Crystal structure of N-(tert-but-oxy-carbon-yl)phenyl-alanylde-hydro-alanine isopropyl ester (Boc-Phe-ΔAla-OiPr).

In the title compound, the de-hydro-dipeptide (Boc-Phe-ΔAla-OiPr, C20H28N2O5), the mol-ecule has a trans conformation of the N-methyl-amide group. The geometry of the de-hydro-alanine moiety is to some extent different from those usually found in simple peptides, indicating conjugation between the H2C=C group and the peptide bond. The bond angles around de-hydro-alanine have unusually high values due to the steric hindrance, the same inter-action influencing the slight distortion from planarity of the de-hydro-alanine. The mol-ecule is stabilized by intra-molecular inter-actions between the isopropyl group and the N atoms of the peptide main chain. In the crystal, an N-H⋯O hydrogen bond links the mol-ecules into ribbons, giving a herringbone head-to-head packing arrangement extending along the [100] direction. In the stacks, the mol-ecules are linked by weak C-H⋯O hydrogen-bonding associations.

Chemical context

De­hydro­peptides are a class of compounds containing at least one residue of an α,β-de­hydro­amino acid. These compounds are of inter­est in many fields of science because of their structural and chemical properties. De­hydro­amino acids are found in natural products (Bonauer et al., 2006 ▶). One of the important classes of natural bacteriocins are lanti­biotics (e.g. nisin, subtilin), which are biosynthesized by Gram-positive bacteria. The <span class="Chemical">unsaturated amino acid is introduced into the structure of these polycyclic peptides by post-translational modification of selected <class="Chemical">span class="Chemical">serine and threonine residues (Willey & van der Donk, 2007 ▶). The development of synthetic methods for de­hydro­peptide preparation has resulted in a search for practical applications for these compounds. The de­hydro­amino acids are considered to be building blocks for the synthesis of new non-proteinogenic amino acids (Ferreira et al., 2010 ▶). The double bond of the de­hydro­peptide can be used in different types of reaction, namely: addition of nucleophiles (Ferreira et al., 2001 ▶); alkyl­ation, providing α,α-disubstituted amino acids (Miyabe et al., 2005 ▶); Rh-catalysed conjugate addition of aryl­boronic acids providing β-aryl­alanine derivatives (Ferreira et al., 2013 ▶); Cu-catalysed asymmetric hydro­boration as a step in the preparation of β-hy­droxy-α-amino acid derivatives being then used for the preparation of chiral drugs and bioactive mol­ecules (He et al., 2014 ▶). Compounds containing de­hydro­amino acid residues also are considered to be inhibitors of enzymes (Makowski et al., 2001 ▶; Latajka et al., 2006 ▶, 2008 ▶). They are more resistant towards proteolytic enzymes than saturated analogues (English & Stammer, 1978 ▶). The presence of sp 2 hybridized carbon atoms in structures of de­hydro­peptides and the coupling of π-electrons between double and peptide bonds entail a number of structural consequences in the conformation of the peptides, and make them excellent subjects for conformational study (e.g. Jewgiński et al., 2014 ▶, 2013 ▶; Demizu et al., 2010 ▶; Lisowski et al., 2008 ▶). In this paper, the preparation of the title compound, N-(tert-but­oxy­carbon­yl)-phenyl­alanylde­hydro­alanine isopropyl ester and its structure determination by single-crystal X-ray crystallographic methods are presented.

