organic compounds
(8aR,9R)-9-Hydroxy-7,8,8a,9-tetrahydrofuro[3,2-f]indolizin-6(4H)-one
aInstitute of Analytical Chemistry, Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinského 9, SK-812 37 Bratislava, Slovak Republic 81237, bInstitute of Organic Chemistry, Catalysis and Petrochemistry, Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinského 9, SK-812 37 Bratislava, Slovak Republic 81237, and cInstitute of Mathematics and Physics, Faculty of Mechanical Engineering STU, Námestie slobody 17, SK-812 37 Bratislava, Slovak Republic
*Correspondence e-mail: viktor.vrabel@stuba.sk
The title compound, C10H11NO3, crystallizes with four independent molecules in the Their geometries are very similar and corresponding bond distances are almost identical. The central six-membered ring of the indolizine moiety adopts a [the displacement of the flap atom (the C atom opposite the N atom) being 0.539 (2), 0.548 (3), 0.509 (3) and 0.544 (3) Å in the four molecules], while the conformation of the oxopyrrolidine ring is close to that of a flat envelope. The displacements of the non-fused C atom opposite the C=O group of the pyrrolidine ring of the four molecules are 0.366 (3), 0.335 (3), 0.173 (3) and −0.310 (3) Å. In the crystal, O—H⋯O hydrogen bonds link the molecules into chains, which run parallel to the c axis. The was assigned from the synthesis.
Related literature
For background to indolizines and their biological activity, see: Gubin et al. (1992); Gundersen et al. (2007); Gupta et al. (2003); Mikael (1999); Pyne (2005); Teklu et al. (2005). For asymmetry parameters, see: Nardelli (1983).
Experimental
Crystal data
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Refinement
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Data collection: CrysAlis CCD (Oxford Diffraction, 2006); cell CrysAlis CCD; data reduction: CrysAlis RED (Oxford Diffraction, 2006); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg, 2001); software used to prepare material for publication: SHELXL97, PLATON (Spek, 2009) and WinGX (Farrugia, 1999).
Supporting information
https://doi.org/10.1107/S1600536812040378/ds2219sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536812040378/ds2219Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S1600536812040378/ds2219Isup3.cml
The title compound (8aR,RS)-9-hydroxy-7,8,8a,9-tetrahydrofuro[3,2-f] indolizin-6(4H)-one was prepared by a reduction of (R)-8,8a-dihydrofuro[3,2-f]indolizine-6,9(4H,7H)-dione with sodium borohydride. To a solution of a freshly crystallized keto-lactam (191 mg, 1 mmoL) in methanol (10 ml) was added in a small portions sodium borohydride (42 mg, 1,1 mmoL) at 0–5°C. The mixture was then stirred at 0°C for 10 h, until total disappearance of starting materials was observed (TLC). The solution was carefully neutralized with 36% HCl, and the solvent was removed under vacuum. The obtained solution was then extracted with dichloromethane (3 x 25 ml). The organic layer was dried over MgSO4, concentrated in vacuo to afford a colourless oil, which quickly crystallized on standing in a fridge. Recrystallization from n-hexane/ethylacetate (9:1) gave colourless crystals of the title compound (150 mg, 78%).
All H atoms bonded to C atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms, with C—H distances in the range 0.93 - 0.98 Å and Uiso set at 1.2Ueq of the parent atom. H atoms of the hidroxyl groups were located in a difference map and finally refined with O—H distance fixed at 0.84 Å. In the absence of significant
Friedel pairs were merged and the was assigned from the starting material.Indolizines are electron-rich heterocycles with very low oxidation potential. Functionalized indolizines are common substructures found in biologically important natural products and synthetic pharmaceuticals. Due to the various biological functions associated with this skeleton, it has been frequently employed as a key scaffold in the drug industry (Gundersen et al., 2007). Indolizine
are excellent inhibitors of biologically important pathways. These include the binding and processing of potent glycosidase inhibitory activities (Pyne, 2005), activity against AIDS virus HIV and some carcinogenic cells (Mikael, 1999). They have also shown to be calcium entry blockers (Gupta et al., 2003) and potent antioxidants inhibiting lipid peroxidation in vitro (Teklu et al., 2005). As such, indolizines are important synthetic targets in view of developing new pharmaceuticals for the treatment of cardiovascular diseases (Gubin et al., 1992). Based on these facts and in contitutation of our interest in developing simple and efficient route for the synthesis of novel indolizine derivatives. The molecular structure and the atom labeling scheme of four independent molecules in the are shown in Fig. 1. The was established by synthesis and is depicted in the scheme and Fig.1. The expected stereochemistry of atoms C4 and C10, C14 and C20, C24 and C30, C34 and C40 in the four molecules was confirmed as R, R, respectively (Fig. 1). The central six-membered rings of the four molecules according to Nardelli (Nardelli, 1983) is not planar and adopts an with atoms C10, C20, C30 and C40 as the flaps. The displacements of atoms C10, C20, C30 and C40 from the mean planes of the remaining five atoms are 0.539 (2), 0.548 (3), 0.509 (3) and 0.544 (3) Å, respectively. The bond lengths of the carbonyl groups C=O in the four molecules are somewhat longer than typical carbonyl bonds. This may be due to the fact that atoms O2, O5, O8 and O11 participates in intermolecular hydrogen bonds, they seem to be effective in the stabilization of the structure. The central six-membered rings form dihedral angles of 21.8 (1), 20.1 (1), 24.9 (1) and 22.5 (1)° with the oxopyrrolidine rings, in the four independent molecules, respectively. Intermolecular O–H···O hydrogen bonds link the molecules into extended chains, which run parallel to the c axis (Fig.2).For background to indolizines and their biological activity, see: Gubin et al. (1992); Gundersen et al. (2007); Gupta et al. (2003); Mikael (1999); Pyne (2005); Teklu et al. (2005). For asymmetry parameters, see: Nardelli (1983).
