3,4,6-Tri-O-acetyl-1,2-O-[1-(exo-ethoxy)ethyl­idene]-β-D-manno­pyranose 0.11-hydrate

The title compound, C₁₆H₂₄O₁₀·0.11H₂O, is a key inter­mediate in the synthesis of 2-de­oxy-2-[¹⁸F]fluoro-D-glucose (¹⁸F-FDG), which is the most widely used mol­ecular-imaging probe for positron emission tomography (PET). The crystal structure has two independent mol­ecules (A and B) in the asymmetric unit, with closely comparable geometries. The pyran­ose ring adopts a ⁴C₁ conformation [Cremer–Pople puckering parameters: Q = 0.553 (2) Å, θ = 16.2 (2)° and φ = 290.4 (8)° for mol­ecule A, and Q = 0.529 (2) Å, θ =15.3 (3)° and φ = 268.2 (9)° for mol­ecule B], and the dioxolane ring adopts an envelope conformation. The chiral centre in the dioxolane ring, introduced during the synthesis of the compound, has an R configuration, with the eth­oxy group exo to the manno­pyran­ose ring. The asymmetric unit also contains one water mol­ecule with a refined site-occupancy factor of 0.222 (8), which bridges between mol­ecules A and B via O—H...O hydrogen bonds.

S1. Comment

To date, 2-deoxy-2-[¹⁸F]fluoro-D-glucose (¹⁸F-FDG) [(III); see scheme] has been the most widely used molecular-imaging probe in positron emission tomography (PET) (Alavi & Reivich, 2002; Nutt, 2002). Due to its structural similarity to glucose, ¹⁸F-FDG is used to measure the cellular uptake and metabolic rates of local glucose in physiological or pathophysiological conditions. Nowadays, ¹⁸F-FDG-PET is used not only in research laboratories to address questions of scientific interest, but also in hospitals as a routine clinical diagnostic tool in cardiology, neurology and oncology (Gambhir et al., 2001).

The title compound, (I), is one of the key intermediates during the synthesis of ¹⁸F-FDG (Fig. 2). Hydrolysis of the 1,2-orthoacetate groups of (I) with 1M aqueous HCl, followed by triflation with Tf₂O-pyridine (Tf is trifluoromethanesulfonate?), yields 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-β-D-mannopyranose (mannose trifluoromethanesulfonate), (II). Nucleophilic [¹⁸F] fluorination and acidic/basic deprotection of (II) then provides ¹⁸F-FDG, (III) (see scheme) (Toyokuni et al., 2004). Although hydrolysis of (I) gives the desired 1,3,4,6-tetra-O-acetyl-β-D-mannopyranose product, the reaction also produces an undesired 2,3,4,6-tetra-O-acetyl-β-D-mannopyranose by-product, and the yield of the desired reaction is as low as 25–30%. The study of the three-dimensional structure of (I) can help us to understand not only its chemical properties but also the mechanism of the hydrolysis reaction.

The crystal structure of (I) has two independment molecules in the asymmetric unit (molecules A and B; Fig. 1) and a water molecule with a refined site-occupancy factor of 0.222 (8). In molecule A, the C—C bonds within the pyranose ring have bond lengths ranging between 1.510 (3) and 1.523 (3) Å, in accordance with those in a survey of 27 pyranoid rings reported by Arnott & Scott (1972). The exocyclic C1—O1 bond length of 1.398 (3) Å is the shortest in the pyranose ring. The C1—O5 and C5—O5 bond lengths are 1.422 (3) and 1.437 (2) Å, respectively, indicating that C1—O1 is equatorial. The bond angles at the C atoms of the ring vary between 107.28 (15) and 114.27 (17)°, with the angles at C1 and C2 larger than the expected values of 109.2 and 110.5°, respectively, and the angle at C5 smaller than the expected 110.0°. Although the O5—C1—O1 angle [106.47 (18)°] appears normal for equatorial C1—O1, the C5—O5—C1 angle [113.45 (17)°] is somewhat larger than the expected 112.0°. These data indicate that C1—O1 is distorted from an idealized equatorial orientation and is bisectional. This could be explained by the presence of the ethoxyethylidene group at the 1,2-positions. The pyranose ring of molecule B exhibits similar structural features to that of molecule A.

The endocyclic torsion angles in the pyranose rings vary from 40.2 (3) to 65.3 (2)° (absolute values), indicating that the six-membered rings are distorted from an idealized ⁴C₁ chair conformation. The conformation in (I) is different from the skew conformation (³S₅) reported for 3,4,6-tri-O-acetyl-l,2-O-[1-(exo-ethoxy)ethylidene]-α-D-glucopyranose (Heitmann et al., 1974). Further insight into the distortions is obtained from the Cremer–Pople puckering parameters (Cremer & Pople, 1975): for molecule A, Q = 0.553 (2) Å, θ = 16.2 (2)° and ϕ = 290.4 (8)°; for molecule B, Q = 0.529 (2) Å, θ = 15.3 (3)° and ϕ = 268.2 (9)°. The extent of the ring distortion, embodied in the value of θ, is slightly greater for molecule A than for molecule B. The direction of the ring distortion, embodied in the value of ϕ, shows a distortion towards a B_C2,C5 conformation for molecule A and ^C1S_C5 for molecule B (Jeffrey & Yates, 1979).

In the five-membered ring of molecule A, the C2—O2—C7—O1 torsion angle [5.2 (2)°] indicates an approximately planar structure for these four atoms (r.m.s. deviation from the mean plane = 0.023 Å). Atom C1 deviates from the mean plane by 0.53 Å. In molecule B, the corresponding values are 3.3 (2)°, r.m.s. deviation = 0.015 Å and deviation of C1' = 0.53Å. Thus, the conformation of the dioxolane ring is an envelope, with Cremer–Pople parameters of Q = 0.3486 (21) Å and ϕ = 43.2 (3)° for molecule A, and Q = 0.3392 (21) Å and ϕ = 40.7 (4)° for molecule B.

