Cinerin C: a macrophyllin-type bicyclo­[3.2.1]octane neolignan from Pleurothyrium cinereum (Lauraceae)

The structure of naturally-occurring cinerin C [systematic name: (7S,8R,3′R,4′S,5′R)-Δ^8′-4′-hy­droxy-5,5′,3′-trimeth­oxy-3,4-methyl­enedi­oxy-2′,3′,4′,5′-tetra­hydro-2′-oxo-7.3′,8.5′-neolignan], isolated from the ethanol extract of leaves of Pleurothyrium cinereum (Lauraceae), has previously been established by NMR and HRMS spectroscopy, and its absolute configuration established by circular dichroism measurements. For the first time, its crystal strucure has now been established by single-crystal X-ray analysis, as the monohydrate, C₂₂H₂₆O₇·H₂O. The bicyclo­octane moiety comprises fused cyclo­pentane and cyclo­hexenone rings which are almost coplanar. An inter­molecular O—H...O hydrogen bond links the 4′-OH and 5′-OCH₃ groups along the c axis.

S1. Comment

The title compound, (I), is a 7.3',8.5'-connected bicyclo[3.2.1]octane neolignan related to the macrophyllin type (Sefkow, 2003). This fascinating class of neolignans has attracted strong attention because of its chemistry, configuration and biological activities, and its occurrence is limited to certain plants belonging to the Magnoliaceae, Piperaceae and Lauraceae families (Coy-Barrera et al., 2009). Although the macrophyllin-type neolignans are less common than the guianin-type, the macrophyllin-type bicyclooctanes have exhibited better platelet-activating factor antagonism (anti-PAF activity) (Wang et al., 2002; Coy-Barrera et al., 2009). Indeed, the title compound, cinerin C was found to be the most potent PAF antagonist (IC₅₀ = 1.1 µM) among 26 evaluated neolignans (Coy et al., 2009a).

As part of our research on Lauraceaous neolignans, cinerin C was first isolated from the chloroform-soluble fraction obtained from an ethanol extract from leaves of Pleurothyrium cinereum (Lauraceae family; Coy et al., 2009b), a tree important to the Awá tribe in Colombia (Coy & Cuca, 2008). The planar structure was previously determined by NMR spectroscopy and high-resolution mass spectrometry (HRMS), establishing the bicyclo[3.2.1]octane moiety as well as the 7S,8R,3'R,4'S,5'R absolute configuration [by circular dichroism (CD) measurements; Coy et al., 2009b]. However, because there are no heavy atoms in the structure with a sufficiently strong anomalous scattering effect, a reliable crystallographic determination for the absolute configuration cannot be assured. Therefore, the enantiomer shown, (I), was chosen to be compatible with the configuration established by the CD measurements. In order to grow suitable crystals of (I), different crystallization methods were investigated, including: (a) recrystallization from various solvents and solvent mixtures by heating and subsequent slow cooling; (b) overlaying a solution of the compound with an antisolvent; and (c) diffusion of an antisolvent into a solution of the compound via the gas phase, in a closed chamber. Procedures (a) and (b) failed to afford any suitable crystals, and only procedure (c), using n-hexane as antisolvent, was successful.

So far, only the crystal structures of three macrophyllin-type neolignans have been reported: the oxidation product from macrophyllin B, (II) [Nectandra spp. Lauraceae; Rodrigues et al., 1984], piperulin A, (III) [Piper puberulum (Piperaceae); Zhang et al., 1995, 1996], and kadsurenin C, (IV) [Piper kadsura (Piperaceae); Jiang et al., 2003] The first two neolignans [which differ structurally from (I) by a methoxy group at C3' and a veratryl group instead of a 5-methoxypiperonyl group, as well as by an acetyl group at C4' in (III)] have similar relative configurations to that of (I), since both molecules have an aryl—C7/methyl—C8 trans-relationship, an endo-methyl group at C8 (which is easily determined from a ¹³C NMR chemical shift at ca 13 p.p.m.), and the 4'-OAc or 4'-OH group, respectively, oriented towards the aryl group. In addition, (I) and (IV) showed negative Cotton effects at 246 and 330 nm by CD measurements (Han et al., 1992), which means that both molecules have identical absolute configurations. On the other hand, although (II) exhibits a mutually trans arrangement of the aryl—C7 and methyl—C8 bonds, there are two significant differences: the OH group is placed at C2' and the methyl group at C8 has an exo orientation (¹³C NMR chemical shift at ca 16 p.p.m.; Guilhon et al., 1992). However, the space group for the two closely related molecules (III) and (IV) is P2₁2₁2₁ (orthorhombic), while (I) crystallizes in the hexagonal space group P6₁. This suggests that the 3'-methoxy group significantly affects the crystal system, possibly through the presence of an intermolecular O—H···O hydrogen bond between the 4'-OH and 3'-OCH₃ groups [O5—H5···O6ⁱ = 2.947 (3) Å; symmetry code: (i) -x + 1, -y, z + 1/2]. These hydrogen bonds link the molecules into chains which run parallel to the crystallographic c axis (Fig. 2).

