N-(2-Carboxy­benzoyl)-L-leucine methyl ester

The title compound (with the systematic name 2-{[(1S)-1-(methoxy­carbonyl)-3-methyl­butyl]amino­carbonyl}benzoic acid), C₁₅H₁₉NO₅, crystallizes in the monoclinic space group P2₁, with two independent mol­ecules per asymmetric unit. The most notable difference between the two mol­ecules is in the dihedral angles between the planes of the carboxyl group and the benzene ring, which are 3.5 (3) and 25.7 (1)°. This difference may account for the fact that two competing reactions are observed in aqueous solution, namely cyclization to form the imide N-phthaloyl­leucine and hydrolysis of N-(2-carboxy­benzoyl)-L-leucine methyl ester to phthalic acid and leucine.

S1. Comment

In a previous paper (Onofrio et al., 2001), we studied the intramolecular acid catalysis of N-(o-carboxybenzoyl)-L-leucine methyl ester, (I), a simple model of aspartic proteinases which has been extensively investigated as a theoretical model (Wu et al., 2003a,b). The intramolecular reactions of (I) in aqueous solution result in both cyclization to form the imide N-phthaloylleucine, and hydrolysis of (I) to phthalic acid and leucine. Imide formation predominates under high acid concentrations ([HCl] > 3 M) and hydrolysis in the range [HCl] < 3 M to pH 5. In this paper, we present the newly solved crystal structure of (I).

N-(o-carboxybenzoyl)-L-leucine methyl ester crystallizes with two independent molecules per asymmetric unit, (I) and (I'). These derived molecular structures, showing the atom-numbering scheme, are displayed in Fig. 1.

Bond lengths (Table 1) in both cases agree with withdrawing groups in the ring, where the carboxyl group has the strongest influence. The dihedral angle between the planes of the carboxyl group and the phenyl ring is only 3.5 (3)° in (I) and 25.7 (1)° in (I'). The most significant differences in the bond lengths of the ring are that the C2—C3 bond is shorter by 0.013 Å and the C4—C5 bond is longer by 0.015 Å in structure (I), which reflects the resonance of the substituents with the phenyl ring. Relevant bond-length correlations are discussed below. Bond lengths in the carboxyl and amide groups of both structures are very similar to those found in the Cambridge Structural Database (CSD, Version?; Allen, 2002) [12 crystal structures of o-carboxybenzoamides, where C1—C16 = 1.483 (7), C16—O4 = 1.202 (11), C6—C7 = 1.509 (11), C7—N8 = 1.346 (11) and C7—O1 = 1.228 (10) Å], with the exception of the C1'—C16' bond length of 1.456 (7) Å, which is significantly shorter than the values in its counterpart and in the other o-carboxybenzoamides, namely CPPHAM (Mornon, 1970), BOLFIR (Kennard et al., 1982), CIBPEI and CIBPIM (Smith et al., 1983), CIBPIM01, VECCAH and VECCEL (Bocelli et al., 1989), CIHFAA (Shin et al., 1984), INODIY, INODUK and INODUK01 (Glidewell et al., 2004), and JINBAJ (Hegde et al., 1991).

The two phenyl rings are virtually planar, with no H atom deviating from the six-atom plane by more than 0.037 Å in (I) or by more than 0.012 Å in (I'). Primary substituents are also virtually planar in (I), with no atom more than 0.062 Å out of the plane. However, in structure (I'), atoms C7' and C16' are 0.154 and 0.136 Å out of the plane, respectively, and they occupy opposite sides in relation to the ring plane, no doubt for steric reasons. This must be because of the requirements of the O4'—C16'—C1'—C6 torsion angle, at 22.5 (9)°, which pushes the amide group to the opposite side. Obviously, this irregular conformation is possible because the carboxyl group is stabilized by hydrogen bonding between atom O4' and the H atom on atom O5 of its counterpart (Fig. 2).

Structures (I) and (I') were optimized in the gas phase (Software and reference?), and at the B3LYP/6–31 G(d,p) level they both converge to the same conformation, which is very similar to the structure of (I'). The most significant observation in relation to this is that the carboxyl group of (I) is twisted in relation to the phenyl ring of the optimized structure by 25.8°, which suggests that (I) is stabilized by an extensive hydrogen-bond network in the crystal structure (Table 2).

