A pipecolic acid (Pip)-containing dipeptide, Boc-D-Ala-L-Pip-NHⁱPr

The title dipeptide, 1-(tert-butoxy­carbonyl-D-alanyl)-N-iso­propyl-L-pipecol­amide or Boc-D-Ala-L-Pip-NHⁱPr (H-Pip-OH is pipecolic acid or piperidine-2-carboxylic acid), C₁₇H₃₁N₃­O₄, with a D–L heterochiral sequence, adopts a type II′ β-­turn conformation, with all-trans amide functions, where the C-terminal amide NH group interacts with the Boc carbonyl O atom to form a classical i+3 i intramolecular hydrogen bond. The C^α substituent takes an axial position [H^α (Pip) equatorial] and the trans pipecolamide function is nearly planar.

S1. Comment

With the advent of the post-genomic era, a larger number either of peptides or peptidomimetics will be designed as available drugs for studying their role in the development and care of diseases. In addition, with sequences of natural amino acids, those with different topologies containing non-coded building blocks will be mandatory to face this challenge.

Of the three main types of structural motifs (β-sheets, helices and turns of loops), the β-turn, which is often involved in molecular recognition processes, offers the significant advantage that it is compact and of such a size that it can readily be encountered in the totally amidated dipeptide sequence R—CO-Xaa-Yaa-NH—R'.

The widespread naturally occurring non-proteinogenic amino acid, pipecolic acid, H-Pip-OH (also known as homoproline or piperidine-2-carboxylic acid), is a proline analogue with a six-membered piperidine ring and which is found in many biologically active compounds. It is a component of several antibiotics, immunosuppressants and inhibitors of HIV protease, and has been extensively used as a proline substitute in numerous syntheses of peptidomimetics studied in structure-activity relationships.

As part of an overall conformational analysis project aimed at exploring local perturbations induced by the substitution either of Pip or AzPip (AzPip is the homologue of Pip in which an N^α atom has been substituted for the Pip C^α atom), we recently reported the crystal structures of Boc-L-Ala-(S)AzPip-NHⁱPr and of Piv-L/DPip-NHMe (Didierjean et al., 2000), and in this paper, we present the molecular crystal-structure resolution of Boc-D-Ala-L-Pip-NHⁱPr, (I), for the purpose of giving prominence to conformational bias. \sch

A view of the molecule of (I) with the atom-numbering scheme is shown in Fig. 1. Selected torsion angles and hydrogen bonds with their geometry and symmetry geometry are given in Tables 1 and 2, respectively. The bond lengths and angles are in agreement with literature data on the geometry of the Pip residue (Bhattacharjee & Chacko, 1979; Rae et al., 1980; Bardi et al., 1992; Didierjean et al., 2000) and Boc urethane derivatives (Benedetti et al., 1980). A type b of this latter N-protecting group is assumed by the trans arrangement of both C1—O1 versus C5—N1 and the CONH amide bond of the urethane group. The C-terminal isopropyl group is disordered and was modelled over two positions with restrained distances and angles.

The piperidine ring adopts a chair (⁴C₁) conformation with the H^α atom in the equatorial disposition, as expected from calculations (Toniolo et al., 1989) and as also found in Piv-D/LPip-NHMe (Didierjean et al., 2000). The piperidyl imide link is trans [ω = 176.8 (3)°] and atom N2 exhibits a very low displacement [0.033 (3) Å] from the plane defined by its three substituents.

The molecule of (I) is folded by a type-II' β-bend conformation, with D-Ala as i+1 and L-Pip as i+2 corner residues. The 4 → 1 intramolecular hydrogen bond takes place between the donor (NHⁱPr) C-terminal amide group and the (Boc)urethane carbonyl acceptor sites (Fig. 1, Table 2).

Concerning the molecular packing, an intermolecular N—H···O═C hydrogen-bonding network occurs along the a axis, involving the urethane (D-Ala)N—H as donor and the amide (Pip)C═O as acceptor (Fig. 2, Table 2). The crystal can be described as forming infinite chains, where each chain forms weak van der Waals interactions with neighbouring chains.