The bond lengths and angles in the acetoxy groups and acetoxymethyl substituent all appear normal, although the bond angles at C6 [107.47 (16)°] and C6' [107.26 (18)°] are, respectively, 4.3 and 4.5° smaller than the average bond angle (111.8°) found in 23 other pyranose derivatives (Arnott & Scott, 1972). The three substituents all adopt the same equatorial orientation as on the parent compound β-D-mannose, due to the ⁴C₁ conformation of the mannopyranose ring. Similar to what is observed for many acetylated sugars, the acetyl groups directly connected to the sugar ring [i.e. C(ring)—O—C(═O)] are close to coplanar with the H atom bound to the same ring C atom (Haines & Hughes, 2007). The O5—C5—C6—O6 [-71.0 (2)°] and O5'—C5'—C6'—O6' [-63.2 (2)°] torsion angles indicate a gg arrangement of the exocyclic C6—O6 (C6'—O6') bond (i.e. H5 anti to O6, and H5' anti to O6').

There are some structural differences on the O1 (O1') and O2 (O2') sides of the five-membered dioxolane ring. In molecule A, the C1—O1 bond [1.398 (3) Å] is the shortest of the four C—O bonds involving O1 and O2, and the other three bonds are almost identical in length [average 1.435 (2) Å]. The O1—C7—C8 angle [113.10 (18)°] is larger than O2—C7—C8 [110.08 (18)°] and the O1—C7—O9 angle [108.90 (17)°] is smaller than O2—C7—O9 [112.19 (17)°]. The C7—O9 bond [1.380 (3) Å] is the shortest of the three ether bonds at C7, with the C7—O1 and C7—O2 bonds effectively identical [average 1.435 (2) Å]. The same structural features are found in molecule B. This might give an indication of why hydrolysis of (I) yields almost equivalent amounts of the two major isomeric products (Toyokuni et al., 2004).

Atom C7 (C7') is the only new chiral centre formed in the synthesis of (I) (Toyokuni et al., 2004). It has an R configuration, with the ethoxy group exo to the mannopyranose ring. The ¹H NMR spectrum (CDCl₃) gives a single peak at 1.75 p.p.m. for the C8 methyl group, consistent with the conclusion of earlier PMR [proton magnetic resonance? Is this not the same as ¹H NMR?] studies of glucopyranose 1,2-(alkyl orthoacetates) (Lemieux & Morgan, 1965), namely that the diastereomer for which the C8 methyl H atoms resonate at a lower field has the configuration in which the alkoxy group is exo to the pyranose ring.

The bicyclic ring structure of (I) has five pendant groups, each of which terminates in a methyl group. In the packing of the crystal structure, the pendant groups of one molecule lie between pendant groups from other molecules (Fig. 2). The partially occupied water molecules bridge between molecules A and B, forming hydrogen bonds (Table 1). Thermogravimetric analysis was carried out for (I), but it is difficult to detect any water loss prior to decomposition of the compound, since the solvent water accounts for only approximately 0.52% of the mass.

Related literature

For related literature, see: Alavi & Reivich (2002); Arnott & Scott (1972); Cremer & Pople (1975); Gambhir et al. (2001); Haines & Hughes (2007); Heitmann et al. (1974); Jeffrey & Yates (1979); Lemieux & Morgan (1965); Nutt (2002); Toyokuni et al. (2004).

S2. Experimental

The title compound was synthesized according to the literature procedure of Toyokuni et al. (2004). The crude product was recrystallized from ethanol (m.p. 375.0–375.8 K; literature value 374–376 K). Spectroscopic analysis: ¹H NMR (400 MHz, CDCl₃, δ, p.p.m.): 1.18 (t, J = 7.1 Hz, 3H, MeCH₂O), 1.75 (s, 3H, MeCO₂), 2.05 (s, 3H, Ac), 2.07 (s, 3H, Ac), 2.12 (s, 3H, Ac), 3.56 (m, 2H, MeCH₂O), 3.68 (ddd, J = 9.5, 4.9 and 2.7 Hz, 1H, H5), 4.14 (dd, J = 12.1 and 2.6 Hz, 1H) and 4.24 (dd, J = 12.1 and 4.9 Hz, 1H, 2 H6), 4.60 (dd, J = 3.9 and 2.7 Hz, 1H, H2), 5.15 (dd, J = 9.9 and 4.0 Hz, 1H, H3), 5.30 (t, J = 9.7 Hz, 1H, H4), 5.48 (d, J = 2.5 Hz, 1H, H1).

S3. Refinement

All H atoms bound to C atoms were placed geometrically and refined using a riding model, with C—H = 0.98–1.00 Å and U_iso(H) = 1.2U_eq(C). The H atoms of the water molecule were placed so as to form hydrogen bonds to atoms O62 and O62', with O—H = 0.85 Å, then refined as riding with U_iso(H) = 1.2U_eq(O). In the absence of significant anomalous scattering, the absolute structure could not be determined. Friedel pairs were not merged. The absolute structure is assigned on the basis of nonchanging chiral centres in the synthetic procedure (Toyokuni et al., 2004).

Computing details

Data collection: CrystalClear (Rigaku, 2008); cell refinement: CrystalClear (Rigaku, 2008); data reduction: CrystalClear (Rigaku, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: DIAMOND (Brandenburg, 1999); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures

	Fig. 1. The asymmetric unit of (I), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. The molecular packing of (I), viewed along the a axis. Dashed lines indicate hydrogen bonds.