The O4—C7 distances [2.690 (5) and 2.781 (5) Å in structures (I) and (I'), respectively] can be used to show the intramolecular attack path to the formation of phthalic anhydride and L-leucine methyl ester through a tetrahedral intermediate mechanism. Indeed, it can be observed that, in the structure of (I'), the torsion of the carboxyl group in relation to the phenyl ring will probably promote the attack of atom O4 on the carbonyl atom C7, which is consistent with the attainment of the transition state. A similar mechanistic pattern has been observed in the formation of 1,8-naphthalic anhydride from 1,8-naphthalic acid (Yunes et al., 1997). Structure–structure relationships between O4—C7 distances and selected bond lengths of compounds (I) and (I') or other o-carboxybenzoamides show that other bond lengths, e.g. C7—O1 and C7—N8, are effectively constant with a decrease in the O4—C7 distance. Furthermore, C16—N8 distances [3.625 (5) and 3.775 (5) Å in structures (I) and (I'), respectively], which are important in the intramolecular cyclization to form the imides, are considerably longer than the O4—C7 distance (see above), which is consistent with the preferential hydrolysis reaction normally observed in aqueous solutions.

S2. Experimental

The title compound was prepared according to the previously published procedure of Onofrio et al. (1999). Colourless crystals of (I) were grown from a pale-yellow oil at room temperature and analytical data were consistent with previous m.p. and ¹H NMR analyses. Configuration of the product undoubtedly corresponds to the S enantiomer, since the synthetic procedure does not involve the asymmetric C atom of the starting material, L-(+)-leucine.

S3. Refinement

H atoms of the amine and carboxylic moieties were found in a Fourier map. These H atoms were treated with a riding model, with U_iso(H) = 1.2U_eq(parent). H atoms bonded to C atoms were added in their calculated positions and included in the structure-factor calculations, with C—H distances in the range 0.93–0.98 Å and with U_iso(H) = 1.2U_eq(C), or 1.5U_eq(C) for methyl H.

Computing details

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994); cell refinement: SET4 in CAD-4 EXPRESS; data reduction: HELENA (Spek, 1996); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ZORTEP (Zsolnai et al., 1996); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. Molecular structures of (a) (I) and (b) (I'), with atom-labelling schemes. Displacement ellipsoids are drawn at the 40% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. A view of the packing of the title compound, showing the intermolecular hydrogen bonds (dashed lines). [Symmetry codes: (i) −x + 1, y − 1/2, −z + 1; (ii) −x, y + 1/2, −z + 1.]

2-{[(1S)-1-(methoxycarbonyl)-3-methylbutyl]aminocarbonyl}benzoic acid

Crystal data

C15H19NO5	F(000) = 624
Mr = 293.31	Dx = 1.217 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
a = 11.735 (3) Å	Cell parameters from 25 reflections
b = 9.263 (3) Å	θ = 5.8–12.1°
c = 15.340 (2) Å	µ = 0.09 mm^−1
β = 106.18 (3)°	T = 293 K
V = 1601.4 (7) Å^3	Irregular block, colourless
Z = 4	0.50 × 0.46 × 0.33 mm

Data collection

Enraf–Nonius CAD-4 diffractometer	Rint = 0.032
Radiation source: fine-focus sealed tube	θmax = 29.0°, θmin = 1.4°
Graphite monochromator	h = −15→15
ω/2θ scans	k = −12→0
4649 measured reflections	l = −20→0
4496 independent reflections	3 standard reflections every 200 reflections
2272 reflections with I > 2σ(I)	intensity decay: <1%

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.060	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.192	H-atom parameters constrained
S = 0.99	w = 1/[σ^2(Fo^2) + (0.1093P)^2] where P = (Fo^2 + 2Fc^2)/3
4496 reflections	(Δ/σ)max < 0.001
387 parameters	Δρmax = 0.30 e Å^−3
1 restraint	Δρmin = −0.19 e Å^−3

