A peptide sequence containing a hydroxy acid residue: (S)-2-hydroxy-3-methylbutanoyl-L-alanyl-L-proline benzyl ester (H–L-Hmb–L-Ala–L-Pro–OBzl)

Crystals of the title compound, C₂₀H₂₈N₂O₅, have been successfully grown from di­methyl­form­amide–water at room temperature. In the packing structure, no NH...O=C interactions were observed. Independent mol­ecules are connected together via an –OH...O=C hydrogen bond.

Key indicators

• Single-crystal X-ray study
• T = 173 K
• Mean [sigma](C-C) = 0.007 Å
• R factor = 0.079
• wR factor = 0.067
• Data-to-parameter ratio = 8.6

checkCIF/PLATON results

No syntax errors found



Alert level A
PLAT201_ALERT_2_A Isotropic non-H Atoms in Main Residue(s) ..... =         13

Author Response: Because of the limited numbers of observed reflections. Even at the low temperature condition (173 K), diffractions from the crystal of (I) were too weak to collect enough numbers. Therefore only main-cain

 atoms were refefined anisotropically.


Alert level B
PLAT432_ALERT_2_B Short Inter X...Y Contact  O131   ..  C136     =       2.91 Ang.

Author Response: It is attributable to the conformational isomerism of the five- membered ring (-C131-C133-C134(C136)-C135-N131-) in the Pro residue.

Alert level C
PLAT066_ALERT_1_C Predicted and Reported Transmissions Identical .          ?
PLAT220_ALERT_2_C Large Non-Solvent    C     Ueq(max)/Ueq(min) ...       2.57 Ratio

Author Response: It is due to the difference of thermal mobility. The chain end atoms often shows higer U(eq) compared with the atoms located inside of the chain.

PLAT241_ALERT_2_C Check High   U(eq) as Compared to Neighbors ....       C141

Author Response: It is due to the difference of thermal mobility. The chain end atoms often shows higer U(eq) compared with the atoms located inside of the chain.

PLAT242_ALERT_2_C Check Low    U(eq) as Compared to Neighbors ....       C142

Author Response: It is due to the low mobility of C142 which is located at the pivot position of the phenyl group.

PLAT250_ALERT_2_C Large U3/U1 ratio for average U(i,j) tensor ....       2.32

Author Response: It is due to the thermal mobility of C141 and O141. Atoms in the chain-end group often show higer U(eq) and larger U3/U1 ratio compared with the atoms located inside of the chain.

PLAT301_ALERT_3_C Main Residue  Disorder .........................       4.00 Perc.

Author Response: It is due to the conformational isomerism of the five- membered ring in the Pro residue.

PLAT340_ALERT_3_C Low Bond Precision on C-C bonds (x 1000) Ang ...          7

Author Response: It is attributable to the conformational isomerism of the five- membered ring in the Pro residue.

PLAT713_ALERT_1_C TORSION Unknown or Inconsistent Label ..........        C11
                    H(3)   C11    C1     H(9)
PLAT779_ALERT_2_C Suspect or Irrelevant (Bond) Angle in CIF ......      39.70 Deg.
              C134 -C133 -C136    1.555   1.555   1.555

Author Response: For both C134-C135-C136 and C134-C133-C136 It is attributable to the conformational isomerism of the five- membered ring in the Pro residue. The explanation has been added into the text.

PLAT779_ALERT_2_C Suspect or Irrelevant (Bond) Angle in CIF ......      38.10 Deg.
              C134 -C135 -C136    1.555   1.555   1.555

Author Response: For both C134-C135-C136 and C134-C133-C136 It is attributable to the conformational isomerism of the five- membered ring in the Pro residue. The explanation has been added into the text.