Structural commentary

The mol­ecular structure of N-(tert-but­oxy­<span class="Chemical">carbon­yl)phenyl­alanylde­hydro­alanine isopropyl ester (<class="Chemical">span class="Gene">Boc–Phe–ΔAla–OiPr, C20H28N2O5) is shown in Fig. 1 ▶. The mol­ecule has a trans-conformation of the N-methyl­amide group. The geometry of the de­hydro­alanine is to some extent different from those usually found in simple peptides (Pauling, 1960 ▶). In particular, the N19—C20 bond length is shorter while C17—N19 is longer [1.402 (3) Å and 1.354 (3) Å, respectively]. This is in excellent agreement with the values reported for N-acetyl­dehydro­alanine (Ajó et al., 1979 ▶), N-acetyl­bis-(de­hydro­phenyl­alanyl)glycine (Pieroni et al. 1975 ▶) and N-acetyl­ode­hydro­di­­meth­yl­amide (Rzeszotarska et al., 2002 ▶) and seems to be typical for α, β-unsaturated peptide systems (Jain & Chauhan, 1996 ▶). This indicates conjugation between the H2C=C group and the peptide bond. The valance angles around de­hydro­alanine have unusually large values [C21—C20—N19 = 126.9 (2), C17—N19—C20 = 126.8 (2) and O18—C17—N19 = 123.5 (2)°] due to the steric hindrance between atoms C21 and O18. The same inter­action influences the slight distortion from planarity of the de­hydro­alanine moiety. The ω, ϕ and ψ torsion angles (C9—C17—N19—C20, C17—N19—C20—C22 and N19—C20—C22—O24, respectively) of the de­hydro­alanine residue are −166.9 (2), 175.1 (2) and 178.0 (2)°. The geom­etries of the phenyl­aniline and the protecting groups are normal. There are four intra­molecular C—H⋯O close contacts but three of them have a D—H⋯A angle of less than 120°.

Figure 1

The mol­ecular structure of N-(tert-but­oxy­carbon­yl)phenyl­alanylde­hydro­alanine isopropyl ester (Boc–Phe–ΔAla–OiPr) showing 50% displacement ellipsoids. Intra­molecular C—H⋯O inter­actions are shown as dashed lines.

Supra­molecular features

In the crystal, strong inter­molecular N8—H⋯O7i <span class="Chemical">hydrogen bonds (Table 1 ▶) link the mol­ecules, giving a herringbone head-to-head packing arrangement, forming ribbons which extend along [100] (Fig. 2 ▶). The ribbon structures are consolidated by weak intra-chain C—H⋯O <class="Chemical">span class="Chemical">hydrogen-bonding inter­actions.

Table 1

Hydrogen-bond geometry (, )

DHA	DH	HA	D A	DHA
N8H8AO7i	0.88	2.21	2.952(2)	141
C3H3CO18ii	0.98	2.51	3.423(3)	155
C21H21AO18	0.95	2.27	2.869(3)	120
C26H26BO23i	0.98	2.52	3.462(3)	162

Symmetry codes: (i) ; (ii) .

Figure 2

The packing diagram of the title compound, viewed along the b axis, showing the inter­molecular hydrogen-bonding scheme (dashed lines).

Synthesis and crystallization

The de­hydro­dipeptide was obtained by condensation of N-protected phenyl­alanyl­amide with <span class="Chemical">pyruvic acid in the presence of p-toluene­sulfonic acid (Makowski et al., 1985 ▶). The esterification of the de­hydro­dipeptide was performed using the methodology described by Cossec et al. (2008 ▶). For this purpose 0.669 g (2 mM) of <class="Chemical">span class="Gene">Boc–Phe–ΔAla was dissolved in 5 ml of methanol and calcium carbonate 0.329 g (1 mM) was added. The mixture was stirred for one h at room temperature, after which the solvent was evaporated. The residue was dissolved in 7 ml of DMF and isopropyl iodide (1.01 ml, 10 mM) was added in portions to the stirred mixture at room temperature during the reaction, the progress of which was monitored by thin-layer chromatography, using 5% methanol in chloro­form as eluent. After completion of the reaction, the solvent was evaporated and the oily residue was dissolved in ethyl acetate and washed consecutively with: 1 M HCl, saturated KHCO3, 0.1 M Na2S2O3 and brine. The organic layer was dried over anhydrous MgSO4 and the title compound was obtained in 81% yield (m.p. = 367–369 K). Recrystallization was performed using mixture of diethyl ether and hexane.

