An ortho­rhom­bic polymorph of a cyclization product of perindopril

Low-temperature X-ray diffraction experiments were em­ployed to investigate the crystal structures of an ortho­rhom­bic polymorph of the intra­molecular cyclization product of perindopril, a popular angiotensive-converting enzyme (ACE) inhibitor, namely ethyl (2S)-2-[(3S,5aS,9aS,10aS)-3-methyl-1,4-dioxo-5a,6,7,8,9,9a,10,10a-octa­hydro-3H-pyrazino­[1,2-a]indol-2-yl]penta­noate, C₁₉H₃₀N₂O₄, (Io), and its tetra­gonal equivalent, (It), which was previously reported at ambient temperature [Bojarska et al. (2013). J. Chil. Chem. Soc. 58, 1415-1417]. Polymorph (Io) crystallizes in the ortho­rhom­bic space group P2₁2₁2₁ with two mol­ecules in the asymmetric unit, while tetra­gonal form (It) crystallizes in the space group P4₁2₁2 with one mol­ecule in the asymmetric unit. The geometric parameters of (Io) are very similar to those of (It). The six-membered rings in both polymorphs adopt a slightly deformed chair conformation and the piperazinedione rings are in a boat conformation. However, the proline rings adopt an envelope conformation in (Io), while in (It) the ring exists in a slightly deformed half-chair conformation. The most significant difference between the two structures is the orientation of the ethyl penta­noate chain. Mol­ecules associate in pairs in a head-to-tail manner forming infinite columns. In (Io), mol­ecules are related by a twofold screw axis forming identical columns, while in (It), mol­ecules in successive neighbouring columns are related by alternating twofold screw axes and fourfold screw axes. In both cases, the crystal packing is stabilized by weak inter­molecular C-H...O inter­actions only.

S1. Comment

Perindopril has particularly valuable pharmacological properties because it belongs to a group of angiotensive-converting enzyme (ACE) inhibitors, which show biological activity in the treatment of high blood pressure and heart failure (Ferrari, 2005, 2008). In view of the medicinal value of this compound, it has been of prime importance to synthesize it with very high purity. Nevertheless, perindopril, similarly to other dipeptide drugs, is liable to degradation inter alia via isomerization at some chiral centres, hydrolysis of the side-chain ester group or cyclization (Harn & Furlan, 2010). Diketopiperazine derivatives (DKP) are degradation products of perindopril, from its intramolecular cyclization (Medenica et al., 2007). The DKP formation mechanism was decribed by Gomes et al. (2007). It is worth mentioning that DKP forming is principally a stability problem not only for perindopril but also for other ACE inhibitors such as enalapril, moexipril, lisinopril, ramipril and quinapril. Despite the fact that perindopril has been known since the early 1980s (Vincent et al., 1982), this compound has not been well structurally characterized. We published recently the first crystal structures of perindopril erbumine (Remko et al., 2011). Currently, we are focusing our attention on the perindopril cyclization products, which resulted in the publication of the first polymorph of DKP-perindopril {systematic name: ethyl (2S)-2-[(3S,5aS,9aS,10aS)-3-methyl-1,4-dioxo-5a,6,7,8,9,9a,10,10a-octahydro-3H-pyrazino[1,2-a]indol-2-yl]pentanoate}, crystallized from a nitrobenzene solution. The room-temperature structure proved to be tetragonal, with the P4₁2₁2 space group (It') (Bojarska et al., 2013).

Herein we report an orthorhombic polymorph, (Io), of (It'), which was recrystallizated from an acetic acid/water solution. To compare the two polymorphs, a redetermination of the crystal structure of the tetragonal polymorph form (It) was carried out at 100 K. As expected, the unit-cell dimensions and atomic coordinates show that the phase is the same at low temperature as at ambient temperature. Likewise, the geometric parameters of the redetermined structure agree well with those previously reported, but with improved precision. The low-temperature structure (It) refined to R = 0.0391 for 3352 data with I > 2σ(I) and R = 0.0391 for all 3356 data, while the structure determined previously at room temperature, (It'), refined to R = 0.0485 for 3549 data with I > 2σ(I) and R = 0.0494 for all 3644 data. It is worth mentioning that at both temperatures the terminal groups of the alkyl chain are disordered and exist in two equally occupied conformations. The Flack parameter at 100 K is 0.1 (3) (Flack, 1983). Thus, the standard uncertainty value is greater than 0.1 (regarded as the upper limit for a compound recognized as enantiopure) (Flack & Bernardinelli, 2000). On the other hand, Bayesian analysis of the Bijvoet-pair intensity differences carried out within PLATON (Spek, 2009) made it possible to calculate the Hooft parameter of 0.12 (7) (Hooft et al., 2008), suggesting that the absolute configuration is correctly established.

We reveal that (Io) crystallizes in the noncentrosymmetric space group P2₁2₁2₁. The crystal structure is comprises two crystallographically independent molecules in the asymmetric unit (Fig. 1), while (It) structure contains one molecule per assymetric unit. There is a good geometrical agreement between the two analyzed polymorphs. The C—C, C—O and C—N bond lengths found in (Io) are very similar to those found in (It). As for (It), both molecules of (Io) (labelled with the suffixes A and B) have the same S configuration at all five chiral C atoms.

In (Io), the conformations of molecules A and B are similar, favouring a slightly deformed chair for both six-membered rings (C3–C8), an envelope conformation for the proline rings (N1/C1–C3/C8) and a boat conformation for the diketopiperazine rings (N1/C1–C15/N2/C9–C10). The ring-puckering parameters (Cremer & Pople, 1975; Spek, 2009) are provided in the Supplementary materials. The diketopiperazine ring conformation defines the position of the O atoms of the carbonyl groups (O1 and O4), which lie on the same side of the pyrrolidine ring in both molecules of (Io). This is the same for (It). For (Io), the conformation of the ethyl pentanoate chain is either antiperiplanar or synclinal, with C17—O3—C18—C19 having torsion angles of 175.7 (5) and 79.2 (4)° for molecules A and B, respectively. In (It), the disordered ethyl pentanoate chain is oriented in an anticlinal or in an antiperiplanar conformation, as indicated by the dihedral [torsion?] angle values of 97.5 (4) and 156.4 (5)°, respectively. We also observed a subtle distinction between the two polymorphs in the conformation of the proline rings. As mentioned previously, the proline rings adopt an envelope conformation for (Io), while in (It) the proline ring exists in a slightly deformed half-chair conformation. Overlaying both structures (Fig. 2) demonstrates that they are conformational polymorphs.

Some similarities between the packing of (Io) and (It) are observed (Figs. 3 and 4). In both polymorphs, the DKP–perindopril molecules pack in separate columns extending through the crystal. However, in (Io), molecules are arranged in a head-to-tail motif in pairs around a crystallographic twofold screw axis in identical columns, while in (It) molecules are arranged in two different types of columns which alternate. Molecules in the first type of column are packed in the same manner as in ((Io), while molecules in the second type are related by the fourfold screw axes, maintaing the same head-to-tail motif.

Both (It) and (Io) are stabilized only by intermolecular C—H···O interactions (Table 1 and 2). However, it is well known that such weak interactions can play an important role in drug action and polymorphism (Umezawa & Nishio, 2005; Desiraju, 1997, 2005; Braga et al., 2009). In the case of (Io), four such contacts exist within the accepted range for C—H···O hydrogen bonds (Desiraju, 1996; Table 1). The C19B–H19E···O1Bⁱⁱⁱ interaction links the molecules into an infinite 10-membered chain along the a axis with the C(10) graph-set motif [symmetry code: (iii) x-1, y, z]. A similar contact, C10A–H10A···O4B, participates in the formation of two additional chains, viz. C₂²(11) along the b axis with C11A–H11A···O2Bⁱⁱ and C₂²(10) along the a axis with C10B–H10B···O4Aⁱ (Etter et al., 1990; Bernstein et al., (1995) [symmetry codes: (i) x+1, y, z; (ii) -x+1, y+1/2, -z+3/2]. These chains together result in the graph-set descriptor R₃³(18). Furthermore, edge-fused rings with the R₅⁵(28) motif are also present (Fig. 5).

In conclusion, (It) and (Io) can be classified as conformational polymorphs displaying significant similarities but also differences, particularly in the packing motifs.

Related literature

For related literature, see: Bernstein et al. (1995); Braga et al. (2009); Cremer & Pople (1975); Desiraju (1996, 1997, 2005); Etter et al. (1990); Ferrari (2005, 2008); Flack (1983); Flack & Bernardinelli (2000); Gomes et al. (2007); Harn & Furlan (2010); Hooft et al. (2008); Medenica et al. (2007); Remko et al. (2011); Spek (2009); Umezawa & Nishio (2005); Vincent et al. (1982).