Data collection: CrysAlis CCD (Oxford Diffraction, 2006); cell
CrysAlis CCD (Oxford Diffraction, 2006); data reduction: CrysAlis RED (Oxford Diffraction, 2006); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg, 2001); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2009) and WinGX (Farrugia, 1999).C10H11NO3 | F(000) = 1632 |
Mr = 193.20 | Dx = 1.411 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 13239 reflections |
a = 14.7603 (10) Å | θ = 2.3–29.5° |
b = 15.1301 (17) Å | µ = 0.11 mm−1 |
c = 16.2847 (9) Å | T = 298 K |
V = 3636.8 (5) Å3 | Prism, colourless |
Z = 16 | 0.58 × 0.34 × 0.09 mm |
Oxford Diffraction Gemini R CCD diffractometer | 3581 independent reflections |
Radiation source: fine-focus sealed tube | 3168 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.036 |
Detector resolution: 10.4340 pixels mm-1 | θmax = 25.0°, θmin = 3.0° |
Rotation method data acquisition using ω and φ scans | h = −17→17 |
Absorption correction: analytical (Clark & Reid, 1995) | k = −18→18 |
Tmin = 0.953, Tmax = 0.989 | l = −18→19 |
55202 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) = 0.086 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.04 | w = 1/[σ2(Fo2) + (0.0452P)2 + 0.6847P] where P = (Fo2 + 2Fc2)/3 |
3581 reflections | (Δ/σ)max < 0.001 |
522 parameters | Δρmax = 0.17 e Å−3 |
4 restraints | Δρmin = −0.15 e Å−3 |
C10H11NO3 | V = 3636.8 (5) Å3 |
Mr = 193.20 | Z = 16 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 14.7603 (10) Å | µ = 0.11 mm−1 |
b = 15.1301 (17) Å | T = 298 K |
c = 16.2847 (9) Å | 0.58 × 0.34 × 0.09 mm |
Oxford Diffraction Gemini R CCD diffractometer | 3581 independent reflections |
Absorption correction: analytical (Clark & Reid, 1995) | 3168 reflections with I > 2σ(I) |
Tmin = 0.953, Tmax = 0.989 | Rint = 0.036 |
55202 measured reflections |
R[F2 > 2σ(F2)] = 0.034 | 4 restraints |
wR(F2) = 0.086 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.04 | Δρmax = 0.17 e Å−3 |
3581 reflections | Δρmin = −0.15 e Å−3 |
522 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 | Occ. (<1) | |
C1 | 0.37091 (18) | −0.0319 (2) | 0.96600 (15) | 0.0505 (7) | |
H1B | 0.3935 | −0.0811 | 0.9982 | 0.061* | |
H1A | 0.4014 | 0.0215 | 0.9841 | 0.061* | |
C2 | 0.4725 (2) | −0.0647 (2) | 0.83402 (17) | 0.0564 (8) | |
H2 | 0.5299 | −0.0706 | 0.8569 | 0.068* | |
C3 | 0.4509 (2) | −0.0705 (2) | 0.75510 (19) | 0.0687 (9) | |
H3 | 0.4924 | −0.0805 | 0.7131 | 0.082* | |
C4 | 0.22570 (19) | −0.02846 (19) | 0.83141 (14) | 0.0460 (6) | |
H4 | 0.1929 | −0.0848 | 0.8307 | 0.055* | |
C5 | 0.12006 (19) | 0.0081 (2) | 0.95377 (15) | 0.0493 (7) | |
H5B | 0.0837 | 0.0598 | 0.9415 | 0.059* | |
H5A | 0.0889 | −0.0441 | 0.9336 | 0.059* | |
C6 | 0.1382 (2) | 0.0008 (2) | 1.04619 (15) | 0.0552 (8) | |
H6B | 0.1293 | 0.0574 | 1.0730 | 0.066* | |
H6A | 0.0985 | −0.0425 | 1.0713 | 0.066* | |
C7 | 0.2351 (2) | −0.02766 (19) | 1.05206 (15) | 0.0475 (7) | |
C8 | 0.38974 (18) | −0.04746 (18) | 0.87672 (14) | 0.0435 (6) | |
C9 | 0.32426 (19) | −0.04454 (19) | 0.81992 (14) | 0.0458 (6) | |
C10 | 0.21457 (17) | 0.01593 (17) | 0.91544 (14) | 0.0401 (6) | |
H10 | 0.2296 | 0.0787 | 0.9099 | 0.048* | |
C11 | 0.85665 (16) | 0.2162 (2) | 0.71399 (14) | 0.0440 (6) | |
H11A | 0.8232 | 0.2569 | 0.7486 | 0.053* | |
H11B | 0.8399 | 0.1564 | 0.7293 | 0.053* | |
C12 | 0.74899 (17) | 0.2316 (2) | 0.58353 (16) | 0.0467 (6) | |
H12 | 0.6925 | 0.2181 | 0.6054 | 0.056* | |
C13 | 0.76729 (17) | 0.2542 (2) | 0.50606 (17) | 0.0524 (7) | |
H13 | 0.7242 | 0.2586 | 0.4646 | 0.063* | |
C14 | 0.99586 (16) | 0.26724 (19) | 0.58311 (14) | 0.0424 (6) | |
H14 | 1.0086 | 0.3302 | 0.5914 | 0.051* | |
C15 | 1.11005 (17) | 0.2440 (2) | 0.70238 (15) | 0.0488 (7) | |
H15A | 1.1594 | 0.2057 | 0.6856 | 0.059* | |
H15B | 1.1256 | 0.3046 | 0.6888 | 0.059* | |
C16 | 1.09142 (17) | 0.2346 (2) | 0.79415 (15) | 0.0510 (7) | |
H16A | 1.1189 | 0.1811 | 0.8155 | 0.061* | |
H16B | 1.1153 | 0.2849 | 0.8241 | 0.061* | |
C17 | 0.99049 (17) | 0.2306 (2) | 0.80141 (14) | 0.0454 (6) | |
