4,4′-[(2R*,3R*,4R*,5R*)-3,4-Dimethyl­tetra­hydro­furan-2,5-di­yl]diphenol

Juan Manuel de Jesús Favela-Hernández; María del Rayo Camacho-Corona; Sylvain Bernès; Marcos Flores-Alamo

doi:10.1107/S1600536812039359

. 2012 Sep 26;68(Pt 10):o3019–o3020. doi: 10.1107/S1600536812039359

4,4′-[(2R,3R,4R,5R)-3,4-Dimethyltetrahydrofuran-2,5-diyl]diphenol

Juan Manuel de Jesús Favela-Hernández ^a, María del Rayo Camacho-Corona ^a, Sylvain Bernès ^a,^*, Marcos Flores-Alamo ^b

PMCID: PMC3470375 PMID: 23125788

Abstract

The title molecule, C₁₈H₂₀O₃, is a furanoid lignan extracted from the leaves of Larrea tridentata. The relative absolute configuration for the four chiral centers was established, showing that this compound is 4-epi-larreatricin, which has been previously reported in the literature. The molecule displays noncrystallographic C ₂ symmetry, with the methyl and phenol substituents alternating above and below the mean plane of the furan ring. The conformation of this ring is described by the pseudorotation phase angle P = 171.3° and the maximum out-of-plane pucker ν_m = 37.7°. These parameters indicate that the furan ring adopts the same conformation as the ribose residues in B-DNA. The packing is dominated by intermolecular O—H⋯O hydrogen bonds. The phenol hydroxy groups form chains in the [110] direction and these chains interact via O—H⋯O(furan) contacts.

Related literature

For the extraction, synthesis, characterization and biological activity of the title compound, see: Konno et al. (1990 ▶); Moinuddin et al. (2003 ▶); Favela-Hernández et al. (2012 ▶). For the conformational analysis of sugar rings, see: Altona & Sundaralingam (1972 ▶); Sun et al. (2004 ▶). For an example of another naturally occurring furanoid lignan, see: Soepadamo et al. (1991 ▶).

Experimental

Crystal data

C₁₈H₂₀O₃
M _r = 284.34
Monoclinic,
a = 6.4225 (4) Å
b = 12.4973 (7) Å
c = 9.8176 (7) Å
β = 101.243 (6)°
V = 772.88 (9) Å³
Z = 2
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 298 K
0.36 × 0.26 × 0.21 mm

Data collection

Agilent Xcalibur (Atlas, Gemini) diffractometer
Absorption correction: analytical [CrysAlis PRO (Oxford Diffraction, 2009 ▶), based on expressions derived by Clark & Reid (1995 ▶)] T _min = 0.980, T _max = 0.985
5223 measured reflections
1592 independent reflections
1107 reflections with I > 2σ(I)
R _int = 0.041

Refinement

R[F ² > 2σ(F ²)] = 0.044
wR(F ²) = 0.106
S = 1.05
1592 reflections
198 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.19 e Å⁻³
Δρ_min = −0.18 e Å⁻³
Absolute structure: 1004 measured Friedel pairs merged for refinement

Data collection: CrysAlis CCD (Oxford Diffraction, 2009 ▶); cell refinement: CrysAlis RED (Oxford Diffraction, 2009 ▶); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶) and Mercury (Macrae et al., 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812039359/mw2082sup1.cif

e-68-o3019-sup1.cif^{(24.2KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812039359/mw2082Isup2.hkl

e-68-o3019-Isup2.hkl^{(78.5KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812039359/mw2082Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H3⋯O2ⁱ	0.92 (5)	1.84 (5)	2.752 (4)	169 (5)
O2—H2⋯O1ⁱⁱ	0.90 (4)	1.89 (4)	2.723 (3)	154 (3)

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

This project was financially supported by Mexican grants CONACYT-SEP-CB-2008-01 (project No. 106107) and PAICYT SA221-09.

supplementary crystallographic information

Comment

The characterization of the title molecule is a part of a long-term project related to the screening of extracts obtained from plants used in Mexican traditional medicine to treat respiratory infections like tuberculosis. The title furanoid lignan is present in the chloroformic extract of Larrea tridentata, a plant found mainly in the southwestern US and northern Mexico. We have recently probed the antibacterial and antimycobacterial activity of this molecule and found that it is active against methicillin resistant S. aureus and M. tuberculosis H37Rv strain (Favela-Hernández et al., 2012). This molecule was previously extracted from L. tridentata samples from Phoenix, Arizona and characterized by MS and NMR (Konno et al., 1990). The synthesis and chiral HPLC analysis of stereoisomers of this compound have also been carried out (Moinuddin et al., 2003).

The relative stereochemistry for the four chiral C atoms in the furan ring was determined (Fig. 1) showing that the crystallized lignan corresponds to 4-epi-larreatricin (Konno et al., 1990; Moinuddin et al., 2003). The same configuration was found in related furanoid lignans from other natural sources, for example grandisin, which is extracted from Cryptocarya crassinervia (Soepadamo et al., 1991). The four substituents of the central furan ring are arranged in an all-transα,α'-diaryl-β,β'-dimethyl manner thus avoiding steric hindrance between aryl and methyl groups. The furan ring adopts a twisted envelope conformation characteristic of ribose sugars in the B-form of DNA (hydrated DNA). This may be checked by computing the phase angle of pseudorotation for the ring, P = 171.3°, and the maximum degree of pucker, ν_m = 37.7° (Altona & Sundaralingam, 1972). The comparison of these data with the distribution of P and ν_m for β-nucleosides found in the CSD clearly shows that the title compound lies in the south hemisphere of the pseudorotational wheel and within the C2'-endo cluster (²E form, P = 162° (See Fig. 3 in Altona & Sundaralingam, 1972 and Fig. 6 in Sun et al., 2004)).

The crystal structure is based on chains formed through intermolecular O—H···O hydrogen bonds involving the hydroxyl groups (Fig. 2, inset). The resulting layer interacts with the neighboring layer packed along the c axis, through O—H···O(furan) contacts, forming the complete three-dimensional framework (Fig. 2).

Experimental

Leaves of L. tridentata were collected in Galeana, Nuevo León, Mexico, and authenticated by Biól. Mauricio González (Voucher 024772, Facultad de Ciencias Biológicas, UANL). Dried and ground leaves (500 g) were extracted with hexane and then with CHCl₃ through maceration. Details of the chromatography of the chloroform fraction have been described previously (Favela-Hernández et al., 2012). This afforded, among other products, 11 mg of the title molecule, which was crystallized from CHCl₃/MeOH (95/5, v/v). m.p. 503–505 K (Lit. 503–505 K, Konno et al., 1990). ¹H and ¹³C NMR data are in agreement with the X-ray structure.