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           65.50
           From the CIF: _reflns_number_total               1844
           Count of symmetry unique reflns         1844
           Completeness (_total/calc)            100.00%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         0
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present           no

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

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

---

S1. Comment

The title compound, (I), is a derivative of the –Ala-Pro- sequence, which has been extensively studied in our laboratory (e.g. Oku et al., 2003; Ishiguro et al., 2001; Abe et al., 2001) to make synthetic antigens and enzyme active sites. In this paper, (I) has been prepared as a hydroxy acid analogue of the –Val-Ala-Pro- sequence. Our ongoing studies of depsipetides have shown that these molecules containing hydroxy acid residues often form single crystals suitable for X-ray crystallography (Ohyama et al., 2000, 2001), in contrast with the corresponding amino acid compounds. In this case, a sequence contaning –Val-Ala-Pro-, such as Boc-Val-Ala-Pro-OBzl (Boc is tert-butyloxycarbonyl) gives an oily state at room temperature. To show an example of the excellent crystallinity of hydroxy acid compounds, the crystal structure of (I) has been determined.

The molecular structure of (I) is shown in Fig. 1. The molecule has an extended sheet-like conformation. Disordered atoms (C134 and C136) were observed in the side chain of Pro, due to the conformational isomerism of the five-membered ring in the Pro residue. This side-chain disorder leads to unusual geometerical parameters, such as the close contact between atoms C136 and O131.

No intermolecular NH···O═C hydrogen bonds were observed in the packing structure of (I). As shown in Fig. 2, the molecules are connected together via an –OH···O═C interaction along the a axis, to give an infinite arrangement.

Generally, intermolecular NH···O═C networks connect peptides together into an infinite anti-parallel β sheet aggregation in crystals (e.g. Antolic et al., 1999; Ashida et al., 1981; Cruse et al., 1982). This is an important crystallizing force for short peptide compounds, although no such interactions were observed in the packing of (I).

S2. Experimental

The title peptide, (I), was prepared by conventional liquid-phase peptide synthesis. Crystals of (I) were successfully grown from dimethylformamide-water (Ratio?). Analytical data (¹H NMR, ESI-MS and [α]_D²⁰) were in accordance with the expected structure; [α]_D²⁰ = −163.5° (c 0.1, methanol).

S3. Refinement

For non-H atoms, refinement was performed with anisotropic displacement parameters for main-chain atoms, and with isotropic refinements for side-chains (Hmb, Ala and Pro) and protecting groups (benzene ring). This is due to the limited numbers of observed reflections. Even with the techniques available, such as a low temperature (173 K), Cu Kα radiation and an area detector, reflections from the crystal of (I) were too weak to collect enough data for anisotropic refinement. H atoms were placed geometrically, except for atoms H1, H17, H18 and H29. How were these H atoms located? They were refined with a riding model and with U_iso(H) = 1.2U_iso of the carrier atom. The absolute stereochemistry of (I) was not established from the diffraction experiment and Friedel pairs were averaged. The absolute configuration was confirmed from the spectroscopic data, α_D, of the compound.

Computing details

Data collection: RAPID-AUTO (Molecular Structure Corporation & Rigaku Corporation, 2003); cell refinement: RAPID-AUTO; data reduction: CrystalStructure (Molecular Structure Corporation & Rigaku Corporation, 2003); program(s) used to solve structure: SIR2002 (Burla et al., 2003); program(s) used to refine structure: CRYSTALS (Watkin et al., 1996); molecular graphics: ORTEP (Johnson, 1965); software used to prepare material for publication: CrystalStructure.

Figures

	Fig. 1. A view of (I) with the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. A packing view of (I). Hydrogen bonds are indicated by dotted lines.

(S)-2-Hydroxy-3-methylbutanoyl-L-alanyl-L-proline benzyl ester

Crystal data

C20H28N2O5	F(000) = 404.00
Mr = 376.45	Dx = 1.233 Mg m^−3
Monoclinic, P21	Melting point: 405 K
Hall symbol: P 2yb	Cu Kα radiation, λ = 1.5418 Å
a = 5.8977 (7) Å	Cell parameters from 9297 reflections
b = 10.1767 (16) Å	θ = 4.3–68.3°
c = 16.941 (2) Å	µ = 0.73 mm^−1
β = 94.394 (10)°	T = 173 K
V = 1013.8 (2) Å^3	Platelet, colourless
Z = 2	0.5 × 0.5 × 0.05 mm

