruker, 2007); cell refinement: SAINT-Plus (Bruker, 2007); data reduction: SAINT-Plus (Bruker, 2007); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).
C9H20O2 | F(000) = 360 |
Mr = 160.25 | Dx = 1.045 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 4198 reflections |
a = 5.964 (2) Å | θ = 2.3–28.4° |
b = 9.777 (4) Å | µ = 0.07 mm−1 |
c = 17.469 (6) Å | T = 105 K |
V = 1018.6 (6) Å3 | Needle, colourless |
Z = 4 | 1.85 × 0.14 × 0.13 mm |
Bruker APEXII CCD area-detector diffractometer | 1487 independent reflections |
Radiation source: fine-focus sealed tube | 1387 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.026 |
Detector resolution: 8.3 pixels mm-1 | θmax = 28.5°, θmin = 2.3° |
Sets of exposures each taken over 0.5° ω rotation scans | h = −7→7 |
Absorption correction: multi-scan (SADABS; Bruker, 2007) | k = −12→12 |
Tmin = 0.851, Tmax = 0.990 | l = −23→23 |
9215 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)] = 0.028 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.074 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.04 | w = 1/[σ2(Fo2) + (0.0462P)2 + 0.0839P] where P = (Fo2 + 2Fc2)/3 |
1487 reflections | (Δ/σ)max < 0.001 |
109 parameters | Δρmax = 0.23 e Å−3 |
0 restraints | Δρmin = −0.14 e Å−3 |
C9H20O2 | V = 1018.6 (6) Å3 |
Mr = 160.25 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 5.964 (2) Å | µ = 0.07 mm−1 |
b = 9.777 (4) Å | T = 105 K |
c = 17.469 (6) Å | 1.85 × 0.14 × 0.13 mm |
Bruker APEXII CCD area-detector diffractometer | 1487 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2007) | 1387 reflections with I > 2σ(I) |
Tmin = 0.851, Tmax = 0.990 | Rint = 0.026 |
9215 measured reflections |
R[F2 > 2σ(F2)] = 0.028 | 0 restraints |
wR(F2) = 0.074 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.04 | Δρmax = 0.23 e Å−3 |
1487 reflections | Δρmin = −0.14 e Å−3 |
109 parameters |
Experimental. Crystal mounted along the ϕ spindle axis |
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 | 0.94157 (16) | 0.67184 (9) | 0.03862 (5) | 0.0216 (2) | |
H1 | 1.073 (3) | 0.6534 (17) | 0.0531 (9) | 0.032* | |
O2 | 0.37216 (14) | 0.62368 (9) | 0.06085 (5) | 0.0220 (2) | |
H2 | 0.424 (3) | 0.6844 (17) | 0.0331 (9) | 0.033* | |
C1 | 0.8331 (2) | 0.54804 (12) | 0.01621 (6) | 0.0207 (2) | |
H11 | 0.9474 | 0.4827 | −0.0026 | 0.025* | |
H12 | 0.7291 | 0.5677 | −0.0266 | 0.025* | |
C2 | 0.7025 (2) | 0.48177 (11) | 0.08139 (6) | 0.0180 (2) | |
H21 | 0.8121 | 0.4548 | 0.1220 | 0.022* | |
C3 | 0.53376 (19) | 0.58161 (11) | 0.11711 (6) | 0.0170 (2) | |
H31 | 0.6163 | 0.6641 | 0.1359 | 0.020* | |
C4 | 0.4048 (2) | 0.51893 (11) | 0.18363 (6) | 0.0199 (2) | |
H41 | 0.5134 | 0.4788 | 0.2201 | 0.024* | |
H42 | 0.3105 | 0.4435 | 0.1638 | 0.024* | |
C5 | 0.2547 (2) | 0.61961 (11) | 0.22686 (6) | 0.0203 (2) | |
H51 | 0.1647 | 0.6720 | 0.1894 | 0.024* | |
H52 | 0.3507 | 0.6854 | 0.2549 | 0.024* | |
C6 | 0.0959 (2) | 0.55018 (12) | 0.28385 (6) | 0.0213 (2) | |
H61 | 0.0109 | 0.4780 | 0.2555 | 0.026* | |
C7 | −0.0741 (2) | 0.65233 (13) | 0.31559 (7) | 0.0280 (3) | |
H71 | −0.1791 | 0.6047 | 0.3495 | 0.042* | |
H72 | −0.1569 | 0.6942 | 0.2732 | 0.042* | |
H73 | 0.0047 | 0.7236 | 0.3444 | 0.042* | |
C8 | 0.5905 (2) | 0.35146 (12) | 0.05142 (7) | 0.0269 (3) | |
H81 | 0.7022 | 0.2950 | 0.0250 | 0.040* | |