C18 | 0.83367 (16) | 0.23212 (18) | 0.62607 (14) | 0.0392 (6) | |
C19 | 0.89690 (16) | 0.25498 (17) | 0.57055 (13) | 0.0391 (6) | |
C20 | 1.02126 (16) | 0.21675 (18) | 0.66021 (14) | 0.0397 (6) | |
H20 | 1.0246 | 0.1537 | 0.6468 | 0.048* | |
C21 | 0.38642 (19) | 0.6723 (3) | 0.70964 (15) | 0.0648 (9) | |
H21B | 0.3492 | 0.6994 | 0.7518 | 0.078* | |
H21A | 0.3754 | 0.6091 | 0.7102 | 0.078* | |
C22 | 0.27775 (19) | 0.7229 (2) | 0.58750 (17) | 0.0563 (8) | |
H22 | 0.2209 | 0.7086 | 0.6082 | 0.068* | |
C23 | 0.29579 (18) | 0.7594 (2) | 0.51509 (18) | 0.0544 (7) | |
H23 | 0.2522 | 0.7751 | 0.4765 | 0.065* | |
C24 | 0.52638 (17) | 0.74252 (19) | 0.58671 (14) | 0.0446 (6) | |
H24 | 0.5454 | 0.8036 | 0.5970 | 0.054* | |
C25 | 0.63795 (18) | 0.7101 (2) | 0.70505 (15) | 0.0539 (7) | |
H25B | 0.6854 | 0.6679 | 0.6925 | 0.065* | |
H25A | 0.6580 | 0.7685 | 0.6883 | 0.065* | |
C26 | 0.61646 (19) | 0.7090 (2) | 0.79567 (16) | 0.0577 (8) | |
H26B | 0.6483 | 0.6611 | 0.8228 | 0.069* | |
H26A | 0.6340 | 0.7643 | 0.8211 | 0.069* | |
C27 | 0.51560 (17) | 0.69575 (19) | 0.80162 (14) | 0.0435 (6) | |
C28 | 0.36308 (17) | 0.7098 (2) | 0.62739 (14) | 0.0477 (7) | |
C29 | 0.42635 (16) | 0.73930 (18) | 0.57528 (14) | 0.0416 (6) | |
C30 | 0.55016 (17) | 0.68515 (18) | 0.66060 (14) | 0.0402 (6) | |
H30 | 0.5549 | 0.6236 | 0.6423 | 0.048* | |
C31 | 0.88814 (18) | 0.9793 (2) | 0.52818 (16) | 0.0516 (7) | |
H31A | 0.9201 | 1.0281 | 0.5025 | 0.062* | |
H31B | 0.9082 | 0.9248 | 0.5027 | 0.062* | |
C32 | 0.99215 (19) | 0.9749 (2) | 0.66191 (17) | 0.0540 (7) | |
H32 | 1.0500 | 0.9713 | 0.6395 | 0.065* | |
C33 | 0.9707 (2) | 0.9787 (2) | 0.74150 (17) | 0.0605 (8) | |
H33 | 1.0127 | 0.9786 | 0.7841 | 0.073* | |
C34 | 0.74269 (18) | 0.98715 (19) | 0.66276 (14) | 0.0427 (6) | |
H34 | 0.7229 | 1.0486 | 0.6695 | 0.051* | |
C35 | 0.63366 (19) | 0.9893 (2) | 0.53834 (17) | 0.0559 (8) | |
H35B | 0.5875 | 0.9439 | 0.5422 | 0.067* | |
H35A | 0.6126 | 1.0416 | 0.5670 | 0.067* | |
C36 | 0.6542 (2) | 1.0103 (3) | 0.45011 (17) | 0.0644 (9) | |
H36B | 0.6268 | 1.0660 | 0.4344 | 0.077* | |
H36A | 0.6312 | 0.9642 | 0.4143 | 0.077* | |
C37 | 0.7559 (2) | 1.0157 (2) | 0.44446 (16) | 0.0495 (7) | |
C38 | 0.90826 (17) | 0.97727 (18) | 0.61805 (14) | 0.0432 (6) | |
C39 | 0.84266 (18) | 0.98120 (18) | 0.67511 (14) | 0.0431 (6) | |
C40 | 0.72346 (17) | 0.95645 (18) | 0.57500 (14) | 0.0420 (6) | |
H40 | 0.7242 | 0.8917 | 0.5736 | 0.050* | |
N1 | 0.27316 (15) | −0.02275 (15) | 0.97777 (12) | 0.0438 (5) | |
N2 | 0.95392 (13) | 0.22898 (15) | 0.72598 (11) | 0.0394 (5) | |
N3 | 0.48159 (14) | 0.69005 (16) | 0.72568 (11) | 0.0445 (5) | |
N4 | 0.79082 (14) | 0.99003 (15) | 0.51692 (12) | 0.0443 (5) | |
O1 | 0.35925 (14) | −0.05982 (16) | 0.74337 (11) | 0.0643 (6) | |
O2 | 0.27650 (15) | −0.05083 (16) | 1.11433 (10) | 0.0666 (6) | |
O3 | 0.18597 (15) | 0.03090 (19) | 0.77435 (11) | 0.0726 (7) | |
O4 | 0.85804 (12) | 0.27000 (15) | 0.49559 (10) | 0.0526 (5) | |
O5 | 0.94469 (13) | 0.22702 (18) | 0.86442 (10) | 0.0684 (7) | |
O6 | 1.04954 (13) | 0.23539 (19) | 0.51857 (11) | 0.0707 (7) | |
O7 | 0.38731 (13) | 0.77089 (14) | 0.50474 (11) | 0.0534 (5) | |
O8 | 0.46942 (13) | 0.69031 (16) | 0.86436 (10) | 0.0597 (8) | 0.997 (7) |
O9 | 0.57598 (15) | 0.7075 (2) | 0.51995 (11) | 0.0767 (8) | |
O10 | 0.87864 (13) | 0.98284 (15) | 0.75233 (10) | 0.0565 (5) | |
O11 | 0.80178 (14) | 1.03788 (18) | 0.38476 (11) | 0.0695 (7) | |
O12 | 0.69166 (14) | 0.93163 (16) | 0.71545 (11) | 0.0595 (6) | |
H3O | 0.2085 (19) | 0.024 (2) | 0.7273 (13) | 0.063 (9)* | |
H6O | 1.034 (3) | 0.260 (3) | 0.4732 (16) | 0.096 (13)* | |
H9O | 0.557 (2) | 0.726 (2) | 0.4740 (14) | 0.080 (11)* | |
H12O | 0.702 (2) | 0.944 (2) | 0.7642 (12) | 0.070 (10)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0463 (16) | 0.0713 (19) | 0.0337 (13) | 0.0001 (14) | −0.0075 (12) | 0.0001 (13) |
C2 | 0.0521 (17) | 0.0692 (19) | 0.0479 (16) | 0.0176 (15) | −0.0010 (14) | −0.0049 (14) |
C3 | 0.062 (2) | 0.095 (3) | 0.0485 (18) | 0.0281 (19) | 0.0087 (15) | −0.0073 (17) |