S2. Experimental

Perindopril has been obtained in accordance with the procedure described by Vincent (Vincent et al., 1982). During recrystallization, colourless needle-shaped crystals of (Io) and plate-shaped crystals of the tetragonal form (It) were grown from solutions in acetic acid and water (1:1 v/v) and methylene chloride, respectively, by slow evaporation at room temperature over a period of several weeks.

S3. Refinement

All H atoms were visible in difference Fourier maps and subsequently positioned geometrically and refined using a riding model, with fixed C—H distances (0.97–1.00 Å) and with U_iso(H) = 1.5U_eq(C) for methyl H atoms or 1.2U_eq(C) otherwise. In the case of (It), the terminal ethyl group (C18—C19) of the n-alkyl chain was treated as disordered over two equal sets of positions using DFIX restraints for the C—C and C—O distances of 1.525 and 1.400 Å, respectively.

Computing details

For both compounds, data collection: APEX2 (Bruker, 2005); cell refinement: SAINT-Plus (Bruker, 2008); data reduction: SAINT-Plus (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009) and Mercury (Macrae et al., 2008); software used to prepare material for publication: PLATON (Spek, 2009).

Figures

	Fig. 1. The molecular structure of the title compound, (Io), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 2. The molecular structure of polymorph (It), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 3. A superimposition of the structures showing the conformational differences between molecules A and B of (Io) (Mercury; Macrae et al., 2008). The overlay was carried out using a least-squares fit of the common amide plane; the A and B molecules of (Io) are shown in blue and green, respectively, and the two conformers of tetragonal polymorph (It) in medium grey and black. H atoms have been omitted for clarity.
	Fig. 4. The crystal packing of (Io), showing the columnar arrangement of the molecules along the a axis. All H atoms have been omitted for clarity.
	Fig. 5. The crystal packing of (It), projected down the b axis. All H atoms have been omitted for clarity.
	Fig. 6. The intermolecular hydrogen bonding in (Io) determining the packing of molecules in the crystal. H atoms not involved in the hydrogen bonds have been omitted for clarity. [Symmetry codes: (i) x+1, y, z; (ii) -x+1, y+1/2, -z+3/2; (iii) x-1, y, z].

(Io) Ethyl (2S)-2-[(3S,5aS,9aS,10aS)-3-methyl-1,4-dioxo-5a,6,7,8,9,9a,10,10a-octahydro-3H-pyrazino[1,2-a]indol-2-yl]pentanoate

Crystal data

C19H30N2O4	F(000) = 1520
Mr = 350.45	Dx = 1.186 Mg m^−3
Orthorhombic, P212121	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: P 2ac 2ab	Cell parameters from 9895 reflections
a = 9.2089 (10) Å	θ = 3.1–73.7°
b = 17.9875 (17) Å	µ = 0.67 mm^−1
c = 23.697 (2) Å	T = 100 K
V = 3925.3 (7) Å^3	Needle, colourless
Z = 8	0.50 × 0.15 × 0.10 mm

Data collection

Bruker APEXII CCD diffractometer	6791 independent reflections
Radiation source: 30W microsource with MonoCap capillary	5706 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.043
ω scan	θmax = 66.0°, θmin = 3.1°
Absorption correction: multi-scan SADABS (Sheldrick, 2003)	h = −10→9
Tmin = 0.886, Tmax = 0.935	k = −21→21
39028 measured reflections	l = −28→28

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.057	w = 1/[σ^2(Fo^2) + (0.04P)^2 + 4.25P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.145	(Δ/σ)max < 0.001
S = 1.12	Δρmax = 0.46 e Å^−3
6791 reflections	Δρmin = −0.37 e Å^−3
458 parameters	Extinction correction: SHELXL97 (Sheldrick, 2008), FC^*=KFC[1+0.001XFC^2Λ^3/SIN(2Θ)]^-1/4
0 restraints	Extinction coefficient: 0.00149 (10)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983), 2958 Friedel pairs
Secondary atom site location: difference Fourier map	Absolute structure parameter: 0.1 (3)

