Crystal structure of a photobiologically active brominated angular pyranocoumarin: bromo-hydroxy-seselin

The title compound, is a brominated product of seselin [8,8-dimethyl-2H,8H-pyrano[2,3-f]chromen-2-one], a photo biologically active compound.


Chemical context
The title compound, rac-(9S,10R)-9-bromo-10-hydroxy-8,8dimethyl-9,10-dihydro-2H,8H-pyrano[2,3-f]chromen-2-one, is a substituted product of the angular pyranocoumarin seselin, with a bromine atom and a hydroxy group at the asymmetric carbon atoms C3 and C4 in the pyrano ring (see Fig. 1). This class of pyranocoumarins have absorption bands in the near UV region due to the presence of an extended conjugated enone system and exhibit photomutagenic (Appendino et al., 2004) and photocarcinogenic properties, binding with purin bases of DNA in living cells to yield photoadducts (Filomena et al., 2009). Based on this property, these compounds are employed to treat numerous inflammatory skin diseases such as atopic dermatitis and pigment disorders such as vitiligo and psoriasis on exposure to ultraviolet (UV) radiation in photodynamic therapy (PDT). As a result of their strong ability to absorb UV radiation, this class of molecules are also utilized as photoprotective agents to prevent the absorption of harmful UV radiation by the skin in the form of a variety of sun-screening lotions, widely used in dermatological applications in the cosmetic and pharmaceutical industries (Chen et al., 2007(Chen et al., , 2009). In addition, in vitro antiproliferative activity and in vivo phototoxicity of the parent molecule has been reported against numerous cancer cell lines, including HL60, A431 (Conconi et al., 1998). These classes of coumarins have been used successfully in combination with ultraviolet irradiation to treat psoriasis and vitiligo and have been found to inhibit proliferation in human hepatocellular carcinoma cell lines (March et al., 1993). Experimental results revealed that their phototoxicity is exerted via Diels-Alder reactions, binding to the double bond of a purin base of DNA in living cells with double bonds of the coumarin, to yield mono-and di-adducts (Conforti et al., 2009). Recently, this type of molecule has been combined with a porphyrin to obtain a scaffold-type macromolecule and employed to study of its interaction (host-guest interaction) with fullerenes, such as C 60 and C 70 in supramolecular chemistry Ghosh et al., 2014). The molecular tweezers containing a coumarin moiety showed better quantum yield and fluorescence absorption due to the presence of the extended conjugated enone of pyranocoumarin. As part of our studies in this area, we now describe the synthesis and structure of the title compound.

Figure 2
A view along the a axis of the crystal packing of the title compound, with hydrogen bonds shown as dashed lines (see Table 1).

Figure 1
The molecular structure of the title compound, with the atom labelling and displacement ellipsoids drawn at the 50% probability level tuents at the C3 and C4 atoms; many of which are natural products.

Synthesis and crystallization
The compound seselin was isolated as a colourless crystalline solid from the methanol extract of T. stictocarpum (in local dialect known as Aajmod) by means of column chromatography over SiO 2 gel, by gradient elution with a mixture of a binary solvent system of hexane and ethyl acetate. It was purified by reverse-phase high-pressure liquid chromatography followed by crystallization to yield a colourless solid. This compound was then brominated using NBS in aqueous tetrahydrofuran (THF) in a 1:1 ratio at room temperature with continuous mechanical stirring over a period of 12 h. The reaction was quenched with ice-cold water and extracted with diethyl ether to yield the crude product. This was then purified by column chromatography over SiO 2 with gradient solvent elution to yield the title compound. Colourless rod-like crystals were obtained after recrystallization three times from ethyl acetate:hexane (1:4) solution at room temperature.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The hydroxyl H atom was located in a difference Fourier map and refined with U iso (H) = 1.2U eq (O). The C-bound H atoms were included in calculated positions and treated as riding atoms: C-H = 0.93-0.98 Å with U iso (H) = 1.2U eq (C).  software used to prepare material for publication: SHELXL97 (Sheldrick, 2008). Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 &gt; 2sigma(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. Rfactors 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.