Crystal structure of Dehydrodieugenol B methyl ether, a neolignan from Nectandra leucantha Nees and Mart (Lauraceae)

In the title compound,the aromatic rings lie almost perpendicular to each other and the allyl side chains show similar configurations. In the crystal, molecules are connected by two C—H⋯O hydrogen bonds, forming undulating layers lying parallel to the bc plane.


Chemical context
Nectandra leucantha belongs to the Lauraceae family, which has a worldwide economic importance (Marques, 2001). Gottlieb (1972) described the chemosystematics of the Lauraceae family, highlighting the occurrence of alkaloids, arylpropanoids, benzoic esthers, flavonoids, benzophenones, fatty acids, mono and sesquiterpenes. The Nectandra genus accumulates alkaloids and lignoids as major secondary metabolites (Grecco et al., 2016). Recent studies from our group describe the antiparasitical (against Leishmania donovani and Trypanosoma cruzi) and cytotoxic activities of N. leucantha and its isolated metabolites. In terms of chemical composition, neolignans and sesquiterpenes were the major compounds from extracts and essential oils, respectively (da Costa-Silva et al., 2015;Grecco et al., 2015Grecco et al., , 2017. These studies allowed the isolation of C-C-and C-O-C-linked neolignans, including the known isomers dehydrodieugenol and dehydrodieugenol B, and of the novel compound dehydrodieugenol B methyl ether, the object of the present study. In order to confirm the constitution of the title compound, its crystal structure was determined and is reported here.

Database survey
The Cambridge Database (Version 5.38; Groom et al., 2016) contains no examples of 3,4 0 -diallyldiphenyl ethers. Neolignans and related natural products are often isolated as oils, so that crystal structure analyses are rare. In the field of neolignans, lignans, phenylpropanoids and eugenyl derivatives the following structures are relevant:   Table 1 Selected bond and torsion angles ( ).

Figure 2
Packing diagram of the title compound viewed perpendicular to the bc plane. For clarity, the allyl side chains and all hydrogen atoms not involved in hydrogen bonding (dashed lines, see Table 2) have been omitted.

Figure 1
Structure of the title compound in the crystal. Displacement ellipsoids represent 50% probability levels. One hydrogen atom is obscured at each of the atoms C17 and C19. specimen (EM357) was deposited at the herbarium of the Institute of Biosciences, University of Sã o Paulo, SP, Brazil. 2.5 kg of dried and milled leaves were exhaustively extracted with n-hexane, affording 55 g of lipophilic extract after vacuum evaporation of the solvent. In order to increase the content of the neolignan target compounds, the n-hexane extract was subjected to a liquid-liquid partition process, using equal parts of n-hexane and acetonitrile. The neolignanenriched fraction (NEF -31.6 g) was obtained from the acetonitrile phase after evaporation. A representative amount of 500 mg NEF was subjected to high-performance countercurrent chromatography (HPCCC) fractionation (Ito, 2005) using a semi-preparative instrument (Spectrum, Dynamic Extractions Ltd, Gwent, UK), a J-type centrifuge equipped with two coil bobbins (PTFE tubing, ID 1.6 mm, column volume 125 ml) operated with the biphasic solvent system n-hexane-ethyl acetate-methanol-water (HEMWat 7:3:7:3, v/v/v/v) as described by Grecco et al. (2017). The evaluation of biphasic solvent systems was guided by LC-ESI-MS analysis of the respective phase layers to detect a suitable distribution of neolignans. The rotation velocity of the HPCCC centrifuge was set to 1600 rpm (240 G field), and the flow rate of the aqueous mobile phase (5.0 ml min À1 ), and reversed phase operation mode (head-to-tail) resulted in a stationary phase retention of 82.0% after system equilibration. For metabolite profiling and target isolation of neolignans, aliquots of the recovered HPCCC fractions were injected in sequence into an ESI-ion trap MS/MS (HCT Ultra ETD II, Bruker Daltonics, Bremen, Germany) in a standard protocol described by Jerz et al. (2014). This procedure afforded C-C-and C-O-C- (19.6), 133.0 (47.7) (ESI-MS-parameter: HV capillary -3500 V, HV end plate offset -500, dry gas N 2 10.0 l min À1 , nebulizer 60 psi, trap drive 55.6, target mass 500, compound stability 80%, ICC target 100000, ICC on). One-dimensional and two-dimensional NMR data were recorded and compared with those reported previously (Costa-Silva et al., 2015), confirming the structure as dehydrodieugenol B methyl ether. The use of semi-preparative HPCCC, as an all-liquid chromatography technique resulted in a single process step to pure dehydrodieugenol B methyl ether. The compound crystallized from the immiscible solvent system by slow evaporation to yield 89 mg. An appropriate colourless block was chosen for X-ray analysis.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. NH hydrogen atoms were refined freely. Methyl hydrogen atoms were refined as idealized rigid groups with C-H 0.98 Å , H-C-H 109.5 (AFIX 137 command). Other hydrogen atoms were included using a riding model starting from calculated positions (C-H aromatic and C-H vinyl = 0.95, C-H methylene = 0.99, C-H methine = 1.00 Å ) with U iso (H) = 1.2 or 1.5U eq (C).

1,2-Dimethoxy-3-[3-methoxy-5-(prop-2-en-1-yl)phenoxy]-5-(prop-2-en-1-yl)benzene
Crystal data 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.