H82 | 0.4706 | 0.3760 | 0.0156 | 0.040* | |
H83 | 0.5272 | 0.3000 | 0.0944 | 0.040* | |
C9 | 0.2233 (3) | 0.48031 (14) | 0.34869 (7) | 0.0315 (3) | |
H91 | 0.1168 | 0.4335 | 0.3824 | 0.047* | |
H92 | 0.3064 | 0.5490 | 0.3781 | 0.047* | |
H93 | 0.3285 | 0.4135 | 0.3272 | 0.047* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0142 (4) | 0.0238 (4) | 0.0268 (4) | −0.0007 (4) | −0.0012 (3) | 0.0068 (3) |
O2 | 0.0143 (4) | 0.0267 (4) | 0.0249 (4) | 0.0012 (4) | −0.0002 (3) | 0.0107 (3) |
C1 | 0.0180 (6) | 0.0235 (5) | 0.0205 (5) | 0.0002 (5) | 0.0017 (4) | 0.0010 (4) |
C2 | 0.0173 (5) | 0.0173 (5) | 0.0196 (5) | 0.0009 (5) | 0.0004 (4) | 0.0016 (4) |
C3 | 0.0154 (5) | 0.0171 (5) | 0.0184 (5) | −0.0002 (4) | 0.0002 (4) | 0.0020 (4) |
C4 | 0.0210 (6) | 0.0184 (5) | 0.0201 (5) | 0.0009 (5) | 0.0034 (4) | 0.0025 (4) |
C5 | 0.0221 (6) | 0.0187 (5) | 0.0203 (5) | 0.0011 (5) | 0.0039 (4) | 0.0014 (4) |
C6 | 0.0224 (6) | 0.0216 (5) | 0.0201 (5) | −0.0020 (5) | 0.0045 (5) | −0.0017 (4) |
C7 | 0.0268 (7) | 0.0316 (6) | 0.0257 (5) | 0.0043 (6) | 0.0063 (5) | −0.0015 (5) |
C8 | 0.0299 (7) | 0.0196 (5) | 0.0312 (6) | −0.0022 (5) | 0.0059 (6) | −0.0045 (5) |
C9 | 0.0400 (8) | 0.0301 (6) | 0.0243 (5) | 0.0086 (6) | 0.0079 (6) | 0.0074 (5) |
O1—C1 | 1.4271 (15) | C5—C6 | 1.5327 (16) |
O1—H1 | 0.844 (19) | C5—H51 | 0.9900 |
O2—C3 | 1.4366 (14) | C5—H52 | 0.9900 |
O2—H2 | 0.827 (17) | C6—C9 | 1.5251 (18) |
C1—C2 | 1.5243 (15) | C6—C7 | 1.5274 (17) |
C1—H11 | 0.9900 | C6—H61 | 1.0000 |
C1—H12 | 0.9900 | C7—H71 | 0.9800 |
C2—C8 | 1.5307 (16) | C7—H72 | 0.9800 |
C2—C3 | 1.5345 (15) | C7—H73 | 0.9800 |
C2—H21 | 1.0000 | C8—H81 | 0.9800 |
C3—C4 | 1.5224 (15) | C8—H82 | 0.9800 |
C3—H31 | 1.0000 | C8—H83 | 0.9800 |
C4—C5 | 1.5295 (15) | C9—H91 | 0.9800 |
C4—H41 | 0.9900 | C9—H92 | 0.9800 |
C4—H42 | 0.9900 | C9—H93 | 0.9800 |
C1—O1—H1 | 108.8 (12) | C6—C5—H51 | 108.9 |
C3—O2—H2 | 110.7 (12) | C4—C5—H52 | 108.9 |
O1—C1—C2 | 112.78 (9) | C6—C5—H52 | 108.9 |
O1—C1—H11 | 109.0 | H51—C5—H52 | 107.7 |
C2—C1—H11 | 109.0 | C9—C6—C7 | 110.72 (10) |
O1—C1—H12 | 109.0 | C9—C6—C5 | 111.91 (11) |
C2—C1—H12 | 109.0 | C7—C6—C5 | 110.88 (10) |
H11—C1—H12 | 107.8 | C9—C6—H61 | 107.7 |
C1—C2—C8 | 108.73 (9) | C7—C6—H61 | 107.7 |
C1—C2—C3 | 111.63 (9) | C5—C6—H61 | 107.7 |
C8—C2—C3 | 112.49 (10) | C6—C7—H71 | 109.5 |
C1—C2—H21 | 107.9 | C6—C7—H72 | 109.5 |
C8—C2—H21 | 107.9 | H71—C7—H72 | 109.5 |
C3—C2—H21 | 107.9 | C6—C7—H73 | 109.5 |
O2—C3—C4 | 107.36 (9) | H71—C7—H73 | 109.5 |
O2—C3—C2 | 110.11 (9) | H72—C7—H73 | 109.5 |
C4—C3—C2 | 112.69 (9) | C2—C8—H81 | 109.5 |
O2—C3—H31 | 108.9 | C2—C8—H82 | 109.5 |
C4—C3—H31 | 108.9 | H81—C8—H82 | 109.5 |
C2—C3—H31 | 108.9 | C2—C8—H83 | 109.5 |
C3—C4—C5 | 114.42 (9) | H81—C8—H83 | 109.5 |
C3—C4—H41 | 108.7 | H82—C8—H83 | 109.5 |
C5—C4—H41 | 108.7 | C6—C9—H91 | 109.5 |
C3—C4—H42 | 108.7 | C6—C9—H92 | 109.5 |
C5—C4—H42 | 108.7 | H91—C9—H92 | 109.5 |
H41—C4—H42 | 107.6 | C6—C9—H93 | 109.5 |
C4—C5—C6 | 113.40 (9) | H91—C9—H93 | 109.5 |
C4—C5—H51 | 108.9 | H92—C9—H93 | 109.5 |
O1—C1—C2—C3 | 54.59 (12) | C4—C5—C6—C7 | −170.92 (10) |
O1—C1—C2—C8 | 179.27 (10) | C4—C5—C6—C9 | 64.91 (13) |
C1—C2—C3—C4 | −178.67 (10) | C8—C2—C3—O2 | −61.06 (11) |
C1—C2—C3—O2 | 61.50 (12) | C8—C2—C3—C4 | 58.78 (12) |
C2—C3—C4—C5 | 173.22 (10) | O2—C3—C4—C5 | −65.37 (12) |
