research communications
Synthesis and 52H60N6O10·0.25H2O
of peptide dimethyl biphenyl hybrid CaDepartment of Chemistry, VNU University of science, Vietnam National University, Hanoi, 19 Le Thanh Tong, Hanoi, Vietnam
*Correspondence e-mail: thaithanhthubui@gmail.com
The synthesis and 2Cl2, amine HN–proline–phenylalanine–alanine–COOMe and Et3N at 273 K under N2 atmosphere and characterized by single-crystal X-ray diffraction. The contains one peptide molecule and a quarter of a water molecule. A disorder of a methyl and methoxycarbonyl group of one alanine residue is observed with occupancy ratio 0.502 (6):0.498 (6). The structure is consolidated by intra- and intermolecular hydrogen bonds.
of peptide 6,6′-dimethyl biphenyl hybrid are described. The title compound was synthesized by reaction between 6,6′-dimethyl-[1,1′-biphenyl]-2,2′-dicarbonyl dichloride in CHCCDC reference: 2026794
1. Chemical context
Since the first application in 1922 of et al., 1922), the chemistry of has become a very important domain in the search of new therapeutic drugs. From 2011 to 2018, the global market of drugs has increased from US $ 14.1 to 24.4 billion. With more than 140 in clinical trials, the number of peptide-based drugs is expected to grow significantly (Fosgerau et al., 2015). Despite their tremendous potential, applications of for pharmaceutical purposes are limited by their instability toward enzymatic systems, short half-life, rapid renal clearance, and formulation challenges (Otvos et al., 2014). These problems can be overcome by modifying the linear peptide to enhance the stability and therefore the selectivity and affinity. The biphenyl structure is present in numerous pharmaceuticals and bioactive compounds, as illustrated by the glycopeptide antibiotic vancomycin, the proteasome inhibitor TMC-95A (Kaiser et al., 2004) and arylomycins (Schimana et al., 2002). A statistical analysis of NMR data indicates that compounds containing the biphenyl structure can bind a wide range of proteins with high levels of specificity (Hajduk et al., 2000). Coupling of a small protein chain to the biphenyl structure is a strategy to create a new family of peptidomimetic compounds, which can be used in medicinal chemistry because of its specific conformation and its particular hydrogen-bonding interactions.
in the treatment of diabetes with insulin (BantingThe synthesis and biological activity as calpain inhibitor of peptide–biphenyl hybrids type I have been reported by Montero and Mann (Montero et al., 2004a,b; Mann et al., 2002). Amine et al. (2002) synthesized a bis amido–copper(II) complex from N-containing tetradentate ligands having two amido groups with a biphenyl skeleton, which is used as a DNA cleaving agent. Recently, we have reported crystallographic studies of a peptide-biphenyl hybrid A (Fig. 1) with tripeptide Pro–Phe–Ala (Le et al., 2020).
We report herein the synthesis and crystallographic study of a peptide-2,2′-biphenyl B (Fig. 1) with the introduction of two methyl groups at the 6-6′ positions to prevent around the central aryl–aryl bond.
2. Structural commentary
The compound dimethyl 2,2′-[((2S,2′S)-2,2′-{[(2S,2′S)-1,1′-(6,6′-dimethyl-[1,1′-biphenyl]-2,2′-dicarbonyl)bis(pyrrolidine-1,2-diyl-2-carbonyl)]bis(azanediyl)}bis(3-phenylpropanoyl))bis(azanediyl)](2S,2′S)-dipropionate (Fig. 2) crystallizes in the monoclinic C2 with one molecule of peptide biphenyl hybrid accompanied by a quarter of a water molecule in the Two methyl groups have been introduced to the biphenyl rings at the 6,6′ position in order to limit the rotation of the two central phenyl rings in solution. In the solid state, the dihedral angle between biphenyl rings C20–C25 and C27-C32 is 73.8 (3)°. However, this value is similar to that of a previous compound not bearing the methyl groups (C50H56N6O10·0.5H2O; Le et al., 2020). A disorder of a methyl and methoxycarbonyl group of alanine is observed in the and was refined with an occupancy ratio of 0.502 (6):0.498 (6).
The backbone conformation of the two tripeptide fragments is characterized by the torsion angles ω, φ, ψ (see Table 1). The torsion angles φ and ψ of amino acids Ala1, Ala2, Phe2 correspond with the usual α-helix (right-handed) region of the Ramachandran plot, and only the torsion angles of amino acid Phe1 fall into the corresponding type β-sheet Ramachandran plot region. For both prolines, the related torsion angles lie in the α region of the Ramachandran plot for proline.
|
There are six intramolecular hydrogen bonds formed in the structure of the title compound (Table 2). Two hydrogen bonds are formed between the NH and CO groups with H⋯O distances of 2.07 Å for N5—H5 ⋯O5 and 2.42 Å for N6—H6⋯O6. The latter value is noticeably longer than the values observed (from 2.04 to 2.29 Å) in other reported (Ranganathan et al., 1997; Le et al., 2020). Four other intramolecular bonds are formed between CH and CO groups with distances from 2.35 to 2.59 Å.
3. Supramolecular features
In the crystal, the packing is characterized by N—H⋯O, O—H⋯O and C—H⋯O hydrogen bonding (see Table 2, Fig. 3). The strongest intermolecular interaction is formed between NH and CO groups of two neighboring peptide residues [N1—H1⋯O4i, with d = 2.01 Å; symmetry code: (i) − x, + y, 1 − z]. Furthermore, there are six additional hydrogen bonds linking the molecules. Two contacts are established between the water molecule and two tripeptides (O11—H11A⋯O8; C13— H13⋯O11). Four C—H⋯O=C contacts with H⋯O distances ranging from 2.39 to 2.60 Å further consolidate the crystal packing. In addition, the molecules are linked by two intermolecular C—H ⋯π interactions, one between a proline H atom and the phenyl ring of a phenylalanine residue, the other between a H atom of the disordered methyl group and a phenyl ring of the central biphenyl fragment.
4. Database survey
A search of the Cambridge Structural Database (version 5.41 with update of March 2020; Groom et al., 2016) for peptide–dimethyl biphenyl hybrids was conducted. There are seven dimethyl biphenyl hybrid structures with only one amino acid, including JITYET (Linden & Rippert, 2018a), JITZEU (Linden & Rippert, 2018b), JITYOD (Linden & Rippert, 2018c), NOSPUG & NOSQAN (Weigand & Feigel, 1998), PITSUJ (Linden et al., 2018d) and NIKJOI (Samadi et al., 2013). For these structures the dihedral angles between the dimethyl biphenyl rings varies from 82.0 to 95.8o, larger than the corresponding angle of the title compound.
5. Synthesis and crystallization
To a round-bottom flask was added 6,6′-dimethyl-[1,1′-biphenyl]-2,2′-dicarboxylic acid (1 eq.) and SOCl2 (3 eq.) respectively under a nitrogen atmosphere. The mixture was heated under reflux for 4 h and was then evaporated under vacuum. The acid chloride was used in the next step without further purification.
To a round-bottom flask was added amine HN–proline–phenylalanine–alanine–COOMe (1 eq.), Et3N (2 eq.) and anhydrous CH2Cl2 (50mL). To this solution was added a solution of (6,6′-dimethyl-[1,1′-biphenyl]-2,2′-dicarbonyl dichloride in CH2Cl2 at 273 K under an N2 atmosphere. After completion of the reaction, the mixture was washed with 1 N HCl solution, water and a solution of brine, respectively. The organic phase was dried over Na2SO4, filtered and evaporated under reduced pressure. The crude product was then purified by flash (AcOEt/hexane 3:2) to give a white solid (60% yield). The compound was recrystallized by slow evaporation in methanol to give crystals suitable for X-ray diffraction.