Special details

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement on F² for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The observed criterion of F² > σ(F²) is used only for calculating -R-factor-obs 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
O1A	0.7338 (3)	0.41481 (16)	0.87882 (11)	0.0527 (10)
O2A	0.1003 (3)	0.50744 (16)	0.76821 (13)	0.0607 (11)
O3A	0.2297 (3)	0.47699 (14)	0.84504 (11)	0.0463 (9)
O4A	0.2614 (3)	0.34392 (13)	0.77119 (10)	0.0395 (8)
N1A	0.5933 (3)	0.32183 (14)	0.84485 (11)	0.0334 (9)
N2A	0.4493 (3)	0.42472 (14)	0.78054 (12)	0.0328 (9)
C1A	0.4916 (4)	0.29456 (17)	0.80141 (13)	0.0325 (10)
C2A	0.4151 (4)	0.22878 (18)	0.82979 (13)	0.0353 (10)
C3A	0.5239 (4)	0.20366 (19)	0.87538 (15)	0.0377 (11)
C4A	0.4633 (5)	0.1542 (2)	0.92239 (16)	0.0463 (14)
C5A	0.3683 (5)	0.1957 (2)	0.96486 (15)	0.0448 (13)
C6A	0.4480 (5)	0.2628 (3)	0.98799 (16)	0.0563 (16)
C7A	0.4896 (5)	0.3151 (2)	0.94022 (15)	0.0469 (14)
C8A	0.5877 (4)	0.27718 (19)	0.89694 (14)	0.0393 (11)
C9A	0.6520 (4)	0.39003 (19)	0.84227 (15)	0.0380 (11)
C10A	0.6091 (4)	0.43329 (18)	0.78956 (15)	0.0366 (11)
C11A	0.3586 (4)	0.48495 (19)	0.75859 (15)	0.0406 (11)
C12A	0.3245 (5)	0.4775 (2)	0.69494 (17)	0.0567 (16)
C13A	0.4523 (5)	0.4716 (3)	0.65728 (19)	0.0637 (17)
C14A	0.4069 (5)	0.4600 (3)	0.59610 (16)	0.0540 (16)
C15A	0.3904 (4)	0.35630 (18)	0.78305 (13)	0.0343 (10)
C16A	0.6593 (5)	0.5132 (2)	0.79400 (19)	0.0516 (15)
C17A	0.2153 (5)	0.48902 (19)	0.79004 (17)	0.0440 (13)
C18A	0.0964 (6)	0.4800 (3)	0.8786 (2)	0.078 (2)
C19A	0.1357 (8)	0.4593 (5)	0.9376 (2)	0.127 (4)
O1B	1.1714 (3)	0.26860 (15)	0.56453 (10)	0.0436 (8)
O2B	0.6227 (3)	0.15899 (13)	0.69843 (11)	0.0432 (8)
O3B	0.7491 (3)	0.19440 (14)	0.62110 (9)	0.0413 (8)
O4B	0.7550 (3)	0.32544 (12)	0.69933 (9)	0.0343 (7)
N1B	1.0488 (3)	0.36023 (15)	0.61012 (11)	0.0339 (9)
N2B	0.9550 (3)	0.25450 (13)	0.68466 (11)	0.0277 (8)
C1B	0.9700 (4)	0.38430 (17)	0.66130 (13)	0.0318 (10)
C2B	0.8816 (5)	0.45143 (18)	0.64114 (15)	0.0398 (11)
C3B	0.9712 (4)	0.48045 (19)	0.59099 (16)	0.0404 (11)
C4B	0.8977 (5)	0.5355 (2)	0.55098 (18)	0.0520 (14)
C5B	0.7866 (5)	0.5011 (2)	0.51198 (17)	0.0533 (16)
C6B	0.8478 (5)	0.4337 (3)	0.48134 (17)	0.0567 (16)
C7B	0.9001 (4)	0.3758 (2)	0.52393 (14)	0.0438 (11)
C8B	1.0181 (4)	0.40849 (19)	0.56144 (14)	0.0382 (11)
C9B	1.1134 (4)	0.29335 (18)	0.60717 (14)	0.0328 (10)
C10B	1.1083 (4)	0.25243 (17)	0.66388 (14)	0.0298 (10)
C11B	0.8782 (4)	0.18962 (17)	0.70666 (13)	0.0309 (10)
C12B	0.8596 (4)	0.1923 (2)	0.77036 (13)	0.0368 (11)
C13B	1.0036 (4)	0.1904 (3)	0.80206 (15)	0.0482 (13)
C14B	0.9805 (5)	0.2035 (3)	0.86498 (16)	0.0653 (18)
C15B	0.8841 (4)	0.31925 (17)	0.68340 (12)	0.0292 (10)
C16B	1.1708 (4)	0.17499 (19)	0.65836 (17)	0.0421 (11)
C17B	0.7341 (4)	0.18089 (18)	0.67560 (14)	0.0358 (10)
C18B	0.6162 (4)	0.1927 (2)	0.58709 (16)	0.0507 (14)
C19B	0.5336 (5)	0.2633 (2)	0.59375 (19)	0.0557 (16)
H1A	0.54780	0.27630	0.76810	0.0390*
H2A	0.32190	0.24440	0.84690	0.0420*
H2B	0.39620	0.18840	0.80240	0.0420*
H3A	0.60360	0.17560	0.85620	0.0450*
H4A	0.54550	0.13100	0.94280	0.0550*
H4B	0.40540	0.11380	0.90510	0.0550*
H5A	0.34220	0.16190	0.99620	0.0540*
H5B	0.27750	0.21200	0.94620	0.0540*
H6A	0.53660	0.24630	1.00810	0.0680*
H6B	0.38510	0.28920	1.01530	0.0680*
H7A	0.40040	0.33290	0.92120	0.0560*
H7B	0.54050	0.35890	0.95600	0.0560*
H8A	0.68730	0.26940	0.91260	0.0470*
H10A	0.65990	0.41020	0.75660	0.0440*
H11A	0.41140	0.53290	0.76460	0.0490*
H12A	0.26670	0.52130	0.68320	0.0680*
H12B	0.26320	0.43290	0.68940	0.0680*
H13A	0.51100	0.51750	0.66020	0.0760*
H13B	0.51360	0.42930	0.66960	0.0760*
H14A	0.34630	0.50180	0.58380	0.0810*
H14B	0.35160	0.41360	0.59290	0.0810*
H14C	0.49360	0.45710	0.57220	0.0810*
H16A	0.64360	0.53840	0.75780	0.0770*
H16B	0.60390	0.53860	0.82360	0.0770*
H16C	0.76290	0.51440	0.80340	0.0770*
H18A	0.02360	0.44480	0.86330	0.0930*
H18B	0.05480	0.53070	0.87760	0.0930*
H19A	0.16400	0.40680	0.93880	0.1910*
H19B	0.21690	0.49010	0.95040	0.1910*
H19C	0.05180	0.46720	0.96230	0.1910*
H1B	1.04140	0.40070	0.69060	0.0380*
H2C	0.87340	0.48950	0.67110	0.0480*
H2D	0.78300	0.43640	0.62910	0.0480*
H3B	1.06030	0.50480	0.60640	0.0490*
H4C	0.97340	0.55990	0.52780	0.0620*
H4D	0.84960	0.57450	0.57370	0.0620*
H5C	0.70040	0.48590	0.53420	0.0640*
H5D	0.75510	0.53850	0.48390	0.0640*
H6C	0.77190	0.41160	0.45700	0.0680*
H6D	0.92980	0.44910	0.45700	0.0680*
H7C	0.93880	0.33190	0.50360	0.0530*
H7D	0.81750	0.35930	0.54750	0.0530*
H8B	1.10870	0.41710	0.53910	0.0460*
H10B	1.16980	0.28070	0.69130	0.0360*
H11B	0.93850	0.14490	0.69770	0.0370*
H12C	0.80690	0.23830	0.78060	0.0440*
H12D	0.79960	0.14950	0.78240	0.0440*
H13C	1.05060	0.14140	0.79630	0.0580*
H13D	1.06910	0.22910	0.78680	0.0580*
H14D	0.93810	0.25290	0.87080	0.0980*
H14E	0.91460	0.16560	0.88000	0.0980*
H14F	1.07400	0.20050	0.88460	0.0980*
H16D	1.17010	0.15060	0.69530	0.0630*
H16E	1.11190	0.14610	0.63180	0.0630*
H16F	1.27080	0.17810	0.64440	0.0630*
H18C	0.64170	0.18550	0.54690	0.0610*
H18D	0.55490	0.15030	0.59910	0.0610*
H19D	0.59440	0.30520	0.58190	0.0840*
H19E	0.44600	0.26150	0.57030	0.0840*
H19F	0.50590	0.26960	0.63340	0.0840*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1A	0.0523 (18)	0.0608 (18)	0.0451 (15)	−0.0187 (14)	−0.0020 (14)	−0.0108 (13)
O2A	0.059 (2)	0.0472 (16)	0.076 (2)	0.0077 (15)	−0.0148 (17)	0.0109 (15)
O3A	0.0462 (16)	0.0469 (15)	0.0458 (15)	0.0085 (13)	0.0123 (13)	0.0016 (12)
O4A	0.0427 (15)	0.0331 (12)	0.0428 (13)	−0.0025 (11)	−0.0072 (12)	−0.0039 (10)
N1A	0.0382 (17)	0.0303 (14)	0.0316 (14)	−0.0032 (13)	−0.0050 (13)	−0.0032 (12)
N2A	0.0359 (17)	0.0239 (13)	0.0386 (15)	−0.0023 (12)	0.0026 (13)	−0.0024 (11)
C1A	0.046 (2)	0.0235 (16)	0.0279 (16)	−0.0017 (14)	−0.0041 (15)	−0.0044 (13)
C2A	0.050 (2)	0.0269 (16)	0.0289 (17)	−0.0063 (16)	−0.0025 (16)	−0.0047 (13)
C3A	0.044 (2)	0.0314 (18)	0.0378 (18)	0.0066 (16)	0.0026 (17)	0.0004 (15)
C4A	0.058 (3)	0.0388 (19)	0.042 (2)	0.0036 (19)	0.0044 (19)	0.0071 (16)
C5A	0.057 (3)	0.045 (2)	0.0325 (18)	−0.0048 (19)	0.0004 (18)	−0.0005 (16)
C6A	0.069 (3)	0.068 (3)	0.032 (2)	−0.020 (2)	0.0030 (19)	−0.0098 (19)
C7A	0.057 (3)	0.046 (2)	0.0378 (19)	−0.015 (2)	0.0030 (18)	−0.0166 (17)
C8A	0.045 (2)	0.0404 (19)	0.0326 (18)	−0.0017 (17)	−0.0034 (16)	0.0000 (15)
C9A	0.042 (2)	0.0371 (19)	0.0349 (18)	−0.0040 (16)	0.0037 (17)	−0.0105 (16)
C10A	0.039 (2)	0.0287 (17)	0.0420 (19)	−0.0094 (15)	0.0023 (16)	−0.0081 (15)
C11A	0.053 (2)	0.0259 (17)	0.043 (2)	0.0091 (17)	0.0085 (18)	0.0012 (15)
C12A	0.070 (3)	0.054 (3)	0.046 (2)	0.016 (2)	0.010 (2)	0.009 (2)
C13A	0.062 (3)	0.076 (3)	0.053 (3)	0.004 (3)	0.007 (2)	0.010 (2)
C14A	0.050 (3)	0.071 (3)	0.041 (2)	−0.004 (2)	0.0072 (19)	0.003 (2)
C15A	0.047 (2)	0.0265 (16)	0.0295 (16)	−0.0034 (15)	−0.0013 (16)	−0.0049 (13)
C16A	0.059 (3)	0.0299 (19)	0.066 (3)	−0.0144 (18)	0.012 (2)	−0.0126 (18)
C17A	0.053 (3)	0.0261 (18)	0.053 (2)	0.0019 (17)	−0.0037 (19)	0.0026 (16)
C18A	0.061 (3)	0.083 (4)	0.089 (4)	0.027 (3)	0.043 (3)	0.030 (3)
C19A	0.108 (6)	0.195 (8)	0.079 (4)	0.062 (5)	0.053 (4)	0.050 (5)
O1B	0.0447 (16)	0.0525 (15)	0.0337 (13)	0.0121 (13)	0.0097 (12)	0.0026 (12)
O2B	0.0450 (16)	0.0354 (13)	0.0492 (14)	−0.0069 (12)	0.0032 (13)	0.0050 (11)
O3B	0.0421 (15)	0.0497 (15)	0.0321 (12)	−0.0026 (12)	−0.0066 (11)	−0.0071 (11)
O4B	0.0401 (14)	0.0319 (12)	0.0310 (11)	0.0022 (10)	0.0071 (11)	−0.0016 (9)
N1B	0.0413 (18)	0.0313 (15)	0.0290 (14)	0.0007 (13)	0.0085 (13)	0.0075 (11)
N2B	0.0324 (15)	0.0223 (13)	0.0285 (14)	−0.0042 (11)	0.0056 (12)	0.0001 (10)
C1B	0.043 (2)	0.0241 (15)	0.0283 (16)	−0.0019 (15)	0.0042 (15)	0.0023 (13)
C2B	0.050 (2)	0.0254 (17)	0.044 (2)	0.0035 (16)	0.0051 (18)	0.0043 (14)
C3B	0.042 (2)	0.0313 (18)	0.048 (2)	−0.0012 (16)	0.0024 (17)	0.0133 (16)
C4B	0.054 (3)	0.044 (2)	0.058 (2)	0.010 (2)	0.007 (2)	0.0239 (19)
C5B	0.052 (3)	0.061 (3)	0.047 (2)	0.018 (2)	0.0051 (19)	0.018 (2)
C6B	0.056 (3)	0.077 (3)	0.037 (2)	0.022 (2)	0.0001 (19)	0.009 (2)
C7B	0.048 (2)	0.054 (2)	0.0293 (17)	0.0089 (19)	0.0064 (17)	0.0008 (16)
C8B	0.041 (2)	0.0408 (19)	0.0327 (18)	0.0049 (17)	0.0069 (16)	0.0140 (15)
C9B	0.0346 (19)	0.0324 (17)	0.0315 (17)	0.0009 (15)	0.0018 (15)	0.0014 (14)
C10B	0.0265 (17)	0.0298 (16)	0.0330 (17)	0.0033 (14)	0.0072 (14)	0.0017 (13)
C11B	0.0344 (19)	0.0251 (15)	0.0331 (17)	−0.0041 (14)	0.0005 (15)	0.0035 (13)
C12B	0.041 (2)	0.0389 (19)	0.0304 (17)	−0.0031 (16)	0.0019 (15)	0.0045 (14)
C13B	0.045 (2)	0.068 (3)	0.0316 (18)	0.005 (2)	−0.0035 (17)	0.0093 (18)
C14B	0.053 (3)	0.109 (4)	0.034 (2)	0.005 (3)	−0.0064 (19)	0.007 (2)
C15B	0.040 (2)	0.0277 (16)	0.0199 (14)	0.0016 (15)	0.0057 (14)	−0.0029 (12)
C16B	0.046 (2)	0.0313 (18)	0.049 (2)	0.0109 (16)	0.0092 (18)	0.0037 (16)
C17B	0.048 (2)	0.0234 (16)	0.0360 (18)	−0.0059 (16)	−0.0021 (17)	−0.0018 (13)
C18B	0.042 (2)	0.069 (3)	0.041 (2)	−0.006 (2)	−0.0149 (18)	−0.0111 (19)
C19B	0.047 (3)	0.065 (3)	0.055 (2)	0.001 (2)	−0.013 (2)	0.002 (2)