C3—C4—C5—C6 | 169.71 (10) |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1···O2i | 0.844 (19) | 1.812 (19) | 2.6395 (16) | 166.4 (16) |
O2—H2···O1ii | 0.827 (17) | 1.886 (16) | 2.6809 (14) | 160.9 (17) |
Symmetry codes: (i) x+1, y, z; (ii) x−1/2, −y+3/2, −z. |
C19H27NO4 | F(000) = 360 |
Mr = 333.42 | Dx = 1.143 Mg m−3 |
Monoclinic, P21 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2yb | Cell parameters from 2875 reflections |
a = 11.459 (3) Å | θ = 2.8–24.7° |
b = 5.7077 (13) Å | µ = 0.08 mm−1 |
c = 15.247 (3) Å | T = 105 K |
β = 103.827 (3)° | Flat needle, colourless |
V = 968.4 (4) Å3 | 1.54 × 0.13 × 0.04 mm |
Z = 2 |
Bruker APEXII CCD area-detector diffractometer | 2047 independent reflections |
Radiation source: fine-focus sealed tube | 1823 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.031 |
Detector resolution: 8.3 pixels mm-1 | θmax = 25.8°, θmin = 1.8° |
Sets of exposures each taken over 0.5° ω rotation scans | h = −14→12 |
Absorption correction: multi-scan (SADABS; Bruker, 2007) | k = −6→6 |
Tmin = 0.837, Tmax = 0.997 | l = −18→18 |
7434 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)] = 0.034 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.087 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.04 | w = 1/[σ2(Fo2) + (0.0465P)2 + 0.1669P] where P = (Fo2 + 2Fc2)/3 |
2047 reflections | (Δ/σ)max < 0.001 |
223 parameters | Δρmax = 0.13 e Å−3 |
1 restraint | Δρmin = −0.25 e Å−3 |
C19H27NO4 | V = 968.4 (4) Å3 |
Mr = 333.42 | Z = 2 |
Monoclinic, P21 | Mo Kα radiation |
a = 11.459 (3) Å | µ = 0.08 mm−1 |
b = 5.7077 (13) Å | T = 105 K |
c = 15.247 (3) Å | 1.54 × 0.13 × 0.04 mm |
β = 103.827 (3)° |
Bruker APEXII CCD area-detector diffractometer | 2047 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2007) | 1823 reflections with I > 2σ(I) |
Tmin = 0.837, Tmax = 0.997 | Rint = 0.031 |
7434 measured reflections |
R[F2 > 2σ(F2)] = 0.034 | 1 restraint |
wR(F2) = 0.087 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.04 | Δρmax = 0.13 e Å−3 |
2047 reflections | Δρmin = −0.25 e Å−3 |
223 parameters |
Experimental. Very difficult crystals, easily bent and split along the needle. Crystal mounted along the ϕ spindle axis |
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 | 0.87786 (12) | 0.4551 (3) | 0.44852 (9) | 0.0254 (4) | |
O2 | 0.86511 (14) | −0.0283 (3) | 0.54877 (9) | 0.0251 (3) | |
H2 | 0.940 (2) | −0.026 (6) | 0.5564 (16) | 0.038* | |
O3 | 0.49699 (12) | 0.5192 (3) | 0.46446 (9) | 0.0238 (3) | |
O4 | 0.61832 (12) | 0.4959 (3) | 0.60301 (9) | 0.0244 (3) | |
N1 | 0.69270 (14) | 0.4801 (3) | 0.47262 (10) | 0.0218 (4) | |
C1 | 0.81682 (18) | 0.4440 (4) | 0.50355 (14) | 0.0217 (5) | |
C2 | 0.86596 (19) | 0.3801 (4) | 0.60155 (15) | 0.0216 (5) | |
H21 | 0.8255 | 0.4807 | 0.6392 | 0.026* | |
C3 | 0.8321 (2) | 0.1211 (4) | 0.61377 (14) | 0.0234 (5) | |
H31 | 0.7425 | 0.1150 | 0.6022 | 0.028* | |
C4 | 0.8814 (2) | 0.0300 (4) | 0.70929 (13) | 0.0279 (5) | |
H41 | 0.9702 | 0.0251 | 0.7215 | 0.033* | |
H42 | 0.8528 | −0.1326 | 0.7128 | 0.033* | |
C5 | 0.8457 (2) | 0.1757 (4) | 0.78304 (15) | 0.0301 (5) | |
H51 | 0.8935 | 0.3221 | 0.7919 | 0.036* | |
H52 | 0.7600 | 0.2196 | 0.7624 | 0.036* | |
C6 | 0.8646 (3) | 0.0488 (5) | 0.87344 (16) | 0.0430 (7) | |