C4 | 0.0547 (16) | 0.0569 (17) | 0.0265 (12) | 0.0028 (14) | −0.0044 (12) | 0.0008 (11) |
C5 | 0.0492 (16) | 0.0630 (19) | 0.0356 (14) | 0.0012 (14) | −0.0005 (12) | 0.0059 (13) |
C6 | 0.0585 (18) | 0.074 (2) | 0.0334 (13) | 0.0039 (16) | 0.0067 (13) | 0.0082 (13) |
C7 | 0.0586 (17) | 0.0567 (17) | 0.0270 (13) | 0.0024 (14) | 0.0016 (13) | 0.0011 (11) |
C8 | 0.0487 (14) | 0.0469 (15) | 0.0351 (13) | 0.0049 (13) | −0.0013 (11) | 0.0021 (11) |
C9 | 0.0570 (16) | 0.0523 (16) | 0.0282 (12) | 0.0073 (13) | 0.0005 (12) | −0.0037 (12) |
C10 | 0.0459 (15) | 0.0437 (14) | 0.0307 (12) | −0.0004 (12) | −0.0002 (11) | 0.0046 (11) |
C11 | 0.0381 (13) | 0.0650 (18) | 0.0290 (12) | −0.0092 (12) | 0.0016 (11) | 0.0032 (12) |
C12 | 0.0360 (13) | 0.0655 (17) | 0.0385 (14) | −0.0063 (13) | −0.0021 (11) | 0.0033 (13) |
C13 | 0.0383 (13) | 0.081 (2) | 0.0377 (14) | −0.0044 (14) | −0.0066 (12) | 0.0073 (14) |
C14 | 0.0354 (13) | 0.0597 (16) | 0.0322 (12) | 0.0023 (12) | 0.0064 (10) | 0.0050 (12) |
C15 | 0.0366 (13) | 0.0696 (19) | 0.0402 (13) | 0.0038 (13) | −0.0027 (11) | 0.0058 (13) |
C16 | 0.0423 (14) | 0.074 (2) | 0.0364 (13) | 0.0063 (14) | −0.0072 (12) | −0.0018 (13) |
C17 | 0.0441 (14) | 0.0644 (18) | 0.0276 (12) | 0.0036 (13) | −0.0016 (11) | −0.0057 (12) |
C18 | 0.0388 (13) | 0.0489 (15) | 0.0300 (12) | −0.0025 (12) | 0.0002 (10) | 0.0016 (11) |
C19 | 0.0379 (13) | 0.0526 (16) | 0.0269 (11) | 0.0010 (12) | −0.0013 (10) | 0.0008 (11) |
C20 | 0.0390 (13) | 0.0499 (15) | 0.0301 (12) | 0.0048 (12) | 0.0037 (10) | 0.0016 (11) |
C21 | 0.0465 (16) | 0.120 (3) | 0.0282 (13) | −0.0248 (18) | 0.0024 (12) | 0.0046 (15) |
C22 | 0.0431 (15) | 0.084 (2) | 0.0418 (15) | −0.0075 (15) | 0.0009 (13) | −0.0131 (15) |
C23 | 0.0444 (15) | 0.0708 (19) | 0.0479 (16) | 0.0022 (14) | −0.0079 (13) | 0.0037 (15) |
C24 | 0.0411 (14) | 0.0574 (17) | 0.0354 (13) | 0.0020 (13) | 0.0113 (11) | 0.0114 (12) |
C25 | 0.0425 (14) | 0.080 (2) | 0.0389 (14) | 0.0026 (14) | 0.0057 (12) | 0.0023 (14) |
C26 | 0.0455 (16) | 0.091 (2) | 0.0362 (14) | 0.0039 (15) | 0.0000 (12) | 0.0066 (15) |
C27 | 0.0448 (14) | 0.0570 (17) | 0.0286 (12) | 0.0020 (13) | 0.0011 (12) | 0.0025 (12) |
C28 | 0.0405 (14) | 0.0725 (19) | 0.0302 (12) | −0.0109 (14) | 0.0048 (11) | −0.0070 (12) |
C29 | 0.0426 (14) | 0.0518 (15) | 0.0303 (12) | −0.0005 (12) | 0.0036 (11) | 0.0008 (12) |
C30 | 0.0437 (14) | 0.0469 (15) | 0.0299 (12) | −0.0004 (12) | 0.0091 (11) | −0.0011 (11) |
C31 | 0.0430 (15) | 0.079 (2) | 0.0326 (13) | 0.0029 (15) | 0.0030 (12) | −0.0012 (13) |
C32 | 0.0477 (16) | 0.0695 (19) | 0.0447 (15) | −0.0013 (14) | −0.0052 (13) | 0.0083 (14) |
C33 | 0.0527 (18) | 0.089 (2) | 0.0401 (15) | −0.0074 (17) | −0.0116 (14) | 0.0112 (15) |
C34 | 0.0466 (15) | 0.0508 (16) | 0.0306 (12) | −0.0007 (12) | 0.0057 (11) | −0.0020 (11) |
C35 | 0.0421 (15) | 0.081 (2) | 0.0444 (15) | 0.0020 (15) | −0.0015 (13) | 0.0031 (15) |
C36 | 0.0514 (17) | 0.096 (3) | 0.0458 (16) | 0.0099 (17) | −0.0055 (14) | 0.0108 (17) |
C37 | 0.0520 (16) | 0.0674 (19) | 0.0291 (13) | 0.0057 (14) | −0.0016 (12) | 0.0018 (13) |
C38 | 0.0450 (14) | 0.0519 (16) | 0.0327 (12) | 0.0028 (13) | −0.0006 (11) | 0.0034 (11) |
C39 | 0.0502 (15) | 0.0506 (15) | 0.0286 (12) | 0.0000 (13) | −0.0017 (12) | −0.0002 (11) |
C40 | 0.0439 (14) | 0.0519 (16) | 0.0303 (12) | 0.0004 (12) | 0.0023 (11) | −0.0014 (11) |
N1 | 0.0482 (12) | 0.0587 (14) | 0.0245 (10) | 0.0018 (11) | −0.0029 (9) | 0.0027 (10) |
N2 | 0.0350 (11) | 0.0571 (13) | 0.0262 (10) | −0.0029 (10) | 0.0009 (8) | −0.0008 (9) |
N3 | 0.0382 (12) | 0.0712 (15) | 0.0241 (10) | −0.0083 (11) | 0.0047 (9) | −0.0022 (10) |
N4 | 0.0414 (12) | 0.0622 (14) | 0.0293 (10) | 0.0036 (11) | 0.0028 (10) | 0.0040 (10) |
O1 | 0.0657 (13) | 0.0953 (17) | 0.0320 (9) | 0.0244 (13) | −0.0005 (9) | −0.0092 (10) |
O2 | 0.0790 (14) | 0.0961 (16) | 0.0246 (9) | 0.0203 (13) | −0.0032 (9) | 0.0025 (10) |
O3 | 0.0677 (14) | 0.123 (2) | 0.0269 (10) | 0.0363 (14) | 0.0015 (10) | 0.0122 (11) |
O4 | 0.0398 (9) | 0.0880 (15) | 0.0299 (8) | −0.0008 (10) | −0.0017 (8) | 0.0116 (10) |