If we compare the conformation of (I) with that of Boc-L-Ala-(S)AzPip-NHⁱPr (Didierjean et al., 2000), the two prominent changes are a cis disposition for the median AzPip imide bond and type-VI β-turn-like folding. Thus, local modification of the three-dimensional structure can be achieved by using the Pip/AzPip couple, and this should be of great interest when designing new building blocks for peptidomimetics.

S2. Experimental

The synthesis of Boc-D-Ala-L-Pip-NHⁱPr was carried out as follows. The classical DIC/AtOH/DIEA (1/1/1) method was applied, starting from Boc-D-Ala-OH and enantiomerically pure H—L-Pip-NHⁱPr, obtained after elimination of the Boc protective group (HCl/AcOEt, ~3 N) of Boc-L-Pip-NHⁱPr, which was previously obtained by reaction of optically pure Boc-L-Pip-OH (BA 14202, Neosystem, Strasbourg, France) with isopropylamine according to the DIC/BtOH/DIEA (1/1/1) method. The crude dipeptide was chromatographed on silica gel using pure AcOEt as eluting solvent, to give Boc-D-Ala-L-Pip-NHⁱPr, (I), as a white solid. Single crystals of (I) were grown from a dilute ethyl acetate solution by slow evaporation at room temperature (F = m.p.? 444 K; yield 80%) Thin layer chromatography: Rf = 0.43, AcOEt/Hexanes 1/1. Spectroscopic analysis: [α]_D = -78.2 (c = 1.0, CHCl₃, at 299 K); ¹H NMR (CDCl₃, δ, p.p.m.): 6.28 [d, bd, 1H, NH(ⁱPr)], 5.3–5.1 [m, 2H, NH(Ala) CH^α(Pip)], 4.53 [m, 1H, CH^α(Ala)], 4.09 [m, 1H, CH(ⁱPr)], 3.80 (d, J = 13.8 Hz, 1H, H^εeq), 3.11 (m, 1H, H^εax), 2.42 (d, J = 12.4 Hz, 1H, H^βeq), 1.8–1.4 (m, 5H, H^βax, H₂^γ, H₂^δ), 1.43 (s, 9H, ^tBu), 1.32 [d, J = 7.4 Hz, 3H, Me(Ala)], 1.2–1.0 [m, 6H, Me₂(ⁱPr)].

S3. Refinement

Because of the lack of any significant anomalous dispersion effects, the absolute conformation could not be determined from the diffraction experiment. Friedel pairs were merged prior to refinement. The C-terminal isopropyl group was found to be disordered and was modelled over two sites [occupancy factors 0.48 (2):0.52 (2)]. All non-H atoms were refined anisotropically, except the C atoms of the two methyl groups of the C-terminal isopropyl group. The H atoms of the disordered methyl group were not placed. Other H atoms connected to C atoms were placed at calculated positions using a riding model, with C—H = 0.96–0.98 Å. The positions of H atoms attached to N atoms were located from a difference map and the N—H bond distance was restrained to 1.03 (1) Å (Taylor & Kennard, 1983). All H atoms were refined with their isotropic displacement parameters fixed at 1.3 times that of the parent atom.

Computing details

Data collection: COLLECT (Nonius, 1998); cell refinement: COLLECT; data reduction: HKL suite (Otwinoski & Minor, 1997); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 (Farrugia, 1997).

Figures

	Fig. 1. The molecular structure of (I) with the atom-numbering scheme and 25% probability displacement ellipsoids. For clarity, only one conformation of the disordered isopropyl group (C15A—C17A) and N-bound H atoms are shown. The intramolecular hydrogen bond is drawn as dashed lines.
	Fig. 2. A view along the a axis showing the crystal packing of (I). The intra- and intermolecular hydrogen-bonding schemes are shown as thin and thick dashed lines, respectively.

