1-Hydr­oxy-3-(3-methyl­but-2-en­yloxy)xanthone

Luis Gales; Raquel A P Castanheiro; Madalena M M Pinto; Ana M Damas

doi:10.1107/S1600536809040069

. 2009 Oct 13;65(Pt 11):o2718–o2719. doi: 10.1107/S1600536809040069

1-Hydroxy-3-(3-methylbut-2-enyloxy)xanthone

Luis Gales ^a, Raquel A P Castanheiro ^b, Madalena M M Pinto ^b, Ana M Damas ^a,^*

PMCID: PMC2971381 PMID: 21578316

Abstract

In the title compound, C₁₈H₁₆O₄, a monoprenylated xanthone, the xanthone skeleton exhibits an essentially planar conformation (r.m.s. deviation 0.0072 Å) and the isoprenyl side chain remains approximately in the mean plane of the xanthone unit, making a dihedral angle of 4.5 (2)°. The hydroxyl group forms an intramolecular O—H⋯O hydrogen bond. Moreover, there is a weak intermolecular C—H⋯O interaction between a ring C atom and the xanthene O atom. In the crystal structure, there are no intermolecular hydrogen bonds and the crystallographic packing is governed by van der Waals forces, leading to an arrangement in which the molecules assemble with their planes parallel to each other, having a separation of 3.6 (3) Å.

Related literature

For a review of the biological activity of prenylated xanthones, see: Pinto et al. (2005 ▶). For background literature and synthesis of prenylated xanthones, see: Pinto et al. (2005 ▶); Epifano et al. (2007 ▶); Castanheiro et al. (2007 ▶). For the synthesis of the title compound using microwave radiation, see: Castanheiro et al. (2009 ▶). For analysis of related structures of xanthone derivatives, see: Gales et al. (2001 ▶, 2005 ▶ a,b); Castanheiro et al. (2007 ▶). For the interaction with biological membranes and target proteins, see: Maia et al. (2005 ▶); Epifano et al. (2007 ▶). For a review of prenylated xanthone crystal structures, see: Gales & Damas, 2005 ▶).

Experimental

Crystal data

C₁₈H₁₆O₄
M _r = 296.31
Triclinic,
a = 4.8199 (3) Å
b = 11.7014 (8) Å
c = 13.6176 (10) Å
α = 77.329 (6)°
β = 88.582 (6)°
γ = 79.039 (6)°
V = 735.54 (9) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 295 K
0.4 × 0.2 × 0.1 mm

Data collection

Oxford Diffraction Gemini PX Ultra CCD area-detector diffractometer
Absorption correction: none
8520 measured reflections
2981 independent reflections
1958 reflections with I > 2σ(I)
R _int = 0.017

Refinement

R[F ² > 2σ(F ²)] = 0.048
wR(F ²) = 0.147
S = 1.07
2981 reflections
202 parameters
H-atom parameters constrained
Δρ_max = 0.16 e Å⁻³
Δρ_min = −0.15 e Å⁻³

Data collection: CrysAlis CCD (Oxford Diffraction, 2004 ▶); cell refinement: CrysAlis CCD; data reduction: CrysAlis RED (Oxford Diffraction, 2004 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Johnson & Burnett, 1996 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809040069/bv2126sup1.cif

e-65-o2718-sup1.cif^{(19.1KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809040069/bv2126Isup2.hkl

e-65-o2718-Isup2.hkl^{(143.3KB, hkl)}

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
O1—H1A⋯O11	0.82	1.85	2.5846 (17)	148
C5—H5A⋯O2ⁱ	0.93	2.60	3.514 (2)	168

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank the Fundaçao para a Ciência e a Tecnologia (FCT), I&D Units 226/2003 (CEQOFFUP) and 4040/2007 (CEQUIMED), FEDER, POCI for financial support and the FCT (projects FCT /FEDER /POCI 2010 and PTDC/CTM/64191/2006) for the PhD grant to RC (SFRH/BD/13167/2003).

supplementary crystallographic information

Comment

Prenylated xanthones have been reported to mediate a number of important biological activities, concerning a large variety of targets with therapeutic value. The presence of the prenyl side chains seems to enhance the interaction with biological membranes and with target proteins (Maia et al., 2005 and Epifano et al., 2007) and we plan to further study these kind of interactions.

However, the synthesis of prenylated xanthones usually involves toxic reagents and is considered not only very demanding but also environmentally unfriendly (Castanheiro et al., 2007). We have looked for an alternative method to obtain prenylated xanthones. The title compound was the first example of a prenylated xanthone synthesized by the microwave irradiation method (Castanheiro et al., 2009). In fact, microwave-assisted heating under controlled conditions is an invaluable technology for medicinal chemistry because it often dramatically reduces reaction times.

In the crystal, the title compound molecules are essentially planar (Fig. 1). The isoprenyl side chain adopts a nearly coplanar conformation relatively to the xanthone skeleton (corresponding dihedral angle 4.5 (2)°). This is an exception because in the crystal structures of other prenylated xanthones, the isoprenyl side chain is usually out of the plane of the xanthones moiety (for a review of prenylated xanthone crystal structures see: Gales & Damas, 2005). Moreover, the hydroxyl substituent bound to C1 forms a strong intramolecular hydrogen bond to O11 [O1—H1A···O11 = 2.5845 (17) Å].

In the crystal structure, the title compound forms stacking planes (Fig. 2) with intermolecular separation of 3.6 Å. The packing of the molecules is governed by van der Waals forces and there are no intermolecular hydrogen bonds.

Experimental

Prenylation was carried out using prenyl bromide in alkaline medium under microwave irradiation according to the procedure reported by Castanheiro et al. (2009). Single crystals suitable for X-ray crystallographic analysis were grown by recrystallization from slow evaporation of a CH₂Cl₂/PE (60–80) solution.