Codeinone

The title compound, 4,5α-ep­oxy-3-meth­oxy-17-methyl­morphin-7-en-6-one, C₁₈H₁₉NO₃, the mol­ecular structure exhibits features typical for morphine derivatives, with a T-shaped configuration. The crystal packing is stabilized by weak inter­molecular C—H...O inter­actions.

Key indicators

• Single-crystal X-ray study
• T = 290 K
• Mean [sigma](C-C) = 0.006 Å
• R factor = 0.060
• wR factor = 0.118
• Data-to-parameter ratio = 10.2

checkCIF/PLATON results

No syntax errors found



Alert level B
RINTA01_ALERT_3_B  The value of Rint is greater than 0.15
            Rint given   0.172
PLAT020_ALERT_3_B The value of Rint is greater than 0.10 .........       0.17

Alert level C
PLAT026_ALERT_3_C Ratio Observed / Unique Reflections too Low ....         49 Perc.
PLAT340_ALERT_3_C Low Bond Precision on C-C bonds (x 1000) Ang ...          6
PLAT480_ALERT_4_C Long H...A H-Bond Reported H18A   ..  O1      ..       2.75 Ang.
PLAT480_ALERT_4_C Long H...A H-Bond Reported H10A   ..  O2      ..       2.62 Ang.
PLAT480_ALERT_4_C Long H...A H-Bond Reported H14    ..  O3      ..       2.66 Ang.
PLAT480_ALERT_4_C Long H...A H-Bond Reported H5     ..  O3      ..       2.70 Ang.

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           27.97
           From the CIF: _reflns_number_total               2032
           Count of symmetry unique reflns         2032
           Completeness (_total/calc)            100.00%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         0
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present         no

   0 ALERT level A = In general: serious problem
   2 ALERT level B = Potentially serious problem
   6 ALERT level C = Check and explain
   1 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   4 ALERT type 3 Indicator that the structure quality may be low
   5 ALERT type 4 Improvement, methodology, query or suggestion

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S1. Comment

The structure of codeinone, (I), was elucidated as part of our synthetic, spectroscopic and structural investigations of morphine alkaloids, which constitute a major class of pain-alleviating drugs. Codeinone has been found to possess antitumour potential, with high cytotoxic activity against human promyelocytic leukaemic cell lines (Hitosugi et al., 2003). The transformation of morphine derivatives into different metabolites is a matter of practical interest for detecting opiates in blood or urine. It is known that codeinone in the living cell is produced from the reaction of codeine with nicotinamide adenine dinucleotide phosphate (NADP+).

The overall configuration of (I) and the atom-numbering scheme are shown in Fig. 1. The absolute configuration of the chiral centres in the molecule is identical to that of the starting material, codeine. The main structural features of the molecule are very close to those of codeine (Canfield et al., 1987), heroin (Canfield et al., 1979), morphine (Gylbert, 1973) and acetylcodeine (Sonar et al., 2005; Kolev et al., 2005).

The molecule of (I) exhibits the T-shaped configuration characteristic of classical morphine opiates. The value of 86.62 (6)° for the dihedral angle between the mean planes of the A/B/C and D/E rings in (I) is comparable with that in codeine (88.94°; Canfield et al., 1987) and differs somewhat with that observed in 6-O-codeine [80.56 (8)°; Sonar et al., 2005; Kolev et al., 2005].

The ring fusions and conformations are similar to those previously reported for morphine derivatives (Gelders & de Ranter, 1979; Petrickova et al., 2002; Moody et al., 1997). Aromatic ring A is planar, B is close to an envelope, C and D assume half-chair conformations and E assumes a chair form (Table 1). The oxidation of codeine to codeinone should mainly affect the shape and properties of ring D. However, no major differences between the geometric parameters of ring D in codeinone, codeine and even 6-O-codeine could be established.

The conformation about the single C—C bonds within the rings is staggered, as in codeine; exceptions such as the C5—C6 eclipsed bond in 6-O-codeine are not present. This difference between the codeinone and 6-acetylcodeine conformations, along with the absence or presence of a chiral centre at the C6 position, is associated with the different functional groups attached to atom C6.

