Di- and tripeptide segments of zervamicin II-2: Z-Thr(OBn)-Aib-N(Me)Ph and Z-Val-Aib-Hyp(OBn)-OMe

The title compounds, O-benzyl-N-(benzyl­oxy­carbonyl)­threonyl-2,N-dimethyl­alanin­anilide, C₃₀H₃₅N₃O₅, and methyl (4R)-4-benzyl­oxy-N-(benzyl­oxy­carbonyl)­valyl-2-(methyl­alanyl)prolinate, C₃₀H₃₉N₃O₇, were obtained from the `azirine coupling' of the corresponding protected amino acids with 2,2,N-trimethyl-2H-azirin-3-amine and methyl (4R)-4-(benzyl­oxy)-N-(2,2-dimethyl-2H-azirin-2-yl)prolinate, respectively. The Aib unit in each mol­ecule has the greatest turn- or helix-inducing effect on the mol­ecular conformation. Inter­molecular N-H...O inter­actions link the mol­ecules of the tripeptide into sheets and those of the dipeptide into extended chains.

S1. Comment

In recent years, 2H-azirin-3-amines have been shown to be useful synthons for 2,2-disubstituted glycines, such as 2-aminoisobutyric acid (Aib, 2-methylalanin), in peptide synthesis (Wipf & Heimgartner, 1990; Heimgartner, 1991). Furthermore, methyl (2H-azirin-3-yl)prolinates have proved to be convenient dipeptide synthons (Luykx et al., 1996; Breitenmoser et al., 2001). This novel method, the `azirine/oxazolone method', for the introduction of sterically hindered α,α-disubstituted α-amino acids into peptides, is especially suitable for the preparation of peptaibols, which are amphiphilic membrane-active peptide antibiotics (Benedetti et al., 1982) containing up to 50% of the non-protein amino acid Aib. These metabolites of some fungi have antibacterial properties because of their ability to self-associate in lipid membranes to form ion channels (Latorre & Alvarez, 1981; Chugh et al., 2002; Duclohier et al., 2003). A condition for this ability is a helical conformation of the molecule, which is induced and stabilized by the presence of Aib (Karle et al., 1989; Toniolo et al., 1993; Di Blasio et al., 1993). The helical structure of some peptaibols has been established by X-ray crystallography; for example, for zervamicin IIB (Karle et al., 1991, 1994; Karle, 1996) and antiamoebin (Karle et al., 1998). The data for more than 300 peptaibols or segments of peptaibols, including crystal structures, are now available from the online peptaibol database maintained by Chugh and Wallace in London (Whitmore & Wallace, 2004; https://www.cryst.bbk.ac.uk/peptaibol).

Recently, the `azirine/oxazolone method' has been used for the synthesis of peptaibols or segments thereof, for example, alamethicin F30 (Wipf & Heimgartner, 1990), trichotoxin A-50(G) (Altherr & Heimgartner, 1991; Altherr, 1994), antiamoebin (Altherr & Heimgartner, 1993), tichovirin I 1B (Luykx et al., 1996, 2003), hypomurocin A1 (Pradeille et al., 2005) and zervamicin II-2 (Pradeille & Heimgartner, 2003). In the last-mentioned paper, the 6–16 segment was prepared by the coupling of the segments 6–7, 8–10 and 11–16, which had been obtained by the reaction of the corresponding amino acids with 2H-azirin-3-amines. Treatment of the threonine derivative, (I), with the Aib synthon, (II), yielded the title dipeptide, (III), and the analogous reaction of the N-protected valine, (IV), with the Aib–Hyp dipeptide synthon, (V), led to the title tripeptide, (VI) (see scheme). The X-ray crystallographic analyses of compounds (III) and (VI) were undertaken in order to elucidate their molecular structures and conformations and to investigate their hydrogen-bonding interactions, and the results are presented here.

The molecular structures of compounds (III) and (VI) are shown in Figs. 1 and 2, respectively. The bond lengths and angles fall within normal ranges. The torsion angles along the peptide backbones of (III) and (VI) are listed in Table 1, together with those of the related compound, Z-Val-Aib-Pro-OH (Pradeille et al., 2005). Although there are small variations in the magnitudes of the torsion angles, their signs are consistent and on the whole the values are quite similar. The two consecutive small torsion angles on either side of atom C14 in the Aib group confirm the turn- or helix-inducing property of Aib in a peptide chain. The turns occur despite the absence of any significant intramolecular hydrogen bonds. The proline ring in compound (VI) has a slightly distorted half-chair conformation twisted on C26—C27, with a value for the ϕ₂ puckering parameter (Cremer & Pople, 1975) of 94.9 (4)° for the atom sequence N16—C17—C27—C26—C25. Atoms C26 and C27 lie 0.367 (2) and −0.206 (2) Å, respectively, from the plane defined by atoms N16, C17 and C25.

In the structure of compound (III), the amide H atom of Aib forms an intermolecular hydrogen bond with the carbonyl O atom of Aib of a neighbouring molecule (Table 2). This thereby links the molecules into extended chains which run parallel to the [010] direction (Fig. 3) and can be described by a graph-set motif (Bernstein et al., 1995) of C(5). The amide H atom of Thr is not involved in any intermolecular interactions. Although this H atom is 2.50 (2) Å from the O atom of the benzoyl substituent on Thr, this intramolecular interaction is probably insignificant, given the very sharp N—H···O angle of 104 (2)°.

In the structure of compound (VI), the amide H atom of Val forms an intermolecular hydrogen bond with the C-terminal carbonyl O atom of a neighbouring molecule (Table 3). This interaction links the molecules into extended chains which run parallel to the [010] direction and can be described by a graph-set motif of C(11). As with compound (III), the amide H atom of Aib forms an intermolecular hydrogen bond with the carbonyl O atom of Aib of a different neighbouring molecule. This interaction links the molecules into extended chains which run parallel to the [100] direction and can be described by a graph-set motif of C(5). The combination of the hydrogen-bonding interactions links the molecules into two-dimensional networks which lie parallel to the (001) plane (Fig. 4). Within these networks, the two different hydrogen-bonding interactions unite to form a ring which can be described by the binary graph-set motif of R₄⁴(28).

S2. Experimental

The syntheses of compounds (III) and (VI) have already been described by Pradeille & Heimgartner (2003). Suitable crystals were obtained by slow evaporation of solutions of the compounds in deuterochloroform and methanol–hexane–ethyl acetate (Ratio?), respectively, at room temperature [m.p. 407–408 K for (III) and 403–407 K for (VI)].

S3. Refinement

The amide H atoms were located in difference Fourier maps and their positions were refined freely along with individual isotropic displacement parameters. The methyl H atoms were constrained to an ideal geometry (C—H = 0.98 Å) with U_iso(H) = 1.5U_eq(C), but were allowed to rotate freely about the C—C bonds. All other H atoms were placed in geometrically idealized positions and constrained to ride on their parent C atom at distances of 0.95, 0.99 or 1.00 Å for phenyl, methylene or methine groups, respectively, and with U_iso(H) = 1.2U_eq(C). As there are no significant anomalous dispersion effects with these compounds, Friedel opposites were merged prior to the final cycles of refinement. The enantiomers used in the refinement models were chosen so as to correspond with the chirality of the stereogenic centres known from the syntheses of the compounds. For (III), two low-angle reflections were omitted from the final cycles of refinement because their observed intensities were much lower than the calculated values, as a result of being partially obscured by the beam stop.

