Different intra- and inter­molecular hydrogen-bonding patterns in (3S,4aS,8aS)-2-[(2R,3S)-3-(2,5-X2-benzamido)-2-(2,5-X2-benzo­yloxy)-4-phenyl­butyl]-N-tert-butyldeca­hydro­iso­quinoline-3-carboxamides (X = H or Cl): compounds with moderate aspartyl protease inhibition activity

Cunico, W.; Ferreira, M. de L.G.; Wardell, J.L.; Harrison, W.T.A.

doi:10.1107/S2056989017007800

research communications

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 73| Part 6| June 2017| Pages 913-917

https://doi.org/10.1107/S2056989017007800

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Different intra- and intermolecular hydrogen-bonding patterns in (3S,4aS,8aS)-2-[(2R,3S)-3-(2,5-X₂-benzamido)-2-(2,5-X₂-benzoyloxy)-4-phenylbutyl]-N-tert-butyldecahydroisoquinoline-3-carboxamides (X = H or Cl): compounds with moderate aspartyl protease inhibition activity

Wilson Cunico,^a Maria de Lourdes G. Ferreira,^b James L. Wardell ^b,^c and William T. A. Harrison ^c ^*

^aDepartamento de Química Orgânica, Universidade Federal de Pelotas (UFPel), Campus Universitário, s/n, Caixa Postal 354, 96010-900 Pelotas, RS, Brazil, ^bInstituto de Tecnologia em Fármacos – Farmanguinhos, Fiocruz. R. Sizenando, Nabuco, 100, Manguinhos, 21041-250, Rio de Janeiro, RJ, Brazil, and ^cDepartment of Chemistry, University of Aberdeen, Meston Walk, Aberdeen AB24 3UE, Scotland
^*Correspondence e-mail: w.harrison@abdn.ac.uk

Edited by S. Parkin, University of Kentucky, USA (Received 20 May 2017; accepted 25 May 2017; online 31 May 2017)

The crystal structures of (3S,4aS,8aS)-2-[(2R,3S)-3-benzamido-2-benzoyloxy-4-phenylbutyl]-N-tert-butyldecahydroisoquinoline-3-carboxamide, C₃₈H₄₇N₃O₄, (I), and (3S,4aS,8aS)-2-[(2R,3S)-3-(2,5-dichlorobenzamido)-2-(2,5-dichlorobenzoyloxy)-4-phenylbutyl]-N-tert-butyldecahydroisoquinoline-3-carboxamide, C₃₈H₄₃Cl₄N₃O₄, (II), are described. Despite their chemical similarity, they adopt different conformations in the solid state: (I) features a bifurcated intramolecular N—H⋯(N,O) hydrogen bond from the tert-butylamide NH group to the piperidine N atom and the benzoate O atom, whereas (II) has an intramolecular N—H⋯O link from the benzamide NH group to the tert-butylamide O atom. In the crystal of (I), molecules are linked by C(4) amide N—H⋯O hydrogen bonds into chains propagating in the [010] direction, with both donor and acceptor parts of the benzamide group. In the extended structure of (II), C(11) N—H⋯O chains propagating in the [010] direction arise, with the donor being the tert-butylamide NH group and the acceptor being the O atom of the benzamide group.

Keywords: crystal structure; malaria; isoquinolinecarboxamide; hydrogen bonding; aspartyl protease inhibition activity.

CCDC references: 1552422; 1552421

1. Chemical context

Malaria remains one of the most devastating infectious diseases with over 200 million cases and more than 600 000 deaths each year – primarily children under the age of five in sub-Saharan Africa. There is an urgent need for effective drugs with new mechanisms of action, due to the high rate of mutation of the parasite, which leads to the development of resistance of current drugs.

One of the critical stages of the life cycle of the parasite during human infection is the degradation of haemoglobin, which provides nutrients for its growth and maturation (Coombs et al., 2001 ). Plasmepsins are a family of aspartic proteases involved in the degradation of human haemoglobin by Plasmodium falciparum (Huizing et al., 2015 ). As the parasite needs the resulting amino acid building blocks for its growth and development, plasmepsins are an important antimalarial drug target. Secondary alcohols (Muthas et al., 2005 ; Ersmark et al., 2006 ) and tertiary alcohols (Motwani et al., 2015 ) have been successfully used to develop potent inhibitors of these enzymes.

Cunico et al. (2008 ) reported the moderate in vitro antimalarial activities of the products of reactions of the 2-aminoethyl compound, 3 (see Scheme 1) with various sulfonyl chlorides and acyl chlorides. In the present article, we report the crystal structures of two compounds (see Scheme 2), C₃₈H₄₇N₃O₄, (I), and C₃₈H₄₃Cl₄N₃O₄, (II), obtained in that study from reactions with acyl chlorides.

2. Structural commentary

Compound (I) crystallizes in the space group P2₁ with a single molecule in the asymmetric unit (Fig. 1). The absolute structure was not definitively established based on refinement of the Flack parameter (Parsons et al., 2013 ) and the configurations of the stereogenic centres (C2 R, C3 S, C7 S, C9 S, C14 S) were set to match those in (II): they are those expected based on the known starting materials. Each atom in the C1—C2—C3—C4 `backbone' of (I) bears a different substituent: C1 is attached to a piperidine+cyclohexane fused-ring system, which in turn bears a tert-butylamide group. C2 is attached to a benzoate group and C3 bears a benzamide group. Finally, C4 is attached to a simple phenyl ring, i.e. a benzyl group. Some key torsion angles are presented in Table 1. These show that with respect to the C2—C3 bond, the C1 + C4, C1 + N3 and N3 + O4 pairings are gauche, whereas the C4 + O4 atoms are mutually anti. In terms of the H atoms, H2 is anti to N3 (171°) and H3 is anti to C1 (176°); the gauche torsion angle between the H atoms is 54°. The N1—C1—C2—C3 torsion angle of 170.4 (3)° indicates an anti conformation and the N1/C7/C8/C9/C14/C5 and C9–C14 rings have a cis-fused junction (H9—C9—C14—H14 = −52°). The amide torsion angles C3—N3—C5—C27 and C17—N2—C16—C7 are −178.3 (3) and −164.7 (4)°, respectively, which reflect the expected near-planar conformations for these groups. The dihedral angles between the aromatic rings C21–C26 (A), C27–C32 (B) and C33–C38 (C) are A/B = 85.7 (2), A/C = 79.2 (2) and B/C = 17.3 (2)°. The conformation of (I) is supported by a bifurcated intramolecular N—H⋯(N,O) hydrogen bond (Table 2) arising from the tert-butylamide group: the acceptor atoms are the N atom of the piperidine ring and the O atom of the C=O group of the benzoate group. The bifurcated bond is very asymmetric in terms of angles and the H⋯O link is long, but given that the assemblage is close to planar (bond-angle sum for the H atom = 353°), we regard it as being just significant.

Table 1
Selected torsion angles (°) for (I)

N1—C1—C2—C3	170.4 (3)	C1—C2—C3—C4	59.4 (4)
C1—C2—C3—N3	−66.3 (4)	C4—C3—N3—C5	138.6 (4)
O4—C2—C3—C4	178.4 (3)	C3—C2—O4—C6	131.5 (3)

Table 2
Hydrogen-bond geometry (Å, °) for (I)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H1N⋯O5	0.90 (5)	2.55 (5)	3.384 (5)	154 (4)
N2—H1N⋯N1	0.90 (5)	2.32 (5)	2.773 (4)	111 (4)
N3—H3N⋯O3ⁱ	0.93 (5)	2.04 (5)	2.929 (4)	161 (4)
C18—H18B⋯O2ⁱⁱ	0.98	2.39	3.310 (5)	157
C20—H20A⋯O2	0.98	2.35	2.963 (6)	120
C29—H29⋯O5ⁱ	0.95	2.58	3.467 (5)	157
Symmetry codes: (i) $[-x, y+{\script{1\over 2}}, -z]$ ; (ii) $[-x+1, y-{\script{1\over 2}}, -z+1]$ .

Figure 1
The asymmetric unit of (I)

, showing 50% probability displacement ellipsoids, with most H atoms omitted for clarity. The bifurcated intramolecular hydrogen bond is shown as a double-dashed line.

Compound (II) crystallizes in the space group P2₁2₁2₁ with one molecule in the asymmetric unit (Fig. 2). Here, the absolute structure is very well established (C2 R, C3 S, C7 S, C9 S, C14 S) and is consistent with the starting materials (Cunico et al., 2008). The C1—C2—C3—C4 backbone bears the equivalent substituents to (I), with the difference that the benzyl and amide rings both bear a pair of Cl atoms at the meta positions. Selected torsion angles for (II) (Table 3) show similarities but also one major difference with respect to (I). In terms of the central C2—C3 bond in (II), the C1 + C4, C1 + N3 and N3 + O4 pairings are gauche, whereas the C4 + O4 atoms are mutually anti. With respect to the H atoms, H2 is anti to N3 (−175°) and H3 is anti to C1 (−166°); the torsion angle between the H atoms is 69°. Thus, the overall conformation of the atoms about the C2—C3 bond in (II) is essentially the same as in (I), although some of the torsion angles differ by as much as 20°. The N1—C1—C2—C3 gauche torsion angle of −69.1 (3)° in (II) is quite different to the value for (I) above, whereas the amide torsion angles C3—N3—C5—C27 [180.0 (3)°] and C17—N2—C16—C7 [–177.5 (3)°] in (II) are similar. The dihedral angles between the aromatic rings C21–C26 (A), C27–C32 (B) and C33–C38 (C) are A/B = 74.84 (17), A/C = 67.99 (17) and B/C = 68.91 (15)°: it may be seen that the first two of these values are similar to the equivalent data for (I), but the third value is very different, possibly reflecting a reorientation in (II) to minimize unfavourable steric interactions between the bichlorinated rings. Compound (II) features a completely different intramolecular N—H⋯O hydrogen bond (Table 4) to (I): in (II), a much shorter (and presumably stronger) bond arises from the benzamide NH group to the tert-butylamide O atom, which no doubt correlates with the very different N1—C1—C2—C3 torsion angles for (I) and (II) already mentioned.