6. Refinement
Crystal data, data collection and structure . The methyl and methoxycarbonyl groups of alanine show two conformations with refined occupancy factors converging to 0.502 (6) and 0.498 (6). Geometrical restraints were applied to the disordered atoms. H atoms were placed at calculated positions (C—H = 0.95–1.08 Å and N—H = 0.88 Å), with isotropic displacement parameters Uiso(H) = 1.5Ueq(C) for methyl H atoms and 1.2Ueq(C,N) for all other H atoms. The solvent water molecule is disordered and was refined with a site occupation factor fixed to 0.25. The H atoms of the water molecule were located in difference-Fourier maps and refined in riding-model approximation with Uiso(H) = 1.5Ueq(O).
details are summarized in Table 3
|
Supporting information
CCDC reference: 2026794
https://doi.org/10.1107/S2056989020012931/vm2240sup1.cif
contains datablock I. DOI:Supporting information file. DOI: https://doi.org/10.1107/S2056989020012931/vm2240Isup3.cdx
Supporting information file. DOI: https://doi.org/10.1107/S2056989020012931/vm2240Isup4.cdx
Supporting information file. DOI: https://doi.org/10.1107/S2056989020012931/vm2240sup5.docx
Supporting information file. DOI: https://doi.org/10.1107/S2056989020012931/vm2240sup6.docx
Supporting information file. DOI: https://doi.org/10.1107/S2056989020012931/vm2240sup7.tif
Supporting information file. DOI: https://doi.org/10.1107/S2056989020012931/vm2240sup8.tif
Data collection: APEX22 (Bruker 2013); cell
SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013); program(s) used to solve structure: ShelXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).C52H60N6O10·0.25H2O | F(000) = 1986 |
Mr = 933.56 | Dx = 1.263 Mg m−3 |
Monoclinic, C2 | Mo Kα radiation, λ = 0.71073 Å |
a = 27.505 (3) Å | Cell parameters from 9371 reflections |
b = 12.3814 (12) Å | θ = 2.8–25.8° |
c = 14.6346 (14) Å | µ = 0.09 mm−1 |
β = 99.999 (3)° | T = 100 K |
V = 4908.2 (8) Å3 | Needle, clear light colourless |
Z = 4 | 0.3 × 0.2 × 0.1 mm |
Bruker D8 Quest CMOS diffractometer | 7959 reflections with I > 2σ(I) |
φ and ω scans | Rint = 0.062 |
Absorption correction: multi-scan (SADABS-; Bruker, 2013) | θmax = 25.8°, θmin = 2.8° |
Tmin = 0.713, Tmax = 0.745 | h = −33→33 |
84318 measured reflections | k = −15→15 |
9371 independent reflections | l = −17→17 |
Refinement on F2 | Hydrogen site location: mixed |
Least-squares matrix: full | H atoms treated by a mixture of independent and constrained refinement |
R[F2 > 2σ(F2)] = 0.038 | w = 1/[σ2(Fo2) + (0.0359P)2 + 2.1291P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.086 | (Δ/σ)max < 0.001 |
S = 1.06 | Δρmax = 0.28 e Å−3 |
9371 reflections | Δρmin = −0.16 e Å−3 |
693 parameters | Absolute structure: Flack x determined using 3323 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013) |
4 restraints | Absolute structure parameter: −0.1 (3) |
Primary atom site location: dual |
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 | Occ. (<1) | |
O5 | 0.33318 (6) | 0.37671 (15) | 0.30911 (12) | 0.0262 (4) | |
O4 | 0.25033 (7) | 0.41245 (17) | 0.49754 (15) | 0.0367 (5) | |
O6 | 0.37283 (7) | 0.35432 (16) | 0.07943 (13) | 0.0314 (4) | |
N3 | 0.36969 (8) | 0.32535 (18) | 0.45153 (14) | 0.0252 (5) | |
N2 | 0.32176 (8) | 0.50351 (19) | 0.50273 (15) | 0.0291 (5) | |
H2 | 0.3537 | 0.4960 | 0.5038 | 0.035* | |
O7 | 0.25946 (8) | 0.5451 (2) | −0.00116 (15) | 0.0531 (6) | |
O3 | 0.38550 (8) | 0.64671 (17) | 0.4803 (2) | 0.0552 (7) | |
O9 | 0.40799 (7) | 0.7684 (2) | 0.02936 (16) | 0.0536 (7) | |
N1 | 0.33544 (8) | 0.7906 (2) | 0.48045 (17) | 0.0351 (6) | |
H1 | 0.3070 | 0.8150 | 0.4917 | 0.042* | |
N5 | 0.29721 (8) | 0.50901 (18) | 0.14594 (15) | 0.0277 (5) | |
H5 | 0.3085 | 0.4583 | 0.1862 | 0.033* | |
N4 | 0.29975 (8) | 0.2897 (2) | 0.10755 (15) | 0.0302 (5) | |
O2A | 0.4152 (8) | 0.8404 (16) | 0.5865 (9) | 0.052 (4) | 0.498 (6) |
O10 | 0.47865 (9) | 0.8022 (2) | 0.12726 (19) | 0.0665 (8) | |
C19 | 0.37162 (9) | 0.35712 (19) | 0.36445 (17) | 0.0221 (5) | |
O8 | 0.36763 (10) | 0.74704 (19) | 0.2248 (2) | 0.0667 (8) | |
N6 | 0.38529 (8) | 0.6049 (2) | 0.14123 (16) | 0.0335 (5) | |
H6 | 0.3742 | 0.5463 | 0.1106 | 0.040* | |
C20 | 0.42128 (9) | 0.3761 (2) | 0.33809 (17) | 0.0224 (5) | |
C14 | 0.29481 (10) | 0.4139 (2) | 0.49355 (18) | 0.0277 (6) | |
C22 | 0.49273 (10) | 0.4901 (2) | 0.34994 (19) | 0.0300 (6) | |
H22 | 0.5116 | 0.5499 | 0.3769 | 0.036* | |
C21 | 0.44813 (10) | 0.4663 (2) | 0.37539 (19) | 0.0264 (6) | |