A view of the solid-state conformation of (I), with the atom-numbering scheme, is provided in Fig. 1. Bond lengths agree in general with expected values (Zhang et al., 1995; Jiang et al., 2003), except for the elongated C7—C3' bond of 1.585 (3) Å, due to repulsion between the aromatic ring at atom C7 and atoms O5 and O6. The molecule of (I) can be subdivided into three parts, namely a 5-methoxypiperonyl group, a bicyclooctane group and an allyl group. The 5-methoxypiperonyl group has a methoxy group at C5 nearly coplanar with the benzene ring, with a C11—O3—C5—C6 torsion angle of 3.5 (5)°, and, as expected, the methylenedioxy group is twisted slightly out of the plane of the benzene ring, having torsion angles of C10—O2—C4—C3 = 6.6 (3)° and C10—O1—C3—C4 = -6.9 (3)°. In addition, the benzene ring is oriented through the C1—C7 bond by a gauche conformation with respect to atoms C7 and C8 of the bicyclooctane group, with torsion angles of C8—C7—C1—C6 = 60.4 (3)° and C3'—C7—C1—C2 = 118.1 (3)°.

The conformation of the bicyclooctane group is characterized by two fragments: a cyclohexenone fragment (comprising atoms C1', C2', C3', C4', C5' and C6') and a cyclopentane fragment (comprising atoms C3', C4', C5', C8 and C7, C5'), fused along C3'—C4'—C5'. Both fragments are almost planar, with maximum deviations from the least-square planes of 0.046 (2) for C2' and 0.108 (2) Å for C8. An approximate C₂ symmetry axis passing through atom C7 and the mid-point of the C5'—C4' bond relates the cyclopentane ring torsion angles, involving a half-chair form. Likewise, the cyclohexenone ring has an approximate mirror plane of symmetry passing through atoms C4' and C1', with two adjacent torsion angles [Cl'—C2'—C3'—C4'= 45.0 (3)° and C1'—C6'—C5'—C4' = -31.7 (3) °] indicating that the ring has a half-boat (1,2-diplanar) form. The dihedral angle between the fragments is 43.6 (2)°. The olefin from the allyl fragment is disordered over two sites, which lie on the same side of the methyl group at C8, with a C1···C7' distance of 5.817 (5) Å. Finally, the methoxy groups at C5' and C3' emerge with a pseudo-1,3-diequatorial orientation, with an O4···O6 distance of 4.866 (3) Å.

Related literature

For related literature, see: Coy & Cuca (2008); Coy et al. (2009a, 2009b); Coy-Barrera, Cuca-Suarez & Sefkow (2009); Guilhon et al. (1992); Han et al. (1992); Jiang et al. (2003); Rodrigues et al. (1984); Sefkow (2003); Spek (2009); Wang et al. (2002); Zhang et al. (1995, 1996).

S2. Experimental

Plant material was collected from P. cinereum in the indigenous reservation Awá at Alto Albí, Tumaco County, Department of Narinho, Colombia, in November 2005 and identified by biologist Ayda Lucia Patino. A voucher specimen (No. COL518334) was deposited at the Herbario Nacional Colombiano of the Universidad Nacional de Colombia in Bogota. Detailed extraction and isolation processes and spectroscopic features for (I) were previously reported (Coy et al., 2009b). The isolated compound was crystallized by the diffusion of n-hexane antisolvent vapour into a solution of the compound in ethyl acetate. Elemental analysis: C 65.7, H 6.3, O 27.9%; C₂₂H₂₆O₇ requires: C 65.7, H 6.5, O 27.8%.