1H NMR (400 MHz, <span class="Chemical">DMSO) δ 1.26 (d, J = 6.2 Hz, 6H, 2 × <class="Chemical">span class="CellLine">CH3Pr), 1.30 (s, 9H, CH3 ), 2.76 (dd, ABX system, J = 13.6, 10.8 Hz, 1H, CHH), 3.02 (dd, ABX system, J = 13.6, 3.9 Hz, 1H, CHH), 4.27–4.39 (m, 1H, CHPhe), 5.01 (hept, J = 6.2 Hz, 1H, CHPr), 5.70 (s, 1H, C=CHH), 6.23 (s, 1H, C=CHH), 7.15–7.36 (m, 6H, ArHPhe overlapped with NHPhe), δ 9.30 (s, 1H, NHΔAla). 13C NMR (101 MHz, DMSO) δ 21.43, 28.10, 36.63, 56.34, 69.40, 78.41, 108.65, 126.29, 128.07, 129.25, 132.71, 138.03, 155.53, 162.81, 171.53. IR (KBr, cm−1) 3600–2800 broad (H-bonding), 1715 (C=Oester), 1700 (C=Ourethane), 1690 IAB (C=Oamide), 1632 (C=C), 1526 IIAB (C–N and N–H), 1317 (CO–N–C=and N–(C=C)–CO), 1196 and 1166 (C–O–C), 896 (=CH2).

Refinement details

Crystal data, data collection and structure refinement details are summarized in Table 2 ▶. All <span class="Chemical">hydrogen atoms were positioned geometrically and treated as riding on their parent atoms with N—H = 0.88 Å and U iso (H) = 1.2U <class="Chemical">span class="Chemical">eq(N), C—Haromatic = 0.95 Å and U iso (H) = 1.2U eq(C), C—Hmeth­yl = 0.98 Å and U iso (H) = 1.5U eq(C); C—Hmethyl­ene = 0.99 Å or C—Hmethine = 0.95 Å and U iso (H) = 1.2U eq(C). Although not definitive, the absolute structure factor (Parsons et al., 2013 ▶) with the C9(S) configuration, was −0.1 (6) for 1095 Friedel pairs.

Table 2

Experimental details

Crystal data
Chemical formula	C20H28N2O5
M r	376.44
Crystal system, space group	Orthorhombic, P212121
Temperature (K)	100
a, b, c ()	5.2123(2), 9.5031(3), 41.3363(17)
V (3)	2047.51(13)
Z	4
Radiation type	Mo K
(mm1)	0.09
Crystal size (mm)	0.33 0.18 0.14
Data collection
Diffractometer	Oxford Diffraction Xcalibur CCD
No. of measured, independent and observed [I > 2(I)] reflections	14003, 4025, 3235
R int	0.046
(sin /)max (1)	0.617
Refinement
R[F 2 > 2(F 2)], wR(F 2), S	0.046, 0.079, 0.98
No. of reflections	4025
No. of parameters	244
H-atom treatment	H-atom parameters constrained
max, min (e 3)	0.22, 0.22
Absolute structure	Flack x determined using 1095 quotients [(I +)(I )]/[(I +)+(I )] (Parsons et al., 2013 ▶)
Absolute structure parameter	0.1(6)

Computer programs: CrysAlis CCD and CrysAlis RED (Oxford Diffraction, 2008 ▶), SHELXL2014 and SHELXTL (Sheldrick, 2008 ▶).

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536814025197/zs2321sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536814025197/zs2321Isup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S1600536814025197/zs2321Isup3.cml

CCDC reference: 1034604

Additional supporting information: crystallographic information; 3D view; checkCIF report

C20H28N2O5	Dx = 1.221 Mg m−3
Mr = 376.44	Melting point = 367–369 K
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
a = 5.2123 (2) Å	Cell parameters from 4025 reflections
b = 9.5031 (3) Å	θ = 3.3–26.0°
c = 41.3363 (17) Å	µ = 0.09 mm−1
V = 2047.51 (13) Å3	T = 100 K
Z = 4	Irregular, colourless
F(000) = 808	0.33 × 0.18 × 0.14 mm

Oxford Diffraction Xcalibur CCD diffractometer	3235 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.046
Graphite monochromator	θmax = 26.0°, θmin = 3.3°
ω scans	h = −3→6
14003 measured reflections	k = −11→11
4025 independent reflections	l = −50→50