1-(tert-butoxycarbonyl-D-alanyl)-N-isopropyl-L-pipecolamide

Crystal data

C17H31N3O4	F(000) = 372
Mr = 341.45	Dx = 1.132 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71070 Å
Hall symbol: P 2yb	Cell parameters from 6016 reflections
a = 9.3630 (2) Å	θ = 3.3–25.7°
b = 9.9720 (5) Å	µ = 0.08 mm^−1
c = 11.1270 (5) Å	T = 293 K
β = 105.330 (3)°	Prismatic, colourless
V = 1001.94 (7) Å^3	0.4 × 0.3 × 0.2 mm
Z = 2

Data collection

Nonius KappaCCD area-detector diffractometer	1616 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.029
Graphite monochromator	θmax = 25.7°, θmin = 3.3°
oscillation scans	h = −11→11
6016 measured reflections	k = −12→12
1978 independent reflections	l = −13→13

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)] = 0.054	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.150	w = 1/[σ^2(Fo^2) + (0.0932P)^2 + 0.135P] where P = (Fo^2 + 2Fc^2)/3
S = 1.06	(Δ/σ)max = 0.005
1978 reflections	Δρmax = 0.41 e Å^−3
232 parameters	Δρmin = −0.19 e Å^−3
9 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: 0.15 (2)

