Isolation and crystal structure of lawinal

The crystal structure of the natural product lawinal is reported. The compound crystallizes with monoclinic (I2) symmetry and with Z′ = 2.

The structure of the natural product lawinal [systematic name: (À)-(2S)-5,7dihydroxy-6-methyl-4-oxo-2-phenylchromane-8-carbaldehyde, C 17 H 14 O 5 ] at 150 K is reported. The compound crystallizes with monoclinic (I2) symmetry and with Z 0 = 2. The absolute configuration could not be determined reliably from X-ray analysis only. However, our analysis returns the S-configuration at the C-2 position, consistent with previous stereochemical assignment from specific rotation. The independent molecules form into alternating hydrogenbonded chains with C-HÁ Á ÁO CH intermolecular linkages that run parallel to the crystallographic a axis and are extended into the ac plane byinteractions between their phenyl substituents.

Chemical context
The small flowering plants of the Desmos genus belong to the Annonaceae family, which comprises about 33 species and is distributed widely throughout Southern Asia and northern Australia (Brophy et al., 2002;Clement et al., 2017). Several species of this genus have been used as Chinese folk medicines (Wu et al., 2003). The aerial part of D. chinensis has been used as an analgesic agent, and to treat vertigo, and parturition (Kummee & Intaraksa, 2008;Rahman et al., 2003). In Thailand it is widely used traditionally to treat fever and dysentery (Bunyapraphatsara et al., 2000). The petroleum ether extracts of D. cochinchinensis roots have mainly been explored for their antimalarial activity (Liao et al., 1989). The Desmos genus is well known as an abundant source of flavonoids (Meesakul et al., 2019;Bajgai et al., 2011;Kuo et al., 2015), and their 2S absolute configuration has been commonly found (Meesakul et al., 2019;Kuo et al., 2015). Flavonoids exhibit interesting biological activities, including inhibition of HIV-1 replication in H9 lymphocytic cells (Wu et al., 2003), antibacterial properties (Liao et al., 1989) and show activities asglucosidase inhibitors (Meesakul et al., 2019), antioxidants (Miller, 1996), aromatase and lipoxygenase inhibitors (Bajgai et al., 2011).

Structural commentary
Lawinal crystallizes in the space group I2 with Z 0 = 2. Because of the large standard deviation of the Flack parameter [À0.1 (5)], the absolute configuration cannot be assigned from the X-ray data (Parsons et al., 2013). We explored applying the Bayesian statistical approach promoted by Hooft et al. (2008). Given that the compound comes from a natural product source and thus should be enantiopure, the analysis, as implemented in PLATON (Spek, 2020), returned a P2(true) value of 0.992 for the S-configuration at C2 in each molecule (Fig. 1). This is consistent with the stereochemical assignment by the method of specific rotation (Prawat et al., 2012;Wu et al., 2005).
The unique molecules adopt extremely similar conformations and an overlay of the molecular structures is shown in Fig. 2. The hydroxyl groups attached to C5 and C7 on each unique molecule act as hydrogen-bond donors to the ketone and aldehyde functionalities, respectively. The positions of the hydroxyl hydrogen atoms were refined, the relatively long D-H distances (Table 1) indicating strong intramolecular stabilization. The hydrogen bond O7-H7Á Á ÁO9 is responsible for bringing the aldehyde group into approximate coplanarity with the chromanone ring system. In contrast, the phenyl substituents attached to C2 in each molecule are approximately orthogonal to the chromanone ring systems [plane-toplane angles of 99.4 (1) and 97.5 (1) to the phenyl rings of the chromanones].

Supramolecular features
The shortest intermolecular contacts to hydrogen-bond acceptors of the unique molecules come from the pseudoequatorial C-H bonds in the CH 2 moieties of the chromanone rings to the aldehyde oxygen atoms, O9 and O9A (Table 1). These C-HÁ Á ÁO CH connections assemble the unique molecules into alternating chains that propagate parallel to the crystallographic a-axis, as shown in An overlay of the independent