H61 | 0.9456 | −0.0270 | 0.8874 | 0.052* | |
C7 | 0.8588 (3) | 0.2198 (6) | 0.94957 (17) | 0.0536 (8) | |
H71 | 0.8741 | 0.1350 | 1.0071 | 0.080* | |
H72 | 0.7789 | 0.2917 | 0.9376 | 0.080* | |
H73 | 0.9197 | 0.3421 | 0.9528 | 0.080* | |
C8 | 1.00082 (18) | 0.4275 (4) | 0.62960 (14) | 0.0264 (5) | |
H81 | 1.0292 | 0.4088 | 0.6951 | 0.040* | |
H82 | 1.0169 | 0.5878 | 0.6126 | 0.040* | |
H83 | 1.0430 | 0.3164 | 0.5990 | 0.040* | |
C9 | 0.7694 (4) | −0.1403 (7) | 0.8686 (2) | 0.0775 (12) | |
H91 | 0.7711 | −0.2474 | 0.8187 | 0.116* | |
H92 | 0.6900 | −0.0672 | 0.8585 | 0.116* | |
H93 | 0.7861 | −0.2279 | 0.9255 | 0.116* | |
C10 | 0.60599 (17) | 0.4963 (4) | 0.52244 (13) | 0.0216 (4) | |
C11 | 0.64050 (18) | 0.5352 (4) | 0.37677 (13) | 0.0219 (5) | |
H111 | 0.6718 | 0.4261 | 0.3364 | 0.026* | |
C12 | 0.50794 (18) | 0.4867 (5) | 0.37205 (13) | 0.0251 (5) | |
H121 | 0.4557 | 0.5980 | 0.3306 | 0.030* | |
H122 | 0.4860 | 0.3249 | 0.3511 | 0.030* | |
C13 | 0.6643 (2) | 0.7912 (4) | 0.35562 (14) | 0.0235 (5) | |
H131 | 0.6164 | 0.8959 | 0.3851 | 0.028* | |
H132 | 0.7504 | 0.8280 | 0.3802 | 0.028* | |
C14 | 0.6314 (2) | 0.8345 (4) | 0.25443 (14) | 0.0253 (5) | |
C15 | 0.7081 (2) | 0.7539 (5) | 0.20272 (16) | 0.0370 (6) | |
H151 | 0.7795 | 0.6723 | 0.2308 | 0.044* | |
C16 | 0.6803 (3) | 0.7930 (6) | 0.10996 (17) | 0.0468 (7) | |
H161 | 0.7327 | 0.7364 | 0.0749 | 0.056* | |
C17 | 0.5775 (3) | 0.9129 (5) | 0.06833 (16) | 0.0430 (7) | |
H171 | 0.5598 | 0.9424 | 0.0052 | 0.052* | |
C18 | 0.5012 (2) | 0.9891 (6) | 0.11928 (15) | 0.0407 (6) | |
H181 | 0.4294 | 1.0692 | 0.0909 | 0.049* | |
C19 | 0.5278 (2) | 0.9502 (4) | 0.21213 (15) | 0.0313 (5) | |
H191 | 0.4741 | 1.0039 | 0.2465 | 0.038* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0262 (8) | 0.0237 (9) | 0.0289 (8) | 0.0018 (7) | 0.0116 (6) | 0.0007 (7) |
O2 | 0.0254 (7) | 0.0202 (8) | 0.0308 (8) | 0.0005 (7) | 0.0087 (6) | −0.0044 (7) |
O3 | 0.0210 (7) | 0.0216 (8) | 0.0295 (7) | 0.0019 (7) | 0.0075 (6) | 0.0017 (7) |
O4 | 0.0264 (7) | 0.0214 (8) | 0.0277 (7) | 0.0030 (7) | 0.0111 (6) | 0.0012 (7) |
N1 | 0.0215 (8) | 0.0209 (9) | 0.0238 (8) | 0.0027 (8) | 0.0074 (7) | 0.0025 (9) |
C1 | 0.0229 (11) | 0.0135 (11) | 0.0289 (11) | 0.0000 (8) | 0.0068 (9) | 0.0002 (9) |
C2 | 0.0225 (11) | 0.0170 (11) | 0.0263 (11) | 0.0011 (9) | 0.0075 (9) | 0.0007 (9) |
C3 | 0.0245 (11) | 0.0177 (11) | 0.0294 (12) | 0.0003 (9) | 0.0093 (9) | −0.0019 (9) |
C4 | 0.0333 (12) | 0.0211 (12) | 0.0301 (11) | 0.0016 (10) | 0.0092 (9) | 0.0037 (10) |
C5 | 0.0344 (13) | 0.0246 (12) | 0.0315 (12) | −0.0003 (10) | 0.0086 (10) | 0.0003 (10) |
C6 | 0.0579 (17) | 0.0411 (17) | 0.0329 (13) | 0.0100 (14) | 0.0166 (12) | 0.0088 (12) |
C7 | 0.076 (2) | 0.054 (2) | 0.0322 (14) | −0.0045 (17) | 0.0153 (14) | −0.0022 (14) |
C8 | 0.0263 (12) | 0.0227 (13) | 0.0303 (11) | −0.0003 (9) | 0.0070 (9) | 0.0007 (10) |
C9 | 0.148 (4) | 0.0402 (19) | 0.063 (2) | −0.022 (2) | 0.062 (2) | −0.0025 (17) |
C10 | 0.0246 (10) | 0.0119 (10) | 0.0303 (11) | 0.0010 (10) | 0.0103 (8) | 0.0015 (10) |
C11 | 0.0244 (10) | 0.0191 (11) | 0.0228 (10) | 0.0011 (9) | 0.0066 (8) | −0.0001 (9) |
C12 | 0.0280 (11) | 0.0219 (11) | 0.0257 (10) | −0.0026 (10) | 0.0067 (8) | −0.0007 (10) |
C13 | 0.0231 (11) | 0.0216 (12) | 0.0254 (11) | −0.0023 (9) | 0.0051 (9) | 0.0002 (9) |