O5 | 0.0515 (11) | 0.127 (2) | 0.0270 (9) | −0.0015 (13) | 0.0019 (9) | −0.0075 (11) |
O6 | 0.0462 (11) | 0.134 (2) | 0.0322 (10) | 0.0249 (13) | 0.0103 (9) | 0.0193 (13) |
O7 | 0.0500 (11) | 0.0663 (13) | 0.0440 (10) | 0.0019 (10) | 0.0007 (9) | 0.0168 (10) |
O8 | 0.0482 (12) | 0.1068 (18) | 0.0241 (10) | −0.0013 (11) | 0.0046 (8) | −0.0012 (10) |
O9 | 0.0595 (13) | 0.140 (2) | 0.0310 (10) | 0.0296 (14) | 0.0184 (10) | 0.0243 (12) |
O10 | 0.0582 (13) | 0.0843 (15) | 0.0270 (9) | −0.0078 (11) | −0.0046 (8) | 0.0028 (9) |
O11 | 0.0577 (12) | 0.1188 (19) | 0.0319 (10) | −0.0001 (13) | 0.0015 (9) | 0.0169 (11) |
O12 | 0.0626 (12) | 0.0833 (15) | 0.0326 (10) | −0.0202 (11) | 0.0071 (9) | −0.0007 (10) |
C1—N1 | 1.462 (3) | C21—H21B | 0.9700 |
C1—C8 | 1.499 (3) | C21—H21A | 0.9700 |
C1—H1B | 0.9700 | C22—C23 | 1.329 (4) |
C1—H1A | 0.9700 | C22—C28 | 1.431 (4) |
C2—C3 | 1.327 (4) | C22—H22 | 0.9300 |
C2—C8 | 1.429 (4) | C23—O7 | 1.372 (3) |
C2—H2 | 0.9300 | C23—H23 | 0.9300 |
C3—O1 | 1.376 (4) | C24—O9 | 1.414 (3) |
C3—H3 | 0.9300 | C24—C29 | 1.489 (3) |
C4—O3 | 1.419 (3) | C24—C30 | 1.525 (3) |
C4—C9 | 1.487 (4) | C24—H24 | 0.9800 |
C4—C10 | 1.533 (3) | C25—C26 | 1.509 (4) |
C4—H4 | 0.9800 | C25—C30 | 1.532 (4) |
C5—C6 | 1.533 (4) | C25—H25B | 0.9700 |
C5—C10 | 1.533 (4) | C25—H25A | 0.9700 |
C5—H5B | 0.9700 | C26—C27 | 1.505 (4) |
C5—H5A | 0.9700 | C26—H26B | 0.9700 |
C6—C7 | 1.496 (4) | C26—H26A | 0.9700 |
C6—H6B | 0.9700 | C27—O8 | 1.231 (3) |
C6—H6A | 0.9700 | C27—N3 | 1.337 (3) |
C7—O2 | 1.235 (3) | C28—C29 | 1.339 (3) |
C7—N1 | 1.336 (3) | C29—O7 | 1.371 (3) |
C8—C9 | 1.338 (3) | C30—N3 | 1.467 (3) |
C9—O1 | 1.369 (3) | C30—H30 | 0.9800 |
C10—N1 | 1.456 (3) | C31—N4 | 1.457 (3) |
C10—H10 | 0.9800 | C31—C38 | 1.494 (3) |
C11—N2 | 1.462 (3) | C31—H31A | 0.9700 |
C11—C18 | 1.491 (3) | C31—H31B | 0.9700 |
C11—H11A | 0.9700 | C32—C33 | 1.336 (4) |
C11—H11B | 0.9700 | C32—C38 | 1.430 (4) |
C12—C13 | 1.335 (4) | C32—H32 | 0.9300 |
C12—C18 | 1.429 (3) | C33—O10 | 1.371 (3) |
C12—H12 | 0.9300 | C33—H33 | 0.9300 |
C13—O4 | 1.371 (3) | C34—O12 | 1.417 (3) |
C13—H13 | 0.9300 | C34—C39 | 1.492 (4) |
C14—O6 | 1.402 (3) | C34—C40 | 1.529 (3) |
C14—C19 | 1.487 (3) | C34—H34 | 0.9800 |
C14—C20 | 1.517 (3) | C35—C36 | 1.502 (4) |
C14—H14 | 0.9800 | C35—C40 | 1.536 (4) |
C15—C16 | 1.526 (3) | C35—H35B | 0.9700 |
C15—C20 | 1.536 (4) | C35—H35A | 0.9700 |
C15—H15A | 0.9700 | C36—C37 | 1.506 (4) |
C15—H15B | 0.9700 | C36—H36B | 0.9700 |
C16—C17 | 1.496 (4) | C36—H36A | 0.9700 |
C16—H16A | 0.9700 | C37—O11 | 1.232 (3) |
C16—H16B | 0.9700 | C37—N4 | 1.345 (3) |
C17—O5 | 1.230 (3) | C38—C39 | 1.343 (3) |
C17—N2 | 1.342 (3) | C39—O10 | 1.365 (3) |
C18—C19 | 1.345 (3) | C40—N4 | 1.463 (3) |
C19—O4 | 1.368 (3) | C40—H40 | 0.9800 |
C20—N2 | 1.473 (3) | O3—H3O | 0.842 (18) |
C20—H20 | 0.9800 | O6—H6O | 0.855 (19) |
C21—N3 | 1.454 (3) | O9—H9O | 0.848 (19) |
C21—C28 | 1.494 (4) | O12—H12O | 0.829 (18) |
N1—C1—C8 | 109.0 (2) | C22—C23—H23 | 124.5 |
N1—C1—H1B | 109.9 | O7—C23—H23 | 124.5 |
C8—C1—H1B | 109.9 | O9—C24—C29 | 113.9 (2) |
N1—C1—H1A | 109.9 | O9—C24—C30 | 105.9 (2) |
C8—C1—H1A | 109.9 | C29—C24—C30 | 108.0 (2) |
H1B—C1—H1A | 108.3 | O9—C24—H24 | 109.6 |
C3—C2—C8 | 106.1 (3) | C29—C24—H24 | 109.6 |
C3—C2—H2 | 126.9 | C30—C24—H24 | 109.6 |
C8—C2—H2 | 126.9 | C26—C25—C30 | 106.3 (2) |
C2—C3—O1 | 111.3 (3) | C26—C25—H25B | 110.5 |
C2—C3—H3 | 124.4 | C30—C25—H25B | 110.5 |
O1—C3—H3 | 124.4 | C26—C25—H25A | 110.5 |
O3—C4—C9 | 115.2 (2) | C30—C25—H25A | 110.5 |
O3—C4—C10 | 105.2 (2) | H25B—C25—H25A | 108.7 |
C9—C4—C10 | 106.8 (2) | C27—C26—C25 | 105.8 (2) |
O3—C4—H4 | 109.8 | C27—C26—H26B | 110.6 |
C9—C4—H4 | 109.8 | C25—C26—H26B | 110.6 |
C10—C4—H4 | 109.8 | C27—C26—H26A | 110.6 |
C6—C5—C10 | 104.2 (2) | C25—C26—H26A | 110.6 |
C6—C5—H5B | 110.9 | H26B—C26—H26A | 108.7 |
C10—C5—H5B | 110.9 | O8—C27—N3 | 123.7 (2) |
C6—C5—H5A | 110.9 | O8—C27—C26 | 127.6 (2) |
C10—C5—H5A | 110.9 | N3—C27—C26 | 108.7 (2) |
H5B—C5—H5A | 108.9 | C29—C28—C22 | 106.3 (2) |
C7—C6—C5 | 104.5 (2) | C29—C28—C21 | 122.3 (2) |
C7—C6—H6B | 110.8 | C22—C28—C21 | 131.5 (2) |