Data collection

Rigaku RAXIS-RAPID area-detector diffractometer	1799 reflections with F^2 > 2.0σ(F^2)
Detector resolution: 10.00 pixels mm^-1	Rint = 0.055
ω scans	θmax = 65.5°
Absorption correction: part of the refinement model (ΔF) (DIFABS; Walker & Stuart, 1983)	h = −7→7
Tmin = 0.730, Tmax = 0.964	k = −11→11
16496 measured reflections	l = −20→20
1844 independent reflections

Refinement

Refinement on F^2	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.079	Chebychev polynomial with 3 parameters (Carruthers & Watkin, 1979), 25758.0000 31369.7000 698.5290
wR(F^2) = 0.067	(Δ/σ)max < 0.001
S = 1.01	Δρmax = 0.59 e Å^−3
1844 reflections	Δρmin = −0.41 e Å^−3
215 parameters

Special details

Refinement. Refinement using all reflections. The weighted R-factor (wR) and goodness of fit (S) are based on F². R-factor (gt) are based on F. The threshold expression of F² > 2.0 σ(F²) is used only for calculating R-factor (gt).

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
O111	1.2011 (4)	0.4494 (4)	0.1492 (1)	0.0451 (9)
O112	0.6301 (4)	0.5643 (3)	0.1351 (1)	0.0421 (9)
O121	1.0652 (4)	0.4970 (3)	0.3807 (1)	0.0410 (8)
O131	0.8572 (7)	0.3977 (4)	0.5506 (2)	0.071 (1)
O141	1.1124 (5)	0.5288 (4)	0.6152 (1)	0.063 (1)
N121	0.8717 (5)	0.4929 (4)	0.2358 (2)	0.0335 (9)
N131	0.7668 (5)	0.5928 (4)	0.4335 (2)	0.037 (1)
C111	1.0116 (6)	0.5105 (5)	0.1059 (2)	0.036 (1)
C112	0.8201 (6)	0.5250 (4)	0.1615 (2)	0.031 (1)
C113	0.9324 (7)	0.4335 (5)	0.0314 (2)	0.038 (1)*
C114	0.8334 (8)	0.3002 (5)	0.0504 (3)	0.061 (1)*
C115	1.1248 (7)	0.4201 (5)	−0.0229 (2)	0.050 (1)*
C121	0.7170 (6)	0.5043 (5)	0.2988 (2)	0.033 (1)
C122	0.8641 (7)	0.5326 (5)	0.3744 (2)	0.033 (1)
C123	0.5830 (7)	0.3763 (5)	0.3073 (2)	0.044 (1)*
C131	0.9013 (7)	0.6217 (5)	0.5079 (2)	0.040 (1)
C132	0.9505 (8)	0.5009 (6)	0.5571 (2)	0.047 (1)
C133	0.7486 (8)	0.7148 (5)	0.5505 (3)	0.049 (1)*
C134	0.515 (1)	0.6737 (8)	0.5202 (4)	0.039 (2)*	0.65
C135	0.5333 (7)	0.6451 (5)	0.4335 (2)	0.041 (1)*
C136	0.562 (2)	0.758 (1)	0.4954 (8)	0.038 (3)*	0.35
C141	1.1412 (9)	0.4328 (7)	0.6778 (2)	0.081 (2)
C142	0.9547 (8)	0.4424 (6)	0.7335 (3)	0.051 (1)*
C143	0.9019 (8)	0.5591 (5)	0.7655 (3)	0.052 (1)*
C144	0.7294 (8)	0.5708 (6)	0.8166 (3)	0.059 (1)*
C145	0.6131 (8)	0.4582 (5)	0.8358 (3)	0.058 (1)*
C146	0.665 (1)	0.3408 (7)	0.8058 (3)	0.075 (2)*
C147	0.8321 (9)	0.3297 (6)	0.7523 (3)	0.069 (2)*
H(1)	1.3219	0.5034	0.1382	0.054*
H(2)	1.0561	0.5957	0.0902	0.044*
H(3)	0.8156	0.4832	0.0036	0.046*
H(4)	0.7108	0.3141	0.0827	0.073*
H(5)	0.7791	0.2564	0.0032	0.073*
H(6)	0.9464	0.2479	0.0782	0.073*
H(7)	1.2445	0.3704	0.0033	0.060*
H(8)	1.0699	0.3761	−0.0700	0.060*
H(9)	1.1801	0.5045	−0.0359	0.060*
H(10)	1.0196	0.4593	0.2498	0.040*
H(11)	0.6155	0.5756	0.2878	0.040*
H(12)	0.4876	0.3855	0.3496	0.053*
H(13)	0.4923	0.3596	0.2595	0.053*
H(14)	0.6851	0.3052	0.3180	0.052*
H(15)	0.5158	0.7229	0.4027	0.049*
H(16)	0.4241	0.5819	0.4143	0.050*
H(17)	0.4128	0.7488	0.5268	0.042*
H(18)	0.4812	0.5982	0.5559	0.042*	0.65
H(19)	0.7704	0.7032	0.6062	0.058*
H(20)	0.7758	0.8040	0.5377	0.058*
H(21)	1.0393	0.6642	0.4976	0.048*
H(22)	1.1347	0.3476	0.6548	0.097*
H(23)	1.2846	0.4448	0.7064	0.097*
H(24)	0.9854	0.6352	0.7531	0.062*
H(25)	0.6922	0.6536	0.8381	0.071*
H(26)	0.4938	0.4648	0.8702	0.070*
H(27)	0.5841	0.2653	0.8212	0.090*
H(28)	0.8657	0.2467	0.7303	0.083*
H(29)	0.5344	0.8606	0.4799	0.042*	0.35

