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Acta Crystallogr Sect E Struct Rep Online. 2009 November 1; 65(Pt 11): o2900.
Published online 2009 October 28. doi:  10.1107/S1600536809042974
PMCID: PMC2971084

(RSS)-[N-Hydroxyethyloxy]-hexafluoroVal–MeLeu–Ala tert-butyl ester

Abstract

The title compound [systematic name: (2S,5S,8R)-tert-butyl 8-(1,1,1,3,3,3-hexafluoropropan-2-yl)-12-hydroxy-5-isobutyl-2,6-dimethyl-4,7-dioxo-10-oxa-3,6,9-triazadodecanoate], C21H36F6N3O6, is a tripeptide crystallizing in the chiral ortho­rhom­bic spacegroup P212121. The absolute configuration (R) of the chiral center in the hexa­fluoro­valine unit is based on the known stereochemistry of MeLeu and Ala (SS). The N-hydroxy­ethyl­oxy substituent of hexa­fluoro­valine is positionally disordered [occupancy ratio 0.543 (9):0.457 (9)]. In the solid state structure there are N—H(...)F and N—H(...)O intra­molecular hydrogen bonds supporting the coiled structure of this tripeptide with the three hydro­phobic substituents on the outside.

Related literature

For biomolecules with fluoro substituents, see: Kirsch (2004 [triangle]); Mikol et al. (1997 [triangle]); Eberle et al. (1998 [triangle]); Zhang et al. (1998 [triangle]); Eberle & Keese (2009 [triangle]). For the tripeptide Val-MeLeu-Ala in cyclo­sporine, an undeca­peptide, and the fact that it can be extracted and reintroduced in the remaining octa­peptide, see: Eberle et al. (1994 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o2900-scheme1.jpg

Experimental

Crystal data

  • C21H35F6N3O6
  • M r = 539.52
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-65-o2900-efi1.jpg
  • a = 11.1608 (7) Å
  • b = 11.2088 (7) Å
  • c = 21.2562 (15) Å
  • V = 2659.1 (3) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.12 mm−1
  • T = 153 K
  • 0.50 × 0.50 × 0.40 mm

Data collection

  • Stoe IPDS diffractometer
  • Absorption correction: none
  • 18889 measured reflections
  • 2917 independent reflections
  • 2554 reflections with I > 2σ(I)
  • R int = 0.063

Refinement

  • R[F 2 > 2σ(F 2)] = 0.077
  • wR(F 2) = 0.201
  • S = 1.14
  • 2917 reflections
  • 358 parameters
  • 8 restraints
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.54 e Å−3
  • Δρmin = −0.37 e Å−3

Data collection: EXPOSE in IPDS-I (Stoe & Cie, 2000 [triangle]); cell refinement: CELL in IPDS-I; data reduction: INTEGRATE in IPDS-I; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: PLATON (Spek, 2009 [triangle]); software used to prepare material for publication: SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809042974/im2143sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809042974/im2143Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

This work was supported financially by the Swiss National Science Foundation (project No. 20–43565.95). We thank Dr L. Tenud (Lonza, Visp AG) for the generous gift of fluorinated chemicals.

supplementary crystallographic information

Comment

Biomolecules with fluoro substituents differ in their properties compared to their congeners by a variety of properties. For example, they tend to be more lipophilic, exhibit a higher stability and may excert specific medicinal effects (Kirsch, 2004; Mikol et al., 1997). As part of our interest in fluorinated biomolecules we have prepared (R)- and (S)-4,4,4,4',4',4'-hexafluorovaline (Eberle et al., 1998; Eberle & Keese, 2009) and (S)-5,5,5,5',5,'5'-hexafluoroleucine (Zhang et al., 1998). Our interest was further stimulated when we realised that cyclosporine, an undecapeptide and an important immunosuppressant, contains (S)-valine as one of the 11 aminoacids (Mikol et al., 1997). Furthermore, earlier work had shown that the tripeptide Val-MeLeu-Ala can be chemically cut out of the undecapeptide and reintroduced eventually into the remaining octapeptide (Eberle et al., 1994).