Refinement on F2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F2 > 2σ(F2)] = 0.046	w = 1/[σ2(Fo2) + (0.0354P)2] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.079	(Δ/σ)max < 0.001
S = 0.98	Δρmax = 0.22 e Å−3
4025 reflections	Δρmin = −0.22 e Å−3
244 parameters	Absolute structure: Flack x determined using 1095 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
0 restraints	Absolute structure parameter: −0.1 (6)

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
C1	1.2709 (4)	0.0969 (2)	0.10948 (7)	0.0184 (6)
C2	1.4195 (5)	0.1063 (3)	0.14083 (7)	0.0249 (7)
H2A	1.5204	0.1933	0.1411	0.037*
H2B	1.5348	0.0252	0.1427	0.037*
H2C	1.2995	0.1065	0.1591	0.037*
C3	1.1120 (5)	−0.0366 (3)	0.10835 (8)	0.0325 (7)
H3A	1.0176	−0.0406	0.0879	0.049*
H3B	0.9903	−0.0369	0.1264	0.049*
H3C	1.2254	−0.1185	0.1100	0.049*
C4	1.4374 (5)	0.1068 (3)	0.07954 (7)	0.0264 (7)
H4A	1.5397	0.1932	0.0804	0.040*
H4B	1.3282	0.1085	0.0602	0.040*
H4C	1.5520	0.0252	0.0786	0.040*
O5	1.0713 (3)	0.20736 (16)	0.10856 (4)	0.0194 (4)
C6	1.1322 (5)	0.3446 (2)	0.10987 (6)	0.0151 (5)
O7	1.3475 (3)	0.39442 (16)	0.10970 (4)	0.0188 (4)
N8	0.9116 (3)	0.4203 (2)	0.11214 (5)	0.0148 (5)
H8A	0.7675	0.3751	0.1160	0.018*
C9	0.9025 (4)	0.5718 (2)	0.10849 (6)	0.0150 (5)
H9A	1.0784	0.6105	0.1122	0.018*
C10	0.8141 (5)	0.6145 (3)	0.07443 (6)	0.0176 (6)
H10A	0.6402	0.5761	0.0707	0.021*
H10B	0.8020	0.7184	0.0734	0.021*
C11	0.9882 (5)	0.5648 (3)	0.04781 (6)	0.0167 (6)
C12	1.1944 (5)	0.6462 (3)	0.03752 (6)	0.0231 (6)
H12A	1.2281	0.7335	0.0479	0.028*
C13	1.3509 (5)	0.6026 (3)	0.01250 (7)	0.0312 (7)
H13A	1.4897	0.6601	0.0056	0.037*
C14	1.3057 (6)	0.4757 (3)	−0.00244 (7)	0.0338 (8)
H14A	1.4134	0.4455	−0.0196	0.041*
C15	1.1046 (5)	0.3924 (3)	0.00748 (7)	0.0317 (7)
H15A	1.0739	0.3046	−0.0028	0.038*
C16	0.9473 (5)	0.4367 (3)	0.03241 (6)	0.0244 (7)
H16A	0.8088	0.3787	0.0391	0.029*
C17	0.7185 (5)	0.6377 (3)	0.13324 (6)	0.0177 (6)
O18	0.6189 (4)	0.75177 (19)	0.12844 (4)	0.0266 (5)
N19	0.6785 (4)	0.5605 (2)	0.16029 (5)	0.0168 (5)
H19A	0.7841	0.4897	0.1636	0.020*
C20	0.4865 (4)	0.5814 (3)	0.18356 (6)	0.0163 (6)
C21	0.3165 (5)	0.6849 (3)	0.18436 (6)	0.0233 (6)
H21A	0.3171	0.7549	0.1679	0.028*
H21B	0.1940	0.6892	0.2013	0.028*
C22	0.4947 (5)	0.4660 (3)	0.20809 (6)	0.0197 (6)
O23	0.6457 (4)	0.36963 (19)	0.20637 (4)	0.0282 (5)
O24	0.3215 (3)	0.48235 (17)	0.23152 (4)	0.0232 (4)
C25	0.3210 (5)	0.3753 (3)	0.25720 (6)	0.0249 (6)
H25A	0.5018	0.3520	0.2633	0.030*
C26	0.1889 (6)	0.2446 (3)	0.24504 (6)	0.0274 (7)
H26A	0.2849	0.2060	0.2267	0.041*
H26B	0.0143	0.2682	0.2381	0.041*
H26C	0.1814	0.1746	0.2624	0.041*
C27	0.1881 (6)	0.4430 (3)	0.28559 (6)	0.0323 (7)
H27A	0.2836	0.5269	0.2923	0.049*
H27B	0.1807	0.3761	0.3036	0.049*
H27C	0.0135	0.4699	0.2793	0.049*