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	Occ. (<1)
C1	1.0553 (4)	−0.0759 (5)	0.6436 (4)	0.0691 (11)
C2	0.9631 (5)	−0.1461 (6)	0.7142 (5)	0.0879 (14)
H2A	0.8775	−0.0927	0.7134	0.114*
H2B	1.0201	−0.1596	0.7987	0.114*
H2C	0.9321	−0.2314	0.6761	0.114*
C3	0.9625 (8)	−0.0412 (7)	0.5114 (5)	0.111 (2)
H3A	0.8765	0.0087	0.5163	0.145*
H3B	0.9323	−0.1224	0.4654	0.145*
H3C	1.0208	0.0118	0.4701	0.145*
C4	1.1887 (6)	−0.1566 (7)	0.6423 (8)	0.128 (3)
H4A	1.2401	−0.1808	0.7261	0.166*
H4B	1.2531	−0.1047	0.6062	0.166*
H4C	1.1589	−0.2364	0.5939	0.166*
O1	1.1195 (3)	0.0476 (3)	0.7071 (3)	0.0714 (8)
C5	1.0326 (4)	0.1490 (4)	0.7269 (3)	0.0544 (8)
O2	0.8992 (2)	0.1546 (3)	0.6887 (2)	0.0668 (7)
N1	1.1166 (3)	0.2456 (3)	0.7958 (3)	0.0564 (8)
H1	1.2291 (13)	0.236 (5)	0.821 (4)	0.073*
C6	1.0471 (3)	0.3662 (4)	0.8254 (3)	0.0533 (8)
H6	0.9983	0.4130	0.7479	0.069*
C7	1.1613 (4)	0.4584 (5)	0.9072 (5)	0.0851 (15)
H7A	1.1134	0.5381	0.9253	0.111*
H7B	1.2344	0.4821	0.8645	0.111*
H7C	1.2085	0.4133	0.9836	0.111*
C8	0.9307 (3)	0.3290 (3)	0.8948 (3)	0.0456 (7)
O3	0.9578 (2)	0.2407 (3)	0.9737 (2)	0.0637 (7)
N2	0.8009 (3)	0.3980 (3)	0.8678 (2)	0.0462 (7)
C9	0.6863 (3)	0.3581 (4)	0.9290 (3)	0.0515 (8)
H9	0.7338	0.3013	1.0002	0.067*
C10	0.6225 (4)	0.4811 (5)	0.9800 (4)	0.0679 (11)
H10A	0.5397	0.4532	1.0112	0.088*
H10B	0.6976	0.5186	1.0492	0.088*
C11	0.5713 (4)	0.5871 (5)	0.8824 (4)	0.0742 (12)
H11A	0.5371	0.6649	0.9192	0.096*
H11B	0.4891	0.5531	0.8170	0.096*
C12	0.6972 (4)	0.6276 (4)	0.8271 (5)	0.0731 (11)
H12A	0.7758	0.6690	0.8910	0.095*
H12B	0.6616	0.6928	0.7612	0.095*
C13	0.7573 (4)	0.5049 (4)	0.7747 (4)	0.0595 (9)
H13A	0.6821	0.4710	0.7036	0.077*
H13B	0.8424	0.5311	0.7459	0.077*
C14	0.5632 (3)	0.2752 (4)	0.8427 (3)	0.0529 (8)
O4	0.4396 (3)	0.2722 (3)	0.8605 (3)	0.0752 (9)
N3	0.5991 (3)	0.2034 (3)	0.7534 (3)	0.0636 (9)
H3	0.698 (3)	0.209 (5)	0.731 (4)	0.083*
C15A	0.4988 (15)	0.1104 (10)	0.6726 (13)	0.089 (8)	0.517 (17)
H15A	0.4037	0.1102	0.6938	0.116*	0.517 (17)
C16A	0.476 (3)	0.160 (3)	0.5407 (17)	0.187 (9)*	0.517 (17)
C17A	0.5687 (12)	−0.0270 (12)	0.6970 (13)	0.094 (4)*	0.517 (17)
C15B	0.4891 (12)	0.1228 (8)	0.6671 (11)	0.058 (6)	0.483 (17)
H15B	0.4247	0.0861	0.7156	0.075*	0.483 (17)
C16B	0.3901 (11)	0.2051 (11)	0.5647 (8)	0.084 (4)*	0.483 (17)
C17B	0.5570 (12)	0.0034 (11)	0.6199 (12)	0.086 (4)*	0.483 (17)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.069 (2)	0.064 (3)	0.078 (2)	−0.0136 (19)	0.0270 (19)	−0.022 (2)
C2	0.084 (3)	0.082 (3)	0.098 (3)	−0.007 (3)	0.024 (2)	0.013 (3)
C3	0.163 (6)	0.102 (5)	0.075 (3)	−0.033 (4)	0.042 (3)	−0.033 (3)
C4	0.090 (3)	0.086 (4)	0.225 (7)	−0.017 (3)	0.073 (4)	−0.079 (5)
O1	0.0528 (13)	0.0653 (18)	0.101 (2)	−0.0087 (13)	0.0291 (13)	−0.0319 (15)
C5	0.0508 (18)	0.058 (2)	0.0583 (18)	−0.0051 (17)	0.0220 (14)	−0.0075 (16)
O2	0.0449 (12)	0.0794 (18)	0.0719 (15)	−0.0037 (13)	0.0083 (10)	−0.0130 (14)
N1	0.0404 (13)	0.0544 (17)	0.0761 (18)	−0.0035 (13)	0.0186 (12)	−0.0140 (15)
C6	0.0468 (16)	0.0446 (18)	0.074 (2)	0.0013 (14)	0.0260 (15)	0.0020 (16)
C7	0.055 (2)	0.061 (3)	0.147 (4)	−0.0160 (19)	0.040 (2)	−0.040 (3)
C8	0.0427 (16)	0.0429 (18)	0.0506 (17)	−0.0022 (13)	0.0111 (12)	−0.0007 (15)
O3	0.0561 (14)	0.0656 (17)	0.0701 (15)	0.0096 (12)	0.0178 (11)	0.0187 (14)
N2	0.0368 (12)	0.0474 (16)	0.0559 (14)	−0.0008 (11)	0.0149 (10)	0.0027 (12)
C9	0.0405 (15)	0.064 (2)	0.0525 (17)	−0.0038 (15)	0.0161 (13)	0.0012 (16)
C10	0.058 (2)	0.081 (3)	0.070 (2)	−0.005 (2)	0.0263 (18)	−0.021 (2)
C11	0.059 (2)	0.066 (3)	0.098 (3)	0.0130 (19)	0.022 (2)	−0.017 (2)
C12	0.058 (2)	0.057 (2)	0.101 (3)	0.0049 (19)	0.0128 (19)	0.000 (2)
C13	0.0558 (19)	0.055 (2)	0.072 (2)	0.0068 (16)	0.0240 (17)	0.0129 (18)
C14	0.0443 (16)	0.049 (2)	0.068 (2)	−0.0023 (14)	0.0182 (15)	0.0031 (16)
O4	0.0446 (12)	0.084 (2)	0.104 (2)	−0.0117 (13)	0.0313 (13)	−0.0115 (17)
N3	0.0434 (15)	0.065 (2)	0.082 (2)	−0.0060 (14)	0.0159 (14)	−0.0205 (18)
C15A	0.085 (13)	0.076 (12)	0.114 (16)	−0.010 (11)	0.042 (11)	−0.017 (12)
C15B	0.040 (7)	0.055 (9)	0.067 (10)	−0.008 (7)	−0.006 (7)	−0.019 (7)