In the three-dimensional arrangement of the molecules of (I) (Fig. 2), no classical hydrogen bonds could be found. A subsequent examination of intermolecular contacts suggested that molecules of (I) are linked in the crystal structure through weak C—H···O interactions (Desiraju, 1996; Steiner & Desiraju, 1998; Zhu et al., 2005). The interactions involving atoms O1 and O3 (Table 2) connect the molecules to form undulating `pseudo'-layers perpendicular to the c axis. The C10—H10A···O2 interaction connects the layers along the c axis, spreading the structure stabilization in all three directions.

S2. Experimental

Codeinone was prepared according to the method of Bakalska et al. (2002). Crystals suitable for X-ray diffraction were obtained by slow evaporation from ethanol at 277 K.

IR spectra were measured on a Bomem–Michelson 100 F T–IR spectrometer in the range 4000–400 cm⁻¹, with 2 cm⁻¹ resolution and 150 scans. Solid-state IR spectra were recorded using the KBr pellet technique. Chloroform (Merck) solutions, at a concentration of 1.10⁻² M, were measured using 0.05 cm KBr pellets. The bands at 2840 and 2807 cm⁻¹ of codeinone are assigned to ν^s[CH₃(O)] and ν^s[CH₃(N)] modes, respectively. The most intense peak at 1677 cm⁻¹ in the IR spectrum of codeinone belongs to the ν(C═O) mode of the conjugated C═O group. The maxima at 1374 and 1388 cm⁻¹ indicate δ^s[CH3(N)] and δ^s[CH3(O)], respectively. Typical for morphine compounds are peaks at about 1633, 1604 and 1506 cm⁻¹, which are assigned as ν(C ═ C), 8a and 19a in-plane (A₁) phenyl modes. The series of in-plane peaks of 1,2,3,4-o-tetrasubstituted benzene at about 1150 and 1050 cm⁻¹ are observed in the 1200–800 cm⁻¹ frequency region. Below 1000 cm⁻¹, an intense maximum at 940 cm⁻¹ and a pair of maxima at about 936 and 804 cm⁻¹ are present, but the exact assignment with conventional IR techniques is ambiguous. A detailed spectroscopic study, combined with ab initio UHF calculations of (I), are in progress and will be published at a later date.

Spectroscopic analysis for codeinone: ¹H NMR (Bruker 250, 250 MHz, CDCl₃, δ, p.p.m.): 6.67 (d, 1H, J = 8.2 Hz, H-2), 6.62 (d, 1H, J = 10.2 Hz, H-8), 6.59 (d, 1H, J = 8.2 Hz, H-1), 6.07 (dd, 1H, J = 10.2 and 2.9 Hz, H-7), 4.68 (s, 1H, H-5), 3.85 (s, 3H OCH₃), 3.45–3.35 (m, 1H, H-9), 3.25–3.17 (m, 1H, H-14), 3.10 (d, 1H, J = 18.5 Hz, H-10β), 2.61 (dm, 1H, J = 11.8 Hz, H-16_e), 2.45 (s, 3H, NCH₃), 2.30 (dd, 1H, J = 18.5 and 5.5 Hz, H-10α), 2.30 (td, 1H, J = 11.9 and 3.7 Hz, H-16_a), 2.06 (td, 1H, J = 12.0 and 4.8 Hz, H-15_a), 1.85 (dm, 1H, J = 12.5 Hz, H-15_e); ¹³C NMR (CDCl₃, δ, p.p.m.): 119.7 (C-1), 114.7 (C-2), 142.3 (C-3), 146.2 (C-4), 88.0 (C-5), 194.1 (C-6), 132.2 (C-7), 149.1 (C-8), 58.9 (C-9), 20.4 (C-10),126.1 (C-11), 129.0 (C-12), 43.1 (C-13), 41.4 (C-14), 33.9 (C-15), 46.7 (C-16), 42.9 (NMe), 56.7 (OMe).

S3. Refinement

All H atoms were placed in idealized positions, with C—H = 0.93–0.98 Å, and constrained to ride on their parent atoms, with U_iso(H) = 1.2U_eq(C and C_aromatic), or 1.5U_eq(C_Me).