In order to replace Val in the tripeptide Val-MeLeu-Ala by hexafluoro-valine the depsipeptide, (S)-1N-methyl-leucine-(S)-alanine-O-tert-butylester-1N-(3,3-bistrifluoromethyl-acryloylamide, was prepared and subsequently the title tripeptide containing an N-functionalized 4,4,4,4',4',4'-hexafluorovaline. The depsipeptide was obtained from (S)-N-methylleucine-(S)-alanine-O-tert-butylester by acylation with 4,4,4,4',4',4'-hexafluoro acrylic acid. Subsequent addition of 2-hydroxyethyloxyamine in α-position of the hexafluoroacrylic moiety in the depsipeptide gave two diastereomers of the title tripeptide. One of these solidified and gave crystals suitable for an X-ray structure analysis, and we describe its crystal structure herein.

Based on the known absolute configuration of MeLeu and Ala, (SS), used in the synthesis, the hexafluoro-valine moiety in the title compound has (R)-configuration (Fig. 1). The geometrical parameters are available in the archived CIF. The –NH—O—CH2—CH2OH side chain of the hexafluoro Valine is disordered over two positions [occupancies A:B = 0.6:0.4]. One methyl group (C23) of the isopropyl substituent in the central amino acid MeLeu is also disordered over two positions [occupancies A:B = 0.5:0.5]. The bond angle in the hexafluoroisopropyl group (C17—C16—C18) in hexafluoro valine is 109.3 (6)°, whereas the bond angles in the isopropyl group of MeLeu within the two orientations (C21—C22—C23A and C21—C22—C23B) are 107.5 (9)° and 111.8 (10)°, respectively. The bond angle C9—C20—C22 of the leucine side chain is 114.7 (4)°. The bond angles at the acylated N-atoms, N1 and N2, are close to 120°, the value expected for tricoordinate sp2 hybridized N-atoms. The torsional angles around the two amide groups [2.2 (10)° for C2—N1—C8—O3, 178.7 (6) ° for C2—N1—C8—C9, and -1.8 (9) ° for C9—N2—C14—O4, 173.6 (5) ° for C9—N2—C14—C15] are within the normal range and provide the evidence for almost planar arrangements (Fig. 1).

In the crystal structure there is a three-centered hydrogen bond located between N3—H3N···F5, whereas a bifurcated hydrogen bond O2—H1N—O5 leads to interactions between the N1—H and atom O5, the N-bonded O-atom of the hydroxyethyloxy side chain, and the carbonyl group of the BOC protecting group (Table 1 and Fig. 1). These intramolecular hydrogen bonds support the coiled structure of this tripeptide with the three hydrophobic substituents on the outside.

Experimental

The synthesis of the title compound is summerized in Fig. 2, and full details will be published elsewhere (Eberle & Keese, 2009). In order to replace Val by hexafluoro-valine in the tripeptide Val-MeLeu-Ala, the depsipeptide (3), and subsequently the tripeptide (RS)-(5) containing an N-functionalized 4,4,4,4',4',4'-hexafluorovaline, were prepared. Compound (3) was obtained from (S)-N-methylleucine-(S)-alanine-O-tert-butylester (1) by acylation with 4,4,4,4',4',4'-hexafluoro acrylic acid (2). The subsequent addition of 2-hydroxyethyloxyamine (4) to the α-position of the hexafluoroacrylic moiety in (3) gave two diastereomers of the title tripeptide (RS)-(5). One of these solidified and crystals, suitable for X-ray analysis, were obtained as colourless rods from ether-hexane (1:5) on slow evaporation at room temperature.

Refinement

In the final cycles of refinement, in the absence of significant anomalous scattering effects, the 2234 Friedel pairs were merged and Δf " set to zero. The coordinates correspond to the absolute structure of the molecule in the crystal assigned with reference to the known stereospecific centers in the molecule. The –NH—O—CH2—CH2OH side chain is disordered over two positions (occupancies A:B = 0.6:0.4). One methyl group (C23) of the isopropyl substituent is also disordered over two positions (occupancies A:B = 0.5:0.5). During refinement a certain number of restraints were applied: ADP's of the pairs of atoms C23A & C21, C23B & C21, C24B & C24A, C25B & C25A were made equal; bonds C22—C23A, C22—C23B, C24B—C25B, C24A—C25A were refined with distance restraints of 1.54 (2) Å and bonds C25A—O6A, C25B—O6B with distant restraints of 1.44 (2) Å. The N—H hydrogen atoms could be located in difference Fourier syntheses. N1—H1N was freely refined (N—H = 0.88 (4) Å), while N3a—H3a was included in the calculated position and treated as riding: N—H = 0.88 Å with Uiso(H) = 1.2Ueq(N-atom). The O– and C-bound H-atoms were included in calculated positions and treated as riding atoms: O—H = 0.84 Å, C—H = 0.98 - 1.00 Å with Uiso(H) = 1.5Ueq(parent O-atom) and = 1.2Ueq(parent C-atom).