S3. Refinement

The R_int value is relatively high because of the overall poor quality of the data, in turn the result of limited crystal quality. Friedel opposites were merged because of the absence of significant anomalous scattering effects. The crystal structure contains channels (ca 3.7 Å in diameter) containing water molecules. In spite of several attempts, the electron density in this area could not be resolved satisfactorily. Therefore, the contribution of the disordered solvent species was subtracted from the structure factor calculations using the SQUEEZE module of PLATON (Spek, 2009). The electron count of 71 per unit cell corresponds to approximately one water molecule per asymmetric unit. Although solvent atoms were not included in the refinement model, they are included in the calculation of the formula weight, density, µ and F(000).

The H atoms of the methyl groups and of the allyl group were placed geometrically and refined as riding with C—H = 0.96 (methyl) or 0.93 Å (allyl), and with U_iso(H) = 1.2U_eq(C). All other H atoms were located from a difference Fourier map and their positions were refined, with displacement parameters constrained to U_iso(H) = 1.2U_eq(C). For atom H5, the isotropic displacement parameter was also allowed to refine. The H atoms attached to C7 were modelled as disordered over two orientations, with the four C7—H and two H···H distances restrained to common refined values with an s.u. of 0.02 Å.

Computing details

Data collection: X-AREA (Stoe & Cie, 2004); cell refinement: X-AREA (Stoe & Cie, 2004); data reduction: X-RED (Stoe & Cie, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997), based on ORTEPIII (Burnett & Johnson, 1996), and DIAMOND (Brandenburg, 2007); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures

	Fig. 1. The molecular structure of (I), showing the atom-labelling scheme. One of the disordered vinyl groups has been omitted for clarity. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 2. The intermolecular hydrogen bonds (dashed lines) in the crystal structure of (I), running along the crystallographic c axis. With the exception of atom H5, all H atoms have been omitted for clarity. [Symmetry code: (i) -x + 1, -y, z + 1/2.]

(7S,8R,3'R,4'S,5'R)-Δ^8'-4'-hydroxy- 5,5',3'-trimethoxy-3,4-methylenedioxy-2',3',4',5'-tetrahydro-2'-oxo- 7.3',8.5'-neolignan monohydrate

Crystal data

C22H26O7·H2O	Melting point: 448 K
Mr = 420.46	Mo Kα radiation, λ = 0.71073 Å
Hexagonal, P61	Cell parameters from 27502 reflections
a = 18.2223 (12) Å	θ = 2.6–50.3°
c = 11.2387 (6) Å	µ = 0.10 mm^−1
V = 3231.9 (3) Å^3	T = 210 K
Z = 6	Needle, colourless
F(000) = 1344	1.0 × 0.35 × 0.34 mm
Dx = 1.296 Mg m^−3

Data collection

Stoe IPDS 2 diffractometer	1816 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.188
Plane graphite monochromator	θmax = 24.7°, θmin = 1.3°
Detector resolution: 6.67 pixels mm^-1	h = −20→21
ω scan, 0.5°	k = −21→21
19695 measured reflections	l = −12→13
1930 independent reflections

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.036	w = 1/[σ^2(Fo^2) + (0.054P)^2] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.092	(Δ/σ)max < 0.001
S = 1.04	Δρmax = 0.20 e Å^−3
1930 reflections	Δρmin = −0.16 e Å^−3
325 parameters	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
8 restraints	Extinction coefficient: 0.0038 (12)
Primary atom site location: structure-invariant direct methods	Absolute structure: Friedel opposites were merged because of the absence of significant anomalous scattering effects
Secondary atom site location: difference Fourier map

Special details

Experimental. Attempts to yield smaller crystals by cutting were not successful because of uncontrolled fragmentation.