Geometric parameters (Å, º)

C1—O1	1.468 (5)	N2—C9	1.469 (4)
C1—C2	1.488 (6)	C9—C14	1.533 (5)
C1—C4	1.489 (7)	C9—C10	1.537 (5)
C1—C3	1.536 (8)	C9—H9	0.9800
C2—H2A	0.9600	C10—C11	1.501 (7)
C2—H2B	0.9600	C10—H10A	0.9700
C2—H2C	0.9600	C10—H10B	0.9700
C3—H3A	0.9600	C11—C12	1.521 (6)
C3—H3B	0.9600	C11—H11A	0.9700
C3—H3C	0.9600	C11—H11B	0.9700
C4—H4A	0.9600	C12—C13	1.526 (6)
C4—H4B	0.9600	C12—H12A	0.9700
C4—H4C	0.9600	C12—H12B	0.9700
O1—C5	1.351 (5)	C13—H13A	0.9700
C5—O2	1.210 (4)	C13—H13B	0.9700
C5—N1	1.348 (5)	C14—O4	1.225 (4)
N1—C6	1.446 (4)	C14—N3	1.338 (5)
N1—H1	1.020 (10)	N3—C15A	1.450 (5)
C6—C7	1.518 (5)	N3—C15B	1.451 (5)
C6—C8	1.538 (4)	N3—H3	1.023 (10)
C6—H6	0.9800	C15A—C16A	1.510 (5)
C7—H7A	0.9600	C15A—C17A	1.512 (5)
C7—H7B	0.9600	C15A—H15A	0.9800
C7—H7C	0.9600	C15B—C16B	1.508 (5)
C8—O3	1.221 (4)	C15B—C17B	1.509 (5)
C8—N2	1.360 (4)	C15B—H15B	0.9800
N2—C13	1.468 (5)
O1—C1—C2	111.2 (4)	N2—C9—C10	111.0 (3)
O1—C1—C4	102.7 (3)	C14—C9—C10	111.1 (3)
C2—C1—C4	110.9 (5)	N2—C9—H9	107.5
O1—C1—C3	109.1 (4)	C14—C9—H9	107.5
C2—C1—C3	110.6 (4)	C10—C9—H9	107.5
C4—C1—C3	112.1 (5)	C11—C10—C9	112.0 (3)
C1—C2—H2A	109.5	C11—C10—H10A	109.2
C1—C2—H2B	109.5	C9—C10—H10A	109.2
H2A—C2—H2B	109.5	C11—C10—H10B	109.2
C1—C2—H2C	109.5	C9—C10—H10B	109.2
H2A—C2—H2C	109.5	H10A—C10—H10B	107.9
H2B—C2—H2C	109.5	C10—C11—C12	110.3 (3)
C1—C3—H3A	109.5	C10—C11—H11A	109.6
C1—C3—H3B	109.5	C12—C11—H11A	109.6
H3A—C3—H3B	109.5	C10—C11—H11B	109.6
C1—C3—H3C	109.5	C12—C11—H11B	109.6
H3A—C3—H3C	109.5	H11A—C11—H11B	108.1
H3B—C3—H3C	109.5	C11—C12—C13	110.2 (3)
C1—C4—H4A	109.5	C11—C12—H12A	109.6
C1—C4—H4B	109.5	C13—C12—H12A	109.6
H4A—C4—H4B	109.5	C11—C12—H12B	109.6
C1—C4—H4C	109.5	C13—C12—H12B	109.6
H4A—C4—H4C	109.5	H12A—C12—H12B	108.1
H4B—C4—H4C	109.5	N2—C13—C12	112.0 (3)
C5—O1—C1	121.2 (3)	N2—C13—H13A	109.2
O2—C5—N1	124.1 (3)	C12—C13—H13A	109.2
O2—C5—O1	126.0 (3)	N2—C13—H13B	109.2
N1—C5—O1	110.0 (3)	C12—C13—H13B	109.2
C5—N1—C6	119.6 (3)	H13A—C13—H13B	107.9
C5—N1—H1	120 (3)	O4—C14—N3	122.7 (3)
C6—N1—H1	120 (3)	O4—C14—C9	119.9 (3)