3,4,6-Tri-O-acetyl-1,2-O-[1-(exo-ethoxy)ethylidene]- β-D-mannopyranose 0.11-hydrate

Crystal data

C16H24O10·0.11H2O	F(000) = 804.1
Mr = 378.35	Dx = 1.336 Mg m^−3
Monoclinic, P21	Melting point: 375(1) K
Hall symbol: P 2yb	Mo Kα radiation, λ = 0.71073 Å
a = 5.6353 (14) Å	Cell parameters from 6897 reflections
b = 30.987 (8) Å	θ = 1.9–29.1°
c = 10.817 (3) Å	µ = 0.11 mm^−1
β = 95.232 (4)°	T = 153 K
V = 1881.0 (8) Å^3	Prism, colourless
Z = 4	0.48 × 0.16 × 0.09 mm

Data collection

Rigaku AFC10/Saturn724+ CCD area-detector diffractometer	9788 independent reflections
Radiation source: Rotating Anode	7008 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.031
Detector resolution: 28.5714 pixels mm^-1	θmax = 29.1°, θmin = 2.0°
ϕ and ω scans	h = −7→7
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)	k = −42→42
Tmin = 0.948, Tmax = 0.990	l = −14→10
16933 measured reflections

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)] = 0.048	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.092	H-atom parameters constrained
S = 1.00	w = 1/[σ^2(Fo^2) + (0.0286P)^2 + 0.126P] where P = (Fo^2 + 2Fc^2)/3
9788 reflections	(Δ/σ)max = 0.001
491 parameters	Δρmax = 0.28 e Å^−3
1 restraint	Δρmin = −0.25 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.