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	Occ. (<1)
C1	0.35526 (15)	−0.09747 (15)	0.0278 (2)	0.0267 (5)
C2	0.32171 (16)	−0.12066 (17)	−0.0858 (2)	0.0307 (6)
H2	0.333 (2)	−0.150 (2)	−0.133 (3)	0.037*
C3	0.27196 (16)	−0.08865 (17)	−0.1265 (2)	0.0327 (6)
C4	0.25688 (17)	−0.03499 (17)	−0.0600 (3)	0.0339 (6)
C5	0.28924 (18)	−0.01127 (17)	0.0528 (3)	0.0356 (6)
C6	0.33845 (16)	−0.04412 (16)	0.0972 (2)	0.0310 (6)
H6	0.3637 (19)	−0.027 (2)	0.183 (3)	0.037*
C7	0.41150 (15)	−0.13042 (15)	0.0737 (2)	0.0256 (5)
H7	0.4149 (18)	−0.1670 (19)	0.003 (3)	0.031*
C8	0.38012 (16)	−0.18409 (16)	0.1880 (2)	0.0293 (6)
H8	0.3560 (19)	−0.1593 (19)	0.241 (3)	0.035*
C9	0.3202 (2)	−0.27837 (18)	0.1671 (3)	0.0440 (7)
H9A	0.2714	−0.2862	0.1239	0.053*
H9B	0.3027	−0.3070	0.2423	0.053*
H9C	0.3488	−0.3013	0.1219	0.053*
C10	0.1862 (2)	−0.0580 (2)	−0.2287 (3)	0.0464 (7)
H10A	0.199 (2)	−0.023 (3)	−0.294 (4)	0.056*
H10B	0.133 (3)	−0.099 (3)	−0.219 (4)	0.056*
C11	0.3140 (3)	0.0772 (2)	0.2215 (3)	0.0540 (9)
H11A	0.3009	0.0307	0.2741	0.065*
H11B	0.2944	0.1126	0.2559	0.065*
H11C	0.3742	0.1098	0.2099	0.065*
C12	0.5135 (2)	−0.1646 (2)	0.4494 (3)	0.0447 (7)
H12A	0.4952	−0.1945	0.5236	0.054*
H12B	0.5417	−0.1047	0.4640	0.054*
H12C	0.5518	−0.1787	0.4108	0.054*
C13	0.59942 (18)	0.08963 (18)	0.0967 (3)	0.0432 (7)
H13A	0.5921	0.1017	0.1776	0.052*
H13B	0.6131	0.1380	0.0479	0.052*
H13C	0.6446	0.0770	0.0926	0.052*
C1'	0.55934 (17)	−0.16483 (17)	0.1008 (2)	0.0330 (6)
C2'	0.56420 (16)	−0.08848 (17)	0.0479 (2)	0.0312 (6)
C3'	0.50582 (15)	−0.05989 (15)	0.1038 (2)	0.0263 (5)
C4'	0.51291 (16)	−0.06382 (15)	0.2390 (2)	0.0271 (6)
H4'	0.575 (2)	−0.0386 (19)	0.262 (3)	0.032*
C5'	0.46184 (16)	−0.16115 (16)	0.2559 (2)	0.0280 (5)
C6'	0.51047 (17)	−0.19813 (17)	0.1973 (2)	0.0328 (6)
H6'	0.505 (2)	−0.244 (2)	0.236 (3)	0.039*
C7'	0.6102 (2)	−0.2003 (2)	0.0447 (3)	0.0430 (7)
H7A'	0.603 (9)	−0.206 (5)	−0.040 (3)	0.052*	0.50
H7B'	0.577 (9)	−0.258 (2)	0.071 (8)	0.052*	0.50
H7C'	0.612 (9)	−0.191 (5)	−0.040 (3)	0.052*	0.50
H7D'	0.580 (9)	−0.261 (2)	0.053 (8)	0.052*	0.50
O1	0.23470 (14)	−0.10028 (14)	−0.23660 (19)	0.0473 (5)
O2	0.20904 (15)	−0.00975 (15)	−0.1233 (2)	0.0503 (6)
O3	0.27330 (16)	0.04545 (16)	0.1098 (2)	0.0532 (6)
O4	0.44152 (12)	−0.18833 (12)	0.37456 (17)	0.0348 (5)
O5	0.47394 (12)	−0.02205 (11)	0.29278 (18)	0.0314 (4)
H5	0.478 (2)	−0.021 (2)	0.367 (4)	0.035 (9)*
O6	0.52241 (11)	0.01819 (10)	0.05493 (16)	0.0308 (4)
O7	0.60851 (14)	−0.05200 (15)	−0.03744 (19)	0.0495 (6)
C8'	0.6960 (6)	−0.1665 (6)	0.1105 (11)	0.053 (2)	0.50
H8'	0.6971	−0.1746	0.1920	0.063*	0.50
C9'	0.7654 (9)	−0.1273 (7)	0.0517 (14)	0.079 (3)	0.50
H9A'	0.7641	−0.1192	−0.0298	0.094*	0.50
H9B'	0.8171	−0.1068	0.0906	0.094*	0.50
C81'	0.7041 (5)	−0.1394 (6)	0.0533 (9)	0.0378 (15)	0.50
H81'	0.7274	−0.0866	0.0169	0.045*	0.50
C91'	0.7536 (9)	−0.1604 (8)	0.1118 (11)	0.072 (3)	0.50
H91C	0.7306	−0.2131	0.1483	0.086*	0.50
H91D	0.8115	−0.1224	0.1167	0.086*	0.50