	U11	U22	U33	U12	U13	U23
C1	0.0114 (11)	0.0108 (13)	0.0330 (15)	0.0059 (10)	−0.0014 (12)	−0.0004 (12)
C2	0.0222 (14)	0.0209 (15)	0.0315 (16)	0.0048 (13)	0.0001 (13)	0.0041 (13)
C3	0.0235 (14)	0.0132 (13)	0.061 (2)	0.0028 (12)	−0.0025 (16)	0.0000 (14)
C4	0.0188 (14)	0.0302 (17)	0.0301 (16)	0.0049 (14)	−0.0019 (12)	−0.0077 (14)
O5	0.0107 (9)	0.0111 (9)	0.0364 (11)	0.0019 (7)	0.0009 (9)	−0.0001 (8)
C6	0.0163 (13)	0.0113 (12)	0.0177 (14)	−0.0004 (11)	−0.0003 (12)	−0.0001 (11)
O7	0.0097 (8)	0.0159 (9)	0.0308 (10)	−0.0025 (8)	0.0001 (8)	0.0022 (8)
N8	0.0084 (9)	0.0100 (10)	0.0261 (12)	0.0007 (8)	0.0041 (9)	0.0023 (10)
C9	0.0126 (11)	0.0106 (12)	0.0218 (14)	−0.0004 (10)	0.0007 (11)	0.0011 (12)
C10	0.0163 (12)	0.0147 (13)	0.0218 (14)	0.0026 (12)	−0.0026 (12)	0.0014 (11)
C11	0.0146 (12)	0.0189 (14)	0.0167 (13)	0.0044 (12)	−0.0036 (11)	0.0053 (12)
C12	0.0219 (14)	0.0228 (15)	0.0246 (15)	0.0011 (14)	−0.0054 (14)	0.0055 (12)
C13	0.0203 (14)	0.047 (2)	0.0261 (16)	0.0016 (16)	0.0003 (14)	0.0160 (15)
C14	0.0245 (15)	0.056 (2)	0.0208 (16)	0.0117 (17)	0.0058 (13)	0.0011 (15)
C15	0.0312 (16)	0.0375 (19)	0.0265 (16)	0.0061 (16)	0.0001 (14)	−0.0093 (14)
C16	0.0197 (14)	0.0281 (16)	0.0254 (16)	−0.0011 (13)	0.0002 (12)	0.0002 (13)
C17	0.0154 (13)	0.0148 (14)	0.0228 (15)	−0.0031 (12)	−0.0022 (12)	−0.0021 (12)
O18	0.0284 (11)	0.0159 (10)	0.0356 (12)	0.0083 (9)	0.0094 (9)	0.0026 (9)
N19	0.0135 (10)	0.0170 (11)	0.0198 (12)	0.0047 (10)	0.0000 (9)	0.0016 (10)
C20	0.0149 (12)	0.0171 (14)	0.0168 (13)	−0.0033 (12)	−0.0017 (11)	−0.0029 (12)
C21	0.0232 (14)	0.0245 (15)	0.0221 (15)	0.0037 (13)	0.0067 (14)	0.0011 (12)
C22	0.0165 (13)	0.0235 (16)	0.0193 (14)	−0.0037 (12)	−0.0031 (12)	0.0003 (12)
O23	0.0242 (10)	0.0282 (11)	0.0322 (11)	0.0096 (10)	0.0027 (10)	0.0085 (9)
O24	0.0231 (10)	0.0256 (11)	0.0207 (10)	0.0009 (9)	0.0058 (9)	0.0035 (8)
C25	0.0228 (14)	0.0280 (15)	0.0238 (15)	−0.0029 (15)	0.0007 (13)	0.0102 (13)
C26	0.0238 (15)	0.0253 (15)	0.0333 (16)	0.0004 (14)	0.0023 (14)	0.0057 (13)
C27	0.0368 (17)	0.0341 (18)	0.0262 (16)	−0.0036 (16)	0.0039 (14)	0.0025 (14)