Table 3
Selected torsion angles (°) for (II)

N1—C1—C2—C3	−69.1 (3)	C1—C2—C3—C4	74.4 (3)
C1—C2—C3—N3	−49.5 (3)	C4—C3—N3—C5	136.6 (3)
O4—C2—C3—C4	−167.3 (2)	C3—C2—O4—C6	158.0 (2)

Table 4
Hydrogen-bond geometry (Å, °) for (II)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H1N⋯O3ⁱ	0.84 (4)	2.13 (4)	2.931 (3)	160 (3)
N3—H2N⋯O2	0.88 (4)	1.99 (4)	2.834 (3)	159 (3)
C4—H4A⋯N1	0.99	2.55	3.149 (4)	119
C18—H18A⋯O2	0.98	2.36	2.975 (4)	120
C34—H34⋯O3	0.95	2.40	3.324 (4)	163
Symmetry code: (i) $[-x+1, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

Figure 2
The asymmetric unit of (II)

, showing 50% probability displacement ellipsoids, with most H atoms omitted for clarity. The intramolecular hydrogen bond is shown as a double-dashed line.

3. Supramolecular features

In the crystal of (I), molecules are linked by classical C(4) amide N—H⋯O hydrogen bonds into chains propagating in the [010] direction, with adjacent molecules related by the 2₁ screw axis. Both donor and acceptor are part of the benzamide group (Fig. 3). Two weak C—H⋯O interactions are also observed.

Figure 3
A fragment of a [010] hydrogen-bonded chain in (I)

, showing 20% probability displacement ellipsoids; the pendant rings and C-bound H atoms have been omitted for clarity. [Symmetry code as in Table 2

; additionally (iii) −x, y − $[{1\over 2}]$ , −z.]

In the extended structure of (II), C(11) [010] N—H⋯O chains arise, with the donor being the tert-butylamide NH group and the acceptor being the O atom of the benzamide ring (Fig. 4). Adjacent molecules are again related by a 2₁ screw axis.

Figure 4
A fragment of a [010] hydrogen-bonded chain in (II)

, showing 20% probability displacement ellipsoids; the pendant rings and C-bound H atoms have been omitted for clarity. [Symmetry code as in Table 4

; additionally (ii) −x + 1, y − $[{1\over 2}]$ , −z + $[{1\over 2}]$ .]

In short, for (I), the tert-butylamide NH moiety forms an intramolecular hydrogen bond and the benzamide NH group forms an intermolecular link, whereas for (II), the situation is reversed: the benzamide NH group forms the intramolecular bond and the tert-butyl NH group forms the intermolecular link.

4. Database survey

A survey of of the Cambridge Structural Database (Groom et al., 2016 : updated to April 2017) for the grouping of atoms about the C1—C2—C3—C4 fragment in (I) and (II) yielded 24 matches. The most similar are the isostructural halide salts YURSUB and YURTAI of the anti-HIV drug saquinavir mesylate (Fandaruff et al., 2015 ), which also act as protease inhibitors. The other hits have little similarity to the title compounds.

5. Synthesis and crystallisation

As summarized in Scheme 1, compounds (I) and (II) were prepared as described previously (Cunico et al., 2008) and recrystallized from methanol solution. (I): colourless needles, m.p. 475–476 K, ESI–HRMS (M + H): calculated for C₃₈H₄₈N₃O₄: 610.3645, found: 610.3638. (II): colourless slabs, m.p. 459–460 K, ESI–HRMS (M + H): calculated for C₃₈H₄₄³⁵Cl₄N₃O₄: 746.2086, found: 746.2078.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 5. The N-bound H atoms were located in difference maps and their positions were freely refined. The C-bound H atoms were placed geometrically (C—H = 0.95–1.00 Å) and refined as riding atoms. The constraint U_iso(H) = 1.2U_eq(C) or 1.5U_eq(methyl C) was applied in all cases. The methyl groups were allowed to rotate, but not to tip, to best fit the electron density.

Table 5
Experimental details

	(I)	(II)
Crystal data
Chemical formula	C₃₈H₄₇N₃O₄	C₃₈H₄₃Cl₄N₃O₄
M_r	609.78	747.55
Crystal system, space group	Monoclinic, P2₁	Orthorhombic, P2₁2₁2₁
Temperature (K)	100	100
a, b, c (Å)	11.4866 (3), 9.4448 (2), 16.8257 (5)	10.4539 (1), 15.1917 (1), 24.3677 (2)
α, β, γ (°)	90, 109.227 (3), 90	90, 90, 90
V (Å³)	1723.58 (8)	3869.90 (6)
Z	2	4
Radiation type	Cu Kα	Cu Kα
μ (mm⁻¹)	0.60	3.12
Crystal size (mm)	0.52 × 0.15 × 0.05	0.25 × 0.20 × 0.04

Data collection
Diffractometer	Rigaku Mercury CCD	Rigaku Mercury CCD
Absorption correction	Multi-scan (SADABS; Sheldrick, 2004 )	Multi-scan (SADABS; Sheldrick, 2004)
T_min, T_max	0.654, 0.971	0.611, 0.886
No. of measured, independent and observed [I > 2σ(I)] reflections	24074, 5349, 4547	44109, 7278, 7140
R_int	0.068	0.046
(sin θ/λ)_max (Å⁻¹)	0.610	0.610

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.056, 0.151, 1.07	0.038, 0.100, 1.05
No. of reflections	5349	7278
No. of parameters	415	451
No. of restraints	1	0
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.35, −0.26	0.28, −0.32
Absolute structure	Flack x determined using 1316 quotients [(I⁺) − (I⁻)]/[(I⁺) + (I⁻)] (Parsons et al., 2013)	Flack x determined using 3021 quotients [(I⁺) − (I⁻)]/[(I⁺) + (I⁻)] (Parsons et al., 2013)
Absolute structure parameter	−0.4 (2)	−0.006 (7)
Computer programs: CrysAlis PRO (Rigaku, 2014 ), SHELXS97 (Sheldrick, 2008 ), SHELXL2014 (Sheldrick, 2015 ), ORTEP-3 for Windows (Farrugia, 2012 ) and publCIF (Westrip, 2010 ).

Supporting information

CCDC references: 1552422; 1552421

Crystal structure: contains datablocks I, II, global. DOI: https://doi.org/10.1107/S2056989017007800/pk2602sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989017007800/pk2602Isup2.hkl

Structure factors: contains datablock II. DOI: https://doi.org/10.1107/S2056989017007800/pk2602IIsup3.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989017007800/pk2602Isup4.cml

Supporting information file. DOI: https://doi.org/10.1107/S2056989017007800/pk2602IIsup5.cml

checkCIF report

Computing details top

For both compounds, data collection: CrysAlis PRO (Rigaku, 2014); cell refinement: CrysAlis PRO (Rigaku, 2014); data reduction: CrysAlis PRO (Rigaku, 2014); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: ORTEP-3 (Farrugia, 2012); software used to prepare material for publication: publCIF (Westrip, 2010).

(I) (3S,4aS,8aS)-2-[(2R,3S)-3-Benzamido-2-benzoyloxy-4-phenylbutyl]-N-tert-butyldecahydroisoquinoline-3-carboxamide top

Crystal data top

C₃₈H₄₇N₃O₄	F(000) = 656
M_r = 609.78	D_x = 1.175 Mg m⁻³
Monoclinic, P2₁	Cu Kα radiation, λ = 1.54184 Å
a = 11.4866 (3) Å	Cell parameters from 8813 reflections
b = 9.4448 (2) Å	θ = 5.4–69.6°
c = 16.8257 (5) Å	µ = 0.60 mm⁻¹
β = 109.227 (3)°	T = 100 K
V = 1723.58 (8) Å³	Needle, colourless
Z = 2	0.52 × 0.15 × 0.05 mm

Data collection top

Rigaku Mercury CCD diffractometer	4547 reflections with I > 2σ(I)
ω scans	R_int = 0.068
Absorption correction: multi-scan (SADABS; Sheldrick, 2004)	θ_max = 70.1°, θ_min = 2.8°
T_min = 0.654, T_max = 0.971	h = −14→13
24074 measured reflections	k = −11→9
5349 independent reflections	l = −20→19

Refinement top

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)] = 0.056	w = 1/[σ²(F_o²) + (0.0894P)² + 0.2672P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.151	(Δ/σ)_max < 0.001
S = 1.07	Δρ_max = 0.35 e Å⁻³
5349 reflections	Δρ_min = −0.26 e Å⁻³
415 parameters	Absolute structure: Flack x determined using 1316 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
1 restraint	Absolute structure parameter: −0.4 (2)
Primary atom site location: structure-invariant direct methods

Special details top

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.