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O111	0.026 (1)	0.076 (3)	0.034 (1)	0.002 (2)	0.004 (1)	0.009 (2)
O112	0.031 (1)	0.065 (2)	0.030 (1)	0.011 (2)	0.005 (1)	0.005 (2)
O121	0.029 (1)	0.059 (2)	0.034 (1)	0.012 (2)	0.002 (1)	−0.005 (2)
O131	0.108 (3)	0.058 (3)	0.045 (2)	0.004 (3)	−0.005 (2)	−0.002 (2)
O141	0.051 (2)	0.103 (3)	0.032 (2)	0.011 (2)	−0.006 (1)	0.002 (2)
N121	0.026 (2)	0.053 (3)	0.023 (1)	0.003 (2)	0.008 (1)	−0.001 (2)
N131	0.029 (2)	0.058 (3)	0.023 (2)	0.004 (2)	0.002 (1)	−0.005 (2)
C111	0.032 (2)	0.048 (3)	0.028 (2)	−0.000 (2)	0.007 (2)	0.001 (2)
C112	0.034 (2)	0.031 (3)	0.030 (2)	−0.003 (2)	0.006 (2)	0.003 (2)
C121	0.031 (2)	0.048 (3)	0.022 (2)	0.000 (2)	0.011 (2)	0.006 (2)
C122	0.036 (2)	0.039 (3)	0.025 (2)	−0.002 (2)	0.009 (2)	0.002 (2)
C131	0.030 (2)	0.061 (4)	0.027 (2)	−0.008 (2)	0.003 (2)	−0.006 (2)
C132	0.049 (3)	0.071 (4)	0.022 (2)	0.014 (3)	0.004 (2)	−0.006 (3)
C141	0.086 (4)	0.129 (6)	0.027 (2)	0.049 (4)	−0.001 (2)	0.008 (3)

Geometric parameters (Å, º)