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

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

	x	y	z	Uiso*/Ueq
O1	−0.0444 (3)	0.3309 (3)	0.4593 (2)	0.0680 (8)
O2	0.0213 (6)	0.2551 (9)	0.2282 (3)	0.180 (3)
O3	−0.1026 (4)	0.1160 (5)	0.2721 (2)	0.0973 (12)
O4	0.1348 (3)	0.2480 (5)	0.6395 (2)	0.0893 (12)
O5	0.1011 (4)	0.2043 (8)	0.7701 (2)	0.132 (2)
H5O	0.1691	0.2349	0.7891	0.159*
N8	0.0272 (3)	0.1099 (4)	0.4456 (2)	0.0523 (8)
H8	0.0323	0.0212	0.4629	0.063*
C1	−0.0481 (4)	0.1418 (5)	0.6406 (3)	0.0597 (11)
C2	−0.1152 (5)	0.0862 (6)	0.6947 (4)	0.0747 (13)
H2	−0.0844	0.0868	0.7575	0.090*
C3	−0.2261 (5)	0.0305 (6)	0.6565 (5)	0.0853 (16)
H3	−0.2701	−0.0075	0.6929	0.102*
C4	−0.2711 (4)	0.0316 (6)	0.5646 (5)	0.0872 (17)
H4	−0.3473	−0.0032	0.5387	0.105*
C5	−0.2061 (4)	0.0831 (5)	0.5091 (4)	0.0713 (13)
H5	−0.2372	0.0790	0.4464	0.086*
C6	−0.0947 (3)	0.1408 (4)	0.5466 (3)	0.0529 (10)
C7	−0.0323 (3)	0.2027 (4)	0.4819 (3)	0.0504 (9)
C9	0.0841 (4)	0.1548 (5)	0.3771 (3)	0.0593 (11)
H9	0.1233	0.2473	0.3972	0.071*
C10	−0.0030 (6)	0.1802 (8)	0.2850 (4)	0.0977 (18)
C11	−0.1855 (7)	0.1321 (13)	0.1803 (4)	0.154 (4)
H11A	−0.2653	0.1166	0.1832	0.230*
H11B	−0.1664	0.0624	0.1402	0.230*
H11C	−0.1786	0.2276	0.1581	0.230*
C12	0.1809 (4)	0.0481 (6)	0.3703 (3)	0.0690 (12)
H12A	0.1439	−0.0443	0.3503	0.083*
H12B	0.2160	0.0822	0.3238	0.083*
C13	0.2793 (4)	0.0247 (5)	0.4571 (3)	0.0686 (12)
H13	0.2439	−0.0166	0.5023	0.082*
C14	0.3408 (5)	0.1611 (7)	0.4953 (4)	0.0916 (16)
H14A	0.4107	0.1386	0.5432	0.137*
H14B	0.2885	0.2194	0.5188	0.137*
H14C	0.3629	0.2132	0.4483	0.137*
C15	0.3694 (5)	−0.0829 (7)	0.4414 (5)	0.108 (2)
H15D	0.3290	−0.1682	0.4133	0.162*
H15E	0.4244	−0.1078	0.4985	0.162*
H15F	0.4116	−0.0405	0.4024	0.162*
C16	0.0706 (4)	0.2026 (6)	0.6818 (3)	0.0713 (13)
O1'	0.4382 (3)	0.5441 (3)	0.9713 (2)	0.0661 (8)
O2'	0.4638 (4)	0.4078 (10)	1.2772 (2)	0.166 (3)
O3'	0.6053 (4)	0.3810 (7)	1.2172 (2)	0.1254 (19)
O4'	0.3230 (3)	0.2875 (6)	0.83975 (19)	0.1006 (15)
O5'	0.3585 (4)	0.3260 (7)	0.7077 (2)	0.1202 (19)
H5O'	0.2863	0.3153	0.6898	0.144*
N8'	0.4732 (3)	0.3372 (4)	1.05161 (18)	0.0482 (8)
