Crystal structure of a photobiologically active furanocoumarin from Artemisia reticulata

The title furanocoumarin, isolated from the Indian herb A. reticulata, crystallizes with two independent molecules (A and B) in the asymmetric unit. The two molecules differ essentially in the orientation of the propenyl group at the 2-position with respect to the mean plane of the furanocoumarin moiety. In the crystal, the two molecules are linked via O—H⋯O hydrogen bonds forming zigzag –A–B–A–B– chains propagating along [001].


Chemical context
The title furanocoumarin was isolated from the Indian herb A. reticulata, by column chromatography over silica gel with a mixture of binary solvent hexane and ethyl acetate by gradient elution. Furanocoumarins, such as oroselone [systematic name: 8-(prop-1-en-2-yl)-2H-furo[2,3-h]chromen-2-one], whose atomic connectivity has been established by spectrometric and spectroscopic analyses (Schroeder et al., 1959;Dorofeenko et al., 1973) but not yet by single crystal X-ray diffraction, exhibit photobiological activity. For example such compounds are employed as photoprotective agents to prevent absorption of harmful UV radiation (Chen et al., 2007(Chen et al., , 2009). Anti-oxidant and anti-inflammatory activities have also been reported for furano as well as pyrano coumarins and their derivatives (Appendino et al., 2004;Scott et al., 1976).
with hydroxyl and propenyl substituents at positions 9 and 2, respectively. The furanocoumarin moieties are essentially planar with r.m.s. deviations of 0.05 Å for molecule A (O1/O2/ C1-C11) and 0.079 Å for molecule B (O5/O6/C16-C25). The furan ring in molecule A has an envelope conformation with atom C2 as the flap, deviating by 0.120 (4) Å from the mean plane of the furanocoumarin moiety. In molecule B, the furan ring has a twisted conformation on bond C17-C16 with atoms C16 and C17 deviating by À0.232 (6) and 0.076 (6) Å , respectively, from the other atoms of the twisted fivemembered ring. The two molecules differ essentially in the orientation of the propenyl group with respect to the mean plane of the furanocoumarin moiety, as shown by AutoMolFit analysis (Spek, 2009); see Fig. 2. The O1-C2-C12 C14 torsion angle is 122.2 (7) in molecule A, while the O5-C16-C26 C28 torsion angle is À10.8 (11) in molecule B. The bond distances and bond angles in the propenyl side chains (C2,C12-C14 in molecule A and C16,C26-C28 in molecule B) also differ in the two molecules (Table 1), probably due to libration and bond rotation. Overall the bond distances and bond angles in the furanocoumarin moieties are in good agreement with the corresponding values reported for related structures (Stemple & Watson, 1972;Gupta et al., 1993;Singh et al. 1995;Magotra et al., 1995;Thailambal et al., 1986;, 1985. The absolute structure of the molecule in the crystal could not be determined by resonant scattering. In order to determine the chirality at atom C2 (in molecule A; C16 in molecule B), the circular dichroism (CD) spectrum was measured in a solution of chloroform at concentration of 1 mg/ml using a cell with path length 1 cm. This CD measurement revealed that the absolute configuration of atom C2 (in molecule A; C16 in molecule B) is S.

Figure 1
The molecular structure of the two independent molecules (A and B) of the title compound, showing the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

Synthesis and crystallization
The title compound was isolated as a colourless solid from the methanol extract of A. reticulata by means of column chromatography over silica gel by gradient elution with a mixture of binary solvents system hexane and ethyl acetate. It was purified by reverse-phase high-pressure liquid chromatography. Colourless rod-like crystals suitable for X ray diffraction analysis were obtained after the title compound was recrystallized three times from ethyl acetate:hexane ( A view along the c axis of the crystal packing of the title compound. Hydrogen bonds and C-HÁ Á Á interactions are shown as dashed lines (see Table 2), and C-bound H atoms not involved in hydrogen bonding have been omitted for clarity.

Figure 3
A view along the a axis of the crystal packing of the title compound (A molecules are blue; B molecules are red). The hydrogen bonds are shown as dashed lines (see Table 2), and C-bound H atoms not involved in hydrogen bonding have been omitted for clarity. Table 2 Hydrogen-bond geometry (Å , ).

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 F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.