Figures

Fig. 1.
The molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level. The intramolecular N—H···F and N—H···O hydrogen bonds are shown as dashed lines ...
Fig. 2.
The preparation of the title compound.

Crystal data

C21H35F6N3O6F(000) = 1136
Mr = 539.52Dx = 1.348 Mg m3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 8000 reflections
a = 11.1608 (7) Åθ = 2.1–25.9°
b = 11.2088 (7) ŵ = 0.12 mm1
c = 21.2562 (15) ÅT = 153 K
V = 2659.1 (3) Å3Rod, colourless
Z = 40.50 × 0.50 × 0.40 mm

Data collection

Stoe IPDS diffractometer2554 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.063
graphiteθmax = 25.9°, θmin = 2.1°
phi oscillation scansh = −13→13
18889 measured reflectionsk = −13→13
2917 independent reflectionsl = −26→25

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.077H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.201w = 1/[σ2(Fo2) + (0.0533P)2 + 7.6569P] where P = (Fo2 + 2Fc2)/3
S = 1.14(Δ/σ)max < 0.001
2917 reflectionsΔρmax = 0.54 e Å3
358 parametersΔρmin = −0.37 e Å3
8 restraintsExtinction correction: SHELXL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.010 (2)

Special details

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell esds are taken into account in the estimation of distances, angles and torsion angles
Refinement. In the final cycles of refinement, in the absence of significant anomalous scattering effects, the 2234 Friedel pairs were merged and Δf " set to zero. The –NH—O—CH2CH2OH side chain is disordered over two positions (A & B: occupancies 0.6 / 0.4). One methyl group (C23) of the isopropyl substituent is disordered over two positions (A & B: occupancies 0.5 / 1/2). The coordinates correspond to the absolute structure of the molecule in the crystal, assigned with reference to the known stereospecific centers in the molecule. During refinement a certain number of restraints were applied, for example, EADP N3A N3B; EADP C23A C21 EADP C23B C21; EADP C25A C25B C24B C24A; DFIX 1.54 .02 C22 C23A C22 C23B C24B C25B C24A C25A; DFIX 1.44 .02 C25A O6A C25B O6B; DFIX 0.88 .02 N1 H1N; DFIX -2.2 .02 H9 H23A; DFIX -3.0 .02 C23A O6B.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/UeqOcc. (<1)
F10.8576 (6)0.5625 (5)0.7742 (2)0.0700 (19)
F21.0348 (6)0.6382 (5)0.7580 (2)0.083 (2)
F30.9114 (5)0.7225 (4)0.82195 (18)0.0505 (14)
F40.9183 (4)0.3504 (4)0.8362 (2)0.0513 (16)
F51.0984 (5)0.3567 (4)0.8715 (3)0.0623 (18)
F61.0617 (5)0.4058 (4)0.7766 (2)0.0670 (19)
O10.9061 (4)0.6526 (4)1.24644 (19)0.0343 (12)
O20.9956 (5)0.6041 (6)1.1539 (3)0.0573 (19)
O30.7713 (5)0.9284 (4)1.0905 (2)0.0357 (14)
O41.0307 (4)0.7163 (4)0.9528 (2)0.0403 (17)
O5A0.9190 (14)0.4938 (14)1.0180 (7)0.042 (4)0.543 (9)
O6A0.6768 (14)0.4094 (14)1.0107 (12)0.127 (8)0.543 (9)
N10.8327 (6)0.7356 (5)1.0887 (3)0.0387 (19)