Computing details

For both compounds, data collection: COLLECT (Nonius, 2000); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997); data reduction: DENZO-SMN and SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2003).

Figures

	Fig. 1. A view of the molecule of (III), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are represented by circles of arbitrary size.
	Fig. 2. A view of the molecule of (VI), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are represented by circles of arbitrary size.
	Fig. 3. The crystal packing in (III), viewed along the a axis and showing the hydrogen-bonded chains. Most of the H atoms have been omitted for clarity. Hydrogen bonds are represented by thin lines.
	Fig. 4. The crystal packing in (VI), showing a hydrogen-bonded sheet with the R^44(28) motif. Most of the H atoms have been omitted for clarity. Hydrogen bonds are represented by thin lines.

(III) O-benzyl-N-(benzyloxycarbonyl)threonyl-2,N-dimethylalaninanilide

Crystal data

C30H35N3O5	Dx = 1.251 Mg m^−3
Mr = 517.62	Melting point: 407 K
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 2773 reflections
a = 10.4178 (2) Å	θ = 2.0–25.0°
b = 10.6996 (2) Å	µ = 0.09 mm^−1
c = 24.6636 (5) Å	T = 160 K
V = 2749.16 (9) Å^3	Tablet, colourless
Z = 4	0.22 × 0.10 × 0.05 mm
F(000) = 1104

Data collection

Nonius KappaCCD area-detector diffractometer	2388 reflections with I > 2σ(I)
Radiation source: Nonius FR590 sealed tube generator	Rint = 0.058
Horizontally mounted graphite crystal monochromator	θmax = 25.0°, θmin = 2.5°
Detector resolution: 9 pixels mm^-1	h = 0→12
ϕ and ω scans with κ offsets	k = 0→12
30620 measured reflections	l = 0→29
2759 independent reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: geom & difmap
R[F^2 > 2σ(F^2)] = 0.037	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.090	w = 1/[σ^2(Fo^2) + (0.0473P)^2 + 0.3586P] where P = (Fo^2 + 2Fc^2)/3
S = 1.07	(Δ/σ)max = 0.001
2757 reflections	Δρmax = 0.17 e Å^−3
356 parameters	Δρmin = −0.15 e Å^−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0090 (13)

Special details

Experimental. Solvent used: deuterochloroform Cooling Device: Oxford Cryosystems Cryostream 700 Crystal mount: glued on a glass fibre Mosaicity (°.): 0.730 (1) Frames collected: 866 Seconds exposure per frame: 200 Degrees rotation per frame: 0.5 Crystal-Detector distance (mm): 36.9