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	Occ. (<1)
O5	0.8636 (2)	0.45959 (5)	0.04398 (14)	0.0312 (3)
O1	0.6685 (2)	0.42257 (5)	−0.11403 (14)	0.0347 (4)
O2	0.3815 (2)	0.47107 (5)	−0.07284 (14)	0.0303 (3)
O9	0.2780 (2)	0.40593 (5)	−0.17216 (14)	0.0337 (4)
O3	0.3927 (2)	0.55907 (5)	−0.04668 (14)	0.0309 (3)
O32	0.5734 (3)	0.62239 (6)	−0.07937 (19)	0.0531 (5)
O4	0.7865 (2)	0.56936 (4)	0.15016 (14)	0.0313 (3)
O42	0.4739 (3)	0.57101 (6)	0.2636 (2)	0.0684 (6)
O6	0.8605 (3)	0.48057 (5)	0.30227 (15)	0.0397 (4)
O62	1.0778 (4)	0.50142 (9)	0.4712 (2)	0.0903 (9)
C1	0.7817 (4)	0.46184 (7)	−0.0841 (2)	0.0325 (5)
H1	0.9159	0.4672	−0.1366	0.039*
C2	0.5820 (3)	0.49448 (7)	−0.1110 (2)	0.0294 (5)
H2	0.5585	0.5003	−0.2022	0.035*
C3	0.6191 (3)	0.53655 (7)	−0.0408 (2)	0.0288 (5)
H3	0.7362	0.5546	−0.0819	0.035*
C4	0.7130 (4)	0.52882 (7)	0.0928 (2)	0.0283 (5)
H4	0.5885	0.5148	0.1393	0.034*
C5	0.9350 (4)	0.50064 (7)	0.0967 (2)	0.0307 (5)
H5	1.0541	0.5143	0.0458	0.037*
C6	1.0480 (4)	0.49292 (8)	0.2268 (2)	0.0313 (5)
H6A	1.1686	0.4697	0.2267	0.038*
H6B	1.1276	0.5195	0.2601	0.038*
C7	0.4279 (4)	0.42573 (7)	−0.0812 (2)	0.0321 (5)
C8	0.3915 (4)	0.40412 (8)	0.0393 (2)	0.0348 (5)
H8A	0.4269	0.3733	0.0332	0.042*
H8B	0.2257	0.4079	0.0577	0.042*
H8C	0.4980	0.4171	0.1058	0.042*
C10	0.2872 (4)	0.42123 (9)	−0.2971 (2)	0.0423 (6)
H10A	0.4471	0.4161	−0.3252	0.051*
H10B	0.2533	0.4526	−0.3018	0.051*
C11	0.1007 (4)	0.39646 (9)	−0.3769 (2)	0.0491 (7)
H11A	−0.0574	0.4031	−0.3508	0.059*
H11B	0.1315	0.3654	−0.3678	0.059*
H11C	0.1066	0.4048	−0.4640	0.059*
C31	0.3969 (4)	0.60271 (7)	−0.0619 (2)	0.0319 (5)
C32	0.1558 (4)	0.62116 (8)	−0.0537 (2)	0.0409 (6)
H32A	0.1642	0.6527	−0.0580	0.049*
H32B	0.0966	0.6126	0.0250	0.049*
H32C	0.0475	0.6104	−0.1229	0.049*
C41	0.6559 (4)	0.58621 (8)	0.2366 (2)	0.0383 (6)
C42	0.7745 (5)	0.62599 (9)	0.2896 (3)	0.0535 (7)
H42A	0.6838	0.6374	0.3555	0.064*
H42B	0.7808	0.6477	0.2241	0.064*
H42C	0.9368	0.6190	0.3242	0.064*
C61	0.8929 (4)	0.48938 (9)	0.4234 (2)	0.0430 (6)
C62	0.6754 (5)	0.47921 (10)	0.4860 (3)	0.0571 (7)
H62A	0.5459	0.4986	0.4551	0.069*
H62B	0.7088	0.4831	0.5759	0.069*
H62C	0.6281	0.4492	0.4684	0.069*
O5'	0.7257 (3)	0.72173 (5)	0.46258 (14)	0.0349 (4)
O1'	0.5646 (2)	0.75239 (5)	0.28572 (13)	0.0326 (4)
O2'	0.2849 (2)	0.77158 (5)	0.41517 (13)	0.0309 (3)
O9'	0.1856 (3)	0.76709 (5)	0.20215 (13)	0.0341 (4)
O3'	0.3304 (3)	0.80834 (5)	0.65264 (14)	0.0320 (3)
O32'	0.4834 (3)	0.87446 (5)	0.63163 (19)	0.0527 (5)
O4'	0.6280 (3)	0.74569 (5)	0.78283 (14)	0.0352 (4)
O42'	0.2669 (3)	0.71985 (6)	0.81867 (16)	0.0476 (4)
O6'	0.6093 (3)	0.65333 (5)	0.60743 (14)	0.0373 (4)
O62'	0.8014 (3)	0.59298 (6)	0.6711 (2)	0.0654 (6)
C1'	0.6854 (4)	0.76166 (7)	0.4009 (2)	0.0329 (5)
H1'	0.8382	0.7773	0.3919	0.039*
C2'	0.5078 (4)	0.79017 (7)	0.4616 (2)	0.0314 (5)
H2'	0.5185	0.8205	0.4311	0.038*
C3'	0.5357 (4)	0.78950 (7)	0.6017 (2)	0.0305 (5)
H3'	0.6800	0.8067	0.6311	0.037*
C4'	0.5674 (4)	0.74414 (7)	0.65092 (19)	0.0297 (5)
H4'	0.4189	0.7269	0.6308	0.036*
C5'	0.7769 (4)	0.72340 (8)	0.5946 (2)	0.0335 (5)
H5'	0.9228	0.7413	0.6152	0.040*
C6'	0.8262 (4)	0.67786 (8)	0.6370 (2)	0.0406 (6)
H6C	0.9580	0.6655	0.5939	0.049*
H6D	0.8722	0.6772	0.7275	0.049*
C7'	0.3158 (4)	0.74908 (7)	0.3021 (2)	0.0306 (5)
C8'	0.2340 (4)	0.70305 (7)	0.3113 (2)	0.0360 (5)
H8D	0.2638	0.6875	0.2354	0.043*
H8E	0.0631	0.7025	0.3217	0.043*
H8F	0.3219	0.6891	0.3829	0.043*
C10'	0.2347 (4)	0.81131 (8)	0.1738 (2)	0.0414 (6)
H10C	0.4038	0.8148	0.1577	0.050*
H10D	0.2024	0.8302	0.2441	0.050*
C11'	0.0741 (5)	0.82293 (9)	0.0600 (3)	0.0558 (7)
H11D	−0.0924	0.8187	0.0765	0.067*
H11E	0.1107	0.8045	−0.0093	0.067*
H11F	0.0993	0.8532	0.0385	0.067*
C31'	0.3278 (4)	0.85167 (8)	0.6655 (2)	0.0344 (5)
C32'	0.1114 (4)	0.86636 (8)	0.7227 (2)	0.0383 (6)
H32D	−0.0231	0.8681	0.6587	0.046*
H32E	0.1409	0.8949	0.7603	0.046*
H32F	0.0738	0.8458	0.7869	0.046*
C41'	0.4646 (4)	0.73065 (8)	0.8572 (2)	0.0360 (5)
C42'	0.5647 (5)	0.72956 (9)	0.9888 (2)	0.0511 (7)
H42D	0.6738	0.7050	1.0018	0.061*
H42E	0.4349	0.7265	1.0426	0.061*
H42F	0.6514	0.7564	1.0091	0.061*
C61'	0.6220 (4)	0.61080 (8)	0.6300 (2)	0.0420 (6)
C62'	0.3890 (5)	0.58903 (8)	0.5965 (3)	0.0502 (7)
H62D	0.3946	0.5596	0.6298	0.060*
H62E	0.3576	0.5880	0.5059	0.060*