N20.8262 (5)0.7377 (5)0.9574 (2)0.0270 (16)
N3A0.982 (2)0.473 (3)0.9578 (16)0.031 (6)0.543 (9)
C10.9169 (7)0.6529 (6)1.1836 (3)0.0350 (19)
C20.8107 (6)0.7148 (6)1.1547 (3)0.0337 (19)
C30.6980 (7)0.6393 (8)1.1630 (3)0.045 (3)
C40.9872 (7)0.5833 (7)1.2875 (3)0.039 (2)
C51.1153 (8)0.6268 (9)1.2817 (4)0.061 (3)
C60.9761 (9)0.4527 (7)1.2725 (4)0.060 (3)
C70.9347 (8)0.6062 (8)1.3525 (3)0.050 (3)
C80.8089 (5)0.8426 (6)1.0615 (3)0.0260 (17)
C90.8399 (6)0.8523 (5)0.9904 (3)0.0293 (17)
C140.9274 (7)0.6796 (6)0.9424 (3)0.0337 (19)
C150.9200 (7)0.5526 (6)0.9140 (3)0.0330 (19)
C161.0017 (7)0.5429 (6)0.8559 (3)0.036 (2)
C171.0167 (7)0.4139 (7)0.8347 (4)0.041 (2)
C180.9518 (8)0.6150 (7)0.8028 (3)0.044 (2)
C190.7068 (6)0.6926 (7)0.9431 (4)0.044 (2)
C200.7694 (7)0.9544 (6)0.9583 (3)0.0357 (19)
C210.7368 (9)1.0861 (8)0.8671 (4)0.056 (3)
C220.8160 (9)0.9903 (7)0.8948 (4)0.059 (3)
C23A0.9457 (15)1.0506 (16)0.9098 (8)0.056 (3)0.500
C23B0.9385 (14)1.0120 (17)0.8825 (8)0.056 (3)0.500
C24A0.8850 (19)0.3851 (14)1.0521 (10)0.080 (4)0.543 (9)
C25A0.7784 (17)0.3265 (15)1.0138 (12)0.080 (4)0.543 (9)
N3B0.947 (3)0.465 (4)0.966 (2)0.031 (6)0.457 (9)
O5B0.8575 (18)0.4829 (19)1.0142 (11)0.059 (6)0.457 (9)
O6B0.9684 (16)0.2308 (12)1.0006 (7)0.073 (6)0.457 (9)
C24B0.803 (2)0.3747 (19)1.0197 (15)0.080 (4)0.457 (9)
C25B0.882 (2)0.2763 (17)1.0439 (11)0.080 (4)0.457 (9)
H3A11.042600.425200.950200.0380*0.543 (9)
H3C0.673500.640601.207300.0680*
H5A1.117300.713701.286300.0920*
H1N0.860 (7)0.667 (4)1.075 (3)0.0470*
H20.798700.793301.176200.0400*
H6A10.613200.372701.019200.1510*0.543 (9)
H3A0.633500.671901.136900.0680*
H3B0.714700.557001.150200.0680*
H7A0.851300.579001.353600.0760*
H7B0.937800.691801.361700.0760*
H7C0.981300.562601.384100.0760*
H90.926600.874000.987700.0350*
H150.835800.526900.905300.0400*
H161.082300.575400.867100.0430*
H19A0.693000.696500.897600.0660*
H19B0.646800.741400.964800.0660*
H19C0.700300.609700.957300.0660*
H20A0.684800.929500.953800.0430*
H20B0.771101.025100.986300.0430*
H21A0.655801.054400.861100.0840*
H21B0.733801.154500.895800.0840*
H21C0.769501.111600.826500.0840*
H22A0.823700.920200.866000.0710*0.500
H22B0.804100.918700.867400.0710*0.500
H23A1.005800.987800.915500.0840*0.500
H23B0.940101.098300.948400.0840*0.500
H23C0.969301.102100.874700.0840*0.500
H23D0.966301.078700.908500.0840*0.500
H23E0.949101.031800.838000.0840*0.500
H23F0.985200.940500.892600.0840*0.500
H24A0.858900.404901.095400.0950*0.543 (9)
H24B0.953700.329501.054600.0950*0.543 (9)
H25A0.805600.306800.970700.0950*0.543 (9)
H25B0.753000.251601.034600.0950*0.543 (9)
H5B1.147200.604601.240400.0920*
H5C1.164300.590101.314800.0920*
H6A1.003800.438201.229400.0900*
H6B0.892100.428301.276400.0900*
H6C1.025100.406501.302000.0900*
H3B11.006000.413300.966700.0380*0.457 (9)