C1—O5	1.478 (3)	C13—C14	1.375 (4)
C1—C2	1.513 (4)	C13—H13A	0.9500
C1—C4	1.514 (4)	C14—C15	1.376 (4)
C1—C3	1.516 (3)	C14—H14A	0.9500
C2—H2A	0.9800	C15—C16	1.382 (4)
C2—H2B	0.9800	C15—H15A	0.9500
C2—H2C	0.9800	C16—H16A	0.9500
C3—H3A	0.9800	C17—O18	1.218 (3)
C3—H3B	0.9800	C17—N19	1.354 (3)
C3—H3C	0.9800	N19—C20	1.402 (3)
C4—H4A	0.9800	N19—H19A	0.8800
C4—H4B	0.9800	C20—C21	1.324 (3)
C4—H4C	0.9800	C20—C22	1.494 (3)
O5—C6	1.343 (3)	C21—H21A	0.9500
C6—O7	1.218 (3)	C21—H21B	0.9500
C6—N8	1.360 (3)	C22—O23	1.209 (3)
N8—C9	1.448 (3)	C22—O24	1.333 (3)
N8—H8A	0.8800	O24—C25	1.470 (3)
C9—C10	1.536 (3)	C25—C26	1.506 (4)
C9—C17	1.536 (3)	C25—C27	1.507 (4)
C9—H9A	1.0000	C25—H25A	1.0000
C10—C11	1.503 (3)	C26—H26A	0.9800
C10—H10A	0.9900	C26—H26B	0.9800
C10—H10B	0.9900	C26—H26C	0.9800
C11—C16	1.390 (4)	C27—H27A	0.9800
C11—C12	1.391 (3)	C27—H27B	0.9800
C12—C13	1.381 (4)	C27—H27C	0.9800
C12—H12A	0.9500
O5—C1—C2	109.9 (2)	C11—C12—H12A	119.4
O5—C1—C4	109.7 (2)	C14—C13—C12	119.9 (3)
C2—C1—C4	113.8 (2)	C14—C13—H13A	120.0
O5—C1—C3	102.06 (17)	C12—C13—H13A	120.0
C2—C1—C3	110.8 (2)	C13—C14—C15	120.1 (3)
C4—C1—C3	109.9 (2)	C13—C14—H14A	120.0
C1—C2—H2A	109.5	C15—C14—H14A	120.0
C1—C2—H2B	109.5	C14—C15—C16	119.9 (3)
H2A—C2—H2B	109.5	C14—C15—H15A	120.0
C1—C2—H2C	109.5	C16—C15—H15A	120.0
H2A—C2—H2C	109.5	C15—C16—C11	121.1 (3)
H2B—C2—H2C	109.5	C15—C16—H16A	119.4
C1—C3—H3A	109.5	C11—C16—H16A	119.4
C1—C3—H3B	109.5	O18—C17—N19	123.5 (2)
H3A—C3—H3B	109.5	O18—C17—C9	121.4 (2)
C1—C3—H3C	109.5	N19—C17—C9	115.1 (2)
H3A—C3—H3C	109.5	C17—N19—C20	126.8 (2)
H3B—C3—H3C	109.5	C17—N19—H19A	116.6
C1—C4—H4A	109.5	C20—N19—H19A	116.6
C1—C4—H4B	109.5	C21—C20—N19	126.9 (2)
H4A—C4—H4B	109.5	C21—C20—C22	123.2 (2)
C1—C4—H4C	109.5	N19—C20—C22	109.9 (2)
H4A—C4—H4C	109.5	C20—C21—H21A	120.0
H4B—C4—H4C	109.5	C20—C21—H21B	120.0
C6—O5—C1	121.48 (18)	H21A—C21—H21B	120.0
O7—C6—O5	126.5 (2)	O23—C22—O24	124.9 (2)
O7—C6—N8	125.0 (2)	O23—C22—C20	122.3 (2)
O5—C6—N8	108.46 (19)	O24—C22—C20	112.8 (2)