H8'	0.5045	0.2526	1.0556	0.058*
C1'	0.5199 (4)	0.3315 (6)	0.8390 (3)	0.0646 (11)
C2'	0.6014 (5)	0.2992 (7)	0.7903 (3)	0.0898 (17)
H2'	0.5739	0.2751	0.7292	0.108*
C3'	0.7201 (6)	0.3027 (8)	0.8313 (4)	0.0956 (17)
H3'	0.7733	0.2801	0.7983	0.115*
C4'	0.7608 (5)	0.3390 (7)	0.9198 (4)	0.0895 (16)
H4'	0.8421	0.3411	0.9475	0.107*
C5'	0.6820 (4)	0.3735 (5)	0.9703 (3)	0.0668 (12)
H5'	0.7110	0.3986	1.0311	0.080*
C6'	0.5624 (3)	0.3704 (4)	0.9301 (2)	0.0503 (9)
C7'	0.4836 (3)	0.4234 (4)	0.9846 (2)	0.0477 (9)
C9'	0.4121 (3)	0.3780 (5)	1.1183 (3)	0.0559 (10)
H9'	0.3824	0.4764	1.1033	0.067*
C10'	0.4941 (4)	0.3828 (7)	1.2130 (3)	0.0809 (16)
C11'	0.6908 (7)	0.3928 (16)	1.3060 (5)	0.187 (6)
H11D	0.7694	0.3992	1.2990	0.280*
H11E	0.6852	0.3092	1.3415	0.280*
H11F	0.6742	0.4778	1.3361	0.280*
C12'	0.3037 (4)	0.2821 (6)	1.1113 (3)	0.0713 (12)
H12C	0.3275	0.1818	1.1111	0.086*
H12D	0.2763	0.2972	1.1647	0.086*
C13'	0.2017 (4)	0.3103 (7)	1.0274 (4)	0.0806 (14)
H13'	0.2335	0.3131	0.9748	0.097*
C14'	0.1083 (5)	0.1934 (9)	1.0117 (6)	0.130 (3)
H14D	0.1411	0.1043	0.9977	0.194*
H14E	0.0418	0.2203	0.9619	0.194*
H14F	0.0825	0.1814	1.0654	0.194*
C15'	0.1458 (6)	0.4519 (9)	1.0344 (7)	0.153 (4)
H15A	0.0879	0.4732	0.9780	0.230*
H15B	0.2055	0.5258	1.0473	0.230*
H15C	0.1079	0.4483	1.0823	0.230*
C16'	0.3934 (5)	0.3135 (6)	0.7961 (3)	0.0764 (15)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0790 (19)	0.0564 (19)	0.0714 (18)	−0.0007 (16)	0.0258 (15)	−0.0024 (15)
O2	0.207 (6)	0.229 (8)	0.079 (3)	−0.066 (6)	−0.003 (3)	0.058 (4)
O3	0.084 (2)	0.120 (3)	0.069 (2)	−0.005 (3)	−0.0092 (18)	−0.013 (2)
O4	0.076 (2)	0.139 (3)	0.0525 (16)	−0.042 (2)	0.0167 (15)	−0.0039 (19)
O5	0.098 (3)	0.246 (6)	0.0529 (19)	−0.062 (4)	0.0223 (18)	−0.010 (3)
N8	0.0596 (19)	0.0522 (19)	0.0487 (17)	−0.0017 (16)	0.0211 (15)	0.0014 (15)
C1	0.060 (2)	0.062 (3)	0.063 (2)	0.000 (2)	0.027 (2)	−0.004 (2)
C2	0.079 (3)	0.077 (3)	0.083 (3)	−0.002 (3)	0.046 (3)	0.002 (3)
C3	0.086 (4)	0.062 (3)	0.134 (5)	−0.003 (3)	0.074 (4)	−0.002 (3)
C4	0.051 (3)	0.072 (3)	0.143 (5)	−0.006 (2)	0.034 (3)	−0.010 (4)
C5	0.056 (3)	0.065 (3)	0.093 (3)	−0.006 (2)	0.023 (2)	−0.012 (3)