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0209 (11)	0.0229 (12)	0.0307 (13)	0.0068 (10)	0.0003 (10)	0.0011 (10)
C2	0.0274 (12)	0.0305 (13)	0.0326 (14)	0.0133 (11)	0.0001 (11)	−0.0048 (11)
C3	0.0296 (13)	0.0335 (13)	0.0284 (13)	0.0109 (11)	−0.0052 (11)	−0.0006 (11)
C4	0.0323 (13)	0.0324 (13)	0.0354 (15)	0.0150 (11)	−0.0054 (12)	0.0014 (12)
C5	0.0384 (14)	0.0356 (14)	0.0374 (15)	0.0219 (12)	−0.0023 (12)	−0.0029 (12)
C6	0.0295 (12)	0.0314 (13)	0.0316 (14)	0.0148 (11)	−0.0037 (11)	−0.0031 (11)
C7	0.0222 (11)	0.0245 (11)	0.0284 (12)	0.0104 (10)	0.0016 (10)	−0.0013 (10)
C8	0.0280 (13)	0.0251 (12)	0.0317 (14)	0.0110 (11)	0.0037 (11)	−0.0012 (11)
C9	0.0431 (16)	0.0280 (14)	0.0452 (16)	0.0059 (13)	0.0024 (14)	0.0020 (13)
C10	0.0512 (18)	0.0415 (17)	0.0488 (18)	0.0248 (15)	−0.0181 (16)	−0.0038 (16)
C11	0.085 (2)	0.0552 (19)	0.0421 (17)	0.0503 (19)	−0.0151 (17)	−0.0143 (16)
C12	0.066 (2)	0.0477 (17)	0.0342 (15)	0.0383 (16)	−0.0069 (15)	0.0019 (13)
C13	0.0348 (15)	0.0306 (14)	0.0487 (16)	0.0048 (12)	−0.0108 (14)	0.0058 (13)
C1'	0.0330 (13)	0.0384 (14)	0.0329 (14)	0.0219 (11)	−0.0020 (12)	−0.0076 (12)
C2'	0.0267 (12)	0.0388 (14)	0.0241 (12)	0.0134 (11)	0.0010 (11)	−0.0013 (12)
C3'	0.0259 (12)	0.0228 (11)	0.0277 (12)	0.0104 (10)	−0.0006 (10)	0.0040 (10)
C4'	0.0304 (13)	0.0229 (12)	0.0285 (13)	0.0138 (10)	0.0005 (10)	−0.0016 (10)
C5'	0.0317 (13)	0.0260 (12)	0.0275 (12)	0.0154 (10)	0.0019 (11)	0.0003 (10)
C6'	0.0381 (14)	0.0256 (13)	0.0390 (16)	0.0193 (12)	−0.0046 (13)	−0.0031 (12)
C7'	0.0376 (16)	0.0461 (16)	0.0512 (18)	0.0253 (14)	−0.0001 (15)	−0.0107 (15)
O1	0.0516 (12)	0.0590 (13)	0.0398 (11)	0.0339 (11)	−0.0198 (10)	−0.0128 (11)
O2	0.0612 (14)	0.0574 (13)	0.0495 (12)	0.0425 (12)	−0.0218 (12)	−0.0114 (11)
O3	0.0777 (16)	0.0636 (14)	0.0456 (12)	0.0559 (14)	−0.0199 (12)	−0.0196 (11)
O4	0.0441 (11)	0.0335 (10)	0.0285 (9)	0.0207 (9)	0.0024 (9)	0.0063 (8)
O5	0.0432 (11)	0.0307 (9)	0.0267 (10)	0.0234 (8)	−0.0020 (8)	−0.0029 (8)
O6	0.0260 (9)	0.0243 (9)	0.0350 (9)	0.0072 (7)	−0.0040 (8)	0.0052 (8)
O7	0.0466 (12)	0.0663 (15)	0.0442 (12)	0.0347 (12)	0.0164 (10)	0.0148 (11)
C8'	0.062 (6)	0.061 (5)	0.053 (5)	0.044 (4)	−0.003 (5)	0.000 (4)
C9'	0.070 (8)	0.062 (6)	0.106 (9)	0.035 (5)	−0.001 (7)	−0.006 (6)
C81'	0.035 (4)	0.048 (4)	0.041 (4)	0.028 (3)	−0.002 (3)	−0.004 (4)
C91'	0.056 (6)	0.084 (8)	0.093 (8)	0.049 (6)	−0.011 (6)	−0.001 (6)