H21 | 0.4355 | 0.5113 | 0.4184 | 0.032* | |
C39 | 0.27589 (10) | 0.4803 (3) | 0.05996 (19) | 0.0336 (7) | |
C34 | 0.34964 (10) | 0.2867 (2) | 0.11713 (18) | 0.0292 (6) | |
C25 | 0.43896 (10) | 0.3099 (2) | 0.27349 (17) | 0.0264 (6) | |
C15 | 0.32173 (10) | 0.3090 (2) | 0.48016 (18) | 0.0290 (6) | |
H15 | 0.3004 | 0.2638 | 0.4327 | 0.035* | |
C23 | 0.50992 (10) | 0.4261 (2) | 0.2846 (2) | 0.0339 (7) | |
H23 | 0.5403 | 0.4441 | 0.2659 | 0.041* | |
C32 | 0.37479 (11) | 0.1926 (2) | 0.1698 (2) | 0.0342 (7) | |
C5 | 0.34545 (10) | 0.6858 (2) | 0.4894 (2) | 0.0362 (7) | |
C42 | 0.22491 (12) | 0.6148 (3) | 0.2431 (2) | 0.0393 (7) | |
C8 | 0.32288 (11) | 0.5941 (3) | 0.6886 (2) | 0.0368 (7) | |
C18 | 0.41107 (10) | 0.2861 (3) | 0.52286 (19) | 0.0355 (7) | |
H18A | 0.4391 | 0.3375 | 0.5316 | 0.043* | |
H18B | 0.4228 | 0.2143 | 0.5062 | 0.043* | |
C24 | 0.48386 (10) | 0.3365 (2) | 0.24582 (19) | 0.0326 (7) | |
C6 | 0.30370 (9) | 0.6123 (2) | 0.5111 (2) | 0.0303 (6) | |
H6A | 0.2743 | 0.6231 | 0.4612 | 0.036* | |
C28 | 0.43711 (12) | 0.1101 (2) | 0.2858 (2) | 0.0382 (7) | |
C38 | 0.27062 (10) | 0.3606 (3) | 0.03950 (19) | 0.0348 (7) | |
H38 | 0.2789 | 0.3459 | −0.0232 | 0.042* | |
C27 | 0.41520 (10) | 0.2032 (2) | 0.2421 (2) | 0.0306 (6) | |
C7 | 0.28776 (10) | 0.6356 (3) | 0.6048 (2) | 0.0360 (7) | |
H7A | 0.2831 (11) | 0.715 (3) | 0.610 (2) | 0.043* | |
H7B | 0.2561 (12) | 0.604 (3) | 0.606 (2) | 0.043* | |
C40 | 0.30215 (11) | 0.6212 (2) | 0.1744 (2) | 0.0344 (7) | |
H40 | 0.2820 | 0.6644 | 0.1237 | 0.041* | |
C48 | 0.35480 (12) | 0.6626 (2) | 0.1841 (2) | 0.0395 (7) | |
C51 | 0.44291 (12) | 0.7469 (3) | 0.1020 (2) | 0.0465 (8) | |
C41 | 0.27949 (12) | 0.6391 (2) | 0.2612 (2) | 0.0403 (7) | |
H41A | 0.2962 | 0.5918 | 0.3116 | 0.048* | |
H41B | 0.2848 | 0.7150 | 0.2818 | 0.048* | |
C49 | 0.43632 (11) | 0.6369 (3) | 0.1441 (2) | 0.0381 (7) | |
H49 | 0.4534 | 0.6375 | 0.2103 | 0.046* | |
C31 | 0.35836 (13) | 0.0900 (2) | 0.1390 (2) | 0.0456 (8) | |
H31 | 0.3315 | 0.0830 | 0.0888 | 0.055* | |
C17 | 0.38721 (11) | 0.2796 (3) | 0.6093 (2) | 0.0461 (8) | |
H17A | 0.3879 | 0.3506 | 0.6406 | 0.055* | |
H17B | 0.4040 | 0.2256 | 0.6538 | 0.055* | |
C43 | 0.20546 (13) | 0.5304 (3) | 0.2867 (2) | 0.0406 (8) | |
H43 | 0.2267 | 0.4876 | 0.3304 | 0.049* | |
C26 | 0.50273 (12) | 0.2713 (3) | 0.1714 (2) | 0.0459 (8) | |
H26A | 0.5078 | 0.1962 | 0.1920 | 0.069* | |
H26B | 0.5341 | 0.3018 | 0.1604 | 0.069* | |
H26C | 0.4785 | 0.2737 | 0.1139 | 0.069* | |
C35 | 0.26820 (12) | 0.2261 (3) | 0.1605 (2) | 0.0403 (8) | |
H35A | 0.2818 | 0.2267 | 0.2278 | 0.048* | |
H35B | 0.2648 | 0.1504 | 0.1386 | 0.048* | |
C9 | 0.36689 (11) | 0.6476 (3) | 0.7211 (3) | 0.0515 (9) | |
H9 | 0.3753 | 0.7096 | 0.6890 | 0.062* | |
C30 | 0.38083 (14) | −0.0007 (3) | 0.1809 (3) | 0.0563 (10) | |
H30 | 0.3697 | −0.0703 | 0.1592 | 0.068* | |
C36 | 0.21906 (12) | 0.2852 (3) | 0.1399 (2) | 0.0492 (9) | |
H36A | 0.2182 | 0.3463 | 0.1833 | 0.059* | |
H36B | 0.1912 | 0.2358 | 0.1441 | 0.059* | |
C44 | 0.15538 (13) | 0.5070 (3) | 0.2676 (2) | 0.0488 (9) | |
H44 | 0.1427 | 0.4490 | 0.2990 | 0.059* | |
C16 | 0.33427 (11) | 0.2449 (3) | 0.5705 (2) | 0.0434 (8) | |
H16A | 0.3324 | 0.1662 | 0.5584 | 0.052* | |
H16B | 0.3117 | 0.2637 | 0.6138 | 0.052* | |
C29 | 0.41922 (14) | 0.0090 (3) | 0.2539 (2) | 0.0520 (9) | |
H29 | 0.4339 | −0.0543 | 0.2834 | 0.062* | |
C33 | 0.48036 (13) | 0.1160 (3) | 0.3656 (2) | 0.0466 (8) | |
H33A | 0.5112 | 0.1201 | 0.3410 | 0.070* | |
H33B | 0.4807 | 0.0514 | 0.4044 | 0.070* | |
H33C | 0.4771 | 0.1804 | 0.4030 | 0.070* | |
C37 | 0.21720 (11) | 0.3253 (3) | 0.0408 (2) | 0.0492 (9) | |
H37A | 0.1941 | 0.3867 | 0.0268 | 0.059* | |
H37B | 0.2070 | 0.2668 | −0.0047 | 0.059* | |
C50 | 0.46145 (12) | 0.5544 (3) | 0.0915 (2) | 0.0498 (9) | |
H50A | 0.4560 | 0.4818 | 0.1145 | 0.075* | |
H50B | 0.4970 | 0.5693 | 0.1008 | 0.075* | |
H50C | 0.4476 | 0.5587 | 0.0252 | 0.075* | |
C13 | 0.31123 (13) | 0.5060 (3) | 0.7362 (2) | 0.0546 (9) | |
H13 | 0.2811 | 0.4689 | 0.7158 | 0.065* | |
C3 | 0.37093 (12) | 0.8660 (3) | 0.4522 (3) | 0.0506 (9) | |
H3A | 0.3893 | 0.8282 | 0.4082 | 0.061* | 0.498 (6) |
H3B | 0.3776 | 0.8469 | 0.3891 | 0.061* | 0.502 (6) |
C45 | 0.12403 (14) | 0.5668 (3) | 0.2040 (3) | 0.0587 (10) | |
H45 | 0.0898 | 0.5502 | 0.1903 | 0.070* | |
C47 | 0.19287 (15) | 0.6750 (4) | 0.1803 (3) | 0.0668 (12) | |
H47 | 0.2053 | 0.7342 | 0.1500 | 0.080* | |
C52 | 0.41693 (14) | 0.8637 (4) | −0.0232 (3) | 0.0722 (13) | |