H6B10.977700.279700.971000.0880*0.457 (9)
H24C0.771800.351100.977900.0950*0.457 (9)
H24D0.733700.382901.048400.0950*0.457 (9)
H25C0.925600.306101.081400.0950*0.457 (9)
H25D0.830800.209401.057800.0950*0.457 (9)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
F10.098 (4)0.064 (3)0.048 (3)−0.004 (3)−0.034 (3)−0.008 (2)
F20.138 (6)0.066 (3)0.044 (3)−0.011 (4)0.050 (3)−0.005 (2)
F30.083 (3)0.040 (2)0.0286 (19)0.005 (3)0.007 (2)−0.0019 (17)
F40.054 (3)0.035 (2)0.065 (3)−0.011 (2)0.003 (2)−0.018 (2)
F50.057 (3)0.039 (2)0.091 (4)0.011 (2)−0.003 (3)−0.017 (3)
F60.085 (4)0.056 (3)0.060 (3)−0.002 (3)0.033 (3)−0.027 (3)
O10.039 (2)0.036 (2)0.028 (2)0.008 (2)−0.005 (2)0.0023 (19)
O20.053 (3)0.075 (4)0.044 (3)0.024 (3)0.009 (3)0.007 (3)
O30.053 (3)0.029 (2)0.025 (2)−0.001 (2)0.003 (2)−0.0058 (19)
O40.038 (3)0.035 (3)0.048 (3)0.003 (2)−0.010 (2)−0.018 (2)
O5A0.074 (10)0.029 (5)0.022 (5)0.000 (8)0.006 (7)0.002 (4)
O6A0.078 (10)0.082 (10)0.22 (2)0.012 (9)0.051 (13)0.056 (13)
N10.062 (4)0.028 (3)0.026 (3)0.008 (3)0.011 (3)0.003 (2)
N20.034 (3)0.026 (3)0.021 (2)−0.003 (2)0.005 (2)−0.003 (2)
N3A0.030 (13)0.035 (6)0.029 (9)0.004 (11)0.016 (9)0.004 (5)
C10.040 (4)0.035 (3)0.030 (3)0.002 (3)0.001 (3)0.001 (3)
C20.042 (4)0.037 (3)0.022 (3)0.003 (3)0.001 (3)0.003 (3)
C30.042 (4)0.054 (5)0.040 (4)0.003 (4)0.006 (3)0.014 (4)
C40.036 (4)0.040 (4)0.040 (4)0.011 (3)−0.005 (3)0.006 (3)
C50.054 (5)0.073 (6)0.057 (5)−0.007 (5)−0.014 (4)0.018 (5)
C60.073 (6)0.040 (4)0.068 (6)0.016 (4)−0.002 (5)0.007 (4)
C70.063 (5)0.051 (5)0.037 (4)0.007 (4)−0.005 (4)0.009 (3)
C80.029 (3)0.027 (3)0.022 (3)−0.003 (3)0.001 (2)−0.001 (2)
C90.038 (3)0.025 (3)0.025 (3)−0.002 (3)0.007 (3)−0.003 (3)
C140.049 (4)0.030 (3)0.022 (3)0.006 (3)−0.003 (3)0.001 (3)
C150.040 (4)0.026 (3)0.033 (3)−0.003 (3)0.002 (3)−0.002 (3)
C160.039 (4)0.037 (4)0.032 (3)0.001 (3)0.004 (3)−0.011 (3)
C170.039 (4)0.034 (4)0.051 (4)−0.004 (3)0.005 (3)−0.014 (3)
C180.065 (5)0.039 (4)0.028 (3)−0.009 (4)0.012 (3)−0.009 (3)
C190.039 (4)0.042 (4)0.050 (4)−0.006 (3)0.008 (4)−0.018 (3)
C200.051 (4)0.026 (3)0.030 (3)0.000 (3)0.002 (3)0.002 (3)
C210.074 (5)0.051 (4)0.044 (4)0.007 (4)0.003 (4)0.013 (3)
C220.107 (8)0.031 (4)0.038 (4)0.009 (5)0.016 (5)0.008 (3)
C23A0.074 (5)0.051 (4)0.044 (4)0.007 (4)0.003 (4)0.013 (3)
C23B0.074 (5)0.051 (4)0.044 (4)0.007 (4)0.003 (4)0.013 (3)
C24A0.093 (8)0.038 (5)0.108 (8)0.016 (6)0.024 (7)0.034 (7)
C25A0.093 (8)0.038 (5)0.108 (8)0.016 (6)0.024 (7)0.034 (7)
N3B0.030 (13)0.035 (6)0.029 (9)0.004 (11)0.016 (9)0.004 (5)
O5B0.080 (14)0.037 (9)0.060 (10)0.013 (11)0.029 (12)−0.002 (7)
O6B0.102 (12)0.043 (8)0.074 (9)0.028 (8)0.018 (9)0.019 (7)
C24B0.093 (8)0.038 (5)0.108 (8)0.016 (6)0.024 (7)0.034 (7)
C25B0.093 (8)0.038 (5)0.108 (8)0.016 (6)0.024 (7)0.034 (7)