Geometric parameters (Å, º)

C1—C2	1.387 (4)	C13—O6	1.434 (3)
C1—C6	1.395 (4)	C13—H13A	0.9600
C1—C7	1.514 (3)	C13—H13B	0.9600
C2—C3	1.379 (4)	C13—H13C	0.9600
C2—H2	0.86 (4)	C1'—C6'	1.340 (4)
C3—C4	1.363 (4)	C1'—C2'	1.474 (4)
C3—O1	1.376 (3)	C1'—C7'	1.508 (4)
C4—O2	1.371 (3)	C2'—O7	1.215 (3)
C4—C5	1.374 (4)	C2'—C3'	1.534 (4)
C5—O3	1.365 (3)	C3'—O6	1.410 (3)
C5—C6	1.396 (4)	C3'—C4'	1.530 (3)
C6—H6	1.05 (3)	C4'—O5	1.410 (3)
C7—C8	1.541 (4)	C4'—C5'	1.548 (3)
C7—C3'	1.585 (3)	C4'—H4'	1.01 (3)
C7—H7	1.06 (3)	C5'—O4	1.406 (3)
C8—C9	1.524 (4)	C5'—C6'	1.507 (4)
C8—C5'	1.534 (4)	C6'—H6'	0.90 (3)
C8—H8	0.98 (3)	C7'—C81'	1.506 (9)
C9—H9A	0.9600	C7'—C8'	1.551 (11)
C9—H9B	0.9600	C7'—H7A'	0.96 (3)
C9—H9C	0.9600	C7'—H7B'	0.96 (3)
C10—O2	1.408 (4)	C7'—H7C'	0.96 (3)
C10—O1	1.438 (4)	C7'—H7D'	0.96 (3)
C10—H10A	0.91 (4)	O5—H5	0.83 (4)
C10—H10B	0.89 (4)	C8'—C9'	1.280 (17)
C11—O3	1.426 (4)	C8'—H8'	0.9300
C11—H11A	0.9600	C9'—H9A'	0.9300
C11—H11B	0.9600	C9'—H9B'	0.9300
C11—H11C	0.9600	C81'—C91'	1.317 (13)
C12—O4	1.431 (4)	C81'—H81'	0.9300
C12—H12A	0.9600	C91'—H91C	0.9300
C12—H12B	0.9600	C91'—H91D	0.9300
C12—H12C	0.9600
C2—C1—C6	120.7 (2)	H13B—C13—H13C	109.5
C2—C1—C7	118.4 (2)	C6'—C1'—C2'	117.8 (2)
C6—C1—C7	120.9 (2)	C6'—C1'—C7'	123.8 (3)
C3—C2—C1	117.4 (3)	C2'—C1'—C7'	118.4 (2)
C3—C2—H2	119 (2)	O7—C2'—C1'	123.0 (3)
C1—C2—H2	124 (2)	O7—C2'—C3'	121.4 (3)
C4—C3—O1	110.0 (2)	C1'—C2'—C3'	115.5 (2)
C4—C3—C2	122.2 (2)	O6—C3'—C4'	117.0 (2)
O1—C3—C2	127.7 (3)	O6—C3'—C2'	110.4 (2)
C3—C4—O2	110.3 (2)	C4'—C3'—C2'	107.6 (2)
C3—C4—C5	121.5 (2)	O6—C3'—C7	109.50 (19)
O2—C4—C5	128.2 (3)	C4'—C3'—C7	104.9 (2)
O3—C5—C4	116.8 (3)	C2'—C3'—C7	107.0 (2)
O3—C5—C6	125.7 (3)	O5—C4'—C3'	108.8 (2)
C4—C5—C6	117.5 (3)	O5—C4'—C5'	112.9 (2)
C1—C6—C5	120.8 (3)	C3'—C4'—C5'	99.13 (19)
C1—C6—H6	120.4 (17)	O5—C4'—H4'	112.8 (17)
C5—C6—H6	118.8 (17)	C3'—C4'—H4'	109.7 (16)
C1—C7—C8	115.2 (2)	C5'—C4'—H4'	112.5 (17)