O111—C111	1.431 (5)	C131—C132	1.501 (7)
O111—H(1)	0.930	C131—C133	1.525 (7)
O112—C112	1.240 (4)	C131—H(21)	0.950
O121—C122	1.237 (5)	C133—C134	1.490 (8)
O131—C132	1.187 (7)	C133—C136	1.449 (13)
O141—C132	1.349 (5)	C133—H(19)	0.950
O141—C141	1.442 (7)	C133—H(20)	0.950
N121—C112	1.314 (4)	C134—C135	1.508 (8)
N121—C121	1.461 (5)	C134—C136	1.004 (13)
N121—H(10)	0.950	C134—H(17)	0.990
N131—C122	1.340 (5)	C134—H(18)	1.010
N131—C131	1.467 (5)	C135—C136	1.556 (13)
N131—C135	1.476 (5)	C135—H(15)	0.950
C111—C112	1.531 (5)	C135—H(16)	0.950
C111—C113	1.529 (5)	C136—H(17)	1.067
C111—H(2)	0.950	C136—H(29)	1.090
C113—C114	1.521 (7)	C141—C142	1.506 (7)
C113—C115	1.521 (6)	C141—H(22)	0.950
C113—H(3)	0.950	C141—H(23)	0.950
C114—H(4)	0.950	C142—C143	1.352 (8)
C114—H(5)	0.950	C142—C147	1.406 (8)
C114—H(6)	0.950	C143—C144	1.391 (7)
C115—H(7)	0.950	C143—H(24)	0.950
C115—H(8)	0.950	C144—C145	1.387 (8)
C115—H(9)	0.950	C144—H(25)	0.950
C121—C122	1.518 (5)	C145—C146	1.342 (8)
C121—C123	1.536 (6)	C145—H(26)	0.950
C121—H(11)	0.950	C146—C147	1.396 (8)
C123—H(12)	0.950	C146—H(27)	0.950
C123—H(13)	0.950	C147—H(28)	0.950
C123—H(14)	0.950
C111—O111—H(1)	102.8	C134—C133—H(20)	110.9
C132—O141—C141	115.5 (4)	C134—C133—C131	103.0 (4)
C112—N121—C121	124.7 (3)	C136—C133—H(19)	135.5
C112—N121—H(10)	118.0	C136—C133—H(20)	72.5
C121—N121—H(10)	117.4	C136—C133—C131	109.1 (6)
C122—N131—C131	120.0 (3)	H(19)—C133—H(20)	109.5
C122—N131—C135	128.2 (3)	H(19)—C133—C131	110.6
C131—N131—C135	111.7 (3)	H(20)—C133—C131	111.6
C112—C111—C113	111.3 (3)	C135—C134—C136	73.4 (9)
C112—C111—H(2)	108.5	C135—C134—H(17)	110.5
C112—C111—O111	108.1 (3)	C135—C134—H(18)	118.1
C113—C111—H(2)	108.0	C135—C134—C133	105.0 (5)
C113—C111—O111	112.1 (4)	C136—C134—H(17)	65.0
H(2)—C111—O111	108.6	C136—C134—H(18)	167.8
O112—C112—N121	124.2 (3)	H(17)—C134—H(18)	111.6
O112—C112—C111	119.9 (3)	H(17)—C134—C133	107.5
N121—C112—C111	115.9 (3)	H(18)—C134—C133	103.2
C114—C113—C115	111.4 (4)	C133—C134—C136	68.2 (8)
C114—C113—H(3)	107.7	C136—C135—H(15)	76.0
C114—C113—C111	112.3 (3)	C136—C135—H(16)	140.0
C115—C113—H(3)	107.1	C136—C135—N131	102.3 (5)
C115—C113—C111	110.5 (3)	H(15)—C135—H(16)	109.5
H(3)—C113—C111	107.5	H(15)—C135—N131	111.2
H(4)—C114—H(5)	109.5	H(15)—C135—C134	111.3
H(4)—C114—H(6)	109.5	H(16)—C135—N131	111.3
H(4)—C114—C113	108.1	H(16)—C135—C134	111.6
H(5)—C114—H(6)	109.5	N131—C135—C134	101.8 (4)
H(5)—C114—C113	110.5	C134—C135—C136	38.1 (6)
H(6)—C114—C113	109.8	H(17)—C136—H(29)	95.1
H(7)—C115—H(8)	109.5	H(29)—C136—C133	122.4
H(7)—C115—H(9)	109.5	H(29)—C136—C134	152.0