C14 | 0.0293 (12) | 0.0208 (12) | 0.0257 (11) | −0.0046 (9) | 0.0065 (10) | 0.0014 (9) |
C15 | 0.0366 (14) | 0.0433 (16) | 0.0329 (13) | 0.0022 (12) | 0.0118 (11) | 0.0027 (12) |
C16 | 0.0570 (18) | 0.0523 (19) | 0.0367 (14) | 0.0024 (15) | 0.0225 (13) | 0.0000 (14) |
C17 | 0.0638 (18) | 0.0391 (17) | 0.0260 (12) | 0.0017 (14) | 0.0105 (12) | 0.0038 (11) |
C18 | 0.0538 (15) | 0.0330 (14) | 0.0312 (11) | 0.0110 (14) | 0.0018 (11) | 0.0055 (12) |
C19 | 0.0406 (13) | 0.0248 (13) | 0.0289 (11) | 0.0034 (11) | 0.0090 (10) | 0.0010 (10) |
O1—C1 | 1.216 (2) | C7—H73 | 0.9800 |
O2—C3 | 1.425 (3) | C8—H81 | 0.9800 |
O2—H2 | 0.84 (3) | C8—H82 | 0.9800 |
O3—C10 | 1.353 (2) | C8—H83 | 0.9800 |
O3—C12 | 1.456 (2) | C9—H91 | 0.9800 |
O4—C10 | 1.203 (2) | C9—H92 | 0.9800 |
N1—C10 | 1.390 (3) | C9—H93 | 0.9800 |
N1—C1 | 1.403 (3) | C11—C12 | 1.529 (3) |
N1—C11 | 1.475 (2) | C11—C13 | 1.534 (3) |
C1—C2 | 1.510 (3) | C11—H111 | 1.0000 |
C2—C8 | 1.526 (3) | C12—H121 | 0.9900 |
C2—C3 | 1.551 (3) | C12—H122 | 0.9900 |
C2—H21 | 1.0000 | C13—C14 | 1.518 (3) |
C3—C4 | 1.522 (3) | C13—H131 | 0.9900 |
C3—H31 | 1.0000 | C13—H132 | 0.9900 |
C4—C5 | 1.531 (3) | C14—C19 | 1.377 (3) |
C4—H41 | 0.9900 | C14—C15 | 1.392 (3) |
C4—H42 | 0.9900 | C15—C16 | 1.391 (4) |
C5—C6 | 1.526 (3) | C15—H151 | 0.9500 |
C5—H51 | 0.9900 | C16—C17 | 1.379 (4) |
C5—H52 | 0.9900 | C16—H161 | 0.9500 |
C6—C9 | 1.523 (5) | C17—C18 | 1.372 (4) |
C6—C7 | 1.530 (4) | C17—H171 | 0.9500 |
C6—H61 | 1.0000 | C18—C19 | 1.393 (3) |
C7—H71 | 0.9800 | C18—H181 | 0.9500 |
C7—H72 | 0.9800 | C19—H191 | 0.9500 |
C3—O2—H2 | 109.1 (19) | H81—C8—H83 | 109.5 |
C10—O3—C12 | 109.90 (15) | H82—C8—H83 | 109.5 |
C10—N1—C1 | 128.74 (16) | C6—C9—H91 | 109.5 |
C10—N1—C11 | 110.70 (16) | C6—C9—H92 | 109.5 |
C1—N1—C11 | 120.20 (15) | H91—C9—H92 | 109.5 |
O1—C1—N1 | 117.70 (18) | C6—C9—H93 | 109.5 |
O1—C1—C2 | 123.75 (19) | H91—C9—H93 | 109.5 |
N1—C1—C2 | 118.45 (17) | H92—C9—H93 | 109.5 |
C1—C2—C8 | 110.35 (17) | O4—C10—O3 | 122.17 (17) |
C1—C2—C3 | 107.70 (18) | O4—C10—N1 | 129.27 (18) |
C8—C2—C3 | 113.63 (18) | O3—C10—N1 | 108.55 (16) |
C1—C2—H21 | 108.3 | N1—C11—C12 | 99.85 (15) |
C8—C2—H21 | 108.3 | N1—C11—C13 | 111.18 (18) |
C3—C2—H21 | 108.3 | C12—C11—C13 | 112.78 (19) |
O2—C3—C4 | 111.18 (19) | N1—C11—H111 | 110.9 |
O2—C3—C2 | 111.79 (17) | C12—C11—H111 | 110.9 |
C4—C3—C2 | 113.23 (19) | C13—C11—H111 | 110.9 |
O2—C3—H31 | 106.7 | O3—C12—C11 | 104.23 (15) |
C4—C3—H31 | 106.7 | O3—C12—H121 | 110.9 |
C2—C3—H31 | 106.7 | C11—C12—H121 | 110.9 |
C3—C4—C5 | 114.44 (19) | O3—C12—H122 | 110.9 |
C3—C4—H41 | 108.6 | C11—C12—H122 | 110.9 |
C5—C4—H41 | 108.6 | H121—C12—H122 | 108.9 |
C3—C4—H42 | 108.6 | C14—C13—C11 | 110.80 (18) |
C5—C4—H42 | 108.6 | C14—C13—H131 | 109.5 |
H41—C4—H42 | 107.6 | C11—C13—H131 | 109.5 |
C6—C5—C4 | 113.6 (2) | C14—C13—H132 | 109.5 |
C6—C5—H51 | 108.8 | C11—C13—H132 | 109.5 |
C4—C5—H51 | 108.8 | H131—C13—H132 | 108.1 |
C6—C5—H52 | 108.8 | C19—C14—C15 | 118.9 (2) |
C4—C5—H52 | 108.8 | C19—C14—C13 | 122.1 (2) |
H51—C5—H52 | 107.7 | C15—C14—C13 | 119.0 (2) |
C9—C6—C5 | 110.3 (2) | C16—C15—C14 | 120.0 (3) |
C9—C6—C7 | 109.2 (2) | C16—C15—H151 | 120.0 |
C5—C6—C7 | 111.1 (2) | C14—C15—H151 | 120.0 |
C9—C6—H61 | 108.7 | C17—C16—C15 | 120.7 (3) |
C5—C6—H61 | 108.7 | C17—C16—H161 | 119.7 |