H62F	0.2617	0.6052	0.6316	0.060*
O21	1.0055 (16)	0.5179 (3)	0.7203 (9)	0.056 (4)	0.222 (8)
H21A	1.0353	0.5099	0.6481	0.067*	0.222 (8)
H21B	0.9379	0.5424	0.7142	0.067*	0.222 (8)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O5	0.0249 (7)	0.0284 (8)	0.0399 (9)	0.0014 (6)	0.0010 (7)	−0.0050 (7)
O1	0.0227 (7)	0.0346 (9)	0.0470 (10)	0.0010 (7)	0.0045 (7)	−0.0137 (8)
O2	0.0205 (7)	0.0285 (8)	0.0426 (9)	−0.0018 (6)	0.0061 (6)	−0.0058 (7)
O9	0.0290 (8)	0.0342 (9)	0.0374 (9)	−0.0035 (7)	−0.0001 (7)	−0.0089 (7)
O3	0.0217 (7)	0.0269 (8)	0.0448 (9)	0.0004 (6)	0.0068 (6)	0.0018 (7)
O32	0.0298 (9)	0.0391 (10)	0.0924 (15)	−0.0003 (8)	0.0156 (9)	0.0164 (10)
O4	0.0271 (7)	0.0281 (8)	0.0398 (9)	−0.0074 (6)	0.0089 (6)	−0.0082 (7)
O42	0.0584 (12)	0.0652 (14)	0.0891 (15)	−0.0256 (11)	0.0477 (11)	−0.0381 (12)
O6	0.0335 (8)	0.0475 (10)	0.0385 (9)	−0.0102 (8)	0.0055 (7)	0.0027 (8)
O62	0.0718 (15)	0.150 (3)	0.0503 (13)	−0.0474 (16)	0.0138 (11)	−0.0256 (14)
C1	0.0220 (10)	0.0372 (13)	0.0391 (13)	−0.0030 (9)	0.0071 (9)	−0.0085 (10)
C2	0.0211 (10)	0.0329 (12)	0.0343 (12)	−0.0012 (9)	0.0037 (9)	−0.0042 (10)
C3	0.0173 (9)	0.0317 (12)	0.0379 (12)	−0.0032 (9)	0.0059 (9)	−0.0025 (10)
C4	0.0232 (10)	0.0276 (11)	0.0350 (12)	−0.0038 (9)	0.0073 (9)	−0.0049 (9)
C5	0.0235 (10)	0.0314 (12)	0.0379 (13)	−0.0071 (9)	0.0068 (9)	−0.0050 (10)
C6	0.0214 (10)	0.0378 (13)	0.0344 (12)	−0.0027 (9)	0.0016 (9)	−0.0011 (10)
C7	0.0245 (11)	0.0291 (11)	0.0423 (13)	0.0021 (9)	0.0011 (10)	−0.0083 (10)
C8	0.0301 (11)	0.0345 (13)	0.0399 (13)	0.0013 (10)	0.0037 (10)	−0.0039 (11)
C10	0.0424 (14)	0.0510 (16)	0.0337 (13)	−0.0057 (12)	0.0043 (11)	−0.0052 (12)
C11	0.0517 (15)	0.0523 (17)	0.0417 (15)	0.0008 (13)	−0.0037 (12)	−0.0106 (13)
C31	0.0265 (11)	0.0300 (12)	0.0394 (13)	−0.0028 (9)	0.0047 (9)	0.0046 (10)
C32	0.0282 (11)	0.0331 (13)	0.0619 (16)	0.0004 (10)	0.0076 (11)	0.0096 (12)
C41	0.0375 (13)	0.0366 (13)	0.0422 (14)	−0.0066 (11)	0.0108 (11)	−0.0090 (11)
C42	0.0563 (17)	0.0431 (15)	0.0621 (18)	−0.0082 (13)	0.0105 (14)	−0.0182 (14)
C61	0.0406 (14)	0.0454 (15)	0.0443 (15)	−0.0006 (12)	0.0102 (12)	−0.0044 (12)
C62	0.0546 (16)	0.0625 (19)	0.0573 (17)	0.0104 (14)	0.0216 (14)	0.0103 (14)
O5'	0.0301 (8)	0.0384 (9)	0.0367 (9)	0.0047 (7)	0.0047 (7)	−0.0031 (7)
O1'	0.0236 (7)	0.0427 (9)	0.0325 (8)	−0.0017 (7)	0.0078 (6)	−0.0032 (7)
O2'	0.0221 (7)	0.0389 (9)	0.0324 (8)	−0.0031 (6)	0.0071 (6)	−0.0055 (7)
O9'	0.0323 (8)	0.0333 (8)	0.0361 (9)	−0.0035 (7)	−0.0005 (7)	−0.0011 (7)
O3'	0.0304 (8)	0.0288 (8)	0.0381 (9)	0.0001 (7)	0.0093 (7)	−0.0060 (7)
O32'	0.0489 (10)	0.0318 (10)	0.0796 (14)	−0.0052 (8)	0.0183 (10)	−0.0051 (9)
O4'	0.0342 (8)	0.0405 (9)	0.0306 (8)	−0.0022 (7)	0.0016 (7)	−0.0056 (7)
O42'	0.0410 (10)	0.0550 (11)	0.0470 (10)	−0.0104 (9)	0.0057 (8)	0.0089 (9)
O6'	0.0359 (9)	0.0348 (9)	0.0402 (9)	0.0054 (7)	−0.0013 (7)	−0.0005 (7)
O62'	0.0569 (12)	0.0533 (13)	0.0837 (15)	0.0252 (10)	−0.0064 (11)	−0.0010 (11)
C1'	0.0261 (11)	0.0362 (12)	0.0370 (12)	−0.0020 (10)	0.0070 (9)	−0.0018 (10)
C2'	0.0230 (10)	0.0343 (12)	0.0376 (13)	−0.0034 (9)	0.0064 (9)	−0.0026 (10)
C3'	0.0233 (10)	0.0314 (11)	0.0374 (13)	−0.0008 (9)	0.0057 (9)	−0.0063 (10)
C4'	0.0266 (10)	0.0334 (12)	0.0289 (11)	−0.0014 (9)	0.0018 (9)	−0.0061 (9)
C5'	0.0259 (11)	0.0399 (13)	0.0341 (12)	0.0003 (10)	0.0004 (9)	−0.0046 (11)
C6'	0.0313 (12)	0.0443 (15)	0.0452 (15)	0.0063 (11)	−0.0027 (11)	−0.0085 (12)
C7'	0.0240 (10)	0.0340 (12)	0.0343 (12)	−0.0002 (9)	0.0049 (9)	−0.0021 (10)
C8'	0.0333 (12)	0.0336 (12)	0.0424 (14)	−0.0035 (10)	0.0103 (11)	−0.0040 (10)
C10'	0.0409 (14)	0.0338 (13)	0.0492 (15)	−0.0025 (11)	0.0024 (12)	0.0006 (11)
C11'	0.0634 (18)	0.0413 (16)	0.0603 (19)	0.0018 (14)	−0.0086 (15)	0.0080 (14)
C31'	0.0358 (13)	0.0322 (12)	0.0341 (13)	0.0001 (10)	−0.0026 (10)	−0.0040 (10)
C32'	0.0381 (13)	0.0374 (13)	0.0389 (14)	0.0076 (11)	0.0006 (11)	−0.0047 (11)
C41'	0.0462 (14)	0.0287 (12)	0.0340 (12)	0.0020 (11)	0.0080 (11)	−0.0026 (10)
C42'	0.0688 (19)	0.0472 (16)	0.0367 (14)	−0.0058 (14)	0.0013 (13)	−0.0019 (13)
C61'	0.0479 (15)	0.0376 (14)	0.0413 (14)	0.0142 (12)	0.0090 (12)	−0.0025 (11)
C62'	0.0541 (16)	0.0362 (14)	0.0608 (18)	0.0011 (12)	0.0075 (14)	−0.0007 (13)
O21	0.076 (7)	0.040 (6)	0.051 (6)	0.001 (5)	0.001 (4)	0.009 (4)