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

	x	y	z	U_iso*/U_eq
C1	0.1094 (4)	0.3195 (4)	0.1956 (2)	0.0347 (8)
H1A	0.1950	0.3530	0.2069	0.042*
H1B	0.0566	0.3672	0.1438	0.042*
C2	0.1046 (3)	0.1585 (4)	0.1806 (2)	0.0322 (8)
H2	0.1668	0.1113	0.2295	0.039*
C3	0.1262 (3)	0.1138 (4)	0.0997 (2)	0.0310 (8)
H3	0.1265	0.0079	0.0988	0.037*
C4	0.2513 (3)	0.1625 (4)	0.0978 (2)	0.0353 (8)
H4A	0.2491	0.2665	0.0900	0.042*
H4B	0.3140	0.1414	0.1530	0.042*
C5	−0.0678 (3)	0.0764 (4)	−0.0162 (2)	0.0322 (8)
C6	−0.0309 (4)	0.0410 (4)	0.2415 (2)	0.0344 (9)
C7	0.1555 (3)	0.4553 (4)	0.3252 (2)	0.0362 (8)
H7	0.1668	0.5406	0.2933	0.043*
C8	0.1086 (4)	0.5037 (5)	0.3955 (3)	0.0408 (9)
H8A	0.1674	0.5733	0.4311	0.049*
H8B	0.1060	0.4213	0.4312	0.049*
C9	−0.0194 (4)	0.5709 (5)	0.3631 (3)	0.0408 (9)
H9	−0.0135	0.6587	0.3314	0.049*
C10	−0.0665 (4)	0.6127 (5)	0.4343 (3)	0.0469 (10)
H10A	−0.1408	0.6726	0.4114	0.056*
H10B	−0.0027	0.6698	0.4759	0.056*
C11	−0.0984 (4)	0.4852 (5)	0.4784 (3)	0.0510 (12)
H11A	−0.0224	0.4307	0.5069	0.061*
H11B	−0.1330	0.5179	0.5218	0.061*
C12	−0.1913 (4)	0.3899 (5)	0.4161 (3)	0.0497 (11)
H12A	−0.2702	0.4415	0.3917	0.060*
H12B	−0.2072	0.3054	0.4457	0.060*
C13	−0.1435 (4)	0.3435 (5)	0.3454 (3)	0.0430 (10)
H13A	−0.0704	0.2821	0.3691	0.052*
H13B	−0.2079	0.2871	0.3038	0.052*
C14	−0.1088 (4)	0.4686 (5)	0.3014 (2)	0.0381 (9)
H14	−0.1863	0.5225	0.2732	0.046*
C15	−0.0557 (3)	0.4256 (4)	0.2330 (3)	0.0379 (9)
H15A	−0.1128	0.3580	0.1944	0.046*
H15B	−0.0501	0.5105	0.1999	0.046*
C16	0.2805 (4)	0.3896 (5)	0.3683 (3)	0.0389 (9)
C17	0.3889 (4)	0.1660 (5)	0.4317 (3)	0.0395 (9)
C18	0.4024 (4)	0.1975 (5)	0.5232 (3)	0.0430 (10)
H18A	0.4144	0.2995	0.5336	0.064*
H18B	0.4737	0.1462	0.5604	0.064*
H18C	0.3277	0.1673	0.5345	0.064*
C19	0.3574 (4)	0.0085 (5)	0.4131 (3)	0.0484 (11)
H19A	0.2764	−0.0113	0.4182	0.073*
H19B	0.4200	−0.0499	0.4533	0.073*
H19C	0.3556	−0.0135	0.3557	0.073*
C20	0.5072 (4)	0.1970 (6)	0.4129 (3)	0.0516 (12)
H20A	0.5284	0.2973	0.4235	0.077*
H20B	0.4952	0.1751	0.3538	0.077*
H20C	0.5742	0.1386	0.4492	0.077*
C21	0.2909 (3)	0.0951 (4)	0.0296 (2)	0.0345 (8)
C22	0.3112 (4)	−0.0514 (5)	0.0303 (3)	0.0381 (9)
H22	0.2960	−0.1089	0.0721	0.046*
C23	0.3533 (4)	−0.1124 (5)	−0.0299 (3)	0.0449 (10)
H23	0.3680	−0.2115	−0.0282	0.054*
C24	0.3743 (4)	−0.0325 (6)	−0.0919 (3)	0.0508 (11)
H24	0.4034	−0.0756	−0.1328	0.061*
C25	0.3523 (4)	0.1131 (6)	−0.0941 (3)	0.0523 (11)
H25	0.3657	0.1698	−0.1369	0.063*
C26	0.3109 (4)	0.1745 (5)	−0.0337 (3)	0.0444 (10)
H26	0.2959	0.2736	−0.0358	0.053*
C27	−0.1602 (3)	0.1360 (4)	−0.0933 (2)	0.0315 (8)
C28	−0.1291 (4)	0.2311 (4)	−0.1467 (2)	0.0335 (8)
H28	−0.0470	0.2653	−0.1323	0.040*
C29	−0.2175 (4)	0.2756 (4)	−0.2206 (3)	0.0370 (9)
H29	−0.1955	0.3395	−0.2568	0.044*
C30	−0.3380 (4)	0.2273 (4)	−0.2417 (3)	0.0386 (9)
H30	−0.3984	0.2582	−0.2923	0.046*
C31	−0.3700 (4)	0.1339 (4)	−0.1889 (3)	0.0382 (9)
H31	−0.4525	0.1011	−0.2033	0.046*
C32	−0.2825 (3)	0.0883 (4)	−0.1156 (3)	0.0353 (8)
H32	−0.3052	0.0240	−0.0798	0.042*
C33	−0.1626 (3)	0.0098 (4)	0.2289 (2)	0.0346 (8)
C34	−0.2557 (4)	0.0418 (5)	0.1540 (3)	0.0400 (9)
H34	−0.2354	0.0806	0.1081	0.048*
C35	−0.3772 (4)	0.0176 (5)	0.1463 (3)	0.0481 (11)
H35	−0.4406	0.0405	0.0952	0.058*
C36	−0.4071 (4)	−0.0400 (5)	0.2126 (3)	0.0493 (11)
H36	−0.4910	−0.0566	0.2068	0.059*
C37	−0.3155 (4)	−0.0735 (5)	0.2872 (3)	0.0506 (11)
H37	−0.3363	−0.1127	0.3328	0.061*
C38	−0.1931 (4)	−0.0496 (5)	0.2950 (3)	0.0449 (10)
H38	−0.1298	−0.0738	0.3458	0.054*
N1	0.0677 (3)	0.3598 (3)	0.26662 (19)	0.0332 (7)
N2	0.2845 (3)	0.2467 (4)	0.3755 (2)	0.0369 (8)
H1N	0.208 (4)	0.209 (6)	0.358 (3)	0.044*
N3	0.0279 (3)	0.1602 (3)	0.02500 (19)	0.0301 (7)
H3N	0.027 (4)	0.252 (6)	0.005 (3)	0.036*
O2	0.3711 (3)	0.4674 (3)	0.3992 (2)	0.0506 (8)
O3	−0.0799 (2)	−0.0457 (3)	0.00716 (17)	0.0344 (6)
O4	−0.0177 (2)	0.1111 (3)	0.17533 (16)	0.0329 (6)
O5	0.0540 (2)	0.0080 (4)	0.30361 (18)	0.0449 (7)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.036 (2)	0.0253 (19)	0.040 (2)	−0.0010 (16)	0.0092 (16)	0.0009 (15)
C2	0.0261 (17)	0.0251 (19)	0.043 (2)	0.0008 (15)	0.0086 (15)	0.0016 (16)
C3	0.0292 (17)	0.0212 (18)	0.0410 (19)	0.0052 (15)	0.0094 (14)	0.0021 (15)
C4	0.0318 (18)	0.027 (2)	0.045 (2)	−0.0015 (16)	0.0095 (15)	0.0010 (17)
C5	0.0328 (19)	0.023 (2)	0.039 (2)	−0.0003 (15)	0.0090 (15)	−0.0032 (15)
C6	0.037 (2)	0.030 (2)	0.038 (2)	0.0008 (16)	0.0138 (17)	0.0014 (16)
C7	0.037 (2)	0.0251 (19)	0.042 (2)	−0.0047 (16)	0.0062 (16)	0.0014 (17)
C8	0.042 (2)	0.031 (2)	0.045 (2)	−0.0043 (18)	0.0092 (17)	−0.0029 (17)
C9	0.045 (2)	0.027 (2)	0.047 (2)	0.0004 (18)	0.0100 (18)	0.0000 (17)
C10	0.050 (2)	0.032 (2)	0.057 (3)	0.006 (2)	0.015 (2)	−0.005 (2)
C11	0.057 (3)	0.049 (3)	0.048 (2)	0.008 (2)	0.020 (2)	−0.002 (2)
C12	0.052 (3)	0.043 (3)	0.059 (3)	0.002 (2)	0.024 (2)	0.005 (2)
C13	0.043 (2)	0.033 (2)	0.053 (2)	−0.0001 (18)	0.0147 (18)	−0.0012 (19)
C14	0.035 (2)	0.033 (2)	0.044 (2)	0.0068 (17)	0.0097 (16)	0.0013 (17)
C15	0.033 (2)	0.032 (2)	0.045 (2)	0.0014 (16)	0.0073 (16)	0.0013 (16)
C16	0.039 (2)	0.030 (2)	0.043 (2)	−0.0064 (17)	0.0076 (17)	−0.0028 (16)
C17	0.0319 (19)	0.033 (2)	0.046 (2)	0.0001 (17)	0.0033 (16)	−0.0008 (18)
C18	0.041 (2)	0.035 (2)	0.047 (2)	0.0005 (18)	0.0055 (17)	0.0029 (18)
C19	0.044 (2)	0.030 (2)	0.059 (3)	0.0076 (19)	0.001 (2)	−0.004 (2)
C20	0.041 (2)	0.051 (3)	0.060 (3)	0.003 (2)	0.013 (2)	−0.004 (2)
C21	0.0264 (17)	0.032 (2)	0.043 (2)	−0.0004 (16)	0.0082 (14)	0.0002 (17)
C22	0.036 (2)	0.031 (2)	0.047 (2)	−0.0002 (17)	0.0132 (16)	−0.0019 (18)
C23	0.036 (2)	0.036 (2)	0.060 (3)	−0.0019 (18)	0.0131 (19)	−0.007 (2)
C24	0.048 (2)	0.050 (3)	0.057 (3)	−0.008 (2)	0.020 (2)	−0.011 (2)
C25	0.059 (3)	0.055 (3)	0.050 (2)	−0.006 (2)	0.026 (2)	0.001 (2)
C26	0.047 (2)	0.035 (2)	0.052 (2)	−0.0017 (19)	0.0174 (18)	0.003 (2)
C27	0.0311 (18)	0.0192 (18)	0.042 (2)	0.0015 (15)	0.0095 (15)	−0.0018 (15)
C28	0.0353 (19)	0.0226 (18)	0.041 (2)	0.0007 (16)	0.0099 (16)	−0.0031 (16)
C29	0.043 (2)	0.023 (2)	0.042 (2)	0.0030 (16)	0.0095 (17)	0.0019 (16)
C30	0.038 (2)	0.028 (2)	0.043 (2)	0.0039 (17)	0.0031 (17)	−0.0025 (17)
C31	0.0310 (18)	0.031 (2)	0.048 (2)	0.0012 (16)	0.0063 (16)	−0.0010 (17)
C32	0.0333 (19)	0.0219 (19)	0.048 (2)	−0.0015 (16)	0.0099 (16)	−0.0005 (16)
C33	0.0347 (19)	0.0245 (18)	0.046 (2)	−0.0012 (16)	0.0156 (16)	0.0015 (16)
C34	0.038 (2)	0.034 (2)	0.047 (2)	−0.0014 (17)	0.0115 (17)	0.0035 (18)
C35	0.036 (2)	0.045 (3)	0.059 (3)	−0.004 (2)	0.0104 (19)	0.003 (2)
C36	0.040 (2)	0.043 (3)	0.065 (3)	−0.008 (2)	0.018 (2)	0.004 (2)
C37	0.047 (2)	0.047 (3)	0.062 (3)	−0.002 (2)	0.024 (2)	0.010 (2)
C38	0.042 (2)	0.042 (3)	0.051 (2)	−0.001 (2)	0.0156 (18)	0.008 (2)
N1	0.0307 (16)	0.0262 (17)	0.0396 (17)	−0.0022 (13)	0.0075 (13)	−0.0028 (13)
N2	0.0325 (16)	0.0274 (18)	0.0445 (18)	0.0014 (14)	0.0040 (14)	0.0008 (14)
N3	0.0289 (15)	0.0188 (16)	0.0398 (16)	0.0015 (12)	0.0075 (12)	0.0012 (13)
O2	0.0407 (16)	0.0357 (17)	0.0652 (19)	−0.0084 (14)	0.0038 (14)	−0.0029 (15)
O3	0.0356 (13)	0.0185 (13)	0.0470 (15)	0.0024 (11)	0.0111 (11)	0.0009 (11)
O4	0.0303 (12)	0.0283 (14)	0.0391 (13)	−0.0033 (11)	0.0100 (10)	0.0022 (11)
O5	0.0361 (15)	0.0494 (18)	0.0457 (16)	0.0009 (14)	0.0087 (12)	0.0121 (14)