C7—C6—H61 | 108.7 | C15—C16—H161 | 119.7 |
C6—C7—H71 | 109.5 | C18—C17—C16 | 119.1 (2) |
C6—C7—H72 | 109.5 | C18—C17—H171 | 120.4 |
H71—C7—H72 | 109.5 | C16—C17—H171 | 120.4 |
C6—C7—H73 | 109.5 | C17—C18—C19 | 120.7 (2) |
H71—C7—H73 | 109.5 | C17—C18—H181 | 119.7 |
H72—C7—H73 | 109.5 | C19—C18—H181 | 119.7 |
C2—C8—H81 | 109.5 | C14—C19—C18 | 120.5 (2) |
C2—C8—H82 | 109.5 | C14—C19—H191 | 119.7 |
H81—C8—H82 | 109.5 | C18—C19—H191 | 119.7 |
C2—C8—H83 | 109.5 | ||
O1—C1—C2—C3 | −102.1 (2) | C1—N1—C10—O3 | −176.8 (2) |
O1—C1—C2—C8 | 22.5 (3) | C10—N1—C1—O1 | −174.0 (2) |
C1—C2—C3—C4 | 177.37 (17) | C11—N1—C1—O1 | −1.5 (3) |
C1—C2—C3—O2 | 50.9 (2) | N1—C1—C2—C8 | −161.17 (18) |
C2—C3—C4—C5 | 55.4 (2) | C8—C2—C3—O2 | −71.7 (2) |
C3—C4—C5—C6 | 163.7 (2) | C8—C2—C3—C4 | 54.8 (2) |
C4—C5—C6—C7 | 165.4 (2) | O2—C3—C4—C5 | −177.72 (19) |
C4—C5—C6—C9 | −73.4 (3) | C12—O3—C10—O4 | −173.5 (2) |
N1—C1—C2—C3 | 74.3 (2) | C1—N1—C10—O4 | 4.5 (4) |
C11—N1—C1—C2 | −178.0 (2) | C11—N1—C10—O4 | −168.6 (2) |
C10—N1—C1—C2 | 9.5 (3) | C10—N1—C11—C13 | 97.2 (2) |
C1—N1—C11—C12 | 164.25 (19) | C13—C11—C12—O3 | −93.1 (2) |
N1—C11—C12—O3 | 25.0 (2) | C12—C11—C13—C14 | −79.4 (2) |
C11—C12—O3—C10 | −21.4 (2) | C19—C14—C15—C16 | 0.7 (4) |
C12—O3—C10—N1 | 7.6 (2) | C13—C14—C15—C16 | −179.6 (2) |
O3—C10—N1—C11 | 10.2 (2) | C14—C15—C16—C17 | 0.6 (5) |
C10—N1—C11—C12 | −22.0 (2) | C15—C16—C17—C18 | −1.5 (5) |
C1—N1—C11—C13 | −76.5 (2) | C16—C17—C18—C19 | 1.2 (4) |
N1—C11—C13—C14 | 169.41 (17) | C15—C14—C19—C18 | −1.0 (4) |
C11—C13—C14—C15 | −75.9 (3) | C13—C14—C19—C18 | 179.3 (2) |
C11—C13—C14—C19 | 103.9 (3) | C17—C18—C19—C14 | 0.0 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
O2—H2···O1i | 0.84 (3) | 2.11 (3) | 2.937 (2) | 170 (2) |
C12—H122···O4ii | 0.99 | 2.42 | 3.217 (3) | 137 |
C8—H83···O1i | 0.98 | 2.43 | 3.379 (3) | 162 |
Symmetry codes: (i) −x+2, y−1/2, −z+1; (ii) −x+1, y−1/2, −z+1. |
Experimental details
(I) | (II) | |
Crystal data | ||
Chemical formula | C9H20O2 | C19H27NO4 |
Mr | 160.25 | 333.42 |
Crystal system, space group | Orthorhombic, P212121 | Monoclinic, P21 |
Temperature (K) | 105 | 105 |
a, b, c (Å) | 5.964 (2), 9.777 (4), 17.469 (6) | 11.459 (3), 5.7077 (13), 15.247 (3) |
α, β, γ (°) | 90, 90, 90 | 90, 103.827 (3), 90 |
V (Å3) | 1018.6 (6) | 968.4 (4) |
Z | 4 | 2 |
Radiation type | Mo Kα | Mo Kα |
µ (mm−1) | 0.07 | 0.08 |
Crystal size (mm) | 1.85 × 0.14 × 0.13 | 1.54 × 0.13 × 0.04 |
Data collection | ||
Diffractometer | Bruker APEXII CCD area-detector diffractometer | Bruker APEXII CCD area-detector diffractometer |
Absorption correction | Multi-scan (SADABS; Bruker, 2007) | Multi-scan (SADABS; Bruker, 2007) |
Tmin, Tmax | 0.851, 0.990 | 0.837, 0.997 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 9215, 1487, 1387 | 7434, 2047, 1823 |
Rint | 0.026 | 0.031 |
(sin θ/λ)max (Å−1) | 0.672 | 0.613 |
Refinement | ||
R[F2 > 2σ(F2)], wR(F2), S | 0.028, 0.074, 1.04 | 0.034, 0.087, 1.04 |
No. of reflections | 1487 | 2047 |
No. of parameters | 109 | 223 |
No. of restraints | 0 | 1 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.23, −0.14 | 0.13, −0.25 |
Computer programs: APEX2 (Bruker, 2007), SAINT-Plus (Bruker, 2007), SHELXTL (Sheldrick, 2008).
O1—C1—C2—C3 | 54.59 (12) | C2—C3—C4—C5 | 173.22 (10) |