Geometric parameters (Å, º)

O5—C1	1.422 (3)	O5'—C5'	1.432 (3)
O5—C5	1.437 (2)	O1'—C1'	1.394 (3)
O1—C1	1.398 (3)	O1'—C7'	1.433 (2)
O1—C7	1.436 (2)	O2'—C2'	1.431 (2)
O2—C7	1.434 (3)	O2'—C7'	1.432 (2)
O2—C2	1.435 (2)	O9'—C7'	1.369 (3)
O9—C7	1.380 (3)	O9'—C10'	1.437 (3)
O9—C10	1.437 (3)	O3'—C31'	1.350 (3)
O3—C31	1.363 (3)	O3'—C3'	1.449 (2)
O3—C3	1.451 (2)	O32'—C31'	1.208 (3)
O32—C31	1.196 (2)	O4'—C41'	1.359 (3)
O4—C41	1.347 (3)	O4'—C4'	1.437 (2)
O4—C4	1.445 (2)	O42'—C41'	1.201 (3)
O42—C41	1.189 (3)	O6'—C61'	1.341 (3)
O6—C61	1.335 (3)	O6'—C6'	1.450 (3)
O6—C6	1.445 (2)	O62'—C61'	1.201 (3)
O62—C61	1.180 (3)	C1'—C2'	1.527 (3)
C1—C2	1.521 (3)	C1'—H1'	1.0000
C1—H1	1.0000	C2'—C3'	1.509 (3)
C2—C3	1.514 (3)	C2'—H2'	1.0000
C2—H2	1.0000	C3'—C4'	1.508 (3)
C3—C4	1.512 (3)	C3'—H3'	1.0000
C3—H3	1.0000	C4'—C5'	1.520 (3)
C4—C5	1.523 (3)	C4'—H4'	1.0000
C4—H4	1.0000	C5'—C6'	1.502 (3)
C5—C6	1.510 (3)	C5'—H5'	1.0000
C5—H5	1.0000	C6'—H6C	0.9900
C6—H6A	0.9900	C6'—H6D	0.9900
C6—H6B	0.9900	C7'—C8'	1.505 (3)
C7—C8	1.496 (3)	C8'—H8D	0.9800
C8—H8A	0.9800	C8'—H8E	0.9800
C8—H8B	0.9800	C8'—H8F	0.9800
C8—H8C	0.9800	C10'—C11'	1.504 (3)
C10—C11	1.508 (3)	C10'—H10C	0.9900
C10—H10A	0.9900	C10'—H10D	0.9900
C10—H10B	0.9900	C11'—H11D	0.9800
C11—H11A	0.9800	C11'—H11E	0.9800
C11—H11B	0.9800	C11'—H11F	0.9800
C11—H11C	0.9800	C31'—C32'	1.489 (3)
C31—C32	1.484 (3)	C32'—H32D	0.9800
C32—H32A	0.9800	C32'—H32E	0.9800
C32—H32B	0.9800	C32'—H32F	0.9800
C32—H32C	0.9800	C41'—C42'	1.484 (3)
C41—C42	1.492 (3)	C42'—H42D	0.9800
C42—H42A	0.9800	C42'—H42E	0.9800
C42—H42B	0.9800	C42'—H42F	0.9800
C42—H42C	0.9800	C61'—C62'	1.491 (4)
C61—C62	1.487 (3)	C62'—H62D	0.9800
C62—H62A	0.9800	C62'—H62E	0.9800
C62—H62B	0.9800	C62'—H62F	0.9800
C62—H62C	0.9800	O21—H21A	0.8500
O5'—C1'	1.414 (3)	O21—H21B	0.8501
C1—O5—C5	113.45 (17)	C1'—O1'—C7'	107.91 (16)
C1—O1—C7	107.76 (15)	C2'—O2'—C7'	108.95 (15)
C7—O2—C2	108.93 (15)	C7'—O9'—C10'	117.25 (17)
C7—O9—C10	116.79 (18)	C31'—O3'—C3'	117.15 (17)
C31—O3—C3	117.23 (16)	C41'—O4'—C4'	117.62 (17)
C41—O4—C4	118.80 (17)	C61'—O6'—C6'	116.43 (19)
C61—O6—C6	117.32 (17)	O1'—C1'—O5'	106.59 (17)
O1—C1—O5	106.47 (18)	O1'—C1'—C2'	102.58 (17)
O1—C1—C2	102.74 (16)	O5'—C1'—C2'	112.74 (18)
O5—C1—C2	112.81 (17)	O1'—C1'—H1'	111.5
O1—C1—H1	111.5	O5'—C1'—H1'	111.5
O5—C1—H1	111.5	C2'—C1'—H1'	111.5
C2—C1—H1	111.5	O2'—C2'—C3'	110.78 (17)
O2—C2—C3	111.52 (17)	O2'—C2'—C1'	101.82 (17)
O2—C2—C1	101.36 (17)	C3'—C2'—C1'	114.29 (18)
C3—C2—C1	114.27 (17)	O2'—C2'—H2'	109.9
O2—C2—H2	109.8	C3'—C2'—H2'	109.9
C3—C2—H2	109.8	C1'—C2'—H2'	109.9
C1—C2—H2	109.8	O3'—C3'—C4'	108.32 (17)
O3—C3—C4	110.38 (16)	O3'—C3'—C2'	111.26 (17)
O3—C3—C2	108.17 (15)	C4'—C3'—C2'	111.43 (18)
C4—C3—C2	111.32 (18)	O3'—C3'—H3'	108.6