Computing details

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997) and Mercury (Version 1.3; Bruno et al., 2002); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures

	Fig. 1. The molecular structure of (I), showing 50% probability displacement ellipsoids.
	Fig. 2. The molecular packing in (I). Intermolecular C—H···O contacts are denoted by dotted lines. H atoms not participating in C—H···O contacts have been omitted for clarity. [Symmetry codes: (i) x − 1/2, −y + 3/2, −z + 1; (ii) −x + 3/2, −y + 1, z + 1/2; (iii) x + 1/2, −y + 1/2, −z + 1.]

4,5α-epoxy-3-methoxy-17-methylmorphin-7-ene-6-one

Crystal data

C18H19NO3	Dx = 1.346 Mg m^−3
Mr = 297.34	Melting point: not measured K
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 22 reflections
a = 7.2541 (10) Å	θ = 16.3–17.7°
b = 14.0943 (14) Å	µ = 0.09 mm^−1
c = 14.3507 (15) Å	T = 290 K
V = 1467.2 (3) Å^3	Prismatic, colourless
Z = 4	0.18 × 0.16 × 0.15 mm
F(000) = 632

Data collection

Enraf–Nonius CAD-4 diffractometer	Rint = 0.172
Radiation source: fine-focus sealed tube	θmax = 28.0°, θmin = 2.0°
Graphite monochromator	h = 0→9
Non–profiled ω/2θ scans	k = −18→18
7258 measured reflections	l = −18→18
2032 independent reflections	3 standard reflections every 120 min
987 reflections with I > 2σ(I)	intensity decay: 2%

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.060	H-atom parameters constrained
wR(F^2) = 0.118	w = 1/[σ^2(Fo^2) + (0.0344P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 1.02	(Δ/σ)max < 0.001
2032 reflections	Δρmax = 0.16 e Å^−3
200 parameters	Δρmin = −0.18 e Å^−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0128 (18)

Special details

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.