C5—C6—H6B | 110.8 | C28—C29—O7 | 110.8 (2) |
C7—C6—H6A | 110.8 | C28—C29—C24 | 128.6 (2) |
C5—C6—H6A | 110.8 | O7—C29—C24 | 120.7 (2) |
H6B—C6—H6A | 108.9 | N3—C30—C24 | 112.5 (2) |
O2—C7—N1 | 123.4 (3) | N3—C30—C25 | 103.28 (18) |
O2—C7—C6 | 127.4 (2) | C24—C30—C25 | 115.3 (2) |
N1—C7—C6 | 109.2 (2) | N3—C30—H30 | 108.5 |
C9—C8—C2 | 106.7 (2) | C24—C30—H30 | 108.5 |
C9—C8—C1 | 122.1 (2) | C25—C30—H30 | 108.5 |
C2—C8—C1 | 131.2 (2) | N4—C31—C38 | 108.8 (2) |
C8—C9—O1 | 110.6 (2) | N4—C31—H31A | 109.9 |
C8—C9—C4 | 128.7 (2) | C38—C31—H31A | 109.9 |
O1—C9—C4 | 120.8 (2) | N4—C31—H31B | 109.9 |
N1—C10—C5 | 103.03 (18) | C38—C31—H31B | 109.9 |
N1—C10—C4 | 112.5 (2) | H31A—C31—H31B | 108.3 |
C5—C10—C4 | 115.3 (2) | C33—C32—C38 | 106.1 (3) |
N1—C10—H10 | 108.6 | C33—C32—H32 | 126.9 |
C5—C10—H10 | 108.6 | C38—C32—H32 | 126.9 |
C4—C10—H10 | 108.6 | C32—C33—O10 | 111.2 (2) |
N2—C11—C18 | 109.3 (2) | C32—C33—H33 | 124.4 |
N2—C11—H11A | 109.8 | O10—C33—H33 | 124.4 |
C18—C11—H11A | 109.8 | O12—C34—C39 | 114.1 (2) |
N2—C11—H11B | 109.8 | O12—C34—C40 | 106.7 (2) |
C18—C11—H11B | 109.8 | C39—C34—C40 | 106.9 (2) |
H11A—C11—H11B | 108.3 | O12—C34—H34 | 109.7 |
C13—C12—C18 | 106.3 (2) | C39—C34—H34 | 109.7 |
C13—C12—H12 | 126.9 | C40—C34—H34 | 109.7 |
C18—C12—H12 | 126.9 | C36—C35—C40 | 105.4 (2) |
C12—C13—O4 | 111.1 (2) | C36—C35—H35B | 110.7 |
C12—C13—H13 | 124.5 | C40—C35—H35B | 110.7 |
O4—C13—H13 | 124.5 | C36—C35—H35A | 110.7 |
O6—C14—C19 | 114.2 (2) | C40—C35—H35A | 110.7 |
O6—C14—C20 | 107.9 (2) | H35B—C35—H35A | 108.8 |
C19—C14—C20 | 107.1 (2) | C35—C36—C37 | 105.7 (2) |
O6—C14—H14 | 109.2 | C35—C36—H36B | 110.6 |
C19—C14—H14 | 109.2 | C37—C36—H36B | 110.6 |
C20—C14—H14 | 109.2 | C35—C36—H36A | 110.6 |
C16—C15—C20 | 105.0 (2) | C37—C36—H36A | 110.6 |
C16—C15—H15A | 110.7 | H36B—C36—H36A | 108.7 |
C20—C15—H15A | 110.7 | O11—C37—N4 | 124.1 (3) |
C16—C15—H15B | 110.7 | O11—C37—C36 | 127.7 (3) |
C20—C15—H15B | 110.7 | N4—C37—C36 | 108.2 (2) |
H15A—C15—H15B | 108.8 | C39—C38—C32 | 106.2 (2) |
C17—C16—C15 | 105.1 (2) | C39—C38—C31 | 122.2 (2) |
C17—C16—H16A | 110.7 | C32—C38—C31 | 131.5 (2) |
C15—C16—H16A | 110.7 | C38—C39—O10 | 110.9 (2) |
C17—C16—H16B | 110.7 | C38—C39—C34 | 128.5 (2) |
C15—C16—H16B | 110.7 | O10—C39—C34 | 120.5 (2) |
H16A—C16—H16B | 108.8 | N4—C40—C34 | 111.9 (2) |
O5—C17—N2 | 122.8 (2) | N4—C40—C35 | 102.9 (2) |
O5—C17—C16 | 128.0 (2) | C34—C40—C35 | 115.2 (2) |
N2—C17—C16 | 109.2 (2) | N4—C40—H40 | 108.9 |
C19—C18—C12 | 106.4 (2) | C34—C40—H40 | 108.9 |
C19—C18—C11 | 122.0 (2) | C35—C40—H40 | 108.9 |
C12—C18—C11 | 131.6 (2) | C7—N1—C10 | 113.8 (2) |
C18—C19—O4 | 110.6 (2) | C7—N1—C1 | 121.9 (2) |
C18—C19—C14 | 128.4 (2) | C10—N1—C1 | 122.2 (2) |
O4—C19—C14 | 120.9 (2) | C17—N2—C11 | 121.3 (2) |
N2—C20—C14 | 111.8 (2) | C17—N2—C20 | 113.4 (2) |
N2—C20—C15 | 102.53 (19) | C11—N2—C20 | 123.30 (19) |
C14—C20—C15 | 116.5 (2) | C27—N3—C21 | 122.7 (2) |
N2—C20—H20 | 108.6 | C27—N3—C30 | 114.3 (2) |
C14—C20—H20 | 108.6 | C21—N3—C30 | 121.8 (2) |
C15—C20—H20 | 108.6 | C37—N4—C31 | 121.4 (2) |
N3—C21—C28 | 108.3 (2) | C37—N4—C40 | 114.0 (2) |
N3—C21—H21B | 110.0 | C31—N4—C40 | 123.4 (2) |
C28—C21—H21B | 110.0 | C9—O1—C3 | 105.3 (2) |
N3—C21—H21A | 110.0 | C4—O3—H3O | 111 (2) |
C28—C21—H21A | 110.0 | C19—O4—C13 | 105.65 (19) |
H21B—C21—H21A | 108.4 | C14—O6—H6O | 111 (3) |
C23—C22—C28 | 106.5 (2) | C29—O7—C23 | 105.5 (2) |
C23—C22—H22 | 126.8 | C24—O9—H9O | 112 (2) |
C28—C22—H22 | 126.8 | C39—O10—C33 | 105.4 (2) |
C22—C23—O7 | 111.0 (2) | C34—O12—H12O | 111 (2) |
C8—C2—C3—O1 | −1.1 (4) | C33—C32—C38—C39 | −0.8 (3) |
C10—C5—C6—C7 | −19.8 (3) | C33—C32—C38—C31 | 176.7 (3) |
C5—C6—C7—O2 | −171.7 (3) | N4—C31—C38—C39 | 2.6 (4) |
C5—C6—C7—N1 | 9.6 (4) | N4—C31—C38—C32 | −174.6 (3) |
C3—C2—C8—C9 | 0.2 (4) | C32—C38—C39—O10 | 0.9 (3) |
C3—C2—C8—C1 | −178.1 (3) | C31—C38—C39—O10 | −176.8 (3) |
N1—C1—C8—C9 | 5.4 (4) | C32—C38—C39—C34 | 178.4 (3) |
N1—C1—C8—C2 | −176.6 (3) | C31—C38—C39—C34 | 0.6 (5) |
C2—C8—C9—O1 | 0.7 (3) | O12—C34—C39—C38 | 136.9 (3) |