H52A | 0.3905 | 0.8713 | −0.0770 | 0.108* | |
H52B | 0.4487 | 0.8563 | −0.0443 | 0.108* | |
H52C | 0.4177 | 0.9278 | 0.0163 | 0.108* | |
C11 | 0.38662 (15) | 0.5233 (4) | 0.8454 (3) | 0.0675 (12) | |
H11 | 0.4085 | 0.4988 | 0.8989 | 0.081* | |
C10 | 0.39836 (14) | 0.6128 (4) | 0.7984 (3) | 0.0665 (12) | |
H10 | 0.4283 | 0.6505 | 0.8195 | 0.080* | |
C12 | 0.34359 (16) | 0.4694 (4) | 0.8155 (3) | 0.0695 (12) | |
H12 | 0.3354 | 0.4074 | 0.8480 | 0.083* | |
C46 | 0.14300 (16) | 0.6512 (4) | 0.1605 (3) | 0.0794 (14) | |
H46 | 0.1217 | 0.6935 | 0.1164 | 0.095* | |
O1B | 0.46376 (18) | 0.8694 (5) | 0.5125 (5) | 0.082 (2) | 0.502 (6) |
C1A | 0.4577 (7) | 0.8657 (13) | 0.6565 (10) | 0.065 (4) | 0.498 (6) |
H1AA | 0.4865 | 0.8781 | 0.6266 | 0.098* | 0.498 (6) |
H1AB | 0.4645 | 0.8052 | 0.7000 | 0.098* | 0.498 (6) |
H1AC | 0.4510 | 0.9308 | 0.6902 | 0.098* | 0.498 (6) |
C4A | 0.3372 (3) | 0.9666 (6) | 0.3947 (6) | 0.0338 (16) | 0.498 (6) |
H4AA | 0.314 (3) | 1.001 (6) | 0.437 (5) | 0.051* | 0.498 (6) |
H4AB | 0.318 (3) | 0.951 (6) | 0.348 (5) | 0.051* | 0.498 (6) |
H4AC | 0.365 (3) | 1.022 (6) | 0.380 (5) | 0.051* | 0.498 (6) |
C2B | 0.4233 (4) | 0.8525 (9) | 0.5327 (8) | 0.051 (3) | 0.502 (6) |
O11 | 0.2727 (2) | 0.8908 (5) | 0.1778 (4) | 0.0166 (14) | 0.25 |
H11A | 0.3048 | 0.8916 | 0.1906 | 0.025* | 0.25 |
H11B | 0.2657 | 0.8381 | 0.1383 | 0.025* | 0.25 |
C4B | 0.3574 (3) | 0.9738 (5) | 0.4551 (7) | 0.049 (2) | 0.502 (6) |
H4BA | 0.3299 | 0.9887 | 0.4044 | 0.074* | 0.502 (6) |
H4BB | 0.3856 | 1.0197 | 0.4483 | 0.074* | 0.502 (6) |
H4BC | 0.3471 | 0.9891 | 0.5146 | 0.074* | 0.502 (6) |
C2A | 0.4049 (2) | 0.9141 (6) | 0.5214 (4) | 0.0317 (15) | 0.498 (6) |
O2B | 0.4184 (6) | 0.8407 (16) | 0.6190 (9) | 0.044 (3) | 0.502 (6) |
O1A | 0.42431 (16) | 1.0015 (3) | 0.5223 (3) | 0.0492 (16) | 0.498 (6) |
C1B | 0.4595 (6) | 0.8377 (14) | 0.6925 (11) | 0.081 (5) | 0.502 (6) |
H1BA | 0.4832 | 0.7835 | 0.6788 | 0.121* | 0.502 (6) |
H1BB | 0.4483 | 0.8188 | 0.7504 | 0.121* | 0.502 (6) |
H1BC | 0.4754 | 0.9088 | 0.6989 | 0.121* | 0.502 (6) |
U11 | U22 | U33 | U12 | U13 | U23 | |
O5 | 0.0269 (9) | 0.0271 (10) | 0.0227 (9) | 0.0019 (8) | −0.0009 (8) | −0.0012 (8) |
O4 | 0.0254 (10) | 0.0376 (12) | 0.0472 (12) | −0.0104 (9) | 0.0069 (8) | −0.0008 (10) |
O6 | 0.0302 (10) | 0.0322 (11) | 0.0318 (10) | 0.0050 (9) | 0.0054 (8) | −0.0008 (9) |
N3 | 0.0254 (12) | 0.0256 (12) | 0.0232 (11) | −0.0044 (9) | 0.0002 (9) | 0.0021 (9) |
N2 | 0.0221 (11) | 0.0308 (13) | 0.0348 (13) | −0.0061 (10) | 0.0056 (9) | −0.0074 (11) |
O7 | 0.0503 (14) | 0.0743 (17) | 0.0343 (11) | 0.0200 (12) | 0.0064 (10) | 0.0256 (12) |
O3 | 0.0292 (12) | 0.0309 (12) | 0.114 (2) | −0.0076 (9) | 0.0349 (13) | −0.0243 (13) |
O9 | 0.0327 (12) | 0.0701 (18) | 0.0595 (15) | 0.0071 (11) | 0.0126 (11) | 0.0410 (13) |
N1 | 0.0259 (12) | 0.0284 (13) | 0.0554 (16) | −0.0076 (10) | 0.0196 (11) | −0.0116 (12) |
N5 | 0.0354 (13) | 0.0248 (12) | 0.0246 (12) | 0.0065 (10) | 0.0099 (10) | 0.0053 (10) |
N4 | 0.0309 (12) | 0.0303 (13) | 0.0290 (12) | −0.0028 (10) | 0.0040 (10) | −0.0103 (10) |
O2A | 0.041 (5) | 0.038 (5) | 0.065 (10) | −0.016 (3) | −0.026 (7) | 0.003 (8) |
O10 | 0.0492 (15) | 0.0653 (18) | 0.0834 (19) | −0.0116 (14) | 0.0069 (13) | 0.0320 (15) |
C19 | 0.0295 (14) | 0.0124 (12) | 0.0231 (13) | −0.0013 (10) | 0.0014 (11) | −0.0028 (10) |
O8 | 0.0794 (18) | 0.0229 (12) | 0.110 (2) | −0.0139 (12) | 0.0500 (16) | −0.0127 (13) |
N6 | 0.0345 (13) | 0.0342 (13) | 0.0325 (13) | −0.0013 (11) | 0.0081 (10) | 0.0046 (11) |
C20 | 0.0277 (13) | 0.0161 (12) | 0.0222 (13) | 0.0028 (10) | 0.0005 (10) | 0.0058 (11) |
C14 | 0.0282 (15) | 0.0322 (15) | 0.0219 (14) | −0.0075 (12) | 0.0020 (11) | 0.0003 (12) |
C22 | 0.0305 (15) | 0.0233 (15) | 0.0342 (15) | −0.0039 (12) | 0.0000 (12) | 0.0053 (12) |
C21 | 0.0305 (15) | 0.0200 (13) | 0.0269 (14) | 0.0013 (11) | 0.0000 (11) | 0.0012 (11) |
C39 | 0.0246 (14) | 0.052 (2) | 0.0257 (15) | 0.0092 (13) | 0.0095 (12) | 0.0095 (14) |
C34 | 0.0337 (15) | 0.0254 (14) | 0.0272 (14) | 0.0013 (12) | 0.0019 (12) | −0.0103 (12) |
C25 | 0.0307 (14) | 0.0229 (14) | 0.0241 (13) | 0.0047 (11) | 0.0006 (11) | 0.0036 (11) |
C15 | 0.0274 (14) | 0.0286 (15) | 0.0300 (15) | −0.0091 (11) | 0.0020 (11) | 0.0045 (12) |
C23 | 0.0269 (14) | 0.0369 (17) | 0.0379 (17) | −0.0005 (13) | 0.0057 (12) | 0.0097 (14) |
C32 | 0.0427 (17) | 0.0248 (15) | 0.0337 (16) | 0.0039 (13) | 0.0028 (13) | −0.0065 (12) |