O1—C1—C2—C8 | 179.27 (10) | C3—C4—C5—C6 | 169.71 (10) |
C1—C2—C3—C4 | −178.67 (10) | C4—C5—C6—C7 | −170.92 (10) |
C1—C2—C3—O2 | 61.50 (12) | C4—C5—C6—C9 | 64.91 (13) |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1···O2i | 0.844 (19) | 1.812 (19) | 2.6395 (16) | 166.4 (16) |
O2—H2···O1ii | 0.827 (17) | 1.886 (16) | 2.6809 (14) | 160.9 (17) |
Symmetry codes: (i) x+1, y, z; (ii) x−1/2, −y+3/2, −z. |
O1—C1—C2—C3 | −102.1 (2) | C1—N1—C11—C12 | 164.25 (19) |
O1—C1—C2—C8 | 22.5 (3) | N1—C11—C12—O3 | 25.0 (2) |
C1—C2—C3—C4 | 177.37 (17) | C11—C12—O3—C10 | −21.4 (2) |
C1—C2—C3—O2 | 50.9 (2) | C12—O3—C10—N1 | 7.6 (2) |
C2—C3—C4—C5 | 55.4 (2) | O3—C10—N1—C11 | 10.2 (2) |
C3—C4—C5—C6 | 163.7 (2) | C10—N1—C11—C12 | −22.0 (2) |
C4—C5—C6—C7 | 165.4 (2) | C1—N1—C11—C13 | −76.5 (2) |
C4—C5—C6—C9 | −73.4 (3) | N1—C11—C13—C14 | 169.41 (17) |
N1—C1—C2—C3 | 74.3 (2) | C11—C13—C14—C15 | −75.9 (3) |
C11—N1—C1—C2 | −178.0 (2) | C11—C13—C14—C19 | 103.9 (3) |
C10—N1—C1—C2 | 9.5 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
O2—H2···O1i | 0.84 (3) | 2.11 (3) | 2.937 (2) | 170 (2) |
C12—H122···O4ii | 0.99 | 2.42 | 3.217 (3) | 137.4 |
C8—H83···O1i | 0.98 | 2.43 | 3.379 (3) | 162.1 |
Symmetry codes: (i) −x+2, y−1/2, −z+1; (ii) −x+1, y−1/2, −z+1. |
The two isoforms of the nuclear oxysterol receptor liver X (LXRα and LXRβ) are relatively new drug targets within the nuclear receptor (NR) family. They are key players for increased cellular lipid accumulation and insulin resistance in skeletal muscle (Steffensen & Gustafsson, 2006; Laffitte et al., 2003). LXR agonists have been developed as desirable potential drugs for the treatment of cardiovascular diseases and metabolic syndrome, the regulation of inflammatory responses and immunity, and the treatment of skin diseases, and are effective for the treatment of murine models of atherosclerosis, diabetes and Alzheimer's disease (Viennois et al., 2011, 2012; Jakobsson et al., 2012). They also display anti-inflammatory activities (Zhu & Bakovic, 2008; Zhu et al., 2012; Solan et al., 2011) and act as agonists to inhibit cell proliferation in a number of major cancer forms (Viennois et al., 2012; Jakobsson et al., 2012). For instance, it has been shown that LXR agonists have anti-proliferative effects on LNCaP human prostate cancer cells, and activation of LXR also inhibits the proliferation of other prostate and breast cancer cell lines (Fukuchi et al., 2004). The ligand-binding pocket (LBP) of LXR allows binding of side-chain oxygenated sterols (OHCs). Recently, OHCs with a specific stereochemistry at the 23-hydroxylated side-chain C atom were also shown to regulate the hedgehog signalling pathway (Hh), a key developmental pathway playing multiple roles in embryonic development, including stem cell differentiation (Corman et al., 2012). This urged us to initiate a drug-design programme, starting with a retrosynthetic analysis for the establishment of synthetic routes to the pharmacophores in the different OHCs reported to affect the various diseases referred to above. Our first focus aimed at a stereoselective synthesis of the oxygenated side chains in 22(R)- and 22(S)-hydroxycholesterol, which have agonistic and antagonistic effects on LXR, respectively (Hessvik et al., 2012; Kase et al., 