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
O8	0.67678 (16)	0.82688 (15)	0.88495 (6)	0.0359 (4)
O9	0.82540 (16)	0.67544 (15)	0.87255 (7)	0.0365 (4)
O12	0.87384 (16)	0.80522 (14)	0.75789 (7)	0.0364 (4)
O15	1.16391 (17)	0.86069 (15)	0.74267 (6)	0.0384 (5)
O24	0.59475 (19)	0.71173 (17)	0.69995 (7)	0.0437 (5)
N10	0.6689 (2)	0.7081 (2)	0.81003 (8)	0.0313 (5)
H10	0.622 (2)	0.766 (2)	0.7980 (10)	0.030 (7)*
N13	0.9445 (2)	0.6198 (2)	0.72662 (8)	0.0299 (5)
H13	0.938 (2)	0.543 (2)	0.7262 (9)	0.021 (6)*
N16	1.1470 (2)	0.70186 (18)	0.80182 (8)	0.0309 (5)
C1	0.6590 (2)	0.9446 (2)	0.96727 (10)	0.0338 (6)
C2	0.5847 (3)	0.9017 (3)	1.00999 (10)	0.0404 (7)
H2	0.5889	0.8162	1.0202	0.048*
C3	0.5043 (3)	0.9826 (3)	1.03795 (11)	0.0488 (8)
H3	0.4528	0.9519	1.0668	0.059*
C4	0.4988 (3)	1.1064 (3)	1.02409 (11)	0.0505 (8)
H4	0.4433	1.1614	1.0432	0.061*
C5	0.5737 (3)	1.1507 (3)	0.98240 (11)	0.0537 (8)
H5	0.5707	1.2368	0.9731	0.064*
C6	0.6537 (3)	1.0705 (3)	0.95382 (11)	0.0446 (7)
H6	0.7050	1.1019	0.9250	0.053*
C7	0.7421 (3)	0.8568 (3)	0.93584 (10)	0.0388 (6)
H71	0.8262	0.8962	0.9283	0.047*
H72	0.7571	0.7795	0.9570	0.047*
C9	0.7325 (2)	0.7327 (2)	0.85660 (9)	0.0303 (6)
C11	0.7332 (2)	0.6287 (2)	0.77056 (9)	0.0295 (6)
H11	0.7573	0.5486	0.7889	0.035*
C12	0.8565 (2)	0.6927 (2)	0.75132 (9)	0.0292 (6)
C14	1.0656 (2)	0.6746 (2)	0.70680 (9)	0.0300 (6)
C15	1.1285 (2)	0.7531 (2)	0.75198 (9)	0.0314 (6)
C17	1.1876 (2)	0.7846 (2)	0.84446 (10)	0.0327 (6)
C18	1.3131 (3)	0.7864 (3)	0.86181 (12)	0.0521 (8)
H18	1.3755	0.7352	0.8446	0.062*
C19	1.3480 (3)	0.8631 (3)	0.90438 (13)	0.0631 (9)
H19	1.4345	0.8638	0.9167	0.076*
C20	1.2583 (3)	0.9385 (3)	0.92911 (11)	0.0532 (8)
H20	1.2833	0.9924	0.9578	0.064*
C21	1.1327 (3)	0.9357 (3)	0.91219 (11)	0.0443 (7)
H21	1.0704	0.9868	0.9295	0.053*
C22	1.0971 (2)	0.8585 (2)	0.86985 (10)	0.0362 (6)
H22	1.0102	0.8562	0.8582	0.043*
C23	0.6429 (3)	0.5978 (2)	0.72318 (10)	0.0361 (6)
H23	0.6926	0.5517	0.6948	0.043*
C25	0.6469 (3)	0.7445 (4)	0.64997 (13)	0.0678 (10)
H251	0.6529	0.6693	0.6268	0.081*
H252	0.7348	0.7774	0.6554	0.081*
C26	0.5668 (3)	0.8414 (2)	0.62200 (10)	0.0384 (6)
C27	0.4374 (3)	0.8555 (2)	0.63249 (10)	0.0383 (6)
H27	0.3974	0.8048	0.6592	0.046*
C28	0.3661 (3)	0.9420 (2)	0.60466 (10)	0.0420 (7)
H28	0.2773	0.9514	0.6125	0.050*
C29	0.4219 (3)	1.0151 (3)	0.56554 (11)	0.0498 (8)
H29	0.3715	1.0737	0.5459	0.060*
C30	0.5511 (3)	1.0035 (3)	0.55473 (12)	0.0513 (8)
H30	0.5901	1.0548	0.5280	0.062*
C31	0.6238 (3)	0.9169 (3)	0.58284 (11)	0.0467 (7)
H31	0.7129	0.9089	0.5754	0.056*
C32	0.5288 (3)	0.5190 (3)	0.73979 (12)	0.0468 (7)
H321	0.4749	0.5026	0.7080	0.070*
H322	0.4785	0.5639	0.7672	0.070*
H323	0.5590	0.4396	0.7549	0.070*
C33	1.0368 (3)	0.7583 (2)	0.65799 (10)	0.0378 (6)
H331	0.9812	0.8275	0.6693	0.057*
H332	0.9934	0.7093	0.6299	0.057*
H333	1.1174	0.7919	0.6435	0.057*
C34	1.1582 (3)	0.5727 (2)	0.68789 (10)	0.0370 (6)
H341	1.1242	0.5328	0.6551	0.055*
H342	1.1679	0.5100	0.7165	0.055*
H343	1.2420	0.6100	0.6799	0.055*
C35	1.1131 (3)	0.5756 (2)	0.82034 (10)	0.0385 (7)
H351	1.1141	0.5181	0.7894	0.058*
H352	1.0272	0.5769	0.8365	0.058*
H353	1.1755	0.5477	0.8475	0.058*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O8	0.0367 (10)	0.0384 (10)	0.0326 (9)	0.0074 (9)	−0.0044 (8)	−0.0084 (8)
O9	0.0323 (10)	0.0370 (9)	0.0402 (10)	0.0054 (9)	−0.0042 (8)	−0.0009 (8)
O12	0.0427 (11)	0.0208 (9)	0.0456 (10)	0.0001 (8)	0.0038 (9)	−0.0020 (7)
O15	0.0498 (11)	0.0246 (9)	0.0409 (10)	−0.0088 (9)	0.0009 (9)	0.0035 (8)
O24	0.0616 (12)	0.0380 (10)	0.0315 (9)	0.0139 (10)	−0.0008 (9)	0.0039 (8)
N10	0.0331 (12)	0.0297 (12)	0.0310 (12)	0.0086 (11)	−0.0024 (10)	−0.0016 (9)
N13	0.0354 (12)	0.0191 (11)	0.0350 (11)	−0.0014 (10)	0.0039 (10)	−0.0004 (9)
N16	0.0390 (12)	0.0237 (10)	0.0301 (11)	−0.0013 (10)	−0.0014 (9)	0.0004 (9)
C1	0.0347 (14)	0.0395 (14)	0.0272 (12)	−0.0009 (13)	−0.0026 (11)	−0.0031 (11)
C2	0.0433 (16)	0.0439 (15)	0.0339 (13)	−0.0085 (14)	−0.0045 (13)	0.0034 (12)
C3	0.0428 (17)	0.076 (2)	0.0281 (14)	−0.0096 (16)	0.0033 (13)	−0.0048 (15)
C4	0.0516 (18)	0.066 (2)	0.0343 (15)	0.0142 (16)	−0.0021 (14)	−0.0115 (15)
C5	0.080 (2)	0.0415 (16)	0.0392 (16)	0.0096 (17)	−0.0059 (16)	−0.0043 (13)
C6	0.0583 (18)	0.0428 (16)	0.0326 (14)	−0.0012 (15)	0.0112 (14)	0.0018 (13)
C7	0.0351 (15)	0.0439 (16)	0.0374 (14)	0.0025 (13)	−0.0077 (12)	−0.0087 (12)
C9	0.0306 (14)	0.0281 (13)	0.0321 (13)	−0.0010 (12)	0.0052 (12)	−0.0014 (11)
C11	0.0332 (14)	0.0244 (12)	0.0308 (13)	0.0036 (11)	0.0006 (11)	−0.0017 (11)
C12	0.0352 (14)	0.0243 (13)	0.0281 (13)	0.0006 (12)	−0.0023 (11)	0.0011 (10)
C14	0.0341 (14)	0.0244 (13)	0.0314 (13)	−0.0029 (12)	0.0046 (11)	0.0007 (10)
C15	0.0334 (14)	0.0254 (14)	0.0354 (14)	0.0005 (12)	0.0029 (11)	−0.0003 (11)
C17	0.0335 (15)	0.0308 (13)	0.0337 (13)	−0.0026 (12)	−0.0044 (12)	0.0034 (11)
C18	0.0388 (17)	0.069 (2)	0.0483 (17)	0.0058 (16)	−0.0035 (14)	−0.0110 (16)
C19	0.0415 (17)	0.092 (3)	0.0564 (19)	−0.0057 (19)	−0.0148 (16)	−0.0133 (19)
C20	0.061 (2)	0.057 (2)	0.0418 (17)	−0.0159 (17)	−0.0096 (15)	−0.0061 (15)
C21	0.0511 (18)	0.0394 (15)	0.0424 (15)	−0.0023 (14)	0.0008 (14)	−0.0052 (13)
C22	0.0333 (14)	0.0324 (13)	0.0428 (15)	−0.0008 (12)	−0.0053 (12)	−0.0029 (12)
C23	0.0419 (15)	0.0304 (13)	0.0360 (14)	0.0045 (12)	−0.0028 (12)	−0.0021 (12)
C25	0.0518 (19)	0.094 (3)	0.0580 (19)	0.025 (2)	0.0115 (16)	0.036 (2)
C26	0.0392 (15)	0.0426 (15)	0.0333 (13)	0.0043 (13)	−0.0035 (12)	0.0020 (12)
C27	0.0420 (15)	0.0343 (14)	0.0386 (14)	−0.0001 (13)	0.0021 (13)	0.0022 (12)
C28	0.0399 (16)	0.0422 (15)	0.0439 (16)	0.0054 (14)	−0.0018 (13)	−0.0021 (13)
C29	0.065 (2)	0.0427 (17)	0.0420 (16)	0.0134 (16)	0.0009 (15)	0.0060 (14)
C30	0.0605 (19)	0.0497 (18)	0.0436 (16)	−0.0010 (16)	0.0071 (15)	0.0127 (14)
C31	0.0395 (16)	0.0602 (19)	0.0404 (15)	−0.0013 (15)	0.0040 (13)	0.0012 (15)
C32	0.0403 (16)	0.0459 (17)	0.0542 (18)	−0.0031 (14)	−0.0063 (14)	−0.0011 (15)
C33	0.0471 (16)	0.0315 (14)	0.0348 (14)	−0.0014 (13)	0.0040 (12)	0.0014 (12)
C34	0.0408 (15)	0.0290 (13)	0.0410 (14)	−0.0020 (12)	0.0111 (13)	−0.0024 (12)
C35	0.0482 (16)	0.0287 (13)	0.0387 (14)	0.0009 (13)	0.0000 (13)	0.0072 (12)

Geometric parameters (Å, º)