C6	0.048 (2)	0.043 (2)	0.071 (3)	0.0010 (17)	0.0212 (19)	−0.0055 (19)
C7	0.050 (2)	0.045 (2)	0.051 (2)	−0.0057 (18)	0.0060 (17)	−0.0049 (18)
C9	0.064 (2)	0.064 (3)	0.051 (2)	−0.007 (2)	0.0186 (19)	0.001 (2)
C10	0.112 (5)	0.117 (5)	0.056 (3)	−0.017 (4)	0.011 (3)	0.000 (3)
C11	0.140 (6)	0.190 (9)	0.088 (4)	0.024 (7)	−0.039 (4)	−0.017 (5)
C12	0.078 (3)	0.074 (3)	0.063 (3)	−0.013 (3)	0.034 (2)	−0.015 (2)
C13	0.067 (3)	0.070 (3)	0.077 (3)	0.004 (2)	0.032 (2)	0.004 (2)
C14	0.079 (3)	0.089 (4)	0.099 (4)	−0.001 (3)	0.011 (3)	−0.014 (3)
C15	0.089 (4)	0.070 (4)	0.178 (7)	0.007 (3)	0.060 (4)	−0.007 (4)
C16	0.070 (3)	0.099 (4)	0.047 (2)	−0.014 (3)	0.019 (2)	−0.009 (2)
O1'	0.0762 (19)	0.0520 (18)	0.0743 (18)	0.0085 (15)	0.0278 (15)	0.0072 (15)
O2'	0.111 (3)	0.333 (10)	0.054 (2)	0.047 (5)	0.025 (2)	−0.035 (4)
O3'	0.079 (2)	0.219 (6)	0.064 (2)	0.023 (3)	−0.0038 (18)	−0.036 (3)
O4'	0.078 (2)	0.178 (4)	0.0489 (16)	−0.040 (3)	0.0213 (16)	−0.021 (2)
O5'	0.098 (3)	0.216 (5)	0.0476 (17)	−0.070 (3)	0.0213 (17)	−0.014 (2)
N8'	0.0503 (17)	0.0531 (19)	0.0432 (16)	0.0068 (15)	0.0161 (14)	−0.0014 (14)
C1'	0.071 (3)	0.074 (3)	0.056 (2)	−0.014 (2)	0.029 (2)	−0.007 (2)
C2'	0.102 (4)	0.110 (5)	0.073 (3)	−0.017 (4)	0.051 (3)	−0.017 (3)
C3'	0.091 (4)	0.104 (4)	0.114 (4)	0.005 (3)	0.064 (4)	−0.011 (4)
C4'	0.059 (3)	0.089 (4)	0.123 (5)	0.007 (3)	0.030 (3)	0.003 (4)
C5'	0.057 (2)	0.073 (3)	0.073 (3)	0.005 (2)	0.022 (2)	0.004 (2)
C6'	0.054 (2)	0.044 (2)	0.052 (2)	−0.0031 (17)	0.0144 (18)	0.0017 (17)
C7'	0.046 (2)	0.050 (2)	0.044 (2)	−0.0051 (18)	0.0063 (17)	−0.0036 (17)
C9'	0.053 (2)	0.063 (3)	0.055 (2)	0.0100 (19)	0.0195 (18)	−0.005 (2)
C10'	0.072 (3)	0.124 (5)	0.049 (2)	0.026 (3)	0.021 (2)	−0.012 (3)
C11'	0.126 (6)	0.322 (17)	0.080 (4)	0.076 (9)	−0.025 (4)	−0.051 (7)
C12'	0.064 (3)	0.073 (3)	0.082 (3)	0.007 (2)	0.030 (2)	0.010 (3)
C13'	0.055 (2)	0.102 (4)	0.092 (3)	−0.009 (3)	0.032 (2)	−0.010 (3)
C14'	0.066 (3)	0.106 (5)	0.206 (8)	−0.012 (4)	0.021 (4)	−0.023 (6)
C15'	0.084 (4)	0.103 (6)	0.242 (10)	0.016 (4)	−0.007 (5)	0.018 (6)
C16'	0.089 (3)	0.100 (4)	0.042 (2)	−0.031 (3)	0.021 (2)	−0.015 (2)