Geometric parameters (Å, º)

O1A—C9A	1.231 (4)	C14A—H14A	0.9800
O2A—C17A	1.224 (5)	C14A—H14B	0.9800
O3A—C17A	1.328 (5)	C14A—H14C	0.9800
O3A—C18A	1.464 (6)	C16A—H16C	0.9800
O4A—C15A	1.241 (5)	C16A—H16A	0.9800
O1B—C9B	1.227 (4)	C16A—H16B	0.9800
O2B—C17B	1.225 (4)	C18A—H18B	0.9900
O3B—C17B	1.321 (4)	C18A—H18A	0.9900
O3B—C18B	1.466 (5)	C19A—H19B	0.9800
O4B—C15B	1.252 (5)	C19A—H19C	0.9800
N1A—C1A	1.476 (4)	C19A—H19A	0.9800
N1A—C8A	1.474 (4)	C1B—C2B	1.533 (5)
N1A—C9A	1.342 (4)	C1B—C15B	1.506 (5)
N2A—C11A	1.464 (4)	C2B—C3B	1.538 (5)
N2A—C15A	1.346 (4)	C3B—C4B	1.529 (5)
N2A—C10A	1.495 (5)	C3B—C8B	1.534 (5)
N1B—C1B	1.478 (4)	C4B—C5B	1.511 (6)
N1B—C8B	1.471 (4)	C5B—C6B	1.521 (6)
N1B—C9B	1.344 (4)	C6B—C7B	1.528 (6)
N2B—C10B	1.496 (5)	C7B—C8B	1.522 (5)
N2B—C11B	1.461 (4)	C9B—C10B	1.533 (5)
N2B—C15B	1.336 (4)	C10B—C16B	1.513 (5)
C1A—C2A	1.533 (5)	C11B—C12B	1.520 (4)
C1A—C15A	1.514 (5)	C11B—C17B	1.526 (5)
C2A—C3A	1.541 (5)	C12B—C13B	1.525 (5)
C3A—C4A	1.531 (5)	C13B—C14B	1.524 (5)
C3A—C8A	1.535 (5)	C18B—C19B	1.489 (5)
C4A—C5A	1.528 (6)	C1B—H1B	1.0000
C5A—C6A	1.515 (6)	C2B—H2C	0.9900
C6A—C7A	1.521 (6)	C2B—H2D	0.9900
C7A—C8A	1.528 (5)	C3B—H3B	1.0000
C9A—C10A	1.524 (5)	C4B—H4C	0.9900
C10A—C16A	1.514 (5)	C4B—H4D	0.9900
C11A—C17A	1.517 (6)	C5B—H5C	0.9900
C11A—C12A	1.547 (5)	C5B—H5D	0.9900
C12A—C13A	1.481 (6)	C6B—H6C	0.9900
C13A—C14A	1.523 (6)	C6B—H6D	0.9900
C18A—C19A	1.491 (7)	C7B—H7C	0.9900
C1A—H1A	1.0000	C7B—H7D	0.9900
C2A—H2B	0.9900	C8B—H8B	1.0000
C2A—H2A	0.9900	C10B—H10B	1.0000
C3A—H3A	1.0000	C11B—H11B	1.0000
C4A—H4B	0.9900	C12B—H12C	0.9900
C4A—H4A	0.9900	C12B—H12D	0.9900
C5A—H5B	0.9900	C13B—H13C	0.9900
C5A—H5A	0.9900	C13B—H13D	0.9900
C6A—H6A	0.9900	C14B—H14D	0.9800
C6A—H6B	0.9900	C14B—H14E	0.9800
C7A—H7B	0.9900	C14B—H14F	0.9800
C7A—H7A	0.9900	C16B—H16D	0.9800
C8A—H8A	1.0000	C16B—H16E	0.9800
C10A—H10A	1.0000	C16B—H16F	0.9800
C11A—H11A	1.0000	C18B—H18C	0.9900
C12A—H12A	0.9900	C18B—H18D	0.9900
C12A—H12B	0.9900	C19B—H19D	0.9800
C13A—H13B	0.9900	C19B—H19E	0.9800
C13A—H13A	0.9900	C19B—H19F	0.9800
C17A—O3A—C18A	116.3 (3)	H18A—C18A—H18B	109.00
C17B—O3B—C18B	116.5 (3)	C18A—C19A—H19A	109.00
C1A—N1A—C8A	112.4 (2)	C18A—C19A—H19B	110.00
C1A—N1A—C9A	121.9 (3)	C18A—C19A—H19C	109.00
C8A—N1A—C9A	123.4 (3)	H19A—C19A—H19B	109.00
C10A—N2A—C15A	119.0 (3)	H19A—C19A—H19C	109.00
C11A—N2A—C15A	117.6 (3)	H19B—C19A—H19C	110.00
C10A—N2A—C11A	122.4 (3)	N1B—C1B—C2B	103.6 (3)
C8B—N1B—C9B	124.9 (3)	N1B—C1B—C15B	108.4 (2)
C1B—N1B—C8B	112.1 (3)	C2B—C1B—C15B	116.2 (3)
C1B—N1B—C9B	121.5 (3)	C1B—C2B—C3B	102.9 (3)
C10B—N2B—C15B	118.4 (3)	C2B—C3B—C4B	117.5 (3)
C11B—N2B—C15B	117.9 (3)	C2B—C3B—C8B	102.6 (3)
C10B—N2B—C11B	123.7 (2)	C4B—C3B—C8B	112.8 (3)
C2A—C1A—C15A	114.2 (3)	C3B—C4B—C5B	114.4 (3)
N1A—C1A—C2A	104.0 (2)	C4B—C5B—C6B	111.6 (4)
N1A—C1A—C15A	110.3 (2)	C5B—C6B—C7B	110.2 (3)
C1A—C2A—C3A	103.6 (3)	C6B—C7B—C8B	110.3 (3)
C2A—C3A—C4A	116.3 (3)	N1B—C8B—C3B	101.2 (3)
C2A—C3A—C8A	103.3 (3)	N1B—C8B—C7B	111.5 (3)
C4A—C3A—C8A	113.5 (3)	C3B—C8B—C7B	113.1 (3)
C3A—C4A—C5A	113.8 (3)	O1B—C9B—N1B	124.1 (3)
C4A—C5A—C6A	110.5 (4)	O1B—C9B—C10B	124.1 (3)
C5A—C6A—C7A	110.2 (3)	N1B—C9B—C10B	111.8 (3)
C6A—C7A—C8A	111.9 (3)	N2B—C10B—C9B	107.8 (3)
N1A—C8A—C7A	109.9 (3)	N2B—C10B—C16B	114.2 (3)
C3A—C8A—C7A	112.5 (3)	C9B—C10B—C16B	110.8 (3)
N1A—C8A—C3A	101.8 (3)	N2B—C11B—C12B	112.6 (3)
N1A—C9A—C10A	113.6 (3)	N2B—C11B—C17B	109.3 (3)
O1A—C9A—N1A	123.0 (3)	C12B—C11B—C17B	112.6 (3)
O1A—C9A—C10A	123.4 (3)	C11B—C12B—C13B	113.0 (3)
C9A—C10A—C16A	110.4 (3)	C12B—C13B—C14B	110.9 (3)
N2A—C10A—C16A	114.1 (3)	O4B—C15B—N2B	122.3 (3)
N2A—C10A—C9A	108.7 (3)	O4B—C15B—C1B	122.3 (3)
N2A—C11A—C12A	113.5 (3)	N2B—C15B—C1B	115.4 (3)
N2A—C11A—C17A	111.0 (3)	O2B—C17B—O3B	125.3 (3)
C12A—C11A—C17A	107.9 (3)	O2B—C17B—C11B	123.3 (3)
C11A—C12A—C13A	115.6 (4)	O3B—C17B—C11B	111.2 (3)
C12A—C13A—C14A	111.4 (4)	O3B—C18B—C19B	110.5 (3)
O4A—C15A—N2A	122.7 (3)	N1B—C1B—H1B	109.00
O4A—C15A—C1A	121.5 (3)	C2B—C1B—H1B	109.00
N2A—C15A—C1A	115.8 (3)	C15B—C1B—H1B	109.00
O2A—C17A—C11A	123.9 (4)	C1B—C2B—H2C	111.00
O2A—C17A—O3A	123.0 (4)	C1B—C2B—H2D	111.00
O3A—C17A—C11A	112.8 (4)	C3B—C2B—H2C	111.00
O3A—C18A—C19A	107.3 (5)	C3B—C2B—H2D	111.00
C15A—C1A—H1A	109.00	H2C—C2B—H2D	109.00
N1A—C1A—H1A	109.00	C2B—C3B—H3B	108.00
C2A—C1A—H1A	109.00	C4B—C3B—H3B	108.00
C1A—C2A—H2A	111.00	C8B—C3B—H3B	108.00
C1A—C2A—H2B	111.00	C3B—C4B—H4C	109.00
C3A—C2A—H2A	111.00	C3B—C4B—H4D	109.00
C3A—C2A—H2B	111.00	C5B—C4B—H4C	109.00
H2A—C2A—H2B	109.00	C5B—C4B—H4D	109.00
C2A—C3A—H3A	108.00	H4C—C4B—H4D	108.00
C4A—C3A—H3A	108.00	C4B—C5B—H5C	109.00
C8A—C3A—H3A	108.00	C4B—C5B—H5D	109.00
C3A—C4A—H4A	109.00	C6B—C5B—H5C	109.00
C3A—C4A—H4B	109.00	C6B—C5B—H5D	109.00
H4A—C4A—H4B	108.00	H5C—C5B—H5D	108.00
C5A—C4A—H4B	109.00	C5B—C6B—H6C	110.00
C5A—C4A—H4A	109.00	C5B—C6B—H6D	110.00
C6A—C5A—H5B	110.00	C7B—C6B—H6C	109.00
C6A—C5A—H5A	110.00	C7B—C6B—H6D	110.00
C4A—C5A—H5B	110.00	H6C—C6B—H6D	108.00
C4A—C5A—H5A	109.00	C6B—C7B—H7C	110.00
H5A—C5A—H5B	108.00	C6B—C7B—H7D	110.00
C5A—C6A—H6A	110.00	C8B—C7B—H7C	110.00
C5A—C6A—H6B	110.00	C8B—C7B—H7D	110.00
C7A—C6A—H6A	110.00	H7C—C7B—H7D	108.00
C7A—C6A—H6B	110.00	N1B—C8B—H8B	110.00