O8—C9	1.357 (3)	C18—C19	1.381 (4)
O8—C7	1.463 (3)	C18—H18	0.9500
O9—C9	1.211 (3)	C19—C20	1.377 (4)
O12—C12	1.228 (3)	C19—H19	0.9500
O15—C15	1.230 (3)	C20—C21	1.374 (4)
O24—C25	1.392 (3)	C20—H20	0.9500
O24—C23	1.437 (3)	C21—C22	1.382 (4)
N10—C9	1.352 (3)	C21—H21	0.9500
N10—C11	1.456 (3)	C22—H22	0.9500
N10—H10	0.84 (3)	C23—C32	1.514 (4)
N13—C12	1.349 (3)	C23—H23	1.0000
N13—C14	1.475 (3)	C25—C26	1.499 (4)
N13—H13	0.82 (2)	C25—H251	0.9900
N16—C15	1.360 (3)	C25—H252	0.9900
N16—C17	1.438 (3)	C26—C27	1.381 (4)
N16—C35	1.469 (3)	C26—C31	1.392 (4)
C1—C2	1.385 (4)	C27—C28	1.371 (4)
C1—C6	1.389 (4)	C27—H27	0.9500
C1—C7	1.495 (4)	C28—C29	1.371 (4)
C2—C3	1.388 (4)	C28—H28	0.9500
C2—H2	0.9500	C29—C30	1.377 (5)
C3—C4	1.369 (4)	C29—H29	0.9500
C3—H3	0.9500	C30—C31	1.383 (4)
C4—C5	1.376 (4)	C30—H30	0.9500
C4—H4	0.9500	C31—H31	0.9500
C5—C6	1.388 (4)	C32—H321	0.9800
C5—H5	0.9500	C32—H322	0.9800
C6—H6	0.9500	C32—H323	0.9800
C7—H71	0.9900	C33—H331	0.9800
C7—H72	0.9900	C33—H332	0.9800
C11—C12	1.531 (3)	C33—H333	0.9800
C11—C23	1.536 (3)	C34—H341	0.9800
C11—H11	1.0000	C34—H342	0.9800
C14—C34	1.529 (3)	C34—H343	0.9800
C14—C33	1.530 (3)	C35—H351	0.9800
C14—C15	1.541 (3)	C35—H352	0.9800
C17—C18	1.376 (4)	C35—H353	0.9800
C17—C22	1.381 (3)
C9—O8—C7	113.93 (19)	C18—C19—H19	119.8
C25—O24—C23	115.5 (2)	C21—C20—C19	120.0 (3)
C9—N10—C11	117.1 (2)	C21—C20—H20	120.0
C9—N10—H10	116.2 (17)	C19—C20—H20	120.0
C11—N10—H10	117.4 (17)	C20—C21—C22	119.9 (3)
C12—N13—C14	120.1 (2)	C20—C21—H21	120.1
C12—N13—H13	121.9 (17)	C22—C21—H21	120.1
C14—N13—H13	117.4 (17)	C17—C22—C21	120.1 (2)
C15—N16—C17	117.05 (19)	C17—C22—H22	119.9
C15—N16—C35	128.2 (2)	C21—C22—H22	119.9
C17—N16—C35	114.15 (19)	O24—C23—C32	107.8 (2)
C2—C1—C6	118.8 (3)	O24—C23—C11	109.57 (19)
C2—C1—C7	120.6 (2)	C32—C23—C11	113.3 (2)
C6—C1—C7	120.6 (2)	O24—C23—H23	108.7
C1—C2—C3	120.5 (3)	C32—C23—H23	108.7
C1—C2—H2	119.7	C11—C23—H23	108.7
C3—C2—H2	119.7	O24—C25—C26	111.4 (2)
C4—C3—C2	120.3 (3)	O24—C25—H251	109.4
C4—C3—H3	119.8	C26—C25—H251	109.4
C2—C3—H3	119.8	O24—C25—H252	109.4
C3—C4—C5	119.8 (3)	C26—C25—H252	109.4
C3—C4—H4	120.1	H251—C25—H252	108.0
C5—C4—H4	120.1	C27—C26—C31	118.9 (2)
C4—C5—C6	120.5 (3)	C27—C26—C25	122.2 (2)
C4—C5—H5	119.8	C31—C26—C25	118.9 (2)
C6—C5—H5	119.8	C28—C27—C26	120.6 (2)
C5—C6—C1	120.1 (3)	C28—C27—H27	119.7
C5—C6—H6	119.9	C26—C27—H27	119.7
C1—C6—H6	119.9	C29—C28—C27	120.5 (3)
O8—C7—C1	108.24 (19)	C29—C28—H28	119.8
O8—C7—H71	110.1	C27—C28—H28	119.8
C1—C7—H71	110.1	C28—C29—C30	120.0 (3)
O8—C7—H72	110.1	C28—C29—H29	120.0
C1—C7—H72	110.1	C30—C29—H29	120.0
H71—C7—H72	108.4	C29—C30—C31	119.9 (3)
O9—C9—N10	124.7 (2)	C29—C30—H30	120.1
O9—C9—O8	123.4 (2)	C31—C30—H30	120.1
N10—C9—O8	111.9 (2)	C30—C31—C26	120.2 (3)
N10—C11—C12	109.43 (19)	C30—C31—H31	119.9
N10—C11—C23	110.6 (2)	C26—C31—H31	119.9
C12—C11—C23	111.97 (19)	C23—C32—H321	109.5
N10—C11—H11	108.2	C23—C32—H322	109.5
C12—C11—H11	108.2	H321—C32—H322	109.5
C23—C11—H11	108.2	C23—C32—H323	109.5
O12—C12—N13	121.8 (2)	H321—C32—H323	109.5
O12—C12—C11	121.4 (2)	H322—C32—H323	109.5
N13—C12—C11	116.8 (2)	C14—C33—H331	109.5
N13—C14—C34	110.93 (19)	C14—C33—H332	109.5
N13—C14—C33	109.0 (2)	H331—C33—H332	109.5
C34—C14—C33	107.53 (19)	C14—C33—H333	109.5
N13—C14—C15	109.92 (19)	H331—C33—H333	109.5
C34—C14—C15	109.9 (2)	H332—C33—H333	109.5
C33—C14—C15	109.47 (19)	C14—C34—H341	109.5
O15—C15—N16	120.2 (2)	C14—C34—H342	109.5
O15—C15—C14	120.1 (2)	H341—C34—H342	109.5
N16—C15—C14	119.6 (2)	C14—C34—H343	109.5
C18—C17—C22	120.0 (2)	H341—C34—H343	109.5
C18—C17—N16	121.0 (2)	H342—C34—H343	109.5
C22—C17—N16	118.9 (2)	N16—C35—H351	109.5
C17—C18—C19	119.7 (3)	N16—C35—H352	109.5
C17—C18—H18	120.2	H351—C35—H352	109.5
C19—C18—H18	120.2	N16—C35—H353	109.5
C20—C19—C18	120.4 (3)	H351—C35—H353	109.5
C20—C19—H19	119.8	H352—C35—H353	109.5
C6—C1—C2—C3	1.5 (4)	N13—C14—C15—N16	51.6 (3)
C7—C1—C2—C3	−177.8 (2)	C34—C14—C15—N16	−70.7 (3)
C1—C2—C3—C4	−0.9 (4)	C33—C14—C15—N16	171.4 (2)
C2—C3—C4—C5	−0.3 (4)	C15—N16—C17—C18	−103.3 (3)
C3—C4—C5—C6	0.8 (4)	C35—N16—C17—C18	85.1 (3)
C4—C5—C6—C1	−0.2 (4)	C15—N16—C17—C22	79.8 (3)
C2—C1—C6—C5	−1.0 (4)	C35—N16—C17—C22	−91.7 (3)
C7—C1—C6—C5	178.3 (2)	C22—C17—C18—C19	−0.5 (4)
C9—O8—C7—C1	−170.0 (2)	N16—C17—C18—C19	−177.3 (3)
C2—C1—C7—O8	101.3 (3)	C17—C18—C19—C20	−0.7 (5)
C6—C1—C7—O8	−78.0 (3)	C18—C19—C20—C21	1.4 (5)
C11—N10—C9—O9	−15.3 (3)	C19—C20—C21—C22	−0.9 (4)
C11—N10—C9—O8	167.11 (19)	C18—C17—C22—C21	0.9 (4)
C7—O8—C9—O9	2.2 (3)	N16—C17—C22—C21	177.8 (2)
C7—O8—C9—N10	179.8 (2)	C20—C21—C22—C17	−0.3 (4)
C9—N10—C11—C12	−62.6 (3)	C25—O24—C23—C32	−130.2 (3)
C9—N10—C11—C23	173.6 (2)	C25—O24—C23—C11	106.1 (3)
C14—N13—C12—O12	0.2 (3)	N10—C11—C23—O24	54.9 (3)
C14—N13—C12—C11	179.82 (19)	C12—C11—C23—O24	−67.5 (3)
N10—C11—C12—O12	−17.9 (3)	N10—C11—C23—C32	−65.5 (3)
C23—C11—C12—O12	105.1 (3)	C12—C11—C23—C32	172.2 (2)
N10—C11—C12—N13	162.4 (2)	C23—O24—C25—C26	163.9 (2)
C23—C11—C12—N13	−74.5 (3)	O24—C25—C26—C27	−25.1 (4)
C12—N13—C14—C34	171.7 (2)	O24—C25—C26—C31	157.1 (3)
C12—N13—C14—C33	−70.0 (3)	C31—C26—C27—C28	0.2 (4)
C12—N13—C14—C15	50.0 (3)	C25—C26—C27—C28	−177.6 (3)
C17—N16—C15—O15	10.6 (4)	C26—C27—C28—C29	0.7 (4)
C35—N16—C15—O15	−179.2 (2)	C27—C28—C29—C30	−1.3 (4)
C17—N16—C15—C14	−170.7 (2)	C28—C29—C30—C31	0.9 (5)
C35—N16—C15—C14	−0.5 (4)	C29—C30—C31—C26	0.0 (4)
N13—C14—C15—O15	−129.7 (2)	C27—C26—C31—C30	−0.6 (4)
C34—C14—C15—O15	107.9 (3)	C25—C26—C31—C30	177.3 (3)
C33—C14—C15—O15	−10.0 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N10—H10···O24	0.84 (3)	2.50 (2)	2.823 (3)	104 (2)
N13—H13···O15^i	0.82 (2)	2.35 (3)	3.088 (3)	149 (2)