Geometric parameters (Å, º)

O1—C7	1.234 (5)	O1'—C7'	1.231 (5)
O2—C10	1.208 (7)	O2'—C10'	1.160 (5)
O3—C10	1.276 (8)	O3'—C10'	1.289 (6)
O3—C11	1.479 (7)	O3'—C11'	1.453 (7)
O4—C16	1.199 (5)	O4'—C16'	1.224 (5)
O5—C16	1.300 (5)	O5'—C16'	1.307 (5)
O5—H5O	0.8200	O5'—H5O'	0.8200
N8—C7	1.325 (5)	N8'—C7'	1.334 (5)
N8—C9	1.454 (5)	N8'—C9'	1.454 (5)
N8—H8	0.8600	N8'—H8'	0.8600
C1—C6	1.391 (6)	C1'—C6'	1.394 (5)
C1—C2	1.392 (6)	C1'—C2'	1.399 (6)
C1—C16	1.472 (6)	C1'—C16'	1.456 (7)
C2—C3	1.371 (8)	C2'—C3'	1.360 (8)
C2—H2	0.9300	C2'—H2'	0.9300
C3—C4	1.360 (8)	C3'—C4'	1.351 (8)
C3—H3	0.9300	C3'—H3'	0.9300
C4—C5	1.377 (7)	C4'—C5'	1.398 (7)
C4—H4	0.9300	C4'—H4'	0.9300
C5—C6	1.381 (6)	C5'—C6'	1.368 (6)
C5—H5	0.9300	C5'—H5'	0.9300
C6—C7	1.502 (6)	C6'—C7'	1.491 (6)
C9—C10	1.514 (7)	C9'—C10'	1.503 (6)
C9—C12	1.531 (7)	C9'—C12'	1.530 (6)
C9—H9	0.9800	C9'—H9'	0.9800
C11—H11A	0.9600	C11'—H11D	0.9600
C11—H11B	0.9600	C11'—H11E	0.9600
C11—H11C	0.9600	C11'—H11F	0.9600
C12—C13	1.516 (7)	C12'—C13'	1.516 (7)
C12—H12A	0.9700	C12'—H12C	0.9700
C12—H12B	0.9700	C12'—H12D	0.9700
C13—C14	1.491 (8)	C13'—C15'	1.483 (10)
C13—C15	1.520 (7)	C13'—C14'	1.512 (9)
C13—H13	0.9800	C13'—H13'	0.9800
C14—H14A	0.9600	C14'—H14D	0.9600
C14—H14B	0.9600	C14'—H14E	0.9600
C14—H14C	0.9600	C14'—H14F	0.9600
C15—H15D	0.9600	C15'—H15A	0.9600
C15—H15E	0.9600	C15'—H15B	0.9600
C15—H15F	0.9600	C15'—H15C	0.9600
C10—O3—C11	115.6 (6)	C10'—O3'—C11'	118.1 (5)
C16—O5—H5O	109.5	C16'—O5'—H5O'	109.5
C7—N8—C9	121.4 (4)	C7'—N8'—C9'	123.8 (4)
C7—N8—H8	119.3	C7'—N8'—H8'	118.1
C9—N8—H8	119.3	C9'—N8'—H8'	118.1
C6—C1—C2	119.4 (4)	C6'—C1'—C2'	118.9 (4)
C6—C1—C16	120.0 (4)	C6'—C1'—C16'	121.2 (4)
C2—C1—C16	120.7 (4)	C2'—C1'—C16'	119.7 (4)
C3—C2—C1	120.8 (5)	C3'—C2'—C1'	120.9 (5)
C3—C2—H2	119.6	C3'—C2'—H2'	119.6
C1—C2—H2	119.6	C1'—C2'—H2'	119.6
C4—C3—C2	119.2 (5)	C4'—C3'—C2'	120.0 (5)
C4—C3—H3	120.4	C4'—C3'—H3'	120.0
C2—C3—H3	120.4	C2'—C3'—H3'	120.0
C3—C4—C5	121.4 (5)	C3'—C4'—C5'	120.7 (5)
C3—C4—H4	119.3	C3'—C4'—H4'	119.7
C5—C4—H4	119.3	C5'—C4'—H4'	119.7
C4—C5—C6	119.9 (5)	C6'—C5'—C4'	120.0 (5)
C4—C5—H5	120.0	C6'—C5'—H5'	120.0
C6—C5—H5	120.0	C4'—C5'—H5'	120.0
C5—C6—C1	119.2 (4)	C5'—C6'—C1'	119.5 (4)