H6A—C6A—H6B	108.00	C3B—C8B—H8B	110.00
C6A—C7A—H7A	109.00	C7B—C8B—H8B	110.00
C8A—C7A—H7B	109.00	N2B—C10B—H10B	108.00
C6A—C7A—H7B	109.00	C9B—C10B—H10B	108.00
C8A—C7A—H7A	109.00	C16B—C10B—H10B	108.00
H7A—C7A—H7B	108.00	N2B—C11B—H11B	107.00
C7A—C8A—H8A	111.00	C12B—C11B—H11B	107.00
N1A—C8A—H8A	111.00	C17B—C11B—H11B	107.00
C3A—C8A—H8A	111.00	C11B—C12B—H12C	109.00
N2A—C10A—H10A	108.00	C11B—C12B—H12D	109.00
C9A—C10A—H10A	108.00	C13B—C12B—H12C	109.00
C16A—C10A—H10A	108.00	C13B—C12B—H12D	109.00
N2A—C11A—H11A	108.00	H12C—C12B—H12D	108.00
C12A—C11A—H11A	108.00	C12B—C13B—H13C	109.00
C17A—C11A—H11A	108.00	C12B—C13B—H13D	110.00
C11A—C12A—H12A	108.00	C14B—C13B—H13C	109.00
C11A—C12A—H12B	108.00	C14B—C13B—H13D	109.00
C13A—C12A—H12B	108.00	H13C—C13B—H13D	108.00
H12A—C12A—H12B	108.00	C13B—C14B—H14D	109.00
C13A—C12A—H12A	108.00	C13B—C14B—H14E	110.00
H13A—C13A—H13B	108.00	C13B—C14B—H14F	109.00
C14A—C13A—H13B	109.00	H14D—C14B—H14E	109.00
C12A—C13A—H13A	109.00	H14D—C14B—H14F	109.00
C12A—C13A—H13B	109.00	H14E—C14B—H14F	109.00
C14A—C13A—H13A	109.00	C10B—C16B—H16D	109.00
C13A—C14A—H14A	110.00	C10B—C16B—H16E	109.00
C13A—C14A—H14B	109.00	C10B—C16B—H16F	110.00
C13A—C14A—H14C	109.00	H16D—C16B—H16E	109.00
H14A—C14A—H14B	110.00	H16D—C16B—H16F	109.00
H14A—C14A—H14C	109.00	H16E—C16B—H16F	109.00
H14B—C14A—H14C	109.00	O3B—C18B—H18C	110.00
C10A—C16A—H16A	109.00	O3B—C18B—H18D	110.00
C10A—C16A—H16B	109.00	C19B—C18B—H18C	110.00
H16A—C16A—H16C	109.00	C19B—C18B—H18D	110.00
C10A—C16A—H16C	110.00	H18C—C18B—H18D	108.00
H16A—C16A—H16B	109.00	C18B—C19B—H19D	109.00
H16B—C16A—H16C	109.00	C18B—C19B—H19E	109.00
C19A—C18A—H18B	110.00	C18B—C19B—H19F	109.00
O3A—C18A—H18A	110.00	H19D—C19B—H19E	109.00
O3A—C18A—H18B	110.00	H19D—C19B—H19F	110.00
C19A—C18A—H18A	110.00	H19E—C19B—H19F	109.00
C17A—O3A—C18A—C19A	175.7 (5)	N1A—C1A—C15A—N2A	36.3 (4)
C18A—O3A—C17A—O2A	5.6 (5)	N1A—C1A—C15A—O4A	−143.6 (3)
C18A—O3A—C17A—C11A	179.9 (3)	C15A—C1A—C2A—C3A	−144.4 (3)
C18B—O3B—C17B—O2B	8.9 (5)	C1A—C2A—C3A—C8A	37.6 (3)
C17B—O3B—C18B—C19B	79.2 (4)	C1A—C2A—C3A—C4A	162.6 (3)
C18B—O3B—C17B—C11B	−176.1 (3)	C8A—C3A—C4A—C5A	46.1 (5)
C1A—N1A—C9A—O1A	177.9 (3)	C2A—C3A—C8A—C7A	81.5 (3)
C8A—N1A—C1A—C2A	1.3 (3)	C4A—C3A—C8A—C7A	−45.3 (4)
C9A—N1A—C1A—C2A	−161.9 (3)	C4A—C3A—C8A—N1A	−162.8 (3)
C8A—N1A—C9A—O1A	16.6 (5)	C2A—C3A—C8A—N1A	−36.0 (3)
C1A—N1A—C9A—C10A	−2.8 (5)	C2A—C3A—C4A—C5A	−73.5 (4)
C9A—N1A—C8A—C7A	65.4 (4)	C3A—C4A—C5A—C6A	−52.8 (4)
C1A—N1A—C8A—C7A	−97.4 (3)	C4A—C5A—C6A—C7A	59.0 (5)
C9A—N1A—C8A—C3A	−175.2 (3)	C5A—C6A—C7A—C8A	−59.6 (5)
C8A—N1A—C1A—C15A	124.2 (3)	C6A—C7A—C8A—C3A	52.4 (4)
C8A—N1A—C9A—C10A	−164.1 (3)	C6A—C7A—C8A—N1A	164.9 (3)
C9A—N1A—C1A—C15A	−39.0 (4)	O1A—C9A—C10A—C16A	−9.6 (5)
C1A—N1A—C8A—C3A	22.0 (3)	N1A—C9A—C10A—C16A	171.0 (3)
C11A—N2A—C10A—C16A	20.2 (5)	N1A—C9A—C10A—N2A	45.2 (4)
C15A—N2A—C10A—C16A	−171.8 (3)	O1A—C9A—C10A—N2A	−135.5 (3)
C10A—N2A—C11A—C12A	100.0 (4)	N2A—C11A—C12A—C13A	−55.8 (4)
C11A—N2A—C15A—O4A	−4.9 (5)	N2A—C11A—C17A—O3A	39.4 (4)
C15A—N2A—C10A—C9A	−48.1 (4)	C12A—C11A—C17A—O2A	−21.4 (5)
C11A—N2A—C10A—C9A	143.9 (3)	C17A—C11A—C12A—C13A	−179.1 (3)
C10A—N2A—C15A—C1A	6.5 (4)	N2A—C11A—C17A—O2A	−146.3 (3)
C11A—N2A—C15A—C1A	175.1 (3)	C12A—C11A—C17A—O3A	164.3 (3)
C10A—N2A—C15A—O4A	−173.5 (3)	C11A—C12A—C13A—C14A	176.7 (4)
C15A—N2A—C11A—C17A	53.4 (4)	N1B—C1B—C15B—O4B	−135.4 (3)
C15A—N2A—C11A—C12A	−68.2 (4)	N1B—C1B—C2B—C3B	−26.1 (3)
C10A—N2A—C11A—C17A	−138.4 (3)	C15B—C1B—C2B—C3B	−144.9 (3)
C9B—N1B—C1B—C2B	−165.1 (3)	N1B—C1B—C15B—N2B	44.4 (4)
C8B—N1B—C9B—O1B	9.8 (6)	C2B—C1B—C15B—N2B	160.6 (3)
C9B—N1B—C1B—C15B	−41.1 (4)	C2B—C1B—C15B—O4B	−19.2 (4)
C1B—N1B—C9B—O1B	174.8 (3)	C1B—C2B—C3B—C4B	165.1 (3)
C8B—N1B—C1B—C2B	1.6 (4)	C1B—C2B—C3B—C8B	40.8 (3)
C1B—N1B—C8B—C7B	−96.9 (3)	C4B—C3B—C8B—N1B	−166.3 (3)
C8B—N1B—C1B—C15B	125.6 (3)	C2B—C3B—C8B—N1B	−38.9 (3)
C1B—N1B—C8B—C3B	23.6 (3)	C4B—C3B—C8B—C7B	−46.9 (4)
C9B—N1B—C8B—C7B	69.2 (4)	C8B—C3B—C4B—C5B	44.9 (5)
C8B—N1B—C9B—C10B	−171.3 (3)	C2B—C3B—C8B—C7B	80.5 (4)
C1B—N1B—C9B—C10B	−6.3 (4)	C2B—C3B—C4B—C5B	−74.2 (4)
C9B—N1B—C8B—C3B	−170.3 (3)	C3B—C4B—C5B—C6B	−50.7 (5)
C15B—N2B—C10B—C16B	−170.8 (3)	C4B—C5B—C6B—C7B	57.8 (5)
C11B—N2B—C15B—C1B	178.9 (3)	C5B—C6B—C7B—C8B	−59.9 (4)
C11B—N2B—C15B—O4B	−1.3 (4)	C6B—C7B—C8B—C3B	54.7 (4)
C11B—N2B—C10B—C16B	9.6 (4)	C6B—C7B—C8B—N1B	168.0 (3)
C10B—N2B—C15B—O4B	179.0 (3)	O1B—C9B—C10B—N2B	−131.3 (3)
C15B—N2B—C10B—C9B	−47.2 (4)	N1B—C9B—C10B—N2B	49.8 (4)
C10B—N2B—C11B—C12B	106.7 (3)	N1B—C9B—C10B—C16B	175.5 (3)
C11B—N2B—C10B—C9B	133.1 (3)	O1B—C9B—C10B—C16B	−5.6 (5)
C15B—N2B—C11B—C17B	53.1 (4)	N2B—C11B—C12B—C13B	−63.7 (4)
C10B—N2B—C11B—C17B	−127.3 (3)	C17B—C11B—C12B—C13B	172.2 (3)
C10B—N2B—C15B—C1B	−0.8 (4)	N2B—C11B—C17B—O2B	−144.0 (3)
C15B—N2B—C11B—C12B	−72.9 (4)	N2B—C11B—C17B—O3B	40.8 (4)
C2A—C1A—C15A—O4A	−26.9 (4)	C12B—C11B—C17B—O2B	−18.1 (4)
C2A—C1A—C15A—N2A	153.1 (3)	C12B—C11B—C17B—O3B	166.7 (3)
N1A—C1A—C2A—C3A	−24.1 (3)	C11B—C12B—C13B—C14B	172.5 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C10A—H10A···O4B	1.00	2.22	3.184 (4)	161
C10B—H10B···O4A^i	1.00	2.36	3.341 (4)	165
C11A—H11A···O2B^ii	1.00	2.45	3.297 (4)	142
C19B—H19E···O1B^iii	0.98	2.54	3.408 (5)	148