C1—C7—C3'	115.20 (19)	O4—C5'—C6'	111.6 (2)
C8—C7—C3'	104.2 (2)	O4—C5'—C8	109.1 (2)
C1—C7—H7	105.1 (16)	C6'—C5'—C8	111.6 (2)
C8—C7—H7	110.1 (16)	O4—C5'—C4'	114.9 (2)
C3'—C7—H7	106.9 (15)	C6'—C5'—C4'	107.9 (2)
C9—C8—C5'	115.8 (2)	C8—C5'—C4'	101.4 (2)
C9—C8—C7	114.6 (2)	C1'—C6'—C5'	123.9 (3)
C5'—C8—C7	103.89 (19)	C1'—C6'—H6'	123 (2)
C9—C8—H8	112.4 (18)	C5'—C6'—H6'	113 (2)
C5'—C8—H8	99.8 (17)	C81'—C7'—C1'	111.9 (3)
C7—C8—H8	109.1 (18)	C1'—C7'—C8'	110.1 (4)
C8—C9—H9A	109.5	C1'—C7'—H7A'	112 (10)
C8—C9—H9B	109.5	C8'—C7'—H7A'	125 (9)
H9A—C9—H9B	109.5	C81'—C7'—H7B'	130 (2)
C8—C9—H9C	109.5	C1'—C7'—H7B'	99 (8)
H9A—C9—H9C	109.5	C8'—C7'—H7B'	104 (10)
H9B—C9—H9C	109.5	H7A'—C7'—H7B'	102 (6)
O2—C10—O1	108.5 (2)	C1'—C7'—H7C'	108 (9)
O2—C10—H10A	110 (2)	C1'—C7'—H7D'	110 (7)
O1—C10—H10A	108 (2)	C8'—C7'—H7D'	107 (10)
O2—C10—H10B	106 (3)	H7C'—C7'—H7D'	104 (6)
O1—C10—H10B	105 (3)	C3—O1—C10	104.5 (2)
H10A—C10—H10B	119 (4)	C4—O2—C10	105.5 (2)
O3—C11—H11A	109.5	C5—O3—C11	117.1 (2)
O3—C11—H11B	109.5	C5'—O4—C12	114.3 (2)
H11A—C11—H11B	109.5	C4'—O5—H5	112 (2)
O3—C11—H11C	109.5	C3'—O6—C13	114.0 (2)
H11A—C11—H11C	109.5	C9'—C8'—C7'	119.6 (14)
H11B—C11—H11C	109.5	C9'—C8'—H8'	120.2
O4—C12—H12A	109.5	C7'—C8'—H8'	120.2
O4—C12—H12B	109.5	C8'—C9'—H9A'	120.0
H12A—C12—H12B	109.5	C8'—C9'—H9B'	120.0
O4—C12—H12C	109.5	H9A'—C9'—H9B'	120.0
H12A—C12—H12C	109.5	C91'—C81'—C7'	120.6 (11)
H12B—C12—H12C	109.5	C91'—C81'—H81'	119.7
O6—C13—H13A	109.5	C7'—C81'—H81'	119.7
O6—C13—H13B	109.5	C81'—C91'—H91C	120.0
H13A—C13—H13B	109.5	C81'—C91'—H91D	120.0
O6—C13—H13C	109.5	H91C—C91'—H91D	120.0
H13A—C13—H13C	109.5
C6—C1—C2—C3	0.3 (4)	O6—C3'—C4'—C5'	161.5 (2)
C7—C1—C2—C3	−178.8 (2)	C2'—C3'—C4'—C5'	−73.6 (2)
C1—C2—C3—C4	1.2 (4)	C7—C3'—C4'—C5'	40.0 (2)
C1—C2—C3—O1	177.5 (3)	C9—C8—C5'—O4	−68.9 (3)
O1—C3—C4—O2	0.3 (3)	C7—C8—C5'—O4	164.60 (19)
C2—C3—C4—O2	177.2 (3)	C9—C8—C5'—C6'	54.9 (3)