C5 | 0.0258 (15) | 0.0318 (17) | 0.054 (2) | −0.0077 (12) | 0.0160 (14) | −0.0184 (14) |
C42 | 0.0492 (18) | 0.0316 (16) | 0.0422 (17) | 0.0097 (14) | 0.0227 (14) | −0.0042 (14) |
C8 | 0.0328 (15) | 0.0426 (18) | 0.0371 (16) | 0.0007 (13) | 0.0116 (13) | −0.0186 (15) |
C18 | 0.0313 (15) | 0.0407 (17) | 0.0315 (15) | −0.0012 (13) | −0.0032 (12) | 0.0135 (14) |
C24 | 0.0320 (15) | 0.0343 (17) | 0.0319 (15) | 0.0077 (13) | 0.0070 (12) | 0.0033 (13) |
C6 | 0.0210 (13) | 0.0302 (15) | 0.0406 (16) | −0.0080 (12) | 0.0084 (11) | −0.0110 (13) |
C28 | 0.0498 (18) | 0.0244 (15) | 0.0389 (17) | 0.0049 (14) | 0.0033 (14) | −0.0024 (14) |
C38 | 0.0255 (14) | 0.057 (2) | 0.0208 (13) | 0.0045 (14) | 0.0019 (11) | −0.0098 (14) |
C27 | 0.0378 (16) | 0.0226 (14) | 0.0316 (15) | 0.0033 (12) | 0.0069 (12) | −0.0036 (12) |
C7 | 0.0213 (14) | 0.043 (2) | 0.0457 (18) | −0.0077 (13) | 0.0109 (13) | −0.0152 (15) |
C40 | 0.0463 (17) | 0.0194 (15) | 0.0407 (16) | 0.0077 (12) | 0.0168 (13) | 0.0088 (12) |
C48 | 0.055 (2) | 0.0228 (16) | 0.0453 (18) | 0.0042 (14) | 0.0211 (15) | 0.0123 (14) |
C51 | 0.0326 (17) | 0.057 (2) | 0.051 (2) | 0.0011 (16) | 0.0109 (15) | 0.0229 (17) |
C41 | 0.058 (2) | 0.0239 (16) | 0.0442 (18) | 0.0049 (14) | 0.0228 (15) | 0.0003 (13) |
C49 | 0.0352 (16) | 0.0478 (19) | 0.0303 (15) | −0.0007 (14) | 0.0030 (12) | 0.0116 (14) |
C31 | 0.059 (2) | 0.0280 (18) | 0.0443 (19) | 0.0017 (15) | −0.0071 (15) | −0.0127 (14) |
C17 | 0.0407 (17) | 0.065 (2) | 0.0304 (16) | −0.0062 (16) | −0.0007 (13) | 0.0203 (16) |
C43 | 0.056 (2) | 0.0351 (18) | 0.0337 (16) | 0.0022 (15) | 0.0160 (14) | −0.0066 (14) |
C26 | 0.0419 (18) | 0.052 (2) | 0.0469 (19) | 0.0102 (16) | 0.0174 (15) | −0.0010 (16) |
C35 | 0.0485 (19) | 0.0351 (17) | 0.0394 (17) | −0.0185 (15) | 0.0138 (14) | −0.0148 (14) |
C9 | 0.0289 (17) | 0.046 (2) | 0.075 (2) | 0.0047 (14) | −0.0034 (16) | −0.0197 (18) |
C30 | 0.079 (3) | 0.0222 (17) | 0.060 (2) | 0.0023 (17) | −0.0101 (19) | −0.0131 (16) |
C36 | 0.0418 (18) | 0.049 (2) | 0.062 (2) | −0.0186 (16) | 0.0242 (16) | −0.0270 (18) |
C44 | 0.060 (2) | 0.042 (2) | 0.051 (2) | −0.0074 (17) | 0.0283 (17) | −0.0189 (17) |
C16 | 0.0408 (18) | 0.051 (2) | 0.0391 (18) | −0.0072 (15) | 0.0079 (14) | 0.0166 (15) |
C29 | 0.071 (2) | 0.0218 (16) | 0.058 (2) | 0.0099 (16) | −0.0032 (18) | −0.0010 (16) |
C33 | 0.057 (2) | 0.0244 (16) | 0.052 (2) | 0.0060 (15) | −0.0065 (16) | 0.0037 (15) |
C37 | 0.0285 (16) | 0.066 (2) | 0.052 (2) | −0.0036 (15) | 0.0053 (14) | −0.0270 (18) |
C50 | 0.0316 (17) | 0.073 (2) | 0.0423 (19) | 0.0083 (17) | 0.0006 (14) | 0.0043 (18) |
C13 | 0.055 (2) | 0.075 (3) | 0.0339 (18) | −0.022 (2) | 0.0101 (15) | −0.0034 (18) |
C3 | 0.048 (2) | 0.0403 (19) | 0.073 (2) | −0.0194 (16) | 0.0389 (18) | −0.0190 (18) |
C45 | 0.047 (2) | 0.069 (3) | 0.063 (2) | 0.009 (2) | 0.0205 (19) | −0.013 (2) |
C47 | 0.060 (2) | 0.064 (3) | 0.085 (3) | 0.023 (2) | 0.035 (2) | 0.034 (2) |
C52 | 0.047 (2) | 0.088 (3) | 0.089 (3) | 0.017 (2) | 0.032 (2) | 0.066 (3) |
C11 | 0.059 (3) | 0.093 (4) | 0.046 (2) | 0.008 (2) | −0.0040 (18) | −0.026 (2) |
C10 | 0.042 (2) | 0.062 (3) | 0.087 (3) | 0.0087 (19) | −0.013 (2) | −0.031 (2) |
C12 | 0.079 (3) | 0.091 (3) | 0.039 (2) | −0.013 (2) | 0.013 (2) | 0.005 (2) |
C46 | 0.053 (3) | 0.095 (4) | 0.094 (3) | 0.031 (2) | 0.022 (2) | 0.029 (3) |
O1B | 0.034 (3) | 0.090 (5) | 0.129 (6) | −0.012 (3) | 0.029 (3) | 0.011 (4) |
C1A | 0.067 (8) | 0.054 (7) | 0.063 (8) | −0.011 (6) | −0.020 (6) | 0.018 (5) |
C4A | 0.029 (4) | 0.035 (4) | 0.038 (4) | 0.007 (3) | 0.007 (3) | 0.009 (3) |
C2B | 0.040 (5) | 0.023 (5) | 0.095 (9) | −0.004 (4) | 0.027 (6) | −0.008 (5) |
O11 | 0.016 (3) | 0.015 (3) | 0.019 (3) | −0.002 (3) | 0.005 (3) | −0.001 (3) |
C4B | 0.051 (5) | 0.035 (4) | 0.069 (6) | −0.002 (3) | 0.028 (5) | 0.012 (4) |
C2A | 0.024 (3) | 0.025 (4) | 0.048 (4) | 0.000 (3) | 0.012 (3) | 0.001 (3) |
O2B | 0.023 (4) | 0.034 (4) | 0.065 (8) | −0.008 (3) | −0.017 (6) | −0.012 (6) |
O1A | 0.041 (3) | 0.027 (3) | 0.074 (3) | −0.017 (2) | −0.006 (2) | 0.009 (2) |
C1B | 0.039 (5) | 0.087 (11) | 0.101 (12) | −0.018 (6) | −0.031 (7) | −0.012 (9) |
O5—C19 | 1.239 (3) | C49—C50 | 1.517 (5) |
O4—C14 | 1.235 (3) | C31—H31 | 0.9500 |
O6—C34 | 1.239 (3) | C31—C30 | 1.374 (5) |
N3—C19 | 1.343 (3) | C17—H17A | 0.9900 |
N3—C15 | 1.466 (3) | C17—H17B | 0.9900 |
N3—C18 | 1.486 (3) | C17—C16 | 1.530 (4) |
N2—H2 | 0.8800 | C43—H43 | 0.9500 |
N2—C14 | 1.328 (3) | C43—C44 | 1.388 (5) |
N2—C6 | 1.449 (4) | C26—H26A | 0.9800 |