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

(It) Ethyl (2S)-2-[(3S,5aS,9aS,10aS)-3-methyl-1,4-dioxo-5a,6,7,8,9,9a,10,10a-octahydro-3H-pyrazino[1,2-a]indol-2-yl]pentanoate

Crystal data

C19H30N2O4	Dx = 1.210 Mg m^−3
Mr = 350.45	Cu Kα radiation, λ = 1.54178 Å
Tetragonal, P41212	Cell parameters from 9913 reflections
Hall symbol: P 4abw 2nw	θ = 3.9–71.7°
a = 9.2606 (8) Å	µ = 0.68 mm^−1
c = 44.847 (4) Å	T = 100 K
V = 3846.0 (7) Å^3	Plate, colourless
Z = 8	0.45 × 0.40 × 0.20 mm
F(000) = 1520

Data collection

Bruker APEXII CCD diffractometer	3359 independent reflections
Radiation source: 30W microsource with MonoCap capillary	3355 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.022
ω scan	θmax = 66.0°, θmin = 3.9°
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)	h = −10→10
Tmin = 0.772, Tmax = 0.872	k = −10→8
39411 measured reflections	l = −53→53

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.039	w = 1/[σ^2(Fo^2) + (0.055P)^2 + 1.8942P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.107	(Δ/σ)max < 0.001
S = 1.05	Δρmax = 0.44 e Å^−3
3359 reflections	Δρmin = −0.26 e Å^−3
250 parameters	Extinction correction: SHELXL, FC^*=KFC[1+0.001XFC^2Λ^3/SIN(2Θ)]^-1/4
13 restraints	Extinction coefficient: 0.00079 (13)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983), 1291 Friedel pairs
Secondary atom site location: difference Fourier map	Absolute structure parameter: 0.1 (2)