H(7)—C115—C113	109.1	H(29)—C136—C135	122.4
H(8)—C115—H(9)	109.5	C133—C136—C134	72.1 (9)
H(8)—C115—C113	109.1	C134—C136—H(17)	57.0
H(9)—C115—C113	110.1	C134—C136—C135	68.5 (9)
C122—C121—C123	110.3 (3)	C135—C136—H(17)	102.9
C122—C121—H(11)	109.4	C135—C136—C133	104.5 (9)
C122—C121—N121	106.4 (3)	C142—C141—H(22)	108.0
C123—C121—H(11)	110.2	C142—C141—H(23)	109.7
C123—C121—N121	110.8 (4)	C142—C141—O141	111.5 (5)
H(11)—C121—N121	109.7	H(22)—C141—H(23)	109.5
O121—C122—N131	122.1 (3)	H(22)—C141—O141	108.6
O121—C122—C121	120.0 (3)	H(23)—C141—O141	109.7
N131—C122—C121	117.8 (3)	C143—C142—C147	119.2 (5)
H(12)—C123—H(13)	109.5	C143—C142—C141	120.7 (5)
H(12)—C123—H(14)	109.5	C147—C142—C141	120.1 (5)
H(12)—C123—C121	109.0	C144—C143—H(24)	118.9
H(13)—C123—H(14)	109.5	C144—C143—C142	121.8 (5)
H(13)—C123—C121	109.5	H(24)—C143—C142	119.2
H(14)—C123—C121	109.9	C145—C144—H(25)	120.7
C132—C131—C133	110.0 (4)	C145—C144—C143	118.3 (5)
C132—C131—H(21)	110.1	H(25)—C144—C143	121.1
C132—C131—N131	112.4 (4)	C146—C145—H(26)	119.6
C133—C131—H(21)	110.5	C146—C145—C144	121.1 (5)
C133—C131—N131	103.3 (3)	H(26)—C145—C144	119.3
H(21)—C131—N131	110.3	C147—C146—H(27)	120.3
O131—C132—O141	123.5 (5)	C147—C146—C145	120.7 (6)
O131—C132—C131	127.2 (4)	H(27)—C146—C145	119.0
O141—C132—C131	109.2 (5)	H(28)—C147—C142	120.7
C134—C133—C136	39.7 (6)	H(28)—C147—C146	120.4
C134—C133—H(19)	111.0	C142—C147—C146	118.9 (5)
O111—C111—C112—N121	6.4 (6)	C136—C133—C134—C135	64.8 (5)
C111—C112—N121—C121	177.5 (4)	C136—C133—C134—H(17)	−52.8
C112—N121—C121—C122	−148.9 (4)	C136—C133—C134—H(18)	−170.9
N121—C121—C122—N131	156.4 (4)	H(19)—C133—C134—C135	−158.0
C121—C122—N131—C131	179.7 (4)	H(19)—C133—C134—C136	137.2
C122—N131—C131—C132	−73.6 (5)	H(19)—C133—C134—H(17)	84.7
N131—C131—C132—O141	167.0 (3)	H(19)—C133—C134—H(18)	−33.7
C131—C132—O141—C141	166.4 (4)	H(20)—C133—C134—C135	80.0
C132—O141—C141—C142	−76.5 (5)	H(20)—C133—C134—C136	15.2
H(1)—O111—C111—C112	−131.1	H(20)—C133—C134—H(17)	−37.6
H(1)—O111—C111—C113	105.7	H(20)—C133—C134—H(18)	−155.7
H(1)—O111—C111—H(2)	−13.5	C131—C133—C136—C134	87.4 (9)
C141—O141—C132—C131	166.4 (3)	C131—C133—C136—C135	26.2 (9)
C132—O141—C141—H(22)	42.3	C131—C133—C136—H(17)	134.3
C132—O141—C141—H(23)	161.9	C131—C133—C136—H(29)	−119.2
C121—N121—C112—C111	177.5 (4)	C134—C133—C136—C135	−61.3 (8)
H(10)—N121—C112—O112	176.7	C134—C133—C136—H(17)	46.8
H(10)—N121—C112—C111	−2.9	C134—C133—C136—H(29)	153.3
C112—N121—C121—C123	91.1 (5)	H(19)—C133—C136—C134	−64.8
C112—N121—C121—H(11)	−30.7	H(19)—C133—C136—C135	−126.1