O7—C39 | 1.228 (4) | C26—H26B | 0.9800 |
O3—C5 | 1.232 (3) | C26—H26C | 0.9800 |
O9—C51 | 1.330 (4) | C35—H35A | 0.9900 |
O9—C52 | 1.452 (4) | C35—H35B | 0.9900 |
N1—H1 | 0.8800 | C35—C36 | 1.521 (5) |
N1—C5 | 1.329 (4) | C9—H9 | 0.9500 |
N1—C3 | 1.461 (4) | C9—C10 | 1.369 (5) |
N5—H5 | 0.8800 | C30—H30 | 0.9500 |
N5—C39 | 1.341 (4) | C30—C29 | 1.371 (5) |
N5—C40 | 1.450 (4) | C36—H36A | 0.9900 |
N4—C34 | 1.355 (3) | C36—H36B | 0.9900 |
N4—C38 | 1.459 (4) | C36—C37 | 1.526 (5) |
N4—C35 | 1.486 (4) | C44—H44 | 0.9500 |
O2A—C1A | 1.449 (14) | C44—C45 | 1.371 (5) |
O2A—C2A | 1.314 (15) | C16—H16A | 0.9900 |
O10—C51 | 1.203 (4) | C16—H16B | 0.9900 |
C19—C20 | 1.501 (4) | C29—H29 | 0.9500 |
O8—C48 | 1.225 (4) | C33—H33A | 0.9800 |
N6—H6 | 0.8800 | C33—H33B | 0.9800 |
N6—C48 | 1.338 (4) | C33—H33C | 0.9800 |
N6—C49 | 1.452 (4) | C37—H37A | 0.9900 |
C20—C21 | 1.397 (4) | C37—H37B | 0.9900 |
C20—C25 | 1.401 (4) | C50—H50A | 0.9800 |
C14—C15 | 1.524 (4) | C50—H50B | 0.9800 |
C22—H22 | 0.9500 | C50—H50C | 0.9800 |
C22—C21 | 1.375 (4) | C13—H13 | 0.9500 |
C22—C23 | 1.387 (4) | C13—C12 | 1.409 (5) |
C21—H21 | 0.9500 | C3—H3A | 1.0000 |
C39—C38 | 1.513 (5) | C3—H3B | 1.0000 |
C34—C32 | 1.498 (4) | C3—C4A | 1.688 (8) |
C25—C24 | 1.404 (4) | C3—C2B | 1.704 (13) |
C25—C27 | 1.510 (4) | C3—C4B | 1.389 (7) |
C15—H15 | 1.0000 | C3—C2A | 1.388 (7) |
C15—C16 | 1.529 (4) | C45—H45 | 0.9500 |
C23—H23 | 0.9500 | C45—C46 | 1.373 (6) |
C23—C24 | 1.388 (4) | C47—H47 | 0.9500 |
C32—C27 | 1.402 (4) | C47—C46 | 1.384 (6) |
C32—C31 | 1.396 (4) | C52—H52A | 0.9800 |
C5—C6 | 1.540 (4) | C52—H52B | 0.9800 |
C42—C41 | 1.509 (5) | C52—H52C | 0.9800 |
C42—C43 | 1.379 (4) | C11—H11 | 0.9500 |
C42—C47 | 1.377 (5) | C11—C10 | 1.372 (6) |
C8—C7 | 1.513 (4) | C11—C12 | 1.363 (6) |
C8—C9 | 1.389 (4) | C10—H10 | 0.9500 |
C8—C13 | 1.363 (5) | C12—H12 | 0.9500 |
C18—H18A | 0.9900 | C46—H46 | 0.9500 |
C18—H18B | 0.9900 | O1B—C2B | 1.218 (10) |
C18—C17 | 1.526 (4) | C1A—H1AA | 0.9800 |
C24—C26 | 1.517 (4) | C1A—H1AB | 0.9800 |
C6—H6A | 1.0000 | C1A—H1AC | 0.9800 |
C6—C7 | 1.537 (4) | C4A—H4AA | 1.05 (7) |
C28—C27 | 1.403 (4) | C4A—H4AB | 0.81 (8) |
C28—C29 | 1.395 (5) | C4A—H4AC | 1.08 (8) |
C28—C33 | 1.517 (4) | C2B—O2B | 1.301 (17) |
C38—H38 | 1.0000 | O11—H11A | 0.8705 |
C38—C37 | 1.537 (4) | O11—H11B | 0.8699 |
C7—H7A | 0.99 (4) | C4B—H4BA | 0.9800 |
C7—H7B | 0.96 (3) | C4B—H4BB | 0.9800 |
C40—H40 | 1.0000 | C4B—H4BC | 0.9800 |
C40—C48 | 1.519 (4) | C2A—O1A | 1.205 (8) |
C40—C41 | 1.525 (4) | O2B—C1B | 1.419 (13) |
C51—C49 | 1.518 (5) | C1B—H1BA | 0.9800 |
C41—H41A | 0.9900 | C1B—H1BB | 0.9800 |
C41—H41B | 0.9900 | C1B—H1BC | 0.9800 |
C49—H49 | 1.0000 | ||
C19—N3—C15 | 119.8 (2) | C16—C17—H17B | 111.2 |
C19—N3—C18 | 127.6 (2) | C42—C43—H43 | 119.4 |
C15—N3—C18 | 111.8 (2) | C42—C43—C44 | 121.1 (3) |
C14—N2—H2 | 116.9 | C44—C43—H43 | 119.4 |
C14—N2—C6 | 126.3 (2) | C24—C26—H26A | 109.5 |
C6—N2—H2 | 116.9 | C24—C26—H26B | 109.5 |
C51—O9—C52 | 114.9 (3) | C24—C26—H26C | 109.5 |
C5—N1—H1 | 119.5 | H26A—C26—H26B | 109.5 |
C5—N1—C3 | 121.0 (2) | H26A—C26—H26C | 109.5 |
C3—N1—H1 | 119.5 | H26B—C26—H26C | 109.5 |
C39—N5—H5 | 119.1 | N4—C35—H35A | 111.2 |
C39—N5—C40 | 121.9 (2) | N4—C35—H35B | 111.2 |
C40—N5—H5 | 119.1 | N4—C35—C36 | 102.8 (3) |
C34—N4—C38 | 120.9 (2) | H35A—C35—H35B | 109.1 |
C34—N4—C35 | 127.2 (3) | C36—C35—H35A | 111.2 |
C38—N4—C35 | 112.0 (2) | C36—C35—H35B | 111.2 |
C2A—O2A—C1A | 114.1 (14) | C8—C9—H9 | 119.3 |
O5—C19—N3 | 120.5 (2) | C10—C9—C8 | 121.4 (4) |
O5—C19—C20 | 120.8 (2) | C10—C9—H9 | 119.3 |
N3—C19—C20 | 118.5 (2) | C31—C30—H30 | 119.9 |
C48—N6—H6 | 119.3 | C29—C30—C31 | 120.2 (3) |
C48—N6—C49 | 121.5 (3) | C29—C30—H30 | 119.9 |
C49—N6—H6 | 119.3 | C35—C36—H36A | 111.1 |
C21—C20—C19 | 117.9 (2) | C35—C36—H36B | 111.1 |
C21—C20—C25 | 120.6 (2) | C35—C36—C37 | 103.1 (2) |
C25—C20—C19 | 121.3 (2) | H36A—C36—H36B | 109.1 |
O4—C14—N2 | 123.2 (3) | C37—C36—H36A | 111.1 |
O4—C14—C15 | 120.1 (2) | C37—C36—H36B | 111.1 |
N2—C14—C15 | 116.7 (2) | C43—C44—H44 | 119.7 |
C21—C22—H22 | 120.3 | C45—C44—C43 | 120.6 (3) |
C21—C22—C23 | 119.4 (3) | C45—C44—H44 | 119.7 |
C23—C22—H22 | 120.3 | C15—C16—C17 | 103.5 (2) |
C20—C21—H21 | 119.9 | C15—C16—H16A | 111.1 |
C22—C21—C20 | 120.1 (3) | C15—C16—H16B | 111.1 |
C22—C21—H21 | 119.9 | C17—C16—H16A | 111.1 |
O7—C39—N5 | 123.8 (3) | C17—C16—H16B | 111.1 |
O7—C39—C38 | 119.0 (3) | H16A—C16—H16B | 109.0 |
N5—C39—C38 | 117.2 (2) | C28—C29—H29 | 119.4 |