Geometric parameters (Å, °)

F1—C181.350 (10)C24B—C25B1.50 (3)
F2—C181.354 (10)C2—H21.0000
F3—C181.349 (9)C3—H3A0.9800
F4—C171.309 (9)C3—H3C0.9800
F5—C171.362 (10)C3—H3B0.9800
F6—C171.336 (10)C5—H5B0.9800
O1—C11.341 (8)C5—H5A0.9800
O1—C41.478 (9)C5—H5C0.9800
O2—C11.212 (9)C6—H6B0.9800
O3—C81.217 (8)C6—H6A0.9800
O4—C141.244 (9)C6—H6C0.9800
O5A—N3A1.48 (4)C7—H7C0.9800
O5A—C24A1.47 (2)C7—H7A0.9800
O5B—C24B1.36 (3)C7—H7B0.9800
O5B—N3B1.45 (4)C9—H91.0000
O6A—C25A1.47 (2)C15—H151.0000
O6B—C25B1.43 (3)C16—H161.0000
O6A—H6A10.8400C19—H19B0.9800
O6B—H6B10.8400C19—H19A0.9800
N1—C81.358 (9)C19—H19C0.9800
N1—C21.443 (9)C20—H20B0.9900
N2—C191.457 (9)C20—H20A0.9900
N2—C141.342 (9)C21—H21A0.9800
N2—C91.472 (8)C21—H21B0.9800
N3A—C151.46 (3)C21—H21C0.9800
N3B—C151.51 (4)C22—H22A1.0000
N1—H1N0.88 (5)C22—H22B1.0000
N3A—H3A10.8800C23A—H23C0.9800
N3B—H3B10.8800C23A—H23D0.3900
C1—C21.505 (10)C23A—H23B0.9800
C2—C31.526 (11)C23A—H23A0.9800
C4—C61.503 (11)C23A—H23F1.3600
C4—C71.523 (10)C23B—H23C1.0800
C4—C51.516 (12)C23B—H23A1.0600
C8—C91.554 (9)C23B—H23F0.9800
C9—C201.547 (9)C23B—H23D0.9800
C14—C151.548 (9)C23B—H23E0.9800
C15—C161.539 (10)C24A—H24A0.9900
C16—C171.524 (10)C24A—H24B0.9900
C16—C181.496 (10)C24B—H24C0.9900
C20—C221.501 (11)C24B—H24D0.9900
C21—C221.510 (13)C25A—H25A0.9900
C22—C23B1.413 (19)C25A—H25B0.9900
C22—C23A1.63 (2)C25B—H25C0.9900
C23A—C23B0.73 (2)C25B—H25D0.9900
C24A—C25A1.58 (3)
C1—O1—C4122.3 (5)C4—C7—H7B109.00
N3A—O5A—C24A114.8 (18)N2—C9—H9107.00
N3B—O5B—C24B104 (3)C8—C9—H9107.00
C25A—O6A—H6A1109.00C20—C9—H9107.00
C25B—O6B—H6B1109.00C14—C15—H15113.00
C2—N1—C8121.6 (6)N3A—C15—H15113.00
C9—N2—C19119.8 (5)C16—C15—H15113.00
C9—N2—C14116.7 (6)N3B—C15—H1598.00
C14—N2—C19123.5 (6)C15—C16—H16108.00
O5A—N3A—C15103.3 (18)C18—C16—H16109.00
O5B—N3B—C15107 (3)C17—C16—H16109.00
C8—N1—H1N135 (4)N2—C19—H19C109.00
C2—N1—H1N104 (4)N2—C19—H19B109.00
C15—N3A—H3A1128.00H19B—C19—H19C109.00
O5A—N3A—H3A1128.00H19A—C19—H19B109.00
C15—N3B—H3B1126.00H19A—C19—H19C110.00
O5B—N3B—H3B1127.00N2—C19—H19A110.00
O1—C1—O2125.6 (7)C22—C20—H20B109.00
O1—C1—C2109.7 (6)H20A—C20—H20B108.00
O2—C1—C2124.5 (6)C9—C20—H20B108.00
C1—C2—C3110.3 (6)C22—C20—H20A109.00
N1—C2—C3110.0 (5)C9—C20—H20A109.00
N1—C2—C1109.7 (6)C22—C21—H21A109.00