Special details

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement on F² for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The observed criterion of F² > σ(F²) is used only for calculating -R-factor-obs 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)
O1	0.62988 (16)	0.03979 (17)	0.04593 (3)	0.0413 (5)
O2	0.39233 (17)	0.63530 (17)	0.11258 (4)	0.0441 (5)
O3	0.45637 (19)	0.52133 (17)	0.07042 (3)	0.0467 (5)
O4	0.71201 (15)	0.50032 (14)	0.10981 (3)	0.0294 (4)
N1	0.79170 (17)	0.18912 (17)	0.06767 (3)	0.0258 (4)
N2	0.57318 (17)	0.30308 (17)	0.10164 (3)	0.0266 (5)
C1	0.82940 (19)	0.2842 (2)	0.09277 (4)	0.0245 (5)
C2	0.9579 (2)	0.3705 (2)	0.08089 (4)	0.0281 (5)
C3	1.0289 (2)	0.2638 (2)	0.05915 (4)	0.0271 (5)
C4	1.1428 (2)	0.3266 (2)	0.03803 (4)	0.0307 (6)
C5	1.0800 (2)	0.4071 (2)	0.01127 (4)	0.0357 (6)
C6	0.9664 (2)	0.3172 (3)	−0.00445 (4)	0.0369 (6)
C7	0.8426 (2)	0.2823 (2)	0.01698 (4)	0.0334 (6)
C8	0.8986 (2)	0.1945 (2)	0.04342 (4)	0.0271 (5)
C9	0.6646 (2)	0.1196 (2)	0.06639 (4)	0.0285 (6)
C10	0.5676 (2)	0.1465 (2)	0.09365 (4)	0.0266 (5)
C11	0.4486 (2)	0.3808 (2)	0.11428 (5)	0.0328 (6)
C12	0.4602 (3)	0.3994 (2)	0.14839 (5)	0.0397 (7)
C13	0.4814 (3)	0.2604 (3)	0.16523 (4)	0.0513 (8)
C14	0.5036 (4)	0.2894 (3)	0.19837 (4)	0.0649 (12)
C15	0.7002 (2)	0.3735 (2)	0.10207 (4)	0.0249 (5)
C16	0.4165 (2)	0.0917 (2)	0.08769 (5)	0.0342 (6)
C17	0.4315 (2)	0.5276 (2)	0.09973 (5)	0.0333 (6)
C18A	0.4387 (6)	0.6446 (6)	0.05262 (18)	0.054 (2)	0.521 (9)
C19A	0.5933 (6)	0.6999 (5)	0.05042 (14)	0.055 (2)	0.521 (9)
C19B	0.5623 (8)	0.6557 (7)	0.02783 (16)	0.067 (3)	0.479 (9)
C18B	0.4772 (12)	0.6563 (4)	0.05692 (18)	0.063 (3)	0.479 (9)
H2B	0.92630	0.45730	0.07070	0.0340*
H3	1.07580	0.18850	0.07110	0.0320*
H4A	1.20390	0.39230	0.04920	0.0370*
H4B	1.20330	0.24850	0.03080	0.0370*
H5A	1.03720	0.49700	0.01790	0.0430*
H5B	1.15690	0.43010	−0.00260	0.0430*
H2A	1.02350	0.39690	0.09680	0.0340*
H6B	0.92930	0.36990	−0.02150	0.0440*
H7A	0.79960	0.37130	0.02410	0.0400*
H7B	0.76880	0.22780	0.00660	0.0400*
H8	0.92290	0.09640	0.03700	0.0330*
H10	0.60720	0.09150	0.11040	0.0320*
H11	0.36150	0.32440	0.11000	0.0390*
H6A	1.00940	0.22820	−0.01160	0.0440*
H12B	0.37290	0.44570	0.15560	0.0480*
H13A	0.56480	0.20990	0.15730	0.0620*
H13B	0.39750	0.19910	0.16250	0.0620*
H14D	0.58890	0.34680	0.20110	0.0970*
H14E	0.51440	0.19930	0.20870	0.0970*
H14F	0.42150	0.34030	0.20610	0.0970*
H16A	0.36010	0.09840	0.10560	0.0510*
H16B	0.42080	−0.00720	0.08130	0.0510*
H16C	0.37250	0.14910	0.07240	0.0510*
H18A	0.37600	0.71480	0.06210	0.0660*	0.521 (9)
H18B	0.40020	0.62020	0.03320	0.0660*	0.521 (9)
H19A	0.62900	0.72120	0.07000	0.0810*	0.521 (9)
H19B	0.59530	0.78590	0.03850	0.0810*	0.521 (9)
H19C	0.65300	0.62740	0.04140	0.0810*	0.521 (9)
H12A	0.54050	0.46320	0.15270	0.0480*
H1	0.86110	0.22510	0.10970	0.0290*
H18C	0.52670	0.71860	0.07100	0.0750*	0.479 (9)
H18D	0.38320	0.69870	0.05310	0.0750*	0.479 (9)
H19D	0.65610	0.61460	0.03120	0.1000*	0.479 (9)
H19E	0.57280	0.75290	0.02070	0.1000*	0.479 (9)
H19F	0.51180	0.59920	0.01320	0.1000*	0.479 (9)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0326 (8)	0.0483 (9)	0.0431 (8)	−0.0083 (7)	−0.0003 (7)	−0.0183 (7)
O2	0.0393 (9)	0.0342 (8)	0.0588 (9)	0.0097 (7)	0.0025 (7)	−0.0052 (7)
O3	0.0557 (10)	0.0446 (9)	0.0398 (8)	0.0176 (8)	−0.0090 (7)	0.0027 (7)
O4	0.0281 (7)	0.0279 (7)	0.0321 (7)	−0.0006 (5)	−0.0012 (5)	−0.0048 (6)
N1	0.0233 (8)	0.0273 (8)	0.0268 (7)	0.0000 (7)	−0.0014 (6)	−0.0032 (6)
N2	0.0199 (8)	0.0273 (8)	0.0327 (8)	0.0016 (7)	−0.0005 (6)	−0.0011 (6)
C1	0.0207 (9)	0.0271 (9)	0.0257 (8)	−0.0003 (7)	−0.0026 (7)	−0.0015 (7)
C2	0.0248 (9)	0.0306 (10)	0.0288 (9)	−0.0030 (8)	0.0007 (7)	−0.0029 (8)
C3	0.0256 (9)	0.0265 (10)	0.0291 (9)	0.0045 (7)	−0.0019 (8)	−0.0001 (7)
C4	0.0260 (9)	0.0316 (11)	0.0346 (9)	−0.0010 (8)	0.0035 (8)	−0.0046 (8)
C5	0.0382 (11)	0.0332 (11)	0.0357 (10)	0.0037 (9)	0.0100 (8)	0.0020 (8)
C6	0.0306 (11)	0.0527 (13)	0.0273 (9)	0.0076 (9)	0.0035 (8)	0.0035 (9)
C7	0.0259 (10)	0.0454 (12)	0.0290 (9)	0.0046 (9)	−0.0002 (8)	−0.0022 (9)
C8	0.0234 (9)	0.0275 (10)	0.0303 (9)	0.0023 (7)	0.0017 (7)	−0.0048 (8)
C9	0.0245 (10)	0.0292 (10)	0.0319 (9)	0.0023 (8)	−0.0048 (7)	−0.0018 (8)
C10	0.0225 (9)	0.0239 (9)	0.0334 (9)	−0.0002 (7)	−0.0037 (7)	−0.0010 (8)
C11	0.0229 (10)	0.0304 (10)	0.0451 (11)	0.0051 (8)	0.0017 (8)	−0.0006 (9)
C12	0.0359 (11)	0.0354 (11)	0.0479 (12)	0.0083 (9)	0.0107 (9)	−0.0007 (9)
C13	0.0683 (17)	0.0351 (12)	0.0506 (13)	0.0031 (11)	0.0205 (12)	−0.0006 (10)
C14	0.117 (3)	0.0350 (13)	0.0428 (13)	0.0058 (14)	0.0272 (15)	0.0022 (10)
C15	0.0252 (9)	0.0281 (10)	0.0215 (8)	0.0016 (8)	−0.0046 (7)	0.0009 (7)
C16	0.0265 (10)	0.0339 (11)	0.0422 (11)	−0.0047 (8)	−0.0007 (8)	−0.0043 (9)
C17	0.0228 (10)	0.0332 (11)	0.0439 (11)	0.0059 (8)	−0.0067 (8)	−0.0041 (9)
C18A	0.056 (5)	0.061 (4)	0.046 (3)	0.029 (3)	−0.014 (3)	0.023 (3)
C19A	0.069 (4)	0.032 (3)	0.063 (4)	0.003 (2)	−0.004 (3)	0.015 (2)
C19B	0.078 (5)	0.055 (4)	0.067 (5)	0.021 (3)	0.010 (3)	0.018 (3)
C18B	0.047 (5)	0.072 (6)	0.070 (6)	0.031 (4)	0.006 (4)	0.026 (4)

Geometric parameters (Å, º)