O6—C34—N4 | 121.7 (3) | C30—C29—C28 | 121.2 (3) |
O6—C34—C32 | 121.8 (2) | C30—C29—H29 | 119.4 |
N4—C34—C32 | 116.3 (3) | C28—C33—H33A | 109.5 |
C20—C25—C24 | 118.9 (2) | C28—C33—H33B | 109.5 |
C20—C25—C27 | 122.3 (2) | C28—C33—H33C | 109.5 |
C24—C25—C27 | 118.3 (2) | H33A—C33—H33B | 109.5 |
N3—C15—C14 | 113.6 (2) | H33A—C33—H33C | 109.5 |
N3—C15—H15 | 109.1 | H33B—C33—H33C | 109.5 |
N3—C15—C16 | 103.9 (2) | C38—C37—H37A | 111.1 |
C14—C15—H15 | 109.1 | C38—C37—H37B | 111.1 |
C14—C15—C16 | 111.9 (2) | C36—C37—C38 | 103.3 (2) |
C16—C15—H15 | 109.1 | C36—C37—H37A | 111.1 |
C22—C23—H23 | 119.2 | C36—C37—H37B | 111.1 |
C22—C23—C24 | 121.7 (3) | H37A—C37—H37B | 109.1 |
C24—C23—H23 | 119.2 | C49—C50—H50A | 109.5 |
C27—C32—C34 | 123.4 (2) | C49—C50—H50B | 109.5 |
C31—C32—C34 | 116.5 (3) | C49—C50—H50C | 109.5 |
C31—C32—C27 | 120.0 (3) | H50A—C50—H50B | 109.5 |
O3—C5—N1 | 123.2 (3) | H50A—C50—H50C | 109.5 |
O3—C5—C6 | 120.2 (3) | H50B—C50—H50C | 109.5 |
N1—C5—C6 | 116.6 (2) | C8—C13—H13 | 119.7 |
C43—C42—C41 | 121.6 (3) | C8—C13—C12 | 120.5 (3) |
C47—C42—C41 | 120.7 (3) | C12—C13—H13 | 119.7 |
C47—C42—C43 | 117.7 (3) | N1—C3—H3A | 108.7 |
C9—C8—C7 | 120.8 (3) | N1—C3—H3B | 110.4 |
C13—C8—C7 | 120.8 (3) | N1—C3—C4A | 106.0 (3) |
C13—C8—C9 | 118.3 (3) | N1—C3—C2B | 105.5 (4) |
N3—C18—H18A | 111.3 | C4A—C3—H3A | 108.7 |
N3—C18—H18B | 111.3 | C2B—C3—H3B | 110.4 |
N3—C18—C17 | 102.3 (2) | C4B—C3—N1 | 114.2 (4) |
H18A—C18—H18B | 109.2 | C4B—C3—H3B | 110.4 |
C17—C18—H18A | 111.3 | C4B—C3—C2B | 105.8 (6) |
C17—C18—H18B | 111.3 | C2A—C3—N1 | 117.8 (4) |
C25—C24—C26 | 120.6 (3) | C2A—C3—H3A | 108.7 |
C23—C24—C25 | 119.2 (3) | C2A—C3—C4A | 106.8 (5) |
C23—C24—C26 | 120.2 (3) | C44—C45—H45 | 120.6 |
N2—C6—C5 | 104.6 (2) | C44—C45—C46 | 118.8 (4) |
N2—C6—H6A | 107.9 | C46—C45—H45 | 120.6 |
N2—C6—C7 | 113.9 (3) | C42—C47—H47 | 119.3 |
C5—C6—H6A | 107.9 | C42—C47—C46 | 121.3 (4) |
C7—C6—C5 | 114.3 (2) | C46—C47—H47 | 119.3 |
C7—C6—H6A | 107.9 | O9—C52—H52A | 109.5 |
C27—C28—C33 | 121.9 (3) | O9—C52—H52B | 109.5 |
C29—C28—C27 | 119.1 (3) | O9—C52—H52C | 109.5 |
C29—C28—C33 | 119.0 (3) | H52A—C52—H52B | 109.5 |
N4—C38—C39 | 115.6 (2) | H52A—C52—H52C | 109.5 |
N4—C38—H38 | 109.3 | H52B—C52—H52C | 109.5 |
N4—C38—C37 | 103.5 (3) | C10—C11—H11 | 120.0 |
C39—C38—H38 | 109.3 | C12—C11—H11 | 120.0 |
C39—C38—C37 | 109.6 (2) | C12—C11—C10 | 120.1 (4) |
C37—C38—H38 | 109.3 | C9—C10—C11 | 119.9 (4) |
C32—C27—C25 | 123.8 (2) | C9—C10—H10 | 120.1 |
C32—C27—C28 | 119.2 (3) | C11—C10—H10 | 120.1 |
C28—C27—C25 | 116.9 (2) | C13—C12—H12 | 120.1 |
C8—C7—C6 | 114.8 (2) | C11—C12—C13 | 119.8 (4) |
C8—C7—H7A | 110.1 (19) | C11—C12—H12 | 120.1 |
C8—C7—H7B | 107.6 (19) | C45—C46—C47 | 120.5 (4) |
C6—C7—H7A | 108.4 (19) | C45—C46—H46 | 119.7 |
C6—C7—H7B | 109.5 (19) | C47—C46—H46 | 119.7 |
H7A—C7—H7B | 106 (3) | O2A—C1A—H1AA | 109.5 |
N5—C40—H40 | 106.6 | O2A—C1A—H1AB | 109.5 |
N5—C40—C48 | 113.0 (2) | O2A—C1A—H1AC | 109.5 |
N5—C40—C41 | 110.3 (2) | H1AA—C1A—H1AB | 109.5 |
C48—C40—H40 | 106.6 | H1AA—C1A—H1AC | 109.5 |
C48—C40—C41 | 113.2 (3) | H1AB—C1A—H1AC | 109.5 |
C41—C40—H40 | 106.6 | C3—C4A—H4AA | 110 (4) |
O8—C48—N6 | 122.2 (3) | C3—C4A—H4AB | 117 (5) |
O8—C48—C40 | 121.5 (3) | C3—C4A—H4AC | 102 (4) |
N6—C48—C40 | 116.2 (3) | H4AA—C4A—H4AB | 102 (6) |
O9—C51—C49 | 112.6 (3) | H4AA—C4A—H4AC | 113 (5) |
O10—C51—O9 | 124.8 (3) | H4AB—C4A—H4AC | 112 (7) |
O10—C51—C49 | 122.3 (3) | O1B—C2B—C3 | 120.9 (9) |
C42—C41—C40 | 111.3 (3) | O1B—C2B—O2B | 120.6 (13) |
C42—C41—H41A | 109.4 | O2B—C2B—C3 | 117.7 (9) |
C42—C41—H41B | 109.4 | H11A—O11—H11B | 104.4 |
C40—C41—H41A | 109.4 | C3—C4B—H4BA | 109.5 |
C40—C41—H41B | 109.4 | C3—C4B—H4BB | 109.5 |
H41A—C41—H41B | 108.0 | C3—C4B—H4BC | 109.5 |
N6—C49—C51 | 114.6 (2) | H4BA—C4B—H4BB | 109.5 |
N6—C49—H49 | 108.6 | H4BA—C4B—H4BC | 109.5 |
N6—C49—C50 | 108.9 (3) | H4BB—C4B—H4BC | 109.5 |
C51—C49—H49 | 108.6 | O2A—C2A—C3 | 105.3 (9) |
C50—C49—C51 | 107.5 (3) | O1A—C2A—O2A | 125.2 (10) |
C50—C49—H49 | 108.6 | O1A—C2A—C3 | 129.3 (6) |
C32—C31—H31 | 119.9 | C2B—O2B—C1B | 122.3 (15) |
C30—C31—C32 | 120.2 (3) | O2B—C1B—H1BA | 109.5 |
C30—C31—H31 | 119.9 | O2B—C1B—H1BB | 109.5 |
C18—C17—H17A | 111.2 | O2B—C1B—H1BC | 109.5 |
C18—C17—H17B | 111.2 | H1BA—C1B—H1BB | 109.5 |
C18—C17—C16 | 103.0 (2) | H1BA—C1B—H1BC | 109.5 |
H17A—C17—H17B | 109.1 | H1BB—C1B—H1BC | 109.5 |
C16—C17—H17A | 111.2 | ||
C20—C19—N3—C15 | 178.3 (2) | C32—C34—N4—C38 | −164.6 (2) |
C19—N3—C15—C14 | −73.4 (3) | C34—N4—C38—C39 | −69.1 (3) |