Geometric parameters (Å, º) top

C1—N1	1.476 (5)	C17—N2	1.472 (5)
C1—C2	1.539 (5)	C17—C20	1.522 (6)
C1—H1A	0.9900	C17—C18	1.526 (6)
C1—H1B	0.9900	C17—C19	1.538 (6)
C2—O4	1.449 (4)	C18—H18A	0.9800
C2—C3	1.521 (5)	C18—H18B	0.9800
C2—H2	1.0000	C18—H18C	0.9800
C3—N3	1.453 (4)	C19—H19A	0.9800
C3—C4	1.519 (5)	C19—H19B	0.9800
C3—H3	1.0000	C19—H19C	0.9800
C4—C21	1.507 (6)	C20—H20A	0.9800
C4—H4A	0.9900	C20—H20B	0.9800
C4—H4B	0.9900	C20—H20C	0.9800
C5—O3	1.241 (5)	C21—C26	1.383 (6)
C5—N3	1.346 (5)	C21—C22	1.403 (6)
C5—C27	1.490 (5)	C22—C23	1.383 (6)
C6—O5	1.213 (5)	C22—H22	0.9500
C6—O4	1.346 (5)	C23—C24	1.372 (7)
C6—C33	1.486 (5)	C23—H23	0.9500
C7—N1	1.465 (5)	C24—C25	1.397 (8)
C7—C16	1.512 (6)	C24—H24	0.9500
C7—C8	1.522 (6)	C25—C26	1.383 (7)
C7—H7	1.0000	C25—H25	0.9500
C8—C9	1.527 (6)	C26—H26	0.9500
C8—H8A	0.9900	C27—C28	1.397 (5)
C8—H8B	0.9900	C27—C32	1.403 (5)
C9—C10	1.520 (6)	C28—C29	1.386 (5)
C9—C14	1.537 (6)	C28—H28	0.9500
C9—H9	1.0000	C29—C30	1.388 (6)
C10—C11	1.522 (7)	C29—H29	0.9500
C10—H10A	0.9900	C30—C31	1.384 (6)
C10—H10B	0.9900	C30—H30	0.9500
C11—C12	1.520 (7)	C31—C32	1.380 (6)
C11—H11A	0.9900	C31—H31	0.9500
C11—H11B	0.9900	C32—H32	0.9500
C12—C13	1.529 (6)	C33—C38	1.390 (6)
C12—H12A	0.9900	C33—C34	1.391 (5)
C12—H12B	0.9900	C34—C35	1.378 (6)
C13—C14	1.516 (6)	C34—H34	0.9500
C13—H13A	0.9900	C35—C36	1.382 (6)
C13—H13B	0.9900	C35—H35	0.9500
C14—C15	1.524 (6)	C36—C37	1.384 (7)
C14—H14	1.0000	C36—H36	0.9500
C15—N1	1.479 (5)	C37—C38	1.387 (6)
C15—H15A	0.9900	C37—H37	0.9500
C15—H15B	0.9900	C38—H38	0.9500
C16—O2	1.240 (5)	N2—H1N	0.90 (5)
C16—N2	1.354 (5)	N3—H3N	0.93 (5)

N1—C1—C2	112.5 (3)	N2—C17—C18	109.8 (3)
N1—C1—H1A	109.1	C20—C17—C18	111.8 (3)
C2—C1—H1A	109.1	N2—C17—C19	106.4 (3)
N1—C1—H1B	109.1	C20—C17—C19	108.1 (4)
C2—C1—H1B	109.1	C18—C17—C19	109.5 (4)
H1A—C1—H1B	107.8	C17—C18—H18A	109.5
O4—C2—C3	107.4 (3)	C17—C18—H18B	109.5
O4—C2—C1	107.3 (3)	H18A—C18—H18B	109.5
C3—C2—C1	114.4 (3)	C17—C18—H18C	109.5
O4—C2—H2	109.2	H18A—C18—H18C	109.5
C3—C2—H2	109.2	H18B—C18—H18C	109.5
C1—C2—H2	109.2	C17—C19—H19A	109.5
N3—C3—C4	111.1 (3)	C17—C19—H19B	109.5
N3—C3—C2	112.4 (3)	H19A—C19—H19B	109.5
C4—C3—C2	111.7 (3)	C17—C19—H19C	109.5
N3—C3—H3	107.1	H19A—C19—H19C	109.5
C4—C3—H3	107.1	H19B—C19—H19C	109.5
C2—C3—H3	107.1	C17—C20—H20A	109.5
C21—C4—C3	114.4 (3)	C17—C20—H20B	109.5
C21—C4—H4A	108.7	H20A—C20—H20B	109.5
C3—C4—H4A	108.7	C17—C20—H20C	109.5
C21—C4—H4B	108.7	H20A—C20—H20C	109.5
C3—C4—H4B	108.7	H20B—C20—H20C	109.5
H4A—C4—H4B	107.6	C26—C21—C22	118.1 (4)
O3—C5—N3	122.8 (3)	C26—C21—C4	121.7 (4)
O3—C5—C27	120.3 (3)	C22—C21—C4	120.1 (4)
N3—C5—C27	116.9 (3)	C23—C22—C21	120.2 (4)
O5—C6—O4	124.2 (4)	C23—C22—H22	119.9
O5—C6—C33	124.3 (4)	C21—C22—H22	119.9
O4—C6—C33	111.5 (3)	C24—C23—C22	121.3 (4)
N1—C7—C16	113.8 (3)	C24—C23—H23	119.4
N1—C7—C8	111.5 (3)	C22—C23—H23	119.4
C16—C7—C8	105.9 (3)	C23—C24—C25	119.0 (4)
N1—C7—H7	108.5	C23—C24—H24	120.5
C16—C7—H7	108.5	C25—C24—H24	120.5
C8—C7—H7	108.5	C26—C25—C24	119.8 (5)
C7—C8—C9	113.1 (3)	C26—C25—H25	120.1
C7—C8—H8A	109.0	C24—C25—H25	120.1
C9—C8—H8A	109.0	C25—C26—C21	121.5 (4)
C7—C8—H8B	109.0	C25—C26—H26	119.2
C9—C8—H8B	109.0	C21—C26—H26	119.2
H8A—C8—H8B	107.8	C28—C27—C32	118.7 (3)
C10—C9—C8	112.2 (3)	C28—C27—C5	122.9 (3)
C10—C9—C14	111.3 (4)	C32—C27—C5	118.3 (3)
C8—C9—C14	109.3 (3)	C29—C28—C27	120.3 (4)
C10—C9—H9	108.0	C29—C28—H28	119.9
C8—C9—H9	108.0	C27—C28—H28	119.9
C14—C9—H9	108.0	C28—C29—C30	120.3 (4)
C9—C10—C11	112.6 (4)	C28—C29—H29	119.9
C9—C10—H10A	109.1	C30—C29—H29	119.9
C11—C10—H10A	109.1	C31—C30—C29	119.8 (4)
C9—C10—H10B	109.1	C31—C30—H30	120.1
C11—C10—H10B	109.1	C29—C30—H30	120.1
H10A—C10—H10B	107.8	C32—C31—C30	120.3 (4)
C12—C11—C10	111.0 (4)	C32—C31—H31	119.9
C12—C11—H11A	109.4	C30—C31—H31	119.9
C10—C11—H11A	109.4	C31—C32—C27	120.6 (4)
C12—C11—H11B	109.4	C31—C32—H32	119.7
C10—C11—H11B	109.4	C27—C32—H32	119.7
H11A—C11—H11B	108.0	C38—C33—C34	119.5 (4)
C11—C12—C13	110.8 (4)	C38—C33—C6	118.6 (3)
C11—C12—H12A	109.5	C34—C33—C6	121.9 (4)
C13—C12—H12A	109.5	C35—C34—C33	120.1 (4)
C11—C12—H12B	109.5	C35—C34—H34	119.9
C13—C12—H12B	109.5	C33—C34—H34	119.9
H12A—C12—H12B	108.1	C34—C35—C36	120.2 (4)
C14—C13—C12	112.1 (4)	C34—C35—H35	119.9
C14—C13—H13A	109.2	C36—C35—H35	119.9
C12—C13—H13A	109.2	C35—C36—C37	120.4 (4)
C14—C13—H13B	109.2	C35—C36—H36	119.8
C12—C13—H13B	109.2	C37—C36—H36	119.8
H13A—C13—H13B	107.9	C36—C37—C38	119.5 (4)
C13—C14—C15	113.3 (4)	C36—C37—H37	120.2
C13—C14—C9	112.6 (3)	C38—C37—H37	120.2
C15—C14—C9	109.4 (3)	C37—C38—C33	120.3 (4)
C13—C14—H14	107.0	C37—C38—H38	119.8
C15—C14—H14	107.0	C33—C38—H38	119.8
C9—C14—H14	107.0	C7—N1—C1	111.6 (3)
N1—C15—C14	113.2 (3)	C7—N1—C15	111.0 (3)
N1—C15—H15A	108.9	C1—N1—C15	108.9 (3)
C14—C15—H15A	108.9	C16—N2—C17	124.8 (3)
N1—C15—H15B	108.9	C16—N2—H1N	111 (3)
C14—C15—H15B	108.9	C17—N2—H1N	120 (3)
H15A—C15—H15B	107.7	C5—N3—C3	122.5 (3)
O2—C16—N2	123.6 (4)	C5—N3—H3N	117 (3)
O2—C16—C7	119.5 (4)	C3—N3—H3N	121 (3)
N2—C16—C7	116.8 (3)	C6—O4—C2	118.2 (3)
N2—C17—C20	111.1 (4)