O1—C9	1.221 (2)	C3—H3	0.9800
O2—C17	1.208 (3)	C4—H4A	0.9700
O3—C17	1.336 (3)	C4—H4B	0.9700
O3—C18A	1.403 (7)	C5—H5A	0.9700
O3—C18B	1.402 (5)	C5—H5B	0.9700
O4—C15	1.230 (2)	C6—H6A	0.9700
N1—C1	1.471 (2)	C6—H6B	0.9700
N1—C8	1.472 (2)	C7—H7A	0.9700
N1—C9	1.343 (2)	C7—H7B	0.9700
N2—C10	1.495 (2)	C8—H8	0.9800
N2—C11	1.473 (2)	C10—H10	0.9800
N2—C15	1.345 (2)	C11—H11	0.9800
C1—C2	1.529 (3)	C12—H12A	0.9700
C1—C15	1.513 (3)	C12—H12B	0.9700
C2—C3	1.536 (3)	C13—H13A	0.9700
C3—C4	1.532 (3)	C13—H13B	0.9700
C3—C8	1.538 (3)	C14—H14D	0.9600
C4—C5	1.528 (3)	C14—H14E	0.9600
C5—C6	1.516 (3)	C14—H14F	0.9600
C6—C7	1.531 (3)	C16—H16A	0.9600
C7—C8	1.528 (3)	C16—H16B	0.9600
C9—C10	1.537 (3)	C16—H16C	0.9600
C10—C16	1.512 (3)	C18A—H18A	0.9700
C11—C12	1.543 (3)	C18A—H18B	0.9700
C11—C17	1.516 (3)	C18B—H18C	0.9700
C12—C13	1.505 (3)	C18B—H18D	0.9700
C13—C14	1.524 (3)	C19A—H19C	0.9600
C18A—C19A	1.524 (8)	C19A—H19A	0.9600
C18B—C19B	1.524 (12)	C19A—H19B	0.9600
C1—H1	0.9800	C19B—H19D	0.9600
C2—H2A	0.9700	C19B—H19E	0.9600
C2—H2B	0.9700	C19B—H19F	0.9600
C17—O3—C18A	120.3 (3)	C5—C6—H6B	110.00
C17—O3—C18B	114.2 (3)	C7—C6—H6A	110.00
C1—N1—C8	112.68 (14)	C7—C6—H6B	110.00
C1—N1—C9	121.85 (15)	H6A—C6—H6B	108.00
C8—N1—C9	125.05 (15)	C6—C7—H7A	110.00
C10—N2—C11	122.63 (15)	C6—C7—H7B	110.00
C10—N2—C15	120.27 (15)	C8—C7—H7A	110.00
C11—N2—C15	116.26 (15)	C8—C7—H7B	110.00
N1—C1—C2	103.35 (14)	H7A—C7—H7B	108.00
N1—C1—C15	110.51 (14)	N1—C8—H8	110.00
C2—C1—C15	115.20 (15)	C3—C8—H8	110.00
C1—C2—C3	102.60 (15)	C7—C8—H8	110.00
C2—C3—C4	116.29 (15)	N2—C10—H10	108.00
C2—C3—C8	102.93 (15)	C9—C10—H10	108.00
C4—C3—C8	114.51 (15)	C16—C10—H10	108.00
C3—C4—C5	114.12 (15)	N2—C11—H11	108.00
C4—C5—C6	111.20 (16)	C12—C11—H11	108.00
C5—C6—C7	110.11 (15)	C17—C11—H11	108.00
C6—C7—C8	110.20 (15)	C11—C12—H12A	109.00
N1—C8—C3	101.71 (14)	C11—C12—H12B	109.00
N1—C8—C7	111.29 (15)	C13—C12—H12A	109.00
C3—C8—C7	113.58 (15)	C13—C12—H12B	109.00
O1—C9—N1	123.58 (17)	H12A—C12—H12B	108.00
O1—C9—C10	122.80 (17)	C12—C13—H13A	109.00
N1—C9—C10	113.61 (15)	C12—C13—H13B	109.00
N2—C10—C9	109.13 (14)	C14—C13—H13A	110.00
N2—C10—C16	113.58 (15)	C14—C13—H13B	110.00
C9—C10—C16	110.23 (15)	H13A—C13—H13B	108.00
N2—C11—C12	112.42 (17)	C13—C14—H14D	109.00
N2—C11—C17	110.75 (16)	C13—C14—H14E	109.00
C12—C11—C17	109.50 (16)	C13—C14—H14F	109.00
C11—C12—C13	114.27 (16)	H14D—C14—H14E	110.00
C12—C13—C14	110.9 (2)	H14D—C14—H14F	110.00
O4—C15—N2	123.02 (17)	H14E—C14—H14F	110.00
O4—C15—C1	121.98 (17)	C10—C16—H16A	110.00
N2—C15—C1	115.00 (16)	C10—C16—H16B	110.00
O2—C17—O3	123.87 (19)	C10—C16—H16C	109.00
O2—C17—C11	124.5 (2)	H16A—C16—H16B	109.00
O3—C17—C11	111.50 (17)	H16A—C16—H16C	109.00
O3—C18A—C19A	101.6 (4)	H16B—C16—H16C	109.00
O3—C18B—C19B	115.9 (5)	O3—C18A—H18A	111.00
N1—C1—H1	109.00	O3—C18A—H18B	111.00
C2—C1—H1	109.00	C19A—C18A—H18A	111.00
C15—C1—H1	109.00	C19A—C18A—H18B	111.00
C1—C2—H2A	111.00	H18A—C18A—H18B	109.00
C1—C2—H2B	111.00	O3—C18B—H18D	108.00
C3—C2—H2A	111.00	C19B—C18B—H18C	108.00
C3—C2—H2B	111.00	C19B—C18B—H18D	108.00
H2A—C2—H2B	109.00	H18C—C18B—H18D	107.00
C2—C3—H3	107.00	O3—C18B—H18C	108.00
C4—C3—H3	108.00	H19A—C19A—H19C	109.00
C8—C3—H3	108.00	H19B—C19A—H19C	110.00
C3—C4—H4A	109.00	C18A—C19A—H19A	110.00
C3—C4—H4B	109.00	C18A—C19A—H19B	109.00
C5—C4—H4A	109.00	C18A—C19A—H19C	109.00
C5—C4—H4B	109.00	H19A—C19A—H19B	109.00
H4A—C4—H4B	108.00	C18B—C19B—H19D	110.00
C4—C5—H5A	110.00	C18B—C19B—H19E	110.00
C4—C5—H5B	109.00	C18B—C19B—H19F	110.00
C6—C5—H5A	109.00	H19D—C19B—H19E	109.00
C6—C5—H5B	109.00	H19D—C19B—H19F	109.00
H5A—C5—H5B	108.00	H19E—C19B—H19F	109.00
C5—C6—H6A	110.00
C17—O3—C18A—C19A	97.5 (4)	C15—C1—C2—C3	−150.98 (15)
C18A—O3—C17—O2	0.6 (4)	N1—C1—C15—N2	39.3 (2)
C18A—O3—C17—C11	176.7 (3)	C2—C1—C15—N2	155.96 (15)
C8—N1—C1—C2	8.57 (19)	C2—C1—C15—O4	−25.0 (2)
C9—N1—C8—C7	68.1 (2)	C1—C2—C3—C4	167.06 (15)
C1—N1—C9—O1	−179.90 (17)	C1—C2—C3—C8	41.03 (17)
C8—N1—C9—O1	8.1 (3)	C4—C3—C8—N1	−162.27 (15)
C1—N1—C9—C10	−1.5 (2)	C2—C3—C8—N1	−35.11 (17)
C9—N1—C1—C2	−164.36 (16)	C4—C3—C8—C7	−42.6 (2)
C8—N1—C1—C15	132.35 (16)	C8—C3—C4—C5	41.2 (2)
C9—N1—C1—C15	−40.6 (2)	C2—C3—C8—C7	84.57 (17)
C9—N1—C8—C3	−170.58 (17)	C2—C3—C4—C5	−78.8 (2)
C1—N1—C8—C7	−104.53 (17)	C3—C4—C5—C6	−50.0 (2)
C1—N1—C8—C3	16.75 (19)	C4—C5—C6—C7	60.2 (2)
C8—N1—C9—C10	−173.52 (16)	C5—C6—C7—C8	−61.3 (2)
C11—N2—C10—C16	23.4 (2)	C6—C7—C8—C3	52.3 (2)
C10—N2—C11—C12	100.56 (19)	C6—C7—C8—N1	166.37 (16)
C15—N2—C10—C16	−167.49 (16)	O1—C9—C10—N2	−138.95 (18)
C11—N2—C10—C9	146.83 (16)	N1—C9—C10—N2	42.6 (2)
C15—N2—C10—C9	−44.1 (2)	N1—C9—C10—C16	168.01 (16)
C11—N2—C15—O4	−6.8 (3)	O1—C9—C10—C16	−13.6 (3)
C10—N2—C15—C1	2.5 (2)	N2—C11—C12—C13	−55.0 (3)
C11—N2—C15—C1	172.25 (15)	C17—C11—C12—C13	−178.5 (2)
C10—N2—C15—O4	−176.51 (16)	N2—C11—C17—O2	−143.77 (19)
C15—N2—C11—C17	53.9 (2)	N2—C11—C17—O3	40.2 (2)
C15—N2—C11—C12	−68.9 (2)	C12—C11—C17—O2	−19.2 (3)
C10—N2—C11—C17	−136.59 (16)	C12—C11—C17—O3	164.71 (18)
N1—C1—C15—O4	−141.67 (17)	C11—C12—C13—C14	175.5 (2)
N1—C1—C2—C3	−30.35 (17)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C1—H1···O4^i	0.98	2.58	3.403 (2)	141
C10—H10···O4^i	0.98	2.30	3.218 (2)	155
C19A—H19B···O1^ii	0.96	2.40	3.172 (5)	138

Symmetry codes: (i) −x+3/2, y−1/2, −z+1/4; (ii) x, y+1, z.