O3—C3—H3	109.0	C4'—C3'—H3'	108.6
C4—C3—H3	109.0	C2'—C3'—H3'	108.6
C2—C3—H3	109.0	O4'—C4'—C3'	109.21 (17)
O4—C4—C3	109.54 (17)	O4'—C4'—C5'	106.81 (16)
O4—C4—C5	106.50 (15)	C3'—C4'—C5'	108.91 (18)
C3—C4—C5	109.44 (16)	O4'—C4'—H4'	110.6
O4—C4—H4	110.4	C3'—C4'—H4'	110.6
C3—C4—H4	110.4	C5'—C4'—H4'	110.6
C5—C4—H4	110.4	O5'—C5'—C6'	106.59 (18)
O5—C5—C6	108.00 (17)	O5'—C5'—C4'	108.75 (17)
O5—C5—C4	107.28 (15)	C6'—C5'—C4'	113.8 (2)
C6—C5—C4	113.12 (18)	O5'—C5'—H5'	109.2
O5—C5—H5	109.5	C6'—C5'—H5'	109.2
C6—C5—H5	109.5	C4'—C5'—H5'	109.2
C4—C5—H5	109.5	O6'—C6'—C5'	107.26 (18)
O6—C6—C5	107.47 (16)	O6'—C6'—H6C	110.3
O6—C6—H6A	110.2	C5'—C6'—H6C	110.3
C5—C6—H6A	110.2	O6'—C6'—H6D	110.3
O6—C6—H6B	110.2	C5'—C6'—H6D	110.3
C5—C6—H6B	110.2	H6C—C6'—H6D	108.5
H6A—C6—H6B	108.5	O9'—C7'—O2'	112.21 (17)
O9—C7—O2	112.19 (17)	O9'—C7'—O1'	109.43 (17)
O9—C7—O1	108.90 (17)	O2'—C7'—O1'	105.51 (16)
O2—C7—O1	105.31 (16)	O9'—C7'—C8'	107.06 (18)
O9—C7—C8	107.35 (18)	O2'—C7'—C8'	110.07 (18)
O2—C7—C8	110.08 (18)	O1'—C7'—C8'	112.65 (18)
O1—C7—C8	113.10 (18)	C7'—C8'—H8D	109.5
C7—C8—H8A	109.5	C7'—C8'—H8E	109.5
C7—C8—H8B	109.5	H8D—C8'—H8E	109.5
H8A—C8—H8B	109.5	C7'—C8'—H8F	109.5
C7—C8—H8C	109.5	H8D—C8'—H8F	109.5
H8A—C8—H8C	109.5	H8E—C8'—H8F	109.5
H8B—C8—H8C	109.5	O9'—C10'—C11'	106.86 (19)
O9—C10—C11	106.7 (2)	O9'—C10'—H10C	110.4
O9—C10—H10A	110.4	C11'—C10'—H10C	110.4
C11—C10—H10A	110.4	O9'—C10'—H10D	110.4
O9—C10—H10B	110.4	C11'—C10'—H10D	110.4
C11—C10—H10B	110.4	H10C—C10'—H10D	108.6
H10A—C10—H10B	108.6	C10'—C11'—H11D	109.5
C10—C11—H11A	109.5	C10'—C11'—H11E	109.5
C10—C11—H11B	109.5	H11D—C11'—H11E	109.5
H11A—C11—H11B	109.5	C10'—C11'—H11F	109.5
C10—C11—H11C	109.5	H11D—C11'—H11F	109.5
H11A—C11—H11C	109.5	H11E—C11'—H11F	109.5
H11B—C11—H11C	109.5	O32'—C31'—O3'	122.3 (2)
O32—C31—O3	123.3 (2)	O32'—C31'—C32'	126.3 (2)
O32—C31—C32	126.3 (2)	O3'—C31'—C32'	111.3 (2)
O3—C31—C32	110.41 (18)	C31'—C32'—H32D	109.5
C31—C32—H32A	109.5	C31'—C32'—H32E	109.5
C31—C32—H32B	109.5	H32D—C32'—H32E	109.5
H32A—C32—H32B	109.5	C31'—C32'—H32F	109.5
C31—C32—H32C	109.5	H32D—C32'—H32F	109.5
H32A—C32—H32C	109.5	H32E—C32'—H32F	109.5
H32B—C32—H32C	109.5	O42'—C41'—O4'	123.2 (2)
O42—C41—O4	123.7 (2)	O42'—C41'—C42'	125.9 (2)
O42—C41—C42	126.8 (2)	O4'—C41'—C42'	110.9 (2)
O4—C41—C42	109.5 (2)	C41'—C42'—H42D	109.5
C41—C42—H42A	109.5	C41'—C42'—H42E	109.5
C41—C42—H42B	109.5	H42D—C42'—H42E	109.5
H42A—C42—H42B	109.5	C41'—C42'—H42F	109.5
C41—C42—H42C	109.5	H42D—C42'—H42F	109.5
H42A—C42—H42C	109.5	H42E—C42'—H42F	109.5
H42B—C42—H42C	109.5	O62'—C61'—O6'	123.3 (2)
O62—C61—O6	122.1 (2)	O62'—C61'—C62'	125.1 (3)
O62—C61—C62	126.8 (3)	O6'—C61'—C62'	111.7 (2)
O6—C61—C62	111.0 (2)	C61'—C62'—H62D	109.5
C61—C62—H62A	109.5	C61'—C62'—H62E	109.5
C61—C62—H62B	109.5	H62D—C62'—H62E	109.5