N1—C1—C2—O4	51.4 (4)	N3—C5—C27—C32	−151.0 (4)
N1—C1—C2—C3	170.4 (3)	C32—C27—C28—C29	−0.7 (6)
O4—C2—C3—N3	52.7 (4)	C5—C27—C28—C29	175.6 (4)
C1—C2—C3—N3	−66.3 (4)	C27—C28—C29—C30	0.7 (6)
O4—C2—C3—C4	178.4 (3)	C28—C29—C30—C31	−0.2 (6)
C1—C2—C3—C4	59.4 (4)	C29—C30—C31—C32	−0.2 (6)
N3—C3—C4—C21	−66.6 (4)	C30—C31—C32—C27	0.1 (6)
C2—C3—C4—C21	167.0 (3)	C28—C27—C32—C31	0.3 (6)
N1—C7—C8—C9	−54.5 (5)	C5—C27—C32—C31	−176.2 (3)
C16—C7—C8—C9	−178.9 (3)	O5—C6—C33—C38	6.1 (6)
C7—C8—C9—C10	177.6 (4)	O4—C6—C33—C38	−173.6 (4)
C7—C8—C9—C14	53.6 (5)	O5—C6—C33—C34	−175.7 (4)
C8—C9—C10—C11	−70.2 (5)	O4—C6—C33—C34	4.6 (6)
C14—C9—C10—C11	52.6 (5)	C38—C33—C34—C35	1.3 (7)
C9—C10—C11—C12	−55.8 (5)	C6—C33—C34—C35	−176.8 (4)
C10—C11—C12—C13	56.2 (5)	C33—C34—C35—C36	−0.6 (7)
C11—C12—C13—C14	−55.1 (5)	C34—C35—C36—C37	0.1 (8)
C12—C13—C14—C15	177.6 (3)	C35—C36—C37—C38	−0.3 (8)
C12—C13—C14—C9	52.7 (5)	C36—C37—C38—C33	1.0 (7)
C10—C9—C14—C13	−51.0 (5)	C34—C33—C38—C37	−1.5 (7)
C8—C9—C14—C13	73.5 (4)	C6—C33—C38—C37	176.7 (4)
C10—C9—C14—C15	−178.0 (3)	C16—C7—N1—C1	−63.7 (4)
C8—C9—C14—C15	−53.6 (4)	C8—C7—N1—C1	176.5 (3)
C13—C14—C15—N1	−69.4 (4)	C16—C7—N1—C15	174.5 (3)
C9—C14—C15—N1	57.3 (4)	C8—C7—N1—C15	54.8 (4)
N1—C7—C16—O2	159.3 (4)	C2—C1—N1—C7	130.4 (3)
C8—C7—C16—O2	−77.9 (5)	C2—C1—N1—C15	−106.6 (3)
N1—C7—C16—N2	−25.0 (5)	C14—C15—N1—C7	−57.9 (4)
C8—C7—C16—N2	97.9 (4)	C14—C15—N1—C1	178.8 (3)
C3—C4—C21—C26	117.9 (4)	O2—C16—N2—C17	10.8 (7)
C3—C4—C21—C22	−63.6 (5)	C7—C16—N2—C17	−164.7 (4)
C26—C21—C22—C23	1.7 (6)	C20—C17—N2—C16	−57.7 (6)
C4—C21—C22—C23	−176.8 (3)	C18—C17—N2—C16	66.5 (5)
C21—C22—C23—C24	−1.0 (6)	C19—C17—N2—C16	−175.1 (4)
C22—C23—C24—C25	−0.1 (7)	O3—C5—N3—C3	1.0 (6)
C23—C24—C25—C26	0.5 (7)	C27—C5—N3—C3	−178.3 (3)
C24—C25—C26—C21	0.2 (7)	C4—C3—N3—C5	138.6 (4)
C22—C21—C26—C25	−1.3 (6)	C2—C3—N3—C5	−95.4 (4)
C4—C21—C26—C25	177.2 (4)	O5—C6—O4—C2	−4.2 (6)
O3—C5—C27—C28	−146.7 (4)	C33—C6—O4—C2	175.5 (3)
N3—C5—C27—C28	32.6 (5)	C3—C2—O4—C6	131.5 (3)
O3—C5—C27—C32	29.7 (5)	C1—C2—O4—C6	−105.0 (4)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H1N···O5	0.90 (5)	2.55 (5)	3.384 (5)	154 (4)
N2—H1N···N1	0.90 (5)	2.32 (5)	2.773 (4)	111 (4)
N3—H3N···O3ⁱ	0.93 (5)	2.04 (5)	2.929 (4)	161 (4)
C18—H18B···O2ⁱⁱ	0.98	2.39	3.310 (5)	157
C20—H20A···O2	0.98	2.35	2.963 (6)	120
C29—H29···O5ⁱ	0.95	2.58	3.467 (5)	157

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

(II) (3S,4aS,8aS)-2-[(2R,3S)-3-(2,5-Dichlorobenzamido)-2-(2,5-dichlorobenzoyloxy)-4-phenylbutyl]-N-tert-butyldecahydroisoquinoline-3-carboxamide top

Crystal data top

C₃₈H₄₃Cl₄N₃O₄	D_x = 1.283 Mg m⁻³
M_r = 747.55	Cu Kα radiation, λ = 1.54184 Å
Orthorhombic, P2₁2₁2₁	Cell parameters from 40379 reflections
a = 10.4539 (1) Å	θ = 3.4–70.0°
b = 15.1917 (1) Å	µ = 3.12 mm⁻¹
c = 24.3677 (2) Å	T = 100 K
V = 3869.90 (6) Å³	Slab, colourless
Z = 4	0.25 × 0.20 × 0.04 mm
F(000) = 1568

Data collection top

Rigaku Mercury CCD diffractometer	7140 reflections with I > 2σ(I)
ω scans	R_int = 0.046
Absorption correction: multi-scan (SADABS; Sheldrick, 2004)	θ_max = 70.1°, θ_min = 3.4°
T_min = 0.611, T_max = 0.886	h = −12→12
44109 measured reflections	k = −15→18
7278 independent reflections	l = −29→29

Refinement top

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(F_o²) + (0.0552P)² + 1.8039P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.100	(Δ/σ)_max < 0.001
S = 1.05	Δρ_max = 0.28 e Å⁻³
7278 reflections	Δρ_min = −0.32 e Å⁻³
451 parameters	Absolute structure: Flack x determined using 3021 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
0 restraints	Absolute structure parameter: −0.006 (7)
Primary atom site location: structure-invariant direct methods