C1—C8—C9—O1 | 179.2 (3) | C40—C34—C39—C38 | 19.2 (4) |
C2—C8—C9—C4 | −179.8 (3) | O12—C34—C39—O10 | −45.9 (4) |
C1—C8—C9—C4 | −1.4 (5) | C40—C34—C39—O10 | −163.6 (2) |
O3—C4—C9—C8 | 135.7 (3) | O12—C34—C40—N4 | −163.2 (2) |
C10—C4—C9—C8 | 19.3 (4) | C39—C34—C40—N4 | −40.8 (3) |
O3—C4—C9—O1 | −44.9 (4) | O12—C34—C40—C35 | 79.8 (3) |
C10—C4—C9—O1 | −161.3 (2) | C39—C34—C40—C35 | −157.8 (2) |
C6—C5—C10—N1 | 22.5 (3) | C36—C35—C40—N4 | 19.1 (3) |
C6—C5—C10—C4 | 145.4 (2) | C36—C35—C40—C34 | 141.1 (3) |
O3—C4—C10—N1 | −163.7 (2) | O2—C7—N1—C10 | −173.1 (3) |
C9—C4—C10—N1 | −40.8 (3) | C6—C7—N1—C10 | 5.6 (3) |
O3—C4—C10—C5 | 78.6 (3) | O2—C7—N1—C1 | −9.3 (5) |
C9—C4—C10—C5 | −158.5 (2) | C6—C7—N1—C1 | 169.4 (3) |
C18—C12—C13—O4 | −0.5 (4) | C5—C10—N1—C7 | −18.2 (3) |
C20—C15—C16—C17 | −16.8 (3) | C4—C10—N1—C7 | −142.9 (2) |
C15—C16—C17—O5 | −176.4 (3) | C5—C10—N1—C1 | 178.0 (3) |
C15—C16—C17—N2 | 5.2 (4) | C4—C10—N1—C1 | 53.3 (3) |
C13—C12—C18—C19 | −0.1 (3) | C8—C1—N1—C7 | 165.1 (3) |
C13—C12—C18—C11 | 177.2 (3) | C8—C1—N1—C10 | −32.4 (4) |
N2—C11—C18—C19 | −0.3 (4) | O5—C17—N2—C11 | −4.6 (5) |
N2—C11—C18—C12 | −177.3 (3) | C16—C17—N2—C11 | 173.8 (3) |
C12—C18—C19—O4 | 0.7 (3) | O5—C17—N2—C20 | −168.9 (3) |
C11—C18—C19—O4 | −177.0 (2) | C16—C17—N2—C20 | 9.5 (3) |
C12—C18—C19—C14 | 178.5 (3) | C18—C11—N2—C17 | 170.8 (3) |
C11—C18—C19—C14 | 0.9 (5) | C18—C11—N2—C20 | −26.5 (4) |
O6—C14—C19—C18 | 140.8 (3) | C14—C20—N2—C17 | −145.3 (2) |
C20—C14—C19—C18 | 21.4 (4) | C15—C20—N2—C17 | −19.8 (3) |
O6—C14—C19—O4 | −41.6 (4) | C14—C20—N2—C11 | 50.7 (3) |
C20—C14—C19—O4 | −161.0 (2) | C15—C20—N2—C11 | 176.3 (2) |
O6—C14—C20—N2 | −165.6 (2) | O8—C27—N3—C21 | −3.2 (5) |
C19—C14—C20—N2 | −42.3 (3) | C26—C27—N3—C21 | 176.5 (3) |
O6—C14—C20—C15 | 77.0 (3) | O8—C27—N3—C30 | −171.4 (3) |
C19—C14—C20—C15 | −159.7 (2) | C26—C27—N3—C30 | 8.3 (3) |
C16—C15—C20—N2 | 21.4 (3) | C28—C21—N3—C27 | 154.5 (3) |
C16—C15—C20—C14 | 143.8 (2) | C28—C21—N3—C30 | −38.1 (4) |
C28—C22—C23—O7 | 0.2 (4) | C24—C30—N3—C27 | −137.6 (3) |
C30—C25—C26—C27 | −7.4 (4) | C25—C30—N3—C27 | −12.7 (3) |
C25—C26—C27—O8 | 179.6 (3) | C24—C30—N3—C21 | 54.1 (4) |
C25—C26—C27—N3 | −0.1 (4) | C25—C30—N3—C21 | 179.0 (3) |
C23—C22—C28—C29 | −0.3 (3) | O11—C37—N4—C31 | −5.3 (5) |
C23—C22—C28—C21 | 179.4 (3) | C36—C37—N4—C31 | 173.6 (3) |
N3—C21—C28—C29 | 10.5 (4) | O11—C37—N4—C40 | −172.8 (3) |
N3—C21—C28—C22 | −169.1 (3) | C36—C37—N4—C40 | 6.1 (4) |
C22—C28—C29—O7 | 0.3 (3) | C38—C31—N4—C37 | 163.3 (3) |
C21—C28—C29—O7 | −179.4 (3) | C38—C31—N4—C40 | −30.4 (4) |
C22—C28—C29—C24 | 178.9 (3) | C34—C40—N4—C37 | −140.3 (2) |
C21—C28—C29—C24 | −0.8 (5) | C35—C40—N4—C37 | −16.1 (3) |
O9—C24—C29—C28 | 131.2 (3) | C34—C40—N4—C31 | 52.5 (4) |
C30—C24—C29—C28 | 13.9 (4) | C35—C40—N4—C31 | 176.7 (3) |
O9—C24—C29—O7 | −50.3 (4) | C8—C9—O1—C3 | −1.3 (3) |
C30—C24—C29—O7 | −167.6 (2) | C4—C9—O1—C3 | 179.2 (3) |
O9—C24—C30—N3 | −158.5 (2) | C2—C3—O1—C9 | 1.5 (4) |
C29—C24—C30—N3 | −36.1 (3) | C18—C19—O4—C13 | −0.9 (3) |
O9—C24—C30—C25 | 83.4 (3) | C14—C19—O4—C13 | −179.0 (3) |
C29—C24—C30—C25 | −154.2 (2) | C12—C13—O4—C19 | 0.9 (4) |
C26—C25—C30—N3 | 11.5 (3) | C28—C29—O7—C23 | −0.2 (3) |
C26—C25—C30—C24 | 134.6 (3) | C24—C29—O7—C23 | −178.9 (3) |
C38—C32—C33—O10 | 0.4 (4) | C22—C23—O7—C29 | 0.0 (3) |
C40—C35—C36—C37 | −16.3 (4) | C38—C39—O10—C33 | −0.7 (3) |
C35—C36—C37—O11 | −174.2 (3) | C34—C39—O10—C33 | −178.4 (3) |
C35—C36—C37—N4 | 7.0 (4) | C32—C33—O10—C39 | 0.1 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
O3—H3O···O2i | 0.84 (2) | 1.90 (2) | 2.681 (2) | 154 (3) |
O6—H6O···O8ii | 0.86 (2) | 1.93 (2) | 2.766 (3) | 166 (4) |
O9—H9O···O5ii | 0.85 (2) | 1.92 (2) | 2.737 (3) | 161 (3) |
O12—H12O···O11iii | 0.83 (2) | 1.98 (2) | 2.797 (3) | 167 (3) |
Symmetry codes: (i) −x+1/2, −y, z−1/2; (ii) −x+3/2, −y+1, z−1/2; (iii) −x+3/2, −y+2, z+1/2. |
Experimental details
Crystal data | |
Chemical formula | C10H11NO3 |
Mr | 193.20 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 298 |
a, b, c (Å) | 14.7603 (10), 15.1301 (17), 16.2847 (9) |