Symmetry code: (i) −x+2, y−1/2, −z+3/2.

(VI) methyl (4R)-N-(benzyloxycarbonyl)valyl-2-methylalanyl-4-(benzyloxy)prolinate

Crystal data

C30H39N3O7	Z = 1
Mr = 553.65	F(000) = 296
Triclinic, P1	Dx = 1.247 Mg m^−3
Hall symbol: P 1	Melting point: 405 K
a = 6.2705 (1) Å	Mo Kα radiation, λ = 0.71073 Å
b = 9.7577 (2) Å	Cell parameters from 3287 reflections
c = 13.2491 (3) Å	θ = 2.0–27.5°
α = 106.6479 (13)°	µ = 0.09 mm^−1
β = 94.2733 (10)°	T = 160 K
γ = 105.7257 (12)°	Prism, colourless
V = 737.36 (3) Å^3	0.33 × 0.25 × 0.15 mm

Data collection

Nonius KappaCCD area-detector diffractometer	3096 reflections with I > 2σ(I)
Radiation source: Nonius FR590 sealed tube generator	Rint = 0.041
Horizontally mounted graphite crystal monochromator	θmax = 27.5°, θmin = 2.4°
Detector resolution: 9 pixels mm^-1	h = 0→8
ϕ and ω scans with κ offsets	k = −12→12
17488 measured reflections	l = −17→16
3359 independent reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: geom & difmap
R[F^2 > 2σ(F^2)] = 0.036	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.085	w = 1/[σ^2(Fo^2) + (0.0367P)^2 + 0.1302P] where P = (Fo^2 + 2Fc^2)/3
S = 1.07	(Δ/σ)max = 0.001
3359 reflections	Δρmax = 0.15 e Å^−3
375 parameters	Δρmin = −0.16 e Å^−3
3 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: 0.090 (9)

Special details

Experimental. Solvent used: MeOH / hexane / ethyl acetate Cooling Device: Oxford Cryosystems Cryostream 700 Crystal mount: glued on a glass fibre Mosaicity (°.): 0.520 (1) Frames collected: 665 Seconds exposure per frame: 15 Degrees rotation per frame: 1.0 Crystal-Detector distance (mm): 30.0