O1—C3—C4—C5	−178.3 (3)	C7—C8—C5'—C6'	−71.7 (3)
C2—C3—C4—C5	−1.4 (4)	C9—C8—C5'—C4'	169.5 (2)
C3—C4—C5—O3	177.3 (3)	C7—C8—C5'—C4'	43.0 (2)
O2—C4—C5—O3	−1.0 (5)	O5—C4'—C5'—O4	−53.7 (3)
C3—C4—C5—C6	0.1 (4)	C3'—C4'—C5'—O4	−168.7 (2)
O2—C4—C5—C6	−178.2 (3)	O5—C4'—C5'—C6'	−178.8 (2)
C2—C1—C6—C5	−1.5 (4)	C3'—C4'—C5'—C6'	66.1 (2)
C7—C1—C6—C5	177.5 (2)	O5—C4'—C5'—C8	63.8 (3)
O3—C5—C6—C1	−175.6 (3)	C3'—C4'—C5'—C8	−51.2 (2)
C4—C5—C6—C1	1.4 (4)	C2'—C1'—C6'—C5'	−1.3 (4)
C2—C1—C7—C8	−120.6 (3)	C7'—C1'—C6'—C5'	177.9 (3)
C6—C1—C7—C8	60.4 (3)	O4—C5'—C6'—C1'	−158.8 (2)
C2—C1—C7—C3'	118.1 (3)	C8—C5'—C6'—C1'	78.8 (3)
C6—C1—C7—C3'	−61.0 (3)	C4'—C5'—C6'—C1'	−31.7 (3)
C1—C7—C8—C9	88.1 (3)	C6'—C1'—C7'—C81'	−115.2 (5)
C3'—C7—C8—C9	−144.8 (2)	C2'—C1'—C7'—C81'	64.1 (5)
C1—C7—C8—C5'	−144.7 (2)	C6'—C1'—C7'—C8'	−83.6 (6)
C3'—C7—C8—C5'	−17.5 (2)	C2'—C1'—C7'—C8'	95.5 (6)
C6'—C1'—C2'—O7	177.8 (3)	C4—C3—O1—C10	−6.9 (3)
C7'—C1'—C2'—O7	−1.4 (4)	C2—C3—O1—C10	176.4 (3)
C6'—C1'—C2'—C3'	−5.1 (3)	O2—C10—O1—C3	11.0 (4)
C7'—C1'—C2'—C3'	175.7 (2)	C3—C4—O2—C10	6.6 (3)
O7—C2'—C3'—O6	−9.2 (3)	C5—C4—O2—C10	−174.9 (3)
C1'—C2'—C3'—O6	173.7 (2)	O1—C10—O2—C4	−10.8 (4)
O7—C2'—C3'—C4'	−137.9 (3)	C4—C5—O3—C11	−173.5 (3)
C1'—C2'—C3'—C4'	45.0 (3)	C6—C5—O3—C11	3.5 (5)
O7—C2'—C3'—C7	109.9 (3)	C6'—C5'—O4—C12	60.8 (3)
C1'—C2'—C3'—C7	−67.2 (3)	C8—C5'—O4—C12	−175.5 (2)
C1—C7—C3'—O6	−13.6 (3)	C4'—C5'—O4—C12	−62.5 (3)
C8—C7—C3'—O6	−140.8 (2)	C4'—C3'—O6—C13	48.9 (3)
C1—C7—C3'—C4'	112.7 (2)	C2'—C3'—O6—C13	−74.5 (3)
C8—C7—C3'—C4'	−14.4 (2)	C7—C3'—O6—C13	168.0 (2)
C1—C7—C3'—C2'	−133.3 (2)	C81'—C7'—C8'—C9'	−24.6 (9)
C8—C7—C3'—C2'	99.6 (2)	C1'—C7'—C8'—C9'	−123.7 (9)
O6—C3'—C4'—O5	43.4 (3)	C1'—C7'—C81'—C91'	118.5 (8)
C2'—C3'—C4'—O5	168.23 (19)	C8'—C7'—C81'—C91'	26.1 (10)
C7—C3'—C4'—O5	−78.1 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O5—H5···O6^i	0.83 (4)	2.12 (4)	2.947 (3)	175 (3)

Symmetry code: (i) −x+1, −y, z+1/2.