H(10)—N121—C121—C122	31.4	H(19)—C133—C136—H(17)	−18.0
H(10)—N121—C121—C123	−88.5	H(19)—C133—C136—H(29)	88.5
H(10)—N121—C121—H(11)	149.6	H(20)—C133—C136—C134	−165.1
C131—N131—C122—O121	1.7 (7)	H(20)—C133—C136—C135	133.6
C135—N131—C122—O121	177.4 (4)	H(20)—C133—C136—H(17)	−118.3
C135—N131—C122—C121	−4.6 (7)	H(20)—C133—C136—H(29)	−11.8
C122—N131—C131—C133	167.9 (4)	C133—C134—C135—N131	33.6 (6)
C122—N131—C131—H(21)	49.7	C133—C134—C135—C136	−61.3 (9)
C135—N131—C131—C132	110.1 (4)	C133—C134—C135—H(15)	−85.0
C135—N131—C131—C133	−8.5 (5)	C133—C134—C135—H(16)	152.5
C135—N131—C131—H(21)	−126.7	C136—C134—C135—N131	94.9 (6)
C122—N131—C135—C134	168.8 (5)	C136—C134—C135—H(15)	−23.7
C122—N131—C135—C136	−152.2 (6)	C136—C134—C135—H(16)	−146.3
C122—N131—C135—H(15)	−72.6	H(17)—C134—C135—N131	149.2
C122—N131—C135—H(16)	49.8	H(17)—C134—C135—C136	54.3
C131—N131—C135—C134	−15.2 (5)	H(17)—C134—C135—H(15)	30.7
C131—N131—C135—C136	23.8 (7)	H(17)—C134—C135—H(16)	−91.9
C131—N131—C135—H(15)	103.4	H(18)—C134—C135—N131	−80.6
C131—N131—C135—H(16)	−134.2	H(18)—C134—C135—C136	−175.5
O111—C111—C112—O112	−173.2 (4)	H(18)—C134—C135—H(15)	160.8
C113—C111—C112—O112	−49.6 (6)	H(18)—C134—C135—H(16)	38.2
C113—C111—C112—N121	130.0 (4)	C133—C134—C136—C135	114.2 (6)
H(2)—C111—C112—O112	69.2	C133—C134—C136—H(17)	−122.8
H(2)—C111—C112—N121	−111.2	C133—C134—C136—H(29)	−126.3
O111—C111—C113—C114	66.5 (4)	C135—C134—C136—C133	−114.2 (6)
O111—C111—C113—C115	−58.6 (5)	C135—C134—C136—H(17)	122.8
O111—C111—C113—H(3)	−175.2	C135—C134—C136—H(29)	119.6
C112—C111—C113—C114	−54.8 (5)	H(17)—C134—C136—C133	123.0
C112—C111—C113—C115	−179.8 (4)	H(17)—C134—C136—C135	−122.8
C112—C111—C113—H(3)	63.5	H(17)—C134—C136—H(29)	−3.3
H(2)—C111—C113—C114	−173.9	H(18)—C134—C136—C133	46.8
H(2)—C111—C113—C115	61.0	H(18)—C134—C136—C135	159.8
H(2)—C111—C113—H(3)	−55.6	H(18)—C134—C136—H(17)	−77.3
C111—C113—C114—H(4)	57.5	H(18)—C134—C136—H(29)	−80.7
C111—C113—C114—H(5)	177.2	C133—C134—H(17)—C136	54.8
C111—C113—C114—H(6)	−61.9	C135—C134—H(17)—C136	−59.3
C115—C113—C114—H(4)	−177.9	H(18)—C134—H(17)—C136	167.3
C115—C113—C114—H(5)	−58.1	N131—C135—C136—C133	−29.8 (8)
C115—C113—C114—H(6)	62.7	N131—C135—C136—C134	−93.5 (8)
H(3)—C113—C114—H(4)	−60.8	N131—C135—C136—H(17)	−139.8
H(3)—C113—C114—H(5)	59.0	N131—C135—C136—H(29)	115.5
H(3)—C113—C114—H(6)	179.7	C134—C135—C136—C133	63.7 (8)
C111—C113—C115—H(7)	63.4	C134—C135—C136—H(17)	−46.3
C111—C113—C115—H(8)	−177.0	C134—C135—C136—H(29)	−151.0
C111—C113—C115—H(9)	−56.8	H(15)—C135—C136—C133	−138.9
C114—C113—C115—H(7)	−62.2	H(15)—C135—C136—C134	157.3