Special details top

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

	x	y	z	U_iso*/U_eq
C1	0.3339 (3)	0.3116 (2)	0.28983 (12)	0.0291 (6)
H1A	0.4228	0.3055	0.2764	0.035*
H1B	0.2948	0.3629	0.2712	0.035*
C2	0.2587 (3)	0.2289 (2)	0.27568 (12)	0.0300 (6)
H2	0.1702	0.2335	0.2910	0.036*
C3	0.3188 (3)	0.1407 (2)	0.29311 (12)	0.0291 (6)
H3	0.2717	0.0929	0.2734	0.035*
C4	0.3109 (3)	0.1206 (2)	0.35483 (13)	0.0330 (7)
H4A	0.3595	0.1657	0.3755	0.040*
H4B	0.2205	0.1235	0.3669	0.040*
C5	0.4901 (3)	0.09795 (19)	0.22901 (12)	0.0283 (6)
C6	0.1687 (3)	0.2720 (2)	0.18833 (14)	0.0339 (7)
C7	0.4476 (3)	0.37726 (19)	0.36694 (12)	0.0269 (6)
H7	0.4450	0.4368	0.3495	0.032*
C8	0.4452 (3)	0.3883 (2)	0.42941 (12)	0.0304 (6)
H8A	0.4500	0.3297	0.4471	0.036*
H8B	0.5209	0.4228	0.4411	0.036*
C9	0.3234 (3)	0.4354 (2)	0.44809 (13)	0.0327 (7)
H9	0.3238	0.4952	0.4309	0.039*
C10	0.3151 (4)	0.4484 (2)	0.51013 (14)	0.0399 (7)
H10A	0.3968	0.4735	0.5235	0.048*
H10B	0.2464	0.4913	0.5183	0.048*
C11	0.2880 (4)	0.3630 (3)	0.54077 (14)	0.0455 (8)
H11A	0.2758	0.3760	0.5802	0.055*
H11B	0.3625	0.3232	0.5372	0.055*
C12	0.1691 (4)	0.3171 (3)	0.51853 (16)	0.0503 (9)
H12A	0.0930	0.3542	0.5257	0.060*
H12B	0.1571	0.2603	0.5378	0.060*
C13	0.1815 (3)	0.3005 (2)	0.45668 (14)	0.0407 (8)
H13A	0.2534	0.2596	0.4498	0.049*
H13B	0.1021	0.2727	0.4428	0.049*
C14	0.2048 (3)	0.3865 (2)	0.42625 (13)	0.0347 (7)
H14	0.1289	0.4252	0.4327	0.042*
C15	0.2175 (3)	0.3736 (2)	0.36460 (13)	0.0318 (6)
H15A	0.1428	0.3399	0.3511	0.038*
H15B	0.2164	0.4319	0.3464	0.038*
C16	0.5715 (3)	0.33129 (19)	0.35033 (12)	0.0255 (6)
C17	0.7959 (3)	0.3617 (2)	0.31935 (14)	0.0311 (6)
C18	0.8574 (3)	0.2958 (3)	0.3576 (2)	0.0518 (10)
H18A	0.8061	0.2418	0.3584	0.078*
H18B	0.8622	0.3208	0.3947	0.078*
H18C	0.9439	0.2821	0.3446	0.078*
C19	0.7847 (4)	0.3250 (3)	0.26108 (16)	0.0478 (9)
H19A	0.7327	0.2714	0.2616	0.072*
H19B	0.8702	0.3112	0.2470	0.072*
H19C	0.7441	0.3689	0.2373	0.072*
C20	0.8752 (3)	0.4461 (2)	0.31835 (15)	0.0369 (7)
H20A	0.8331	0.4897	0.2949	0.055*
H20B	0.9606	0.4333	0.3038	0.055*
H20C	0.8829	0.4694	0.3557	0.055*
C21	0.3644 (4)	0.0305 (2)	0.36758 (13)	0.0378 (7)
C22	0.4947 (4)	0.0212 (3)	0.38043 (15)	0.0451 (8)
H22	0.5464	0.0723	0.3843	0.054*
C23	0.5494 (5)	−0.0614 (3)	0.38766 (17)	0.0558 (10)
H23	0.6376	−0.0664	0.3965	0.067*
C24	0.4763 (6)	−0.1352 (3)	0.38198 (17)	0.0620 (12)
H24	0.5144	−0.1916	0.3858	0.074*
C25	0.3478 (5)	−0.1284 (3)	0.37081 (18)	0.0601 (12)
H25	0.2969	−0.1800	0.3679	0.072*
C26	0.2912 (4)	−0.0445 (2)	0.36356 (16)	0.0503 (9)
H26	0.2024	−0.0400	0.3559	0.060*
C27	0.6317 (3)	0.10128 (19)	0.21805 (13)	0.0296 (6)
C28	0.7207 (3)	0.0856 (2)	0.25959 (14)	0.0335 (7)
H28	0.6934	0.0722	0.2958	0.040*
C29	0.8505 (3)	0.0899 (2)	0.24673 (15)	0.0363 (7)
C30	0.8922 (3)	0.1106 (2)	0.19463 (16)	0.0385 (7)
H30	0.9810	0.1148	0.1867	0.046*
C31	0.8013 (3)	0.1254 (2)	0.15382 (15)	0.0365 (7)
C32	0.6711 (3)	0.12013 (19)	0.16489 (13)	0.0318 (6)
H32	0.6100	0.1293	0.1366	0.038*
C33	0.1663 (3)	0.2464 (2)	0.12927 (13)	0.0331 (7)
C34	0.2152 (3)	0.1651 (2)	0.11265 (14)	0.0341 (7)
H34	0.2583	0.1278	0.1379	0.041*
C35	0.1993 (3)	0.1402 (2)	0.05848 (14)	0.0361 (7)
C36	0.1413 (3)	0.1945 (2)	0.02003 (14)	0.0396 (7)
H36	0.1330	0.1769	−0.0172	0.047*
C37	0.0960 (3)	0.2754 (2)	0.03776 (15)	0.0396 (7)
C38	0.1059 (3)	0.3019 (2)	0.09184 (15)	0.0377 (7)
H38	0.0721	0.3570	0.1033	0.045*
N1	0.3352 (2)	0.32700 (16)	0.34911 (10)	0.0269 (5)
N2	0.6672 (2)	0.38628 (17)	0.33856 (10)	0.0271 (5)
H1N	0.651 (4)	0.440 (3)	0.3363 (14)	0.033*
N3	0.4523 (2)	0.13695 (16)	0.27536 (10)	0.0278 (5)
H2N	0.510 (4)	0.166 (2)	0.2945 (15)	0.033*
O2	0.58152 (19)	0.24951 (13)	0.34972 (9)	0.0289 (4)
O3	0.4177 (2)	0.06170 (14)	0.19576 (9)	0.0328 (5)
O4	0.2526 (2)	0.22167 (14)	0.21627 (9)	0.0322 (4)
O5	0.1021 (2)	0.32785 (16)	0.20878 (10)	0.0423 (6)
Cl1	0.96231 (8)	0.07105 (6)	0.29804 (4)	0.0481 (2)
Cl2	0.85139 (8)	0.14928 (6)	0.08777 (4)	0.0480 (2)
Cl3	0.24876 (9)	0.03602 (6)	0.03774 (4)	0.0465 (2)
Cl4	0.01738 (10)	0.34193 (6)	−0.00931 (4)	0.0512 (2)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0196 (12)	0.0323 (15)	0.0355 (15)	0.0010 (11)	−0.0018 (12)	−0.0014 (12)
C2	0.0208 (13)	0.0339 (15)	0.0352 (15)	−0.0008 (12)	−0.0024 (12)	−0.0035 (12)
C3	0.0211 (13)	0.0293 (14)	0.0370 (15)	−0.0019 (11)	0.0016 (12)	−0.0011 (12)
C4	0.0298 (15)	0.0296 (15)	0.0395 (16)	−0.0019 (12)	0.0019 (13)	−0.0014 (13)
C5	0.0230 (14)	0.0251 (13)	0.0369 (15)	0.0010 (11)	−0.0014 (12)	−0.0036 (12)
C6	0.0234 (14)	0.0331 (16)	0.0452 (17)	0.0005 (13)	−0.0064 (13)	0.0006 (13)
C7	0.0178 (13)	0.0267 (14)	0.0362 (15)	−0.0012 (11)	0.0003 (11)	−0.0007 (11)
C8	0.0228 (13)	0.0319 (15)	0.0364 (15)	−0.0038 (12)	−0.0005 (12)	−0.0019 (12)
C9	0.0299 (15)	0.0318 (15)	0.0365 (16)	−0.0012 (13)	0.0037 (13)	0.0006 (12)
C10	0.0424 (18)	0.0403 (18)	0.0370 (16)	−0.0024 (14)	0.0042 (14)	−0.0017 (14)
C11	0.054 (2)	0.047 (2)	0.0358 (17)	−0.0020 (16)	0.0048 (15)	0.0032 (15)
C12	0.052 (2)	0.052 (2)	0.048 (2)	−0.0100 (18)	0.0109 (17)	0.0066 (17)
C13	0.0362 (17)	0.0417 (18)	0.0442 (18)	−0.0095 (14)	0.0065 (15)	0.0009 (15)
C14	0.0253 (14)	0.0387 (17)	0.0401 (17)	0.0016 (13)	0.0059 (12)	−0.0006 (13)
C15	0.0199 (14)	0.0337 (16)	0.0417 (17)	0.0023 (12)	0.0016 (12)	−0.0036 (13)
C16	0.0180 (12)	0.0292 (15)	0.0292 (13)	−0.0016 (11)	−0.0014 (10)	0.0004 (11)
C17	0.0180 (13)	0.0272 (14)	0.0480 (17)	−0.0006 (11)	0.0045 (12)	0.0042 (13)
C18	0.0219 (15)	0.046 (2)	0.088 (3)	−0.0029 (14)	−0.0063 (17)	0.026 (2)
C19	0.049 (2)	0.044 (2)	0.051 (2)	−0.0072 (16)	0.0195 (17)	−0.0077 (16)
C20	0.0225 (14)	0.0325 (16)	0.0557 (19)	−0.0026 (12)	0.0025 (14)	0.0076 (14)
C21	0.0472 (19)	0.0304 (16)	0.0358 (16)	−0.0009 (15)	0.0006 (14)	0.0002 (13)
C22	0.049 (2)	0.0421 (19)	0.0438 (19)	0.0047 (16)	−0.0052 (16)	0.0011 (15)
C23	0.062 (3)	0.053 (2)	0.052 (2)	0.012 (2)	−0.006 (2)	0.0051 (18)
C24	0.096 (4)	0.042 (2)	0.048 (2)	0.016 (2)	−0.006 (2)	0.0015 (17)
C25	0.091 (4)	0.0340 (19)	0.056 (2)	−0.012 (2)	−0.006 (2)	−0.0001 (17)
C26	0.066 (3)	0.0379 (19)	0.0471 (19)	−0.0139 (18)	−0.0119 (18)	0.0062 (16)
C27	0.0217 (14)	0.0256 (14)	0.0416 (16)	0.0008 (11)	0.0001 (12)	−0.0066 (12)
C28	0.0255 (15)	0.0314 (15)	0.0437 (17)	0.0010 (12)	0.0003 (12)	−0.0056 (13)
C29	0.0214 (14)	0.0329 (16)	0.0546 (19)	0.0036 (12)	−0.0048 (14)	−0.0096 (14)
C30	0.0255 (15)	0.0283 (15)	0.062 (2)	0.0003 (12)	0.0058 (14)	−0.0119 (14)
C31	0.0311 (16)	0.0308 (16)	0.0476 (18)	−0.0032 (12)	0.0060 (14)	−0.0076 (14)
C32	0.0256 (14)	0.0263 (14)	0.0436 (17)	−0.0019 (12)	0.0003 (13)	−0.0057 (12)
C33	0.0241 (14)	0.0340 (16)	0.0411 (16)	−0.0003 (13)	−0.0041 (13)	0.0017 (13)
C34	0.0244 (14)	0.0362 (16)	0.0418 (16)	0.0002 (12)	−0.0024 (12)	0.0021 (14)
C35	0.0332 (16)	0.0354 (16)	0.0397 (16)	−0.0014 (13)	−0.0010 (13)	0.0010 (13)
C36	0.0371 (18)	0.0451 (18)	0.0365 (17)	−0.0038 (15)	−0.0013 (14)	0.0021 (14)
C37	0.0325 (16)	0.0402 (18)	0.0460 (18)	−0.0040 (14)	−0.0052 (14)	0.0090 (15)
C38	0.0287 (15)	0.0354 (17)	0.0491 (19)	−0.0012 (13)	−0.0061 (14)	0.0028 (14)
N1	0.0177 (11)	0.0294 (12)	0.0336 (12)	−0.0025 (10)	0.0009 (10)	−0.0021 (10)
N2	0.0201 (11)	0.0249 (12)	0.0364 (13)	−0.0005 (10)	0.0006 (10)	0.0002 (10)
N3	0.0198 (11)	0.0277 (12)	0.0358 (13)	0.0006 (10)	−0.0018 (10)	−0.0039 (10)
O2	0.0217 (9)	0.0253 (10)	0.0395 (11)	−0.0011 (8)	−0.0028 (8)	0.0001 (8)
O3	0.0254 (10)	0.0300 (11)	0.0432 (12)	0.0010 (8)	−0.0046 (9)	−0.0076 (9)
O4	0.0250 (10)	0.0356 (11)	0.0361 (11)	0.0038 (9)	−0.0054 (9)	−0.0030 (9)
O5	0.0332 (11)	0.0429 (13)	0.0507 (14)	0.0121 (10)	−0.0066 (10)	−0.0081 (11)
Cl1	0.0266 (4)	0.0544 (5)	0.0632 (5)	0.0083 (4)	−0.0099 (4)	−0.0119 (4)
Cl2	0.0419 (4)	0.0490 (5)	0.0529 (5)	−0.0093 (4)	0.0139 (4)	−0.0051 (4)
Cl3	0.0514 (5)	0.0428 (4)	0.0452 (4)	0.0061 (4)	0.0023 (4)	−0.0044 (3)
Cl4	0.0557 (5)	0.0457 (5)	0.0523 (5)	0.0007 (4)	−0.0155 (4)	0.0113 (4)