V (Å3) | 3636.8 (5) |
Z | 16 |
Radiation type | Mo Kα |
µ (mm−1) | 0.11 |
Crystal size (mm) | 0.58 × 0.34 × 0.09 |
Data collection | |
Diffractometer | Oxford Diffraction Gemini R CCD |
Absorption correction | Analytical (Clark & Reid, 1995) |
Tmin, Tmax | 0.953, 0.989 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 55202, 3581, 3168 |
Rint | 0.036 |
(sin θ/λ)max (Å−1) | 0.595 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.034, 0.086, 1.04 |
No. of reflections | 3581 |
No. of parameters | 522 |
No. of restraints | 4 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.17, −0.15 |
Computer programs: CrysAlis CCD (Oxford Diffraction, 2006), CrysAlis RED (Oxford Diffraction, 2006), SHELXS97 (Sheldrick, 2008), DIAMOND (Brandenburg, 2001), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2009) and WinGX (Farrugia, 1999).
D—H···A | D—H | H···A | D···A | D—H···A |
O3—H3O···O2i | 0.842 (18) | 1.90 (2) | 2.681 (2) | 154 (3) |
O6—H6O···O8ii | 0.855 (19) | 1.93 (2) | 2.766 (3) | 166 (4) |
O9—H9O···O5ii | 0.848 (19) | 1.92 (2) | 2.737 (3) | 161 (3) |
O12—H12O···O11iii | 0.829 (18) | 1.98 (2) | 2.797 (3) | 167 (3) |
Symmetry codes: (i) −x+1/2, −y, z−1/2; (ii) −x+3/2, −y+1, z−1/2; (iii) −x+3/2, −y+2, z+1/2. |
Acknowledgements
The authors thank the Grant Agency of Slovak Republic (grant Nos. 1/0429/11, 1/0679/11) and the Slovak Research and Development Agency (under contract Nos. APVV-0797–11 and APVV-0204–10) for financial support of these research programs.
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This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
Indolizines are electron-rich heterocycles with very low oxidation potential. Functionalized indolizines are common substructures found in biologically important natural products and synthetic pharmaceuticals. Due to the various biological functions associated with this skeleton, it has been frequently employed as a key scaffold in the drug industry (Gundersen et al., 2007). Indolizine alkaloids are excellent inhibitors of biologically important pathways. These include the binding and processing of glycoproteins, potent glycosidase inhibitory activities (Pyne, 2005), activity against AIDS virus HIV and some carcinogenic cells (Mikael, 1999). They have also shown to be calcium entry blockers (Gupta et al., 2003) and potent antioxidants inhibiting lipid peroxidation in vitro (Teklu et al., 2005). As such, indolizines are important synthetic targets in view of developing new pharmaceuticals for the treatment of cardiovascular diseases (Gubin et al., 1992). Based on these facts and in contitutation of our interest in developing simple and efficient route for the synthesis of novel indolizine derivatives. The molecular structure and the atom labeling scheme of four independent molecules in the asymmetric unit are shown in Fig. 1. The absolute configuration was established by synthesis and is depicted in the scheme and Fig.1. The expected stereochemistry of atoms C4 and C10, C14 and C20, C24 and C30, C34 and C40 in the four molecules was confirmed as R, R, respectively (Fig. 1). The central six-membered rings of the four molecules according to Nardelli (Nardelli, 1983) is not planar and adopts an envelope conformation, with atoms C10, C20, C30 and C40 as the flaps. The displacements of atoms C10, C20, C30 and C40 from the mean planes of the remaining five atoms are 0.539 (2), 0.548 (3), 0.509 (3) and 0.544 (3) Å, respectively. The bond lengths of the carbonyl groups C=O in the four molecules are somewhat longer than typical carbonyl bonds. This may be due to the fact that atoms O2, O5, O8 and O11 participates in intermolecular hydrogen bonds, they seem to be effective in the stabilization of the structure. The central six-membered rings form dihedral angles of 21.8 (1), 20.1 (1), 24.9 (1) and 22.5 (1)° with the oxopyrrolidine rings, in the four independent molecules, respectively. Intermolecular O–H···O hydrogen bonds link the molecules into extended chains, which run parallel to the c axis (Fig.2).