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

	x	y	z	Uiso*/Ueq
N1	1.2910 (6)	0.4138 (3)	0.7428 (2)	0.0481 (10)
O1	0.5791 (5)	0.6486 (2)	0.5119 (2)	0.0575 (9)
O2	0.7983 (4)	0.48246 (17)	0.49336 (18)	0.0429 (8)
O3	0.6008 (6)	0.3076 (2)	0.4889 (2)	0.0700 (11)
C1	0.7832 (7)	0.6168 (3)	0.7470 (3)	0.0467 (12)
H1	0.7759	0.6433	0.8062	0.056*
C2	0.6847 (8)	0.6569 (3)	0.6747 (3)	0.0468 (12)
H2	0.6181	0.7122	0.6858	0.056*
C3	0.6818 (7)	0.6173 (3)	0.5859 (3)	0.0409 (11)
C4	0.7905 (6)	0.5387 (3)	0.5723 (3)	0.0367 (10)
C5	0.8760 (6)	0.3921 (3)	0.5255 (3)	0.0382 (11)
H5	0.9501	0.3635	0.4758	0.046*
C6	0.7138 (7)	0.3272 (3)	0.5490 (3)	0.0474 (12)
C7	0.6934 (8)	0.2932 (3)	0.6438 (3)	0.0580 (14)
H7	0.5832	0.2643	0.6609	0.070*
C8	0.8256 (8)	0.3018 (3)	0.7074 (3)	0.0564 (14)
H8	0.8029	0.2795	0.7673	0.068*
C9	1.0988 (7)	0.3944 (3)	0.7720 (3)	0.0436 (12)
H9	1.1039	0.3481	0.8228	0.052*
C10	0.9879 (7)	0.4799 (3)	0.8073 (3)	0.0548 (14)
H10A	0.8951	0.4574	0.8506	0.066*
H10B	1.0703	0.5214	0.8415	0.066*
C11	0.8938 (7)	0.5371 (3)	0.7325 (3)	0.0403 (11)
C12	0.8970 (7)	0.5025 (3)	0.6428 (3)	0.0374 (11)
C13	0.9998 (6)	0.4165 (3)	0.6086 (3)	0.0370 (11)
C14	1.0065 (7)	0.3447 (3)	0.6874 (3)	0.0432 (12)
H14	1.0889	0.2934	0.6677	0.052*
C15	1.1965 (7)	0.4410 (3)	0.5809 (3)	0.0467 (12)
H15A	1.2568	0.3850	0.5562	0.056*
H15B	1.1949	0.4889	0.5324	0.056*
C16	1.3037 (7)	0.4777 (3)	0.6639 (3)	0.0529 (13)
H16A	1.4321	0.4854	0.6466	0.063*
H16B	1.2561	0.5394	0.6816	0.063*
C17	1.4038 (8)	0.4485 (4)	0.8207 (3)	0.0691 (16)
H17A	1.3950	0.4049	0.8720	0.104*
H17B	1.3601	0.5097	0.8399	0.104*
H17C	1.5300	0.4534	0.8012	0.104*
C18	0.4366 (8)	0.7148 (4)	0.5298 (4)	0.082 (2)
H18A	0.3755	0.7304	0.4725	0.122*
H18B	0.4884	0.7712	0.5566	0.122*
H18C	0.3494	0.6875	0.5724	0.122*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.041 (2)	0.058 (2)	0.045 (2)	0.001 (2)	−0.006 (2)	0.0044 (19)
O1	0.063 (2)	0.0458 (18)	0.063 (2)	0.0188 (19)	−0.009 (2)	0.0017 (17)
O2	0.0564 (19)	0.0374 (14)	0.0349 (15)	0.0056 (16)	−0.0042 (17)	−0.0022 (13)
O3	0.073 (3)	0.069 (2)	0.068 (2)	−0.020 (2)	−0.020 (2)	−0.0067 (19)
C1	0.058 (3)	0.041 (3)	0.041 (3)	−0.001 (3)	0.006 (3)	−0.010 (2)
C2	0.054 (3)	0.033 (2)	0.053 (3)	0.001 (3)	0.003 (3)	−0.005 (2)
C3	0.045 (3)	0.034 (2)	0.044 (3)	−0.002 (2)	−0.008 (3)	0.010 (2)
C4	0.044 (3)	0.030 (2)	0.036 (2)	−0.003 (2)	0.001 (2)	0.0016 (19)
C5	0.040 (3)	0.031 (2)	0.043 (3)	0.011 (2)	0.006 (2)	0.0003 (19)
C6	0.050 (3)	0.046 (3)	0.047 (3)	−0.001 (3)	0.000 (3)	−0.011 (2)
C7	0.058 (4)	0.052 (3)	0.064 (3)	−0.023 (3)	0.007 (3)	0.002 (3)
C8	0.061 (4)	0.062 (3)	0.046 (3)	−0.014 (3)	0.008 (3)	0.013 (2)
C9	0.045 (3)	0.052 (3)	0.034 (2)	0.006 (3)	−0.002 (2)	0.010 (2)
C10	0.057 (3)	0.068 (3)	0.040 (3)	0.001 (3)	−0.005 (3)	−0.003 (2)
C11	0.042 (3)	0.038 (2)	0.041 (3)	−0.005 (2)	−0.001 (2)	−0.002 (2)
C12	0.039 (3)	0.034 (2)	0.038 (3)	−0.008 (2)	0.000 (2)	0.003 (2)
C13	0.034 (3)	0.039 (2)	0.039 (3)	−0.003 (2)	0.004 (2)	0.002 (2)
C14	0.047 (3)	0.042 (2)	0.041 (2)	0.001 (3)	0.001 (2)	0.006 (2)
C15	0.044 (3)	0.051 (3)	0.045 (3)	0.004 (3)	0.006 (3)	0.003 (2)
C16	0.036 (3)	0.059 (3)	0.064 (3)	−0.005 (3)	0.003 (3)	0.003 (3)
C17	0.049 (3)	0.089 (4)	0.070 (4)	0.003 (3)	−0.018 (3)	−0.008 (3)
C18	0.093 (5)	0.068 (4)	0.084 (4)	0.034 (4)	−0.028 (4)	−0.003 (3)

Geometric parameters (Å, º)