C5—C4—C6112.0 (7)C22—C21—H21B109.00
O1—C4—C7102.2 (6)H21B—C21—H21C109.00
O1—C4—C6109.6 (6)H21A—C21—H21C110.00
C6—C4—C7109.0 (7)H21A—C21—H21B109.00
O1—C4—C5111.1 (6)C22—C21—H21C109.00
C5—C4—C7112.5 (6)C21—C22—H22A112.00
O3—C8—N1123.4 (6)C20—C22—H22B105.00
N1—C8—C9115.6 (6)C23A—C22—H22B124.00
O3—C8—C9120.9 (6)C21—C22—H22B105.00
C8—C9—C20111.6 (5)C23A—C22—H22A112.00
N2—C9—C8112.3 (5)H22A—C22—H22B13.00
N2—C9—C20112.5 (5)C20—C22—H22A112.00
N2—C14—C15119.6 (6)C23B—C22—H22A86.00
O4—C14—C15115.0 (6)C23B—C22—H22B99.00
O4—C14—N2125.3 (6)C22—C23A—H23A110.00
N3B—C15—C14107.6 (17)C22—C23A—H23B109.00
C14—C15—C16110.3 (6)C22—C23A—H23C110.00
N3A—C15—C14106.7 (14)C22—C23A—H23D147.00
N3A—C15—C16100.8 (12)C23B—C23A—H23C77.00
N3B—C15—C16115.1 (15)C23B—C23A—H23D119.00
C15—C16—C18110.3 (6)C23B—C23A—H23F44.00
C17—C16—C18109.3 (6)H23A—C23A—H23B109.00
C15—C16—C17111.7 (6)H23A—C23A—H23C109.00
F6—C17—C16112.3 (6)H23A—C23A—H23D101.00
F5—C17—F6104.3 (6)H23A—C23A—H23F33.00
F4—C17—C16114.6 (6)H23B—C23A—H23C109.00
F4—C17—F5107.0 (6)H23B—C23A—H23D70.00
F4—C17—F6107.5 (6)H23B—C23A—H23F138.00
F5—C17—C16110.5 (6)H23C—C23A—H23D47.00
F1—C18—F3105.4 (7)H23C—C23A—H23F104.00
F2—C18—F3105.6 (6)C22—C23A—H23F82.00
F3—C18—C16112.3 (5)C23B—C23A—H23A75.00
F2—C18—C16112.3 (7)C23B—C23A—H23B169.00
F1—C18—F2107.5 (5)H23D—C23A—H23F121.00
F1—C18—C16113.2 (6)C22—C23B—H23E110.00
C9—C20—C22114.7 (6)C22—C23B—H23F109.00
C20—C22—C23A104.1 (8)C22—C23B—H23D109.00
C23A—C22—C23B26.5 (10)C23A—C23B—H23C62.00
C20—C22—C21109.8 (7)C23A—C23B—H23D20.00
C21—C22—C23B111.8 (10)C23A—C23B—H23A63.00
C21—C22—C23A107.5 (9)C23A—C23B—H23F105.00
C20—C22—C23B123.2 (10)H23A—C23B—H23C97.00
C22—C23A—C23B60.0 (17)H23A—C23B—H23D66.00
C22—C23B—C23A94 (2)H23A—C23B—H23E128.00
O5A—C24A—C25A106.5 (16)H23A—C23B—H23F43.00
O5B—C24B—C25B114.9 (19)H23C—C23B—H23D43.00
O6A—C25A—C24A109.9 (15)C23A—C23B—H23E128.00
O6B—C25B—C24B116 (2)H23C—C23B—H23F129.00
N1—C2—H2109.00H23D—C23B—H23E109.00
C1—C2—H2109.00H23D—C23B—H23F109.00
C3—C2—H2109.00H23E—C23B—H23F109.00
C2—C3—H3A109.00H23C—C23B—H23E66.00
H3A—C3—H3C109.00C22—C23B—H23A121.00
H3B—C3—H3C109.00C22—C23B—H23C120.00
C2—C3—H3B109.00O5A—C24A—H24A110.00
C2—C3—H3C109.00O5A—C24A—H24B110.00
H3A—C3—H3B109.00C25A—C24A—H24A110.00
C4—C5—H5A109.00C25A—C24A—H24B110.00
