(Z)-2-{2,4-Dimethoxy-6-[(E)-4-methoxystyryl]benzylidene}quinuclidin-3-one

The crystal structure of the title compound, C25H27NO4, shows the presence of a double bond with Z geometry which connects the quinuclidin-3-one ring and the trimethoxyresveratrol moiety. The dihedral angle between the two benzene rings in the stilbene skeleton is 32.80 (8)°.

The crystal structure of the title compound, C 25 H 27 NO 4 , shows the presence of a double bond with Z geometry which connects the quinuclidin-3-one ring and the trimethoxyresveratrol moiety. The dihedral angle between the two benzene rings in the stilbene skeleton is 32.80 (8) . Resveratrol (trans-3,4′,5-trihydroxystilbene) is a phytochemical which is found in more than 70 plant species. This phytolaxine was proven to have diverse biological beneficial activities with no adverse effects in animal models (Aggarwal et al. 2004, Pettit et al. 1995. Resveratrol was also reported to be a potential cancer chemotherapeutic agent based on its striking inhibitory effects on cellular events associated with cancer initiation, promotion, and progression (Cushman et al. 1991). Unfortunately, resveratrol cannot be used as a drug because of its chemical and metabolic instability (Jeandet et al. 1979, Trela et al. 1996. trans-3,4′,5-trimethoxystilbene, an analog of resveratrol, was found to have greater chemical and metabolic stability with improved anticancer activity. Based on several SAR studies on trimethoxyresveratrol analogues we have designed and synthesized a series of novel trimethoxy resveratrol analogues that are expected to function as potent cytotoxic agents against breast and lung cancer cells. The X-ray analysis of the titled compound was performed to determine the geometry (i.e. E versus Z) of the double bond connecting the quinuclidin-3one ring and the trimethoxyresveratrol moiety, and to obtain detailed information on the structural conformation of the molecule that may be useful in structure-activity relationship (SAR) analysis. The title compound was synthesized in two steps. In step one, the formylation of trans-3,4′,5-trimethoxystilbene was achieved with a slight excess of phosphorous oxychloride in dimethylformamide at 0 °C to yield trans-2-formyl-3,4′,5-trimethoxystilbene. In step two, a mixture of trans-2-formyl-3, 4′, 5-trimethoxystilbene and quinuclidin-3-one were refluxed in ethanol in the presence of 10% NaOH to yield the title compound, (Z)-2-(2,4-dimethoxy-6-((E)-4-methoxystyryl) benzylidene)quinuclidin-3-one in 40% yield.

Related literature
The X-ray analysis studies revealed that the double bond connecting the quinuclidin-3-one ring and the trimethoxyresveratrol moiety had the Z geometry. The dihederal angle between the two phenyl rings in the stilbene skeletone is 32.80 (8)°. The crystal packing is stabilized by van der Waals forces with no intermolecular hydrogen bonding interactions.

Experimental
A mixture of trans-2-formyl-3,4′,5-trimethoxystilbene (150 mg, 1 mmol), quinuclidin-3-one (89.44 mg, 1.1 mmol), 10% NaOH and ethanol (10 ml) was refluxed for 5 hrs and completion of reaction was monitored by TLC. The resulting reaction mixture was concentrated to remove ethanol and extracted into ethyl acetate; the ethyl acetate extract washed with water to remove residual NaOH. The organic layer was then dried over anhydrous magnesium sulfate, filtered, and the solvent evaporated to afford the crude product. Purification was achieved by flash silica gel chromatography eluting with 4:1 hexane/ethyl acetate as moblile phase. The title compound, benzylidene)quinuclidin-3-one, was crystallized from methanol to afford a white crystalline product which was suitable for X-ray analysis.  2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and local procedures.

Figure 1
A view of the molecule with the atom numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.

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 > 2σ(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.