Geometric parameters (Å, º) top

C1—N1	1.463 (4)	C17—N2	1.473 (4)
C1—C2	1.522 (4)	C17—C18	1.512 (5)
C1—H1A	0.9900	C17—C20	1.527 (4)
C1—H1B	0.9900	C17—C19	1.530 (5)
C2—O4	1.453 (4)	C18—H18A	0.9800
C2—C3	1.540 (4)	C18—H18B	0.9800
C2—H2	1.0000	C18—H18C	0.9800
C3—N3	1.462 (4)	C19—H19A	0.9800
C3—C4	1.537 (4)	C19—H19B	0.9800
C3—H3	1.0000	C19—H19C	0.9800
C4—C21	1.511 (4)	C20—H20A	0.9800
C4—H4A	0.9900	C20—H20B	0.9800
C4—H4B	0.9900	C20—H20C	0.9800
C5—O3	1.238 (4)	C21—C26	1.376 (5)
C5—N3	1.335 (4)	C21—C22	1.405 (5)
C5—C27	1.505 (4)	C22—C23	1.391 (5)
C6—O5	1.206 (4)	C22—H22	0.9500
C6—O4	1.348 (4)	C23—C24	1.364 (7)
C6—C33	1.491 (5)	C23—H23	0.9500
C7—N1	1.467 (3)	C24—C25	1.374 (8)
C7—C16	1.526 (4)	C24—H24	0.9500
C7—C8	1.532 (4)	C25—C26	1.416 (6)
C7—H7	1.0000	C25—H25	0.9500
C8—C9	1.530 (4)	C26—H26	0.9500
C8—H8A	0.9900	C27—C32	1.389 (5)
C8—H8B	0.9900	C27—C28	1.395 (4)
C9—C10	1.527 (4)	C28—C29	1.395 (4)
C9—C14	1.540 (4)	C28—H28	0.9500
C9—H9	1.0000	C29—C30	1.379 (5)
C10—C11	1.523 (5)	C29—Cl1	1.735 (3)
C10—H10A	0.9900	C30—C31	1.393 (5)
C10—H10B	0.9900	C30—H30	0.9500
C11—C12	1.525 (6)	C31—C32	1.391 (4)
C11—H11A	0.9900	C31—Cl2	1.731 (4)
C11—H11B	0.9900	C32—H32	0.9500
C12—C13	1.534 (5)	C33—C38	1.394 (5)
C12—H12A	0.9900	C33—C34	1.397 (5)
C12—H12B	0.9900	C34—C35	1.383 (5)
C13—C14	1.522 (5)	C34—H34	0.9500
C13—H13A	0.9900	C35—C36	1.388 (5)
C13—H13B	0.9900	C35—Cl3	1.740 (3)
C14—C15	1.521 (4)	C36—C37	1.385 (5)
C14—H14	1.0000	C36—H36	0.9500
C15—N1	1.470 (4)	C37—C38	1.382 (5)
C15—H15A	0.9900	C37—Cl4	1.736 (3)
C15—H15B	0.9900	C38—H38	0.9500
C16—O2	1.247 (4)	N2—H1N	0.84 (4)
C16—N2	1.335 (4)	N3—H2N	0.88 (4)