C4—C5—H5B110.00H24A—C24A—H24B109.00
C4—C5—H5C109.00O5B—C24B—H24C109.00
H5B—C5—H5C109.00C25B—C24B—H24D108.00
H5A—C5—H5B110.00O5B—C24B—H24D109.00
H5A—C5—H5C109.00C25B—C24B—H24C109.00
C4—C6—H6A109.00H24C—C24B—H24D108.00
C4—C6—H6B109.00O6A—C25A—H25A110.00
C4—C6—H6C109.00O6A—C25A—H25B110.00
H6A—C6—H6B110.00C24A—C25A—H25B110.00
H6B—C6—H6C109.00H25A—C25A—H25B108.00
H6A—C6—H6C110.00C24A—C25A—H25A110.00
C4—C7—H7C109.00O6B—C25B—H25C108.00
H7A—C7—H7B109.00O6B—C25B—H25D108.00
H7B—C7—H7C109.00C24B—C25B—H25C108.00
C4—C7—H7A110.00C24B—C25B—H25D109.00
H7A—C7—H7C109.00H25C—C25B—H25D107.00
C4—O1—C1—O2−4.5 (11)C8—C9—C20—C22165.1 (6)
C4—O1—C1—C2170.9 (6)O4—C14—C15—N3A57.1 (13)
C1—O1—C4—C562.9 (8)O4—C14—C15—C16−51.5 (8)
C1—O1—C4—C6−61.4 (8)N2—C14—C15—N3A−118.8 (12)
C1—O1—C4—C7−176.9 (6)N2—C14—C15—C16132.6 (6)
C24A—O5A—N3A—C15132.9 (18)N3A—C15—C16—C1755.9 (14)
N3A—O5A—C24A—C25A−72 (2)N3A—C15—C16—C18177.7 (13)
C8—N1—C2—C1−134.2 (6)C14—C15—C16—C17168.4 (6)
C8—N1—C2—C3104.4 (7)C14—C15—C16—C18−69.9 (8)
C2—N1—C8—O32.2 (10)C15—C16—C17—F441.6 (9)
C2—N1—C8—C9178.7 (6)C15—C16—C17—F5−79.4 (8)
C14—N2—C9—C8−105.0 (6)C15—C16—C17—F6164.6 (6)
C14—N2—C9—C20128.2 (6)C18—C16—C17—F4−80.8 (8)
C19—N2—C9—C874.6 (7)C18—C16—C17—F5158.3 (7)
C19—N2—C9—C20−52.3 (8)C18—C16—C17—F642.3 (9)
C9—N2—C14—O4−1.8 (9)C15—C16—C18—F1−76.2 (8)
C9—N2—C14—C15173.6 (5)C15—C16—C18—F2161.9 (6)
C19—N2—C14—O4178.6 (6)C15—C16—C18—F343.0 (9)
C19—N2—C14—C15−6.0 (9)C17—C16—C18—F147.0 (9)
O5A—N3A—C15—C1455.9 (18)C17—C16—C18—F2−75.0 (8)
O5A—N3A—C15—C16171.0 (14)C17—C16—C18—F3166.2 (7)
O1—C1—C2—N1169.0 (5)C9—C20—C22—C21177.4 (6)
O1—C1—C2—C3−69.6 (7)C9—C20—C22—C23A−67.8 (9)
O2—C1—C2—N1−15.5 (10)C9—C20—C22—C23B−47.6 (13)
O2—C1—C2—C3105.8 (8)C20—C22—C23A—C23B140 (2)
O3—C8—C9—N2−152.0 (6)C21—C22—C23A—C23B−104 (2)
O3—C8—C9—C20−24.6 (8)C20—C22—C23B—C23A−49 (2)
N1—C8—C9—N231.5 (8)C21—C22—C23B—C23A86 (2)
N1—C8—C9—C20158.8 (6)O5A—C24A—C25A—O6A−60 (2)
N2—C9—C20—C22−67.7 (8)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N3A—H3A1···F50.881.942.60 (3)130
N1—H1N···O20.88 (5)2.37 (7)2.720 (9)104 (5)
N1—H1N···O5A0.88 (5)2.38 (6)3.245 (17)169 (6)

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: IM2143).

References

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