N3—C15—C14—N2 | −17.5 (3) | N4—C38—C39—N5 | −14.4 (4) |
C15—C14—N2—C6 | 176.5 (2) | C38—C39—N5—C40 | −177.2 (2) |
C14—N2—C6—C5 | −163.0 (2) | C39—N5—C40—C48 | −106.8 (3) |
N2—C6—C5—N1 | 171.4 (2) | N5—C40—C48—N6 | 18.6 (3) |
C6—C5—N1—C3 | −174.8 (3) | C40—C48—N6—C49 | 179.1 (2) |
C5—N1—C3—C2B | −58.0 (5) | C48—N6—C49—C51 | −60.9 (3) |
N1—C3—C2B—O2B | −39.6 (13) | N6—C49—C51—O9 | −35.0 (4) |
Cg3 and Cg5 are the centroids of the C8–C13 and C27–C32 rings, respectively. |
D—H···A | D—H | H···A | D···A | D—H···A |
N5—H5···O5 | 0.88 | 2.07 | 2.923 (3) | 162 |
N6—H6···O6 | 0.88 | 2.42 | 3.233 (3) | 154 |
C9—H9···O2B | 0.95 | 2.35 | 3.270 (18) | 164 |
C21—H21···O3 | 0.95 | 2.44 | 3.352 (4) | 161 |
C35—H35A···O5 | 0.99 | 2.51 | 3.171 (4) | 124 |
C43—H43···O4 | 0.95 | 2.59 | 3.443 (4) | 149 |
N1—H1···O4i | 0.88 | 2.01 | 2.865 (3) | 163 |
C1B—H1BB···O10ii | 0.98 | 2.46 | 2.913 (16) | 108 |
C30—H30···O8iii | 0.95 | 2.46 | 3.222 (4) | 137 |
C35—H35···O7iv | 0.99 | 2.39 | 3.228 (4) | 142 |
C52—H52B···O10v | 0.98 | 2.60 | 3.559 (5) | 166 |
O11—H11A···O8 | 0.87 | 2.48 | 3.136 (6) | 133 |
C13—H13···O11vi | 0.95 | 2.52 | 3.155 (7) | 124 |
C36—H36B···Cg3vi | 0.99 | 2.94 | 3.845 (4) | 152 |
C4A—H4AC···Cg5vii | 1.05 (8) | 2.93 (7) | 3.770 (8) | 135 (5) |
Symmetry codes: (i) −x+1/2, y+1/2, −z+1; (ii) −x+1, y, −z+1; (iii) x, y−1, z; (iv) −x+1/2, y−1/2, −z; (v) −x+1, y, −z; (vi) −x+1/2, y−1/2, −z+1; (vii) x, y+1, z. |
Funding information
TTTB is thankful to the Asia Research Center–Vietnam National University (ARC–VNU) and the Korea Foundation for Advanced Studies (KFAS) for financial support (Project CA.20.7 A).
References
Amine, A., Atmani, Z., El Hallaoui, A., Giorgi, M., Pierrot, M. & Réglier, M. (2002). Bioorg. Med. Chem. Lett. 12, 57–60. CSD CrossRef PubMed CAS Google Scholar
Banting, F. G., Best, C. H., Collip, J. B., Campbell, W. R. & Fletcher, A. A. (1922). Can. Med. Assoc. J. 12, 141–146. CAS PubMed Google Scholar
Bruker (2013). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
Fosgerau, K. & Hoffmann, T. (2015). Drug Discovery Today, 20, 122–128. CrossRef CAS PubMed Google Scholar
Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179. Web of Science CrossRef IUCr Journals Google Scholar
Hajduk, P. J., Bures, M., Praestgaard, J. & Fesik, S. W. (2000). J. Med. Chem. 43, 3443–3447. CrossRef PubMed CAS Google Scholar
Kaiser, M., Groll, M., Siciliano, C., Assfalg-Machleidt, I., Weyher, E., Kohno, J., Milbradt, A. G., Renner, C., Huber, R. & Moroder, L. (2004). ChemBioChem, 5, 1256–1266. Web of Science CrossRef PubMed CAS Google Scholar
Le, T. Q., Nguyen, X. T., Nguyen, H. H., Mac, D. H. & Bui, T. T. T. (2020). Acta Cryst. E76, 257–260. CSD CrossRef IUCr Journals Google Scholar
Linden, A., Furegati, M. & Rippert, A. J. (2018d). Private communication (CCDC refcode 1885480). CCDC, Cambridge, England. Google Scholar
Linden, A. & Rippert, A. J. (2018a). Private communication (CCDC refcode 1884542). CCDC, Cambridge, England. Google Scholar
Linden, A. & Rippert, A. J. (2018b). Private communication (CCDC refcode 1884572). CCDC, Cambridge, England. Google Scholar
Linden, A. & Rippert, A. J. (2018c). Private communication (CCDC refcode 1884549). CCDC, Cambridge, England. Google Scholar
Mann, E., Montero, A., Maestro, M. & Herradón, B. (2002). Helv. Chim. Acta, 85, 3624–3638. Web of Science CSD CrossRef CAS Google Scholar
Montero, A., Albericio, F., Royo, M. & Herradón, B. (2004b). Org. Lett. 6, 4089–4092. CrossRef PubMed CAS Google Scholar
Montero, A., Mann, E., Chana, A. & Herradón, B. (2004a). Chem. Biodiv. 1, 442–457. CrossRef CAS Google Scholar
Otvos, L. Jr & Wade, J. D. (2014). Front. Chem, 2, 62. PubMed Google Scholar
Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249–259. Web of Science CrossRef CAS IUCr Journals Google Scholar
Ranganathan, D., Kurur, S., Madhusudanan, K. P. & Karle, I. L. (1997). Tetrahedron Lett. 38, 4659–4662. CrossRef CAS Web of Science Google Scholar
Samadi, S., Nazari, S., Arvinnezhad, H., Jadidi, K. & Notash, B. (2013). Tetrahedron, 69, 6679–6686. CSD CrossRef CAS Google Scholar
Schimana, J., Gebhardt, K., Holtzel, A., Schmid, D. G., Sussmuth, R., Muller, J., Pukall, R. & Fiedler, H.-P. (2002). J. Antibiot. 55, 565–570. CrossRef PubMed CAS Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Weigand, C. & Feigel, M. (1998). Chem. Commun. pp. 679–680. CSD CrossRef Google Scholar
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.