N1—C1—C2	111.1 (2)	N2—C17—C20	106.8 (2)
N1—C1—H1A	109.4	C18—C17—C20	109.6 (3)
C2—C1—H1A	109.4	N2—C17—C19	108.5 (3)
N1—C1—H1B	109.4	C18—C17—C19	111.4 (3)
C2—C1—H1B	109.4	C20—C17—C19	109.4 (3)
H1A—C1—H1B	108.0	C17—C18—H18A	109.5
O4—C2—C1	108.1 (2)	C17—C18—H18B	109.5
O4—C2—C3	103.1 (2)	H18A—C18—H18B	109.5
C1—C2—C3	116.5 (2)	C17—C18—H18C	109.5
O4—C2—H2	109.6	H18A—C18—H18C	109.5
C1—C2—H2	109.6	H18B—C18—H18C	109.5
C3—C2—H2	109.6	C17—C19—H19A	109.5
N3—C3—C4	109.5 (2)	C17—C19—H19B	109.5
N3—C3—C2	110.0 (2)	H19A—C19—H19B	109.5
C4—C3—C2	114.9 (2)	C17—C19—H19C	109.5
N3—C3—H3	107.4	H19A—C19—H19C	109.5
C4—C3—H3	107.4	H19B—C19—H19C	109.5
C2—C3—H3	107.4	C17—C20—H20A	109.5
C21—C4—C3	111.2 (3)	C17—C20—H20B	109.5
C21—C4—H4A	109.4	H20A—C20—H20B	109.5
C3—C4—H4A	109.4	C17—C20—H20C	109.5
C21—C4—H4B	109.4	H20A—C20—H20C	109.5
C3—C4—H4B	109.4	H20B—C20—H20C	109.5
H4A—C4—H4B	108.0	C26—C21—C22	118.2 (3)
O3—C5—N3	124.7 (3)	C26—C21—C4	122.0 (3)
O3—C5—C27	120.0 (3)	C22—C21—C4	119.7 (3)
N3—C5—C27	115.3 (3)	C23—C22—C21	121.2 (4)
O5—C6—O4	124.5 (3)	C23—C22—H22	119.4
O5—C6—C33	124.9 (3)	C21—C22—H22	119.4
O4—C6—C33	110.5 (3)	C24—C23—C22	119.9 (4)
N1—C7—C16	111.3 (2)	C24—C23—H23	120.0
N1—C7—C8	109.8 (2)	C22—C23—H23	120.0
C16—C7—C8	109.1 (2)	C23—C24—C25	120.4 (4)
N1—C7—H7	108.9	C23—C24—H24	119.8
C16—C7—H7	108.9	C25—C24—H24	119.8
C8—C7—H7	108.9	C24—C25—C26	120.1 (4)
C9—C8—C7	111.1 (2)	C24—C25—H25	120.0
C9—C8—H8A	109.4	C26—C25—H25	120.0
C7—C8—H8A	109.4	C21—C26—C25	120.3 (4)
C9—C8—H8B	109.4	C21—C26—H26	119.9
C7—C8—H8B	109.4	C25—C26—H26	119.9
H8A—C8—H8B	108.0	C32—C27—C28	121.0 (3)
C10—C9—C8	113.7 (3)	C32—C27—C5	117.6 (3)
C10—C9—C14	111.0 (3)	C28—C27—C5	121.4 (3)
C8—C9—C14	110.0 (2)	C29—C28—C27	118.5 (3)
C10—C9—H9	107.3	C29—C28—H28	120.7
C8—C9—H9	107.3	C27—C28—H28	120.7
C14—C9—H9	107.3	C30—C29—C28	121.7 (3)
C11—C10—C9	112.7 (3)	C30—C29—Cl1	119.2 (2)
C11—C10—H10A	109.1	C28—C29—Cl1	119.1 (3)
C9—C10—H10A	109.1	C29—C30—C31	118.6 (3)
C11—C10—H10B	109.1	C29—C30—H30	120.7
C9—C10—H10B	109.1	C31—C30—H30	120.7
H10A—C10—H10B	107.8	C32—C31—C30	121.3 (3)
C10—C11—C12	111.5 (3)	C32—C31—Cl2	119.2 (3)
C10—C11—H11A	109.3	C30—C31—Cl2	119.4 (3)
C12—C11—H11A	109.3	C27—C32—C31	118.9 (3)
C10—C11—H11B	109.3	C27—C32—H32	120.6
C12—C11—H11B	109.3	C31—C32—H32	120.6
H11A—C11—H11B	108.0	C38—C33—C34	120.8 (3)
C11—C12—C13	110.8 (3)	C38—C33—C6	118.8 (3)
C11—C12—H12A	109.5	C34—C33—C6	120.3 (3)
C13—C12—H12A	109.5	C35—C34—C33	118.3 (3)
C11—C12—H12B	109.5	C35—C34—H34	120.8
C13—C12—H12B	109.5	C33—C34—H34	120.8
H12A—C12—H12B	108.1	C34—C35—C36	122.3 (3)
C14—C13—C12	110.6 (3)	C34—C35—Cl3	119.3 (3)
C14—C13—H13A	109.5	C36—C35—Cl3	118.3 (3)
C12—C13—H13A	109.5	C37—C36—C35	117.8 (3)
C14—C13—H13B	109.5	C37—C36—H36	121.1
C12—C13—H13B	109.5	C35—C36—H36	121.1
H13A—C13—H13B	108.1	C38—C37—C36	122.1 (3)
C15—C14—C13	112.6 (3)	C38—C37—Cl4	119.7 (3)
C15—C14—C9	109.5 (2)	C36—C37—Cl4	118.2 (3)
C13—C14—C9	112.0 (3)	C37—C38—C33	118.7 (3)
C15—C14—H14	107.5	C37—C38—H38	120.6
C13—C14—H14	107.5	C33—C38—H38	120.6
C9—C14—H14	107.5	C1—N1—C7	112.5 (2)
N1—C15—C14	112.9 (3)	C1—N1—C15	108.8 (2)
N1—C15—H15A	109.0	C7—N1—C15	110.1 (2)
C14—C15—H15A	109.0	C16—N2—C17	126.5 (3)
N1—C15—H15B	109.0	C16—N2—H1N	118 (3)
C14—C15—H15B	109.0	C17—N2—H1N	114 (3)
H15A—C15—H15B	107.8	C5—N3—C3	123.4 (3)
O2—C16—N2	123.9 (3)	C5—N3—H2N	118 (2)
O2—C16—C7	122.1 (2)	C3—N3—H2N	119 (2)
N2—C16—C7	114.0 (2)	C6—O4—C2	119.3 (2)
N2—C17—C18	111.1 (3)

N1—C1—C2—O4	175.5 (2)	C27—C28—C29—Cl1	179.7 (2)
N1—C1—C2—C3	−69.1 (3)	C28—C29—C30—C31	−1.6 (5)
O4—C2—C3—N3	68.7 (3)	Cl1—C29—C30—C31	179.8 (2)
C1—C2—C3—N3	−49.5 (3)	C29—C30—C31—C32	0.5 (5)
O4—C2—C3—C4	−167.3 (2)	C29—C30—C31—Cl2	−178.7 (2)
C1—C2—C3—C4	74.4 (3)	C28—C27—C32—C31	−1.6 (5)
N3—C3—C4—C21	−59.4 (3)	C5—C27—C32—C31	178.7 (3)
C2—C3—C4—C21	176.4 (3)	C30—C31—C32—C27	1.1 (5)
N1—C7—C8—C9	−58.6 (3)	Cl2—C31—C32—C27	−179.7 (2)
C16—C7—C8—C9	179.2 (2)	O5—C6—C33—C38	15.3 (5)
C7—C8—C9—C10	179.9 (3)	O4—C6—C33—C38	−167.0 (3)
C7—C8—C9—C14	54.7 (3)	O5—C6—C33—C34	−159.9 (3)
C8—C9—C10—C11	−72.6 (4)	O4—C6—C33—C34	17.8 (4)
C14—C9—C10—C11	52.1 (4)	C38—C33—C34—C35	−1.6 (5)
C9—C10—C11—C12	−53.9 (4)	C6—C33—C34—C35	173.5 (3)
C10—C11—C12—C13	55.9 (4)	C33—C34—C35—C36	2.6 (5)
C11—C12—C13—C14	−57.1 (4)	C33—C34—C35—Cl3	−175.4 (2)
C12—C13—C14—C15	−179.9 (3)	C34—C35—C36—C37	−1.5 (5)
C12—C13—C14—C9	56.2 (4)	Cl3—C35—C36—C37	176.5 (3)
C10—C9—C14—C15	−179.2 (3)	C35—C36—C37—C38	−0.7 (5)
C8—C9—C14—C15	−52.4 (3)	C35—C36—C37—Cl4	−177.4 (3)
C10—C9—C14—C13	−53.5 (4)	C36—C37—C38—C33	1.7 (5)
C8—C9—C14—C13	73.3 (3)	Cl4—C37—C38—C33	178.3 (2)
C13—C14—C15—N1	−69.1 (3)	C34—C33—C38—C37	−0.5 (5)
C9—C14—C15—N1	56.2 (3)	C6—C33—C38—C37	−175.6 (3)
N1—C7—C16—O2	−35.0 (4)	C2—C1—N1—C7	153.7 (2)
C8—C7—C16—O2	86.4 (3)	C2—C1—N1—C15	−84.0 (3)
N1—C7—C16—N2	147.1 (2)	C16—C7—N1—C1	−57.2 (3)
C8—C7—C16—N2	−91.6 (3)	C8—C7—N1—C1	−178.2 (2)
C3—C4—C21—C26	−85.2 (4)	C16—C7—N1—C15	−178.8 (2)
C3—C4—C21—C22	90.5 (4)	C8—C7—N1—C15	60.3 (3)
C26—C21—C22—C23	1.5 (5)	C14—C15—N1—C1	175.6 (2)
C4—C21—C22—C23	−174.3 (3)	C14—C15—N1—C7	−60.7 (3)
C21—C22—C23—C24	0.4 (6)	O2—C16—N2—C17	4.7 (5)
C22—C23—C24—C25	−2.0 (6)	C7—C16—N2—C17	−177.5 (3)
C23—C24—C25—C26	1.8 (7)	C18—C17—N2—C16	−53.9 (4)
C22—C21—C26—C25	−1.7 (5)	C20—C17—N2—C16	−173.3 (3)
C4—C21—C26—C25	174.0 (4)	C19—C17—N2—C16	68.9 (4)
C24—C25—C26—C21	0.1 (6)	O3—C5—N3—C3	0.8 (5)
O3—C5—C27—C32	42.1 (4)	C27—C5—N3—C3	180.0 (3)
N3—C5—C27—C32	−137.1 (3)	C4—C3—N3—C5	136.6 (3)
O3—C5—C27—C28	−137.6 (3)	C2—C3—N3—C5	−96.3 (3)
N3—C5—C27—C28	43.2 (4)	O5—C6—O4—C2	4.8 (5)
C32—C27—C28—C29	0.5 (5)	C33—C6—O4—C2	−172.9 (2)
C5—C27—C28—C29	−179.8 (3)	C1—C2—O4—C6	−78.2 (3)
C27—C28—C29—C30	1.2 (5)	C3—C2—O4—C6	158.0 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H1N···O3ⁱ	0.84 (4)	2.13 (4)	2.931 (3)	160 (3)
N3—H2N···O2	0.88 (4)	1.99 (4)	2.834 (3)	159 (3)
C4—H4A···N1	0.99	2.55	3.149 (4)	119
C18—H18A···O2	0.98	2.36	2.975 (4)	120
C34—H34···O3	0.95	2.40	3.324 (4)	163

Symmetry code: (i) −x+1, y+1/2, −z+1/2.

Acknowledgements

We thank the EPSRC National Crystallography Service (University of Southampton) for the X-ray data collections.

References

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