C5—C6—C7	116.8 (4)	C5'—C6'—C7'	117.3 (3)
C1—C6—C7	124.0 (3)	C1'—C6'—C7'	122.9 (4)
O1—C7—N8	122.6 (4)	O1'—C7'—N8'	122.9 (4)
O1—C7—C6	120.9 (4)	O1'—C7'—C6'	120.9 (4)
N8—C7—C6	116.2 (4)	N8'—C7'—C6'	116.0 (4)
N8—C9—C10	113.1 (4)	N8'—C9'—C10'	112.3 (3)
N8—C9—C12	111.3 (4)	N8'—C9'—C12'	111.3 (4)
C10—C9—C12	110.9 (4)	C10'—C9'—C12'	112.4 (4)
N8—C9—H9	107.0	N8'—C9'—H9'	106.8
C10—C9—H9	107.0	C10'—C9'—H9'	106.8
C12—C9—H9	107.0	C12'—C9'—H9'	106.8
O2—C10—O3	123.1 (6)	O2'—C10'—O3'	120.4 (5)
O2—C10—C9	121.9 (6)	O2'—C10'—C9'	124.2 (5)
O3—C10—C9	115.0 (5)	O3'—C10'—C9'	114.5 (4)
O3—C11—H11A	109.5	O3'—C11'—H11D	109.5
O3—C11—H11B	109.5	O3'—C11'—H11E	109.5
H11A—C11—H11B	109.5	H11D—C11'—H11E	109.5
O3—C11—H11C	109.5	O3'—C11'—H11F	109.5
H11A—C11—H11C	109.5	H11D—C11'—H11F	109.5
H11B—C11—H11C	109.5	H11E—C11'—H11F	109.5
C13—C12—C9	115.5 (3)	C13'—C12'—C9'	113.8 (4)
C13—C12—H12A	108.4	C13'—C12'—H12C	108.8
C9—C12—H12A	108.4	C9'—C12'—H12C	108.8
C13—C12—H12B	108.4	C13'—C12'—H12D	108.8
C9—C12—H12B	108.4	C9'—C12'—H12D	108.8
H12A—C12—H12B	107.5	H12C—C12'—H12D	107.7
C14—C13—C12	113.0 (4)	C15'—C13'—C14'	109.2 (5)
C14—C13—C15	109.6 (4)	C15'—C13'—C12'	110.6 (5)
C12—C13—C15	110.3 (4)	C14'—C13'—C12'	112.2 (5)
C14—C13—H13	107.9	C15'—C13'—H13'	108.2
C12—C13—H13	107.9	C14'—C13'—H13'	108.2
C15—C13—H13	107.9	C12'—C13'—H13'	108.2
C13—C14—H14A	109.5	C13'—C14'—H14D	109.5
C13—C14—H14B	109.5	C13'—C14'—H14E	109.5
H14A—C14—H14B	109.5	H14D—C14'—H14E	109.5
C13—C14—H14C	109.5	C13'—C14'—H14F	109.5
H14A—C14—H14C	109.5	H14D—C14'—H14F	109.5
H14B—C14—H14C	109.5	H14E—C14'—H14F	109.5
C13—C15—H15D	109.5	C13'—C15'—H15A	109.5
C13—C15—H15E	109.5	C13'—C15'—H15B	109.5
H15D—C15—H15E	109.5	H15A—C15'—H15B	109.5
C13—C15—H15F	109.5	C13'—C15'—H15C	109.5
H15D—C15—H15F	109.5	H15A—C15'—H15C	109.5
H15E—C15—H15F	109.5	H15B—C15'—H15C	109.5
O4—C16—O5	121.8 (4)	O4'—C16'—O5'	121.4 (5)
O4—C16—C1	124.3 (4)	O4'—C16'—C1'	122.2 (4)
O5—C16—C1	113.9 (4)	O5'—C16'—C1'	116.4 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O5—H5O···O4′	0.82	1.82	2.639 (5)	174
N8—H8···O1^i	0.86	2.11	2.946 (5)	164
O5′—H5O′···O4	0.82	1.84	2.641 (5)	166
N8′—H8′···O1′^ii	0.86	2.12	2.962 (5)	165

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