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
O8	0.6029 (3)	0.01347 (18)	0.72453 (13)	0.0367 (4)
O9	0.8323 (3)	0.20356 (18)	0.68077 (14)	0.0404 (4)
O12	0.3181 (2)	0.08475 (17)	0.45076 (13)	0.0316 (4)
O15	0.1107 (2)	0.35873 (17)	0.40511 (11)	0.0264 (3)
O18	0.3253 (3)	0.69548 (18)	0.55051 (14)	0.0404 (4)
O19	0.0282 (3)	0.68588 (18)	0.63548 (15)	0.0381 (4)
O26	0.5756 (2)	0.50285 (18)	0.83369 (11)	0.0298 (3)
N10	0.6265 (3)	−0.0152 (2)	0.55360 (15)	0.0290 (4)
H10	0.514 (5)	−0.100 (3)	0.543 (2)	0.036 (7)*
N13	0.6146 (3)	0.25728 (19)	0.42662 (14)	0.0226 (4)
H13	0.759 (4)	0.281 (3)	0.4188 (19)	0.021 (6)*
N16	0.3376 (3)	0.42052 (19)	0.56014 (13)	0.0217 (4)
C1	0.5127 (5)	0.0380 (3)	0.89971 (19)	0.0411 (6)
C2	0.5358 (5)	−0.0829 (3)	0.9290 (2)	0.0505 (7)
H2	0.6520	−0.1245	0.9072	0.061*
C3	0.3924 (7)	−0.1437 (3)	0.9895 (3)	0.0630 (9)
H3	0.4105	−0.2266	1.0092	0.076*
C4	0.2235 (6)	−0.0855 (4)	1.0214 (2)	0.0646 (10)
H4	0.1245	−0.1282	1.0629	0.078*
C5	0.1979 (6)	0.0340 (4)	0.9935 (3)	0.0664 (9)
H5	0.0816	0.0750	1.0160	0.080*
C6	0.3415 (6)	0.0959 (4)	0.9324 (2)	0.0533 (7)
H6	0.3221	0.1786	0.9128	0.064*
C7	0.6666 (6)	0.1081 (4)	0.8353 (2)	0.0603 (9)
H71	0.6556	0.2095	0.8418	0.072*
H72	0.8239	0.1183	0.8617	0.072*
C9	0.6987 (4)	0.0785 (2)	0.65437 (18)	0.0299 (5)
C11	0.6791 (4)	0.0402 (2)	0.46491 (17)	0.0257 (4)
H11	0.8360	0.1104	0.4844	0.031*
C12	0.5192 (3)	0.1280 (2)	0.44646 (16)	0.0240 (4)
C14	0.4796 (3)	0.3381 (2)	0.38722 (16)	0.0232 (4)
C15	0.2934 (3)	0.3663 (2)	0.45236 (16)	0.0207 (4)
C17	0.1785 (3)	0.4866 (2)	0.61538 (16)	0.0217 (4)
H17	0.0225	0.4152	0.5918	0.026*
C18	0.1897 (4)	0.6336 (2)	0.59441 (17)	0.0260 (4)
C19	0.0239 (5)	0.8304 (3)	0.6265 (3)	0.0516 (7)
H191	0.1553	0.9098	0.6726	0.077*
H192	−0.1134	0.8504	0.6486	0.077*
H193	0.0268	0.8283	0.5522	0.077*
C20	0.6665 (4)	−0.0905 (2)	0.36341 (18)	0.0323 (5)
H20	0.7594	−0.1499	0.3840	0.039*
C21	0.4316 (4)	−0.1981 (3)	0.3176 (2)	0.0399 (6)
H211	0.3366	−0.1449	0.2935	0.060*
H212	0.3679	−0.2373	0.3727	0.060*
H213	0.4387	−0.2816	0.2570	0.060*
C22	0.7722 (5)	−0.0307 (3)	0.2782 (2)	0.0447 (6)
H221	0.7835	−0.1147	0.2192	0.067*
H222	0.9226	0.0398	0.3095	0.067*
H223	0.6784	0.0211	0.2514	0.067*
C23	0.3782 (4)	0.2522 (3)	0.27015 (17)	0.0311 (5)
H231	0.4991	0.2445	0.2281	0.047*
H232	0.2874	0.3057	0.2434	0.047*
H233	0.2831	0.1512	0.2638	0.047*
C24	0.6377 (4)	0.4953 (2)	0.39816 (18)	0.0286 (5)
H241	0.6957	0.5512	0.4739	0.043*
H242	0.5544	0.5497	0.3676	0.043*
H243	0.7633	0.4846	0.3600	0.043*
C25	0.5262 (3)	0.4245 (3)	0.63516 (16)	0.0257 (4)
H251	0.6716	0.4614	0.6122	0.031*
H252	0.5103	0.3238	0.6417	0.031*
C26	0.5077 (3)	0.5345 (2)	0.74051 (16)	0.0247 (4)
H26	0.5913	0.6399	0.7457	0.030*
C27	0.2584 (3)	0.5135 (2)	0.73279 (16)	0.0258 (4)
H271	0.2298	0.6043	0.7786	0.031*
H272	0.1815	0.4262	0.7546	0.031*
C28	0.8116 (3)	0.5319 (3)	0.85671 (17)	0.0290 (5)
H281	0.8904	0.6358	0.8591	0.035*
H282	0.8605	0.4617	0.8001	0.035*
C29	0.8692 (4)	0.5121 (2)	0.96309 (16)	0.0272 (4)
C30	1.0503 (4)	0.4624 (3)	0.98270 (18)	0.0322 (5)
H30	1.1388	0.4412	0.9285	0.039*
C31	1.1047 (4)	0.4430 (3)	1.07985 (19)	0.0350 (5)
H31	1.2296	0.4088	1.0917	0.042*
C32	0.9785 (4)	0.4730 (3)	1.1591 (2)	0.0418 (6)