C6—N8—C9	123.12 (19)	C22—O24—C25	116.4 (2)
C6—N8—H8A	118.4	O24—C25—C26	109.3 (2)
C9—N8—H8A	118.4	O24—C25—C27	105.5 (2)
N8—C9—C10	111.61 (19)	C26—C25—C27	113.7 (2)
N8—C9—C17	110.89 (19)	O24—C25—H25A	109.4
C10—C9—C17	108.39 (19)	C26—C25—H25A	109.4
N8—C9—H9A	108.6	C27—C25—H25A	109.4
C10—C9—H9A	108.6	C25—C26—H26A	109.5
C17—C9—H9A	108.6	C25—C26—H26B	109.5
C11—C10—C9	114.0 (2)	H26A—C26—H26B	109.5
C11—C10—H10A	108.7	C25—C26—H26C	109.5
C9—C10—H10A	108.7	H26A—C26—H26C	109.5
C11—C10—H10B	108.7	H26B—C26—H26C	109.5
C9—C10—H10B	108.7	C25—C27—H27A	109.5
H10A—C10—H10B	107.6	C25—C27—H27B	109.5
C16—C11—C12	117.8 (2)	H27A—C27—H27B	109.5
C16—C11—C10	121.2 (2)	C25—C27—H27C	109.5
C12—C11—C10	121.0 (2)	H27A—C27—H27C	109.5
C13—C12—C11	121.2 (3)	H27B—C27—H27C	109.5
C13—C12—H12A	119.4
C2—C1—O5—C6	60.9 (3)	C12—C11—C16—C15	−0.6 (4)
C4—C1—O5—C6	−65.0 (3)	C10—C11—C16—C15	178.7 (2)
C3—C1—O5—C6	178.5 (2)	N8—C9—C17—O18	−156.2 (2)
C1—O5—C6—O7	5.3 (4)	C10—C9—C17—O18	−33.4 (3)
C1—O5—C6—N8	−173.4 (2)	N8—C9—C17—N19	24.2 (3)
O7—C6—N8—C9	12.2 (4)	C10—C9—C17—N19	147.0 (2)
O5—C6—N8—C9	−169.1 (2)	O18—C17—N19—C20	13.5 (4)
C6—N8—C9—C10	99.5 (3)	C9—C17—N19—C20	−166.9 (2)
C6—N8—C9—C17	−139.5 (2)	C17—N19—C20—C21	−3.8 (4)
N8—C9—C10—C11	−61.4 (3)	C17—N19—C20—C22	175.1 (2)
C17—C9—C10—C11	176.2 (2)	C21—C20—C22—O23	177.4 (2)
C9—C10—C11—C16	91.7 (3)	N19—C20—C22—O23	−1.5 (3)
C9—C10—C11—C12	−89.0 (3)	C21—C20—C22—O24	−3.0 (3)
C16—C11—C12—C13	1.0 (4)	N19—C20—C22—O24	178.0 (2)
C10—C11—C12—C13	−178.3 (2)	O23—C22—O24—C25	1.1 (4)
C11—C12—C13—C14	−0.7 (4)	C20—C22—O24—C25	−178.4 (2)
C12—C13—C14—C15	0.1 (4)	C22—O24—C25—C26	−78.0 (3)
C13—C14—C15—C16	0.3 (4)	C22—O24—C25—C27	159.4 (2)
C14—C15—C16—C11	0.0 (4)

D—H···A	D—H	H···A	D···A	D—H···A
N8—H8A···O7i	0.88	2.21	2.952 (2)	141
C2—H2A···O7	0.98	2.48	3.049 (3)	117
C3—H3C···O18ii	0.98	2.51	3.423 (3)	155
C4—H4A···O7	0.98	2.47	3.040 (3)	116
C21—H21A···O18	0.95	2.27	2.869 (3)	120
C26—H26A···O23	0.98	2.58	3.104 (3)	114
C26—H26B···O23i	0.98	2.52	3.462 (3)	162