N1—C16	1.450 (5)	C9—C10	1.535 (6)
N1—C17	1.469 (6)	C9—C14	1.553 (6)
N1—C9	1.482 (6)	C9—H9	0.9800
O1—C3	1.371 (5)	C10—C11	1.506 (6)
O1—C18	1.415 (6)	C10—H10A	0.9700
O2—C4	1.384 (4)	C10—H10B	0.9700
O2—C5	1.468 (4)	C11—C12	1.377 (5)
O3—C6	1.221 (5)	C12—C13	1.505 (6)
C1—C2	1.380 (6)	C13—C14	1.519 (5)
C1—C11	1.396 (6)	C13—C15	1.521 (6)
C1—H1	0.9300	C14—H14	0.9800
C2—C3	1.391 (5)	C15—C16	1.513 (6)
C2—H2	0.9300	C15—H15A	0.9700
C3—C4	1.374 (5)	C15—H15B	0.9700
C4—C12	1.370 (5)	C16—H16A	0.9700
C5—C6	1.527 (6)	C16—H16B	0.9700
C5—C13	1.532 (6)	C17—H17A	0.9600
C5—H5	0.9800	C17—H17B	0.9600
C6—C7	1.450 (6)	C17—H17C	0.9600
C7—C8	1.329 (7)	C18—H18A	0.9600
C7—H7	0.9300	C18—H18B	0.9600
C8—C14	1.473 (6)	C18—H18C	0.9600
C8—H8	0.9300
C16—N1—C17	110.6 (4)	H10A—C10—H10B	107.5
C16—N1—C9	113.3 (4)	C12—C11—C1	115.7 (4)
C17—N1—C9	111.7 (4)	C12—C11—C10	118.0 (4)
C3—O1—C18	117.9 (4)	C1—C11—C10	125.8 (4)
C4—O2—C5	104.8 (3)	C4—C12—C11	123.3 (4)
C2—C1—C11	121.0 (4)	C4—C12—C13	109.8 (4)
C2—C1—H1	119.5	C11—C12—C13	126.7 (4)
C11—C1—H1	119.5	C12—C13—C14	108.0 (3)
C1—C2—C3	122.1 (4)	C12—C13—C15	111.6 (4)
C1—C2—H2	118.9	C14—C13—C15	108.4 (4)
C3—C2—H2	118.9	C12—C13—C5	98.3 (4)
O1—C3—C4	117.5 (4)	C14—C13—C5	116.6 (4)
O1—C3—C2	126.1 (4)	C15—C13—C5	113.4 (4)
C4—C3—C2	116.4 (4)	C8—C14—C13	113.0 (4)
C12—C4—C3	121.2 (4)	C8—C14—C9	114.7 (4)
C12—C4—O2	111.6 (3)	C13—C14—C9	107.2 (4)
C3—C4—O2	127.0 (4)	C8—C14—H14	107.2
O2—C5—C6	107.0 (3)	C13—C14—H14	107.2
O2—C5—C13	105.9 (3)	C9—C14—H14	107.2
C6—C5—C13	114.5 (3)	C16—C15—C13	110.7 (4)
O2—C5—H5	109.8	C16—C15—H15A	109.5
C6—C5—H5	109.8	C13—C15—H15A	109.5
C13—C5—H5	109.8	C16—C15—H15B	109.5
O3—C6—C7	121.3 (5)	C13—C15—H15B	109.5
O3—C6—C5	119.7 (4)	H15A—C15—H15B	108.1
C7—C6—C5	118.9 (4)	N1—C16—C15	111.7 (4)
C8—C7—C6	122.7 (5)	N1—C16—H16A	109.3
C8—C7—H7	118.6	C15—C16—H16A	109.3
C6—C7—H7	118.6	N1—C16—H16B	109.3
C7—C8—C14	123.1 (4)	C15—C16—H16B	109.3
C7—C8—H8	118.4	H16A—C16—H16B	107.9
C14—C8—H8	118.4	N1—C17—H17A	109.5
N1—C9—C10	116.2 (4)	N1—C17—H17B	109.5
N1—C9—C14	105.5 (4)	H17A—C17—H17B	109.5
C10—C9—C14	112.7 (4)	N1—C17—H17C	109.5
N1—C9—H9	107.3	H17A—C17—H17C	109.5
C10—C9—H9	107.3	H17B—C17—H17C	109.5