H32	1.0143	0.4589	1.2256	0.050*
C33	0.7987 (5)	0.5242 (4)	1.1409 (2)	0.0523 (8)
H33	0.7120	0.5466	1.1957	0.063*
C34	0.7433 (5)	0.5430 (3)	1.0434 (2)	0.0422 (6)
H34	0.6185	0.5773	1.0317	0.051*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O8	0.0439 (9)	0.0333 (8)	0.0280 (8)	0.0040 (7)	0.0031 (7)	0.0106 (7)
O9	0.0416 (10)	0.0329 (9)	0.0364 (9)	−0.0008 (7)	0.0034 (7)	0.0079 (7)
O12	0.0249 (8)	0.0275 (8)	0.0454 (9)	0.0075 (6)	0.0085 (6)	0.0159 (7)
O15	0.0210 (7)	0.0333 (8)	0.0254 (7)	0.0099 (6)	0.0014 (6)	0.0091 (6)
O18	0.0521 (11)	0.0252 (8)	0.0461 (10)	0.0097 (7)	0.0187 (8)	0.0142 (7)
O19	0.0315 (9)	0.0324 (9)	0.0552 (11)	0.0189 (7)	0.0059 (7)	0.0128 (8)
O26	0.0217 (7)	0.0474 (9)	0.0229 (7)	0.0108 (6)	0.0042 (6)	0.0149 (7)
N10	0.0349 (10)	0.0232 (9)	0.0296 (9)	0.0077 (8)	0.0017 (8)	0.0114 (7)
N13	0.0194 (9)	0.0255 (8)	0.0264 (9)	0.0084 (7)	0.0062 (7)	0.0114 (7)
N16	0.0184 (8)	0.0269 (8)	0.0226 (8)	0.0100 (7)	0.0046 (6)	0.0092 (7)
C1	0.0483 (15)	0.0376 (13)	0.0257 (11)	0.0012 (11)	0.0020 (10)	0.0048 (10)
C2	0.0606 (18)	0.0385 (14)	0.0438 (15)	0.0110 (12)	0.0040 (13)	0.0052 (11)
C3	0.089 (3)	0.0398 (16)	0.0464 (17)	−0.0012 (16)	−0.0015 (17)	0.0165 (13)
C4	0.071 (2)	0.060 (2)	0.0362 (15)	−0.0131 (17)	0.0114 (14)	0.0056 (14)
C5	0.0515 (19)	0.077 (2)	0.0516 (18)	0.0088 (17)	0.0104 (14)	0.0006 (17)
C6	0.0629 (19)	0.0470 (16)	0.0471 (16)	0.0161 (14)	0.0007 (14)	0.0134 (13)
C7	0.0666 (19)	0.0590 (18)	0.0292 (13)	−0.0134 (15)	0.0024 (12)	0.0068 (12)
C9	0.0314 (11)	0.0289 (11)	0.0327 (12)	0.0127 (9)	0.0044 (9)	0.0116 (9)
C11	0.0277 (10)	0.0229 (10)	0.0280 (11)	0.0089 (8)	0.0032 (8)	0.0095 (8)
C12	0.0238 (10)	0.0229 (10)	0.0253 (10)	0.0068 (8)	0.0051 (8)	0.0079 (8)
C14	0.0237 (10)	0.0281 (10)	0.0224 (9)	0.0114 (8)	0.0051 (8)	0.0114 (8)
C15	0.0199 (9)	0.0198 (9)	0.0244 (10)	0.0064 (7)	0.0037 (7)	0.0098 (7)
C17	0.0181 (9)	0.0247 (10)	0.0237 (10)	0.0086 (8)	0.0053 (7)	0.0075 (8)
C18	0.0263 (10)	0.0235 (10)	0.0265 (10)	0.0087 (8)	0.0019 (8)	0.0053 (8)
C19	0.0493 (16)	0.0324 (13)	0.076 (2)	0.0245 (12)	0.0016 (14)	0.0130 (13)
C20	0.0377 (12)	0.0267 (11)	0.0340 (12)	0.0147 (9)	0.0044 (10)	0.0077 (9)
C21	0.0470 (15)	0.0299 (12)	0.0382 (13)	0.0091 (10)	0.0053 (11)	0.0067 (10)
C22	0.0527 (16)	0.0390 (14)	0.0377 (14)	0.0113 (12)	0.0170 (12)	0.0053 (11)
C23	0.0315 (12)	0.0426 (13)	0.0226 (10)	0.0169 (10)	0.0041 (8)	0.0103 (9)
C24	0.0283 (11)	0.0311 (11)	0.0338 (11)	0.0115 (9)	0.0111 (9)	0.0179 (9)
C25	0.0220 (10)	0.0364 (11)	0.0219 (10)	0.0125 (8)	0.0037 (8)	0.0105 (8)
C26	0.0214 (10)	0.0327 (11)	0.0213 (9)	0.0082 (8)	0.0036 (7)	0.0103 (8)
C27	0.0215 (10)	0.0341 (11)	0.0236 (10)	0.0105 (8)	0.0065 (8)	0.0096 (8)
C28	0.0223 (10)	0.0421 (12)	0.0237 (10)	0.0102 (9)	0.0042 (8)	0.0114 (9)
C29	0.0247 (10)	0.0323 (11)	0.0230 (10)	0.0061 (8)	0.0015 (8)	0.0096 (8)
C30	0.0291 (11)	0.0447 (13)	0.0261 (11)	0.0148 (10)	0.0069 (9)	0.0123 (9)
C31	0.0302 (12)	0.0463 (14)	0.0333 (12)	0.0154 (10)	0.0040 (9)	0.0166 (10)
C32	0.0443 (15)	0.0616 (17)	0.0292 (12)	0.0224 (13)	0.0082 (11)	0.0227 (12)
C33	0.0558 (17)	0.091 (2)	0.0341 (14)	0.0455 (17)	0.0209 (12)	0.0308 (14)
C34	0.0436 (14)	0.0664 (17)	0.0324 (12)	0.0326 (13)	0.0148 (11)	0.0226 (12)