C114—C113—C115—H(8)	57.4	H(15)—C135—C136—H(17)	111.1
C114—C113—C115—H(9)	177.6	H(15)—C135—C136—H(29)	6.3
H(3)—C113—C115—H(7)	−179.8	H(16)—C135—C136—C133	117.3
H(3)—C113—C115—H(8)	−60.1	H(16)—C135—C136—C134	53.5
H(3)—C11—C1—H(9)	60.0	H(16)—C135—C136—H(17)	7.3
N121—C121—C122—O121	−25.5 (6)	H(16)—C135—C136—H(29)	−97.4
C123—C121—C122—O121	94.7 (5)	C133—C136—H(17)—C134	−55.9
C123—C121—C122—N131	−83.3 (5)	C135—C136—H(17)—C134	53.3
H(11)—C121—C122—O121	−143.9	H(29)—C136—H(17)—C134	178.5
H(11)—C121—C122—N131	38.0	O141—C141—C142—C143	−50.8 (6)
N121—C121—C123—H(12)	178.2	O141—C141—C142—C147	128.6 (5)
N121—C121—C123—H(13)	−62.1	H(22)—C141—C142—C143	−170.0
N121—C121—C123—H(14)	58.2	H(22)—C141—C142—C147	9.5
C122—C121—C123—H(12)	60.6	H(23)—C141—C142—C143	70.8
C122—C121—C123—H(13)	−179.7	H(23)—C141—C142—C147	−109.7
C122—C121—C123—H(14)	−59.4	C141—C142—C143—C144	179.5 (4)
H(11)—C121—C123—H(12)	−60.3	C141—C142—C143—H(24)	−0.9
H(11)—C121—C123—H(13)	59.4	C147—C142—C143—C144	0.0 (7)
H(11)—C121—C123—H(14)	179.7	C147—C142—C143—H(24)	179.6
N131—C131—C132—O131	−16.9 (7)	C141—C142—C147—C146	178.2 (4)
C133—C131—C132—O131	97.7 (6)	C141—C142—C147—H(28)	0.2
C133—C131—C132—O141	−78.4 (4)	C143—C142—C147—C146	−2.3 (7)
H(21)—C131—C132—O131	−140.3	C143—C142—C147—H(28)	179.7
H(21)—C131—C132—O141	43.6	C142—C143—C144—C145	1.3 (7)
N131—C131—C133—C134	29.1 (5)	C142—C143—C144—H(25)	−179.0
N131—C131—C133—C136	−11.8 (7)	H(24)—C143—C144—C145	−178.3
N131—C131—C133—H(19)	147.8	H(24)—C143—C144—H(25)	1.4
N131—C131—C133—H(20)	−90.0	C143—C144—C145—C146	−0.2 (7)
C132—C131—C133—C134	−91.1 (5)	C143—C144—C145—H(26)	−179.4
C132—C131—C133—C136	−132.0 (7)	H(25)—C144—C145—C146	−179.7
C132—C131—C133—H(19)	27.6	H(25)—C144—C145—H(26)	0.9
C132—C131—C133—H(20)	149.7	C144—C145—C146—C147	−2.1 (8)
H(21)—C131—C133—C134	147.1	C144—C145—C146—H(27)	178.5
H(21)—C131—C133—C136	106.2	H(26)—C145—C146—C147	177.1
H(21)—C131—C133—H(19)	−94.2	H(26)—C145—C146—H(27)	−2.5
H(21)—C131—C133—H(20)	28.0	C145—C146—C147—C142	3.4 (8)
C131—C133—C134—C135	−39.5	C145—C146—C147—H(28)	−178.6
C131—C133—C134—C136	−104.4 (9)	H(27)—C146—C147—C142	−177.3
C131—C133—C134—H(17)	−157.1	H(27)—C146—C147—H(28)	0.7
C131—C133—C134—H(18)	84.7

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O111—H1···O112^i	0.93	1.93	2.814 (4)	159
N121—H10···O111	0.95	2.08	2.562 (3)	110
N121—H10···O121	0.95	2.25	2.628 (4)	103
C134—H17···O131^ii	0.99	2.50	3.324 (8)	142
C136—H17···O131^ii	1.07	2.50	2.910 (11)	102
C136—H29···O131^ii	1.09	2.36	2.910 (11)	110

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