H62A—C62—H62B	109.5	C61'—C62'—H62F	109.5
C61—C62—H62C	109.5	H62D—C62'—H62F	109.5
H62A—C62—H62C	109.5	H62E—C62'—H62F	109.5
H62B—C62—H62C	109.5	H21A—O21—H21B	108.1
C1'—O5'—C5'	116.61 (17)
C7—O1—C1—O5	84.09 (19)	C7'—O1'—C1'—O5'	84.20 (19)
C7—O1—C1—C2	−34.7 (2)	C7'—O1'—C1'—C2'	−34.5 (2)
C5—O5—C1—O1	−166.39 (15)	C5'—O5'—C1'—O1'	−160.68 (15)
C5—O5—C1—C2	−54.4 (2)	C5'—O5'—C1'—C2'	−48.9 (2)
C7—O2—C2—C3	−147.16 (17)	C7'—O2'—C2'—C3'	−145.17 (18)
C7—O2—C2—C1	−25.2 (2)	C7'—O2'—C2'—C1'	−23.2 (2)
O1—C1—C2—O2	36.21 (19)	O1'—C1'—C2'—O2'	35.0 (2)
O5—C1—C2—O2	−78.0 (2)	O5'—C1'—C2'—O2'	−79.3 (2)
O1—C1—C2—C3	156.28 (17)	O1'—C1'—C2'—C3'	154.44 (17)
O5—C1—C2—C3	42.1 (2)	O5'—C1'—C2'—C3'	40.2 (3)
C31—O3—C3—C4	97.2 (2)	C31'—O3'—C3'—C4'	152.51 (18)
C31—O3—C3—C2	−140.77 (19)	C31'—O3'—C3'—C2'	−84.7 (2)
O2—C2—C3—O3	−49.7 (2)	O2'—C2'—C3'—O3'	−51.8 (2)
C1—C2—C3—O3	−163.94 (17)	C1'—C2'—C3'—O3'	−166.11 (18)
O2—C2—C3—C4	71.7 (2)	O2'—C2'—C3'—C4'	69.2 (2)
C1—C2—C3—C4	−42.5 (2)	C1'—C2'—C3'—C4'	−45.1 (2)
C41—O4—C4—C3	109.4 (2)	C41'—O4'—C4'—C3'	111.8 (2)
C41—O4—C4—C5	−132.3 (2)	C41'—O4'—C4'—C5'	−130.5 (2)
O3—C3—C4—O4	−70.19 (19)	O3'—C3'—C4'—O4'	−65.7 (2)
C2—C3—C4—O4	169.67 (16)	C2'—C3'—C4'—O4'	171.59 (16)
O3—C3—C4—C5	173.39 (16)	O3'—C3'—C4'—C5'	177.99 (16)
C2—C3—C4—C5	53.3 (2)	C2'—C3'—C4'—C5'	55.3 (2)
C1—O5—C5—C6	−172.48 (16)	C1'—O5'—C5'—C6'	−176.82 (17)
C1—O5—C5—C4	65.3 (2)	C1'—O5'—C5'—C4'	60.1 (2)
O4—C4—C5—O5	178.00 (16)	O4'—C4'—C5'—O5'	−179.19 (17)
C3—C4—C5—O5	−63.7 (2)	C3'—C4'—C5'—O5'	−61.4 (2)
O4—C4—C5—C6	59.0 (2)	O4'—C4'—C5'—C6'	62.2 (2)
C3—C4—C5—C6	177.33 (18)	C3'—C4'—C5'—C6'	180.00 (18)
C61—O6—C6—C5	−152.7 (2)	C61'—O6'—C6'—C5'	175.28 (19)
O5—C5—C6—O6	−71.0 (2)	O5'—C5'—C6'—O6'	−63.2 (2)
C4—C5—C6—O6	47.6 (2)	C4'—C5'—C6'—O6'	56.7 (2)
C10—O9—C7—O2	60.1 (2)	C10'—O9'—C7'—O2'	59.8 (2)
C10—O9—C7—O1	−56.0 (2)	C10'—O9'—C7'—O1'	−57.0 (2)
C10—O9—C7—C8	−178.82 (18)	C10'—O9'—C7'—C8'	−179.35 (18)
C2—O2—C7—O9	−113.11 (19)	C2'—O2'—C7'—O9'	−115.75 (18)
C2—O2—C7—O1	5.2 (2)	C2'—O2'—C7'—O1'	3.3 (2)
C2—O2—C7—C8	127.43 (18)	C2'—O2'—C7'—C8'	125.14 (19)
C1—O1—C7—O9	139.93 (18)	C1'—O1'—C7'—O9'	141.51 (18)
C1—O1—C7—O2	19.4 (2)	C1'—O1'—C7'—O2'	20.6 (2)
C1—O1—C7—C8	−100.8 (2)	C1'—O1'—C7'—C8'	−99.5 (2)
C7—O9—C10—C11	−177.13 (18)	C7'—O9'—C10'—C11'	178.8 (2)
C3—O3—C31—O32	5.6 (3)	C3'—O3'—C31'—O32'	3.1 (3)
C3—O3—C31—C32	−174.50 (18)	C3'—O3'—C31'—C32'	−178.02 (17)
C4—O4—C41—O42	−4.8 (4)	C4'—O4'—C41'—O42'	−6.7 (3)
C4—O4—C41—C42	175.65 (19)	C4'—O4'—C41'—C42'	173.17 (19)
C6—O6—C61—O62	−9.9 (4)	C6'—O6'—C61'—O62'	−0.8 (4)
C6—O6—C61—C62	173.8 (2)	C6'—O6'—C61'—C62'	179.8 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O21—H21A···O62	0.85	1.97	2.808 (10)	170
O21—H21B···O62′	0.85	1.79	2.629 (9)	169