Geometric parameters (Å, º)

O8—C9	1.357 (3)	C17—H17	1.0000
O8—C7	1.450 (3)	C19—H191	0.9800
O9—C9	1.213 (3)	C19—H192	0.9800
O12—C12	1.227 (3)	C19—H193	0.9800
O15—C15	1.237 (2)	C20—C21	1.518 (3)
O18—C18	1.193 (3)	C20—C22	1.527 (3)
O19—C18	1.336 (3)	C20—H20	1.0000
O19—C19	1.456 (3)	C21—H211	0.9800
O26—C26	1.418 (2)	C21—H212	0.9800
O26—C28	1.421 (3)	C21—H213	0.9800
N10—C9	1.345 (3)	C22—H221	0.9800
N10—C11	1.451 (3)	C22—H222	0.9800
N10—H10	0.90 (3)	C22—H223	0.9800
N13—C12	1.350 (3)	C23—H231	0.9800
N13—C14	1.464 (3)	C23—H232	0.9800
N13—H13	0.89 (2)	C23—H233	0.9800
N16—C15	1.351 (2)	C24—H241	0.9800
N16—C17	1.461 (2)	C24—H242	0.9800
N16—C25	1.471 (3)	C24—H243	0.9800
C1—C2	1.383 (4)	C25—C26	1.532 (3)
C1—C6	1.385 (4)	C25—H251	0.9900
C1—C7	1.493 (4)	C25—H252	0.9900
C2—C3	1.376 (5)	C26—C27	1.512 (3)
C2—H2	0.9500	C26—H26	1.0000
C3—C4	1.370 (5)	C27—H271	0.9900
C3—H3	0.9500	C27—H272	0.9900
C4—C5	1.365 (6)	C28—C29	1.508 (3)
C4—H4	0.9500	C28—H281	0.9900
C5—C6	1.387 (5)	C28—H282	0.9900
C5—H5	0.9500	C29—C34	1.384 (3)
C6—H6	0.9500	C29—C30	1.385 (3)
C7—H71	0.9900	C30—C31	1.385 (3)
C7—H72	0.9900	C30—H30	0.9500
C11—C12	1.533 (3)	C31—C32	1.374 (3)
C11—C20	1.545 (3)	C31—H31	0.9500
C11—H11	1.0000	C32—C33	1.383 (4)
C14—C23	1.527 (3)	C32—H32	0.9500
C14—C15	1.540 (3)	C33—C34	1.389 (4)
C14—C24	1.543 (3)	C33—H33	0.9500
C17—C18	1.522 (3)	C34—H34	0.9500
C17—C27	1.523 (3)
C9—O8—C7	114.49 (19)	C21—C20—C22	110.6 (2)
C18—O19—C19	116.3 (2)	C21—C20—C11	114.25 (19)
C26—O26—C28	113.10 (15)	C22—C20—C11	110.76 (18)
C9—N10—C11	119.64 (18)	C21—C20—H20	107.0
C9—N10—H10	117.2 (17)	C22—C20—H20	107.0
C11—N10—H10	120.5 (17)	C11—C20—H20	107.0
C12—N13—C14	121.82 (17)	C20—C21—H211	109.5
C12—N13—H13	119.4 (15)	C20—C21—H212	109.5
C14—N13—H13	116.5 (15)	H211—C21—H212	109.5
C15—N16—C17	117.81 (15)	C20—C21—H213	109.5
C15—N16—C25	130.18 (16)	H211—C21—H213	109.5
C17—N16—C25	112.01 (15)	H212—C21—H213	109.5
C2—C1—C6	118.4 (3)	C20—C22—H221	109.5
C2—C1—C7	122.2 (3)	C20—C22—H222	109.5
C6—C1—C7	119.4 (3)	H221—C22—H222	109.5
C3—C2—C1	120.7 (3)	C20—C22—H223	109.5
C3—C2—H2	119.7	H221—C22—H223	109.5
C1—C2—H2	119.7	H222—C22—H223	109.5
C4—C3—C2	120.4 (3)	C14—C23—H231	109.5
C4—C3—H3	119.8	C14—C23—H232	109.5
C2—C3—H3	119.8	H231—C23—H232	109.5
C5—C4—C3	119.8 (3)	C14—C23—H233	109.5
C5—C4—H4	120.1	H231—C23—H233	109.5
C3—C4—H4	120.1	H232—C23—H233	109.5
C4—C5—C6	120.1 (3)	C14—C24—H241	109.5
C4—C5—H5	119.9	C14—C24—H242	109.5
C6—C5—H5	119.9	H241—C24—H242	109.5
C1—C6—C5	120.5 (3)	C14—C24—H243	109.5
C1—C6—H6	119.7	H241—C24—H243	109.5
C5—C6—H6	119.7	H242—C24—H243	109.5
O8—C7—C1	108.7 (2)	N16—C25—C26	103.19 (16)
O8—C7—H71	110.0	N16—C25—H251	111.1
C1—C7—H71	110.0	C26—C25—H251	111.1
O8—C7—H72	110.0	N16—C25—H252	111.1
C1—C7—H72	110.0	C26—C25—H252	111.1
H71—C7—H72	108.3	H251—C25—H252	109.1
O9—C9—N10	125.7 (2)	O26—C26—C27	106.96 (16)
O9—C9—O8	123.7 (2)	O26—C26—C25	115.04 (17)
N10—C9—O8	110.64 (19)	C27—C26—C25	103.52 (16)
N10—C11—C12	109.27 (17)	O26—C26—H26	110.3
N10—C11—C20	110.81 (17)	C27—C26—H26	110.3
C12—C11—C20	111.64 (17)	C25—C26—H26	110.3
N10—C11—H11	108.3	C26—C27—C17	104.44 (16)
C12—C11—H11	108.3	C26—C27—H271	110.9
C20—C11—H11	108.3	C17—C27—H271	110.9
O12—C12—N13	122.15 (19)	C26—C27—H272	110.9
O12—C12—C11	122.28 (18)	C17—C27—H272	110.9
N13—C12—C11	115.57 (17)	H271—C27—H272	108.9
N13—C14—C23	109.11 (16)	O26—C28—C29	109.00 (17)
N13—C14—C15	114.15 (16)	O26—C28—H281	109.9
C23—C14—C15	110.13 (17)	C29—C28—H281	109.9
N13—C14—C24	107.50 (17)	O26—C28—H282	109.9
C23—C14—C24	110.20 (18)	C29—C28—H282	109.9
C15—C14—C24	105.64 (16)	H281—C28—H282	108.3
O15—C15—N16	119.42 (17)	C34—C29—C30	118.4 (2)
O15—C15—C14	119.07 (17)	C34—C29—C28	121.1 (2)
N16—C15—C14	120.77 (16)	C30—C29—C28	120.53 (19)
N16—C17—C18	109.82 (16)	C31—C30—C29	121.2 (2)
N16—C17—C27	103.95 (15)	C31—C30—H30	119.4
C18—C17—C27	111.17 (17)	C29—C30—H30	119.4
N16—C17—H17	110.6	C32—C31—C30	120.2 (2)
C18—C17—H17	110.6	C32—C31—H31	119.9
C27—C17—H17	110.6	C30—C31—H31	119.9
O18—C18—O19	124.8 (2)	C31—C32—C33	119.2 (2)
O18—C18—C17	125.43 (19)	C31—C32—H32	120.4
O19—C18—C17	109.72 (17)	C33—C32—H32	120.4
O19—C19—H191	109.5	C32—C33—C34	120.7 (2)
O19—C19—H192	109.5	C32—C33—H33	119.6
H191—C19—H192	109.5	C34—C33—H33	119.6
O19—C19—H193	109.5	C29—C34—C33	120.3 (2)
H191—C19—H193	109.5	C29—C34—H34	119.8
H192—C19—H193	109.5	C33—C34—H34	119.8
C6—C1—C2—C3	−0.2 (4)	C15—N16—C17—C18	−69.2 (2)
C7—C1—C2—C3	179.3 (3)	C25—N16—C17—C18	110.97 (18)
C1—C2—C3—C4	0.2 (4)	C15—N16—C17—C27	171.81 (17)
C2—C3—C4—C5	−0.3 (5)	C25—N16—C17—C27	−8.0 (2)
C3—C4—C5—C6	0.4 (5)	C19—O19—C18—O18	−1.1 (3)
C2—C1—C6—C5	0.3 (4)	C19—O19—C18—C17	177.1 (2)
C7—C1—C6—C5	−179.1 (3)	N16—C17—C18—O18	−8.3 (3)
C4—C5—C6—C1	−0.5 (5)	C27—C17—C18—O18	106.2 (2)
C9—O8—C7—C1	167.3 (2)	N16—C17—C18—O19	173.53 (16)
C2—C1—C7—O8	77.5 (4)	C27—C17—C18—O19	−72.0 (2)
C6—C1—C7—O8	−103.0 (3)	N10—C11—C20—C21	67.3 (2)
C11—N10—C9—O9	−10.6 (3)	C12—C11—C20—C21	−54.8 (3)
C11—N10—C9—O8	170.08 (18)	N10—C11—C20—C22	−167.1 (2)
C7—O8—C9—O9	2.2 (4)	C12—C11—C20—C22	70.9 (2)
C7—O8—C9—N10	−178.5 (2)	C15—N16—C25—C26	165.96 (19)
C9—N10—C11—C12	−78.8 (2)	C17—N16—C25—C26	−14.2 (2)
C9—N10—C11—C20	157.74 (19)	C28—O26—C26—C27	−174.39 (18)
C14—N13—C12—O12	−13.0 (3)	C28—O26—C26—C25	71.3 (2)
C14—N13—C12—C11	167.92 (17)	N16—C25—C26—O26	147.06 (16)
N10—C11—C12—O12	−41.5 (3)	N16—C25—C26—C27	30.7 (2)
C20—C11—C12—O12	81.4 (3)	O26—C26—C27—C17	−158.15 (16)
N10—C11—C12—N13	137.62 (18)	C25—C26—C27—C17	−36.3 (2)
C20—C11—C12—N13	−99.5 (2)	N16—C17—C27—C26	27.4 (2)
C12—N13—C14—C23	−73.2 (2)	C18—C17—C27—C26	−90.6 (2)
C12—N13—C14—C15	50.5 (2)	C26—O26—C28—C29	173.58 (18)
C12—N13—C14—C24	167.33 (18)	O26—C28—C29—C34	−31.3 (3)
C17—N16—C15—O15	−8.1 (3)	O26—C28—C29—C30	148.7 (2)
C25—N16—C15—O15	171.74 (19)	C34—C29—C30—C31	0.4 (4)
C17—N16—C15—C14	161.98 (17)	C28—C29—C30—C31	−179.7 (2)
C25—N16—C15—C14	−18.2 (3)	C29—C30—C31—C32	0.0 (4)
N13—C14—C15—O15	−142.91 (18)	C30—C31—C32—C33	−0.6 (4)
C23—C14—C15—O15	−19.8 (3)	C31—C32—C33—C34	0.9 (5)
C24—C14—C15—O15	99.2 (2)	C30—C29—C34—C33	−0.1 (4)
N13—C14—C15—N16	47.0 (2)	C28—C29—C34—C33	−180.0 (3)
C23—C14—C15—N16	170.14 (18)	C32—C33—C34—C29	−0.6 (5)
C24—C14—C15—N16	−70.9 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N10—H10···O18^i	0.90 (3)	2.06 (3)	2.927 (3)	163 (2)
N13—H13···O15^ii	0.89 (2)	2.17 (3)	3.060 (2)	175 (2)

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