N1—C6—C7	110.6 (3)	N3—C14—C9	117.3 (3)
N1—C6—C8	109.5 (3)	C14—N3—C15A	123.6 (8)
C7—C6—C8	109.0 (3)	C14—N3—C15B	120.9 (7)
N1—C6—H6	109.2	C15A—N3—C15B	6.2 (7)
C7—C6—H6	109.2	C14—N3—H3	125 (3)
C8—C6—H6	109.2	C15A—N3—H3	111 (3)
C6—C7—H7A	109.5	C15B—N3—H3	114 (3)
C6—C7—H7B	109.5	N3—C15A—C16A	107.2 (13)
H7A—C7—H7B	109.5	N3—C15A—C17A	106.8 (8)
C6—C7—H7C	109.5	C16A—C15A—C17A	114.4 (16)
H7A—C7—H7C	109.5	N3—C15A—H15A	109.4
H7B—C7—H7C	109.5	C16A—C15A—H15A	109.4
O3—C8—N2	121.8 (3)	C17A—C15A—H15A	109.4
O3—C8—C6	119.7 (3)	N3—C15B—C16B	112.7 (7)
N2—C8—C6	118.5 (3)	N3—C15B—C17B	112.1 (8)
C8—N2—C13	126.1 (3)	C16B—C15B—C17B	113.4 (10)
C8—N2—C9	118.7 (3)	N3—C15B—H15B	106.0
C13—N2—C9	115.0 (3)	C16B—C15B—H15B	106.0
N2—C9—C14	112.1 (3)	C17B—C15B—H15B	106.0
C2—C1—O1—C5	−61.5 (5)	N2—C9—C14—O4	−155.5 (3)
C4—C1—O1—C5	179.8 (5)	C10—C9—C14—O4	−30.7 (5)
C3—C1—O1—C5	60.7 (5)	C10—C9—C14—N3	152.4 (3)
C1—O1—C5—O2	−5.7 (6)	O4—C14—N3—C15A	−2.9 (8)
O2—C5—N1—C6	−1.5 (5)	O4—C14—N3—C15B	3.6 (8)
C5—N1—C6—C7	178.0 (4)	C14—N3—C15A—C16A	119.0 (14)
N1—C6—C8—O3	40.6 (4)	C15B—N3—C15A—C16A	53 (13)
C7—C6—C8—O3	−80.6 (4)	C14—N3—C15A—C17A	−117.9 (11)
C7—C6—C8—N2	98.1 (4)	C15B—N3—C15A—C17A	176 (14)
O3—C8—N2—C13	−179.6 (3)	C14—N3—C15B—C16B	78.8 (13)
C6—C8—N2—C13	1.7 (5)	C15A—N3—C15B—C16B	−163 (14)
O3—C8—N2—C9	−4.6 (5)	C14—N3—C15B—C17B	−151.7 (9)
C13—N2—C9—C14	73.9 (4)	C15A—N3—C15B—C17B	−34 (12)
C8—N2—C9—C10	133.4 (3)	C1—O1—C5—N1	174.7 (3)
C13—N2—C9—C10	−51.0 (4)	O1—C5—N1—C6	178.1 (3)
N2—C9—C10—C11	52.4 (4)	C5—N1—C6—C8	57.9 (4)
C14—C9—C10—C11	−73.0 (4)	N1—C6—C8—N2	−140.7 (3)
C9—C10—C11—C12	−56.0 (4)	C6—C8—N2—C9	176.8 (3)
C10—C11—C12—C13	56.4 (4)	C8—N2—C9—C14	−101.7 (3)
C8—N2—C13—C12	−131.9 (3)	N2—C9—C14—N3	27.6 (5)
C9—N2—C13—C12	52.9 (4)	C9—C14—N3—C15A	173.9 (7)
C11—C12—C13—N2	−54.3 (4)	C9—C14—N3—C15B	−179.6 (6)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O4^i	1.02 (1)	1.94 (2)	2.929 (3)	164 (4)
N3—H3···O2	1.02 (1)	2.13 (2)	3.118 (4)	162 (4)

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