2012). (2S,3S)-2,6-Dimethylheptane-1,3-diol, (I), is a new chemical entity representing the oxygenated side chain in 22(S)-hydroxycholesterol, and is the starting material in a synthetic programme aimed at a new class of potential drug candidates as selective regulators of LXR receptor and the Hh pathway. This diol was obtained from the chiral ketone (R)-4-benzyl-3-[(2R,3S)-3-hydroxy-2,6-dimethylheptanoyl]-1,3-oxazolidin-2-one, (II), a compound with one asymmetric C atom with known absolute stereochemistry, which was made from commercially available starting materials.
The common fragment of (I) and (II) is easily recognized (Fig. 1) but their conformations are different at the C3—C4 bond, as the C2—C3—C4—C5 torsion angle is 173.22 (19)° for (I) (Table 1) but 55.4 (2)° for (II) (Table 2). The conformation of the bicyclic fragment of (II), characterized by a trans orientation [N1—C11—C13—C14 = 169.41 (17)°], is found for 53% of the molecules in the Cambridge Structural Database (CSD, Version 5.33 of November 2011; Allen, 2002) containing this group (157 occurrences in 141 entries). The trans configuration for the C11—N1—C1—C2 part is typical. Two structural analogues of (II), with a methoxy group attached to atom C4, have been described (Horneff et al., 2006) and they have different stereochemistries at atoms C2 and C3 [(2S,3S) and (2R,3R)], as well as different conformations for the aliphatic chain.
In the crystal structure of (I), individual diol molecules related by a twofold screw operation are connected by hydrogen bonds into tapes running along the a axis (Fig. 2a). A detailed illustration of a tape is provided in Fig. 3, revealing a ladder-like structure based on second-level R33(10) ring motifs (Bernstein et al., 1995). Hydrogen-bonding data are given in Table 3.
The structure of (II) has higher density (1.143 Mg m-3) than (I)?, but displays easily observable voids in the structure (Fig. 2b). Two voids within the unit cell together account for approximately 3.6% of the unit-cell volume. The void volume is approximately 17 Å3, which in theory is enough to accommodate a single water molecule, but there is no electron density indicating the presence of such. There is only one strong hydrogen-bond donor in the molecule, which participates in the generation of chains of molecules related by twofold screw symmetry parallel to the b axis. The simple chain is possibly strengthened by C8—H83···O1(-x + 2, y - 1/2, -z + 1) interactions (Fig. 4a and Table 4). The terminal isopentyl and phenyl groups of (II) are not involved in short contacts, but the five-membered oxazolidine rings stack parallel to the hydrogen-bonded chain and create not only a weaker C12—H122···O4(-x + 1,y - 1/2, -z + 1) hydrogen bond, but also a direct contact between atoms C10 and O3 [C···O = 2.993 (3) Å]. According to the classification scheme developed by Bertolasi et al. (2011, 2012), this represents a π* ← n electron donor–acceptor interaction. Using C—O—C and C—(C═O)—C as search fragments, we found 230 such contacts shorter than 3.2 Å in the CSD, usually associated with O-atom electron donors in cyclic systems. In a simple molecule like tetrahydrofuran-3,4-dione, with a pair of carbonyl groups (Muller & Jacobson, 1980), this type of interaction is very marked (Fig. 4b).