C14—C9—H9	107.3	O1—C18—H18A	109.5
C11—C10—C9	115.0 (4)	O1—C18—H18B	109.5
C11—C10—H10A	108.5	H18A—C18—H18B	109.5
C9—C10—H10A	108.5	O1—C18—H18C	109.5
C11—C10—H10B	108.5	H18A—C18—H18C	109.5
C9—C10—H10B	108.5	H18B—C18—H18C	109.5
C18—O1—C3—C2	−13.1 (7)	C6—C5—C13—C15	154.1 (4)
C18—O1—C3—C4	165.8 (4)	O3—C6—C7—C8	170.2 (5)
C5—O2—C4—C3	−159.3 (4)	C5—C6—C7—C8	−12.2 (7)
C5—O2—C4—C12	15.8 (4)	C6—C7—C8—C14	−1.2 (8)
C4—O2—C5—C6	93.4 (4)	C7—C8—C14—C9	150.2 (5)
C4—O2—C5—C13	−29.1 (4)	C7—C8—C14—C13	26.9 (7)
C16—N1—C9—C10	−63.2 (5)	N1—C9—C10—C11	85.8 (5)
C16—N1—C9—C14	62.5 (5)	C14—C9—C10—C11	−36.2 (6)
C17—N1—C9—C10	62.6 (5)	N1—C9—C14—C8	168.3 (4)
C17—N1—C9—C14	−171.8 (4)	N1—C9—C14—C13	−65.4 (5)
C9—N1—C16—C15	−56.6 (5)	C10—C9—C14—C8	−63.9 (5)
C17—N1—C16—C15	177.1 (4)	C10—C9—C14—C13	62.4 (5)
C11—C1—C2—C3	3.8 (7)	C9—C10—C11—C1	179.0 (4)
C2—C1—C11—C10	−171.8 (5)	C9—C10—C11—C12	7.3 (6)
C2—C1—C11—C12	0.1 (7)	C1—C11—C12—C4	−4.2 (6)
C1—C2—C3—O1	175.6 (5)	C1—C11—C12—C13	−178.3 (4)
C1—C2—C3—C4	−3.4 (7)	C10—C11—C12—C4	168.3 (4)
O1—C3—C4—O2	−5.1 (6)	C10—C11—C12—C13	−5.8 (7)
O1—C3—C4—C12	−179.8 (4)	C4—C12—C13—C5	−21.0 (4)
C2—C3—C4—O2	173.9 (4)	C4—C12—C13—C14	−142.6 (4)
C2—C3—C4—C12	−0.7 (6)	C4—C12—C13—C15	98.4 (4)
O2—C4—C12—C11	−170.7 (4)	C11—C12—C13—C5	153.7 (4)
O2—C4—C12—C13	4.2 (5)	C11—C12—C13—C14	32.1 (6)
C3—C4—C12—C11	4.7 (6)	C11—C12—C13—C15	−86.9 (5)
C3—C4—C12—C13	179.6 (4)	C5—C13—C14—C8	−39.1 (6)
O2—C5—C6—O3	58.9 (5)	C5—C13—C14—C9	−166.4 (4)
O2—C5—C6—C7	−118.7 (4)	C12—C13—C14—C8	70.3 (5)
C13—C5—C6—O3	176.0 (4)	C12—C13—C14—C9	−56.9 (5)
C13—C5—C6—C7	−1.6 (5)	C15—C13—C14—C8	−168.6 (4)
O2—C5—C13—C12	29.7 (4)	C15—C13—C14—C9	64.1 (5)
O2—C5—C13—C14	144.8 (4)	C5—C13—C15—C16	172.0 (3)
O2—C5—C13—C15	−88.2 (4)	C12—C13—C15—C16	62.1 (4)
C6—C5—C13—C12	−87.9 (4)	C14—C13—C15—C16	−56.7 (5)
C6—C5—C13—C14	27.1 (5)	C13—C15—C16—N1	52.0 (5)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C18—H18A···O1^i	0.96	2.75	3.285 (6)	116
C10—H10A···O2^ii	0.97	2.62	3.423 (5)	140
C14—H14···O3^iii	0.98	2.66	3.389 (6)	131
C5—H5···O3^iii	0.98	2.70	3.260 (5)	117

Symmetry codes: (i) x−1/2, −y+3/2, −z+1; (ii) −x+3/2, −y+1, z+1/2; (iii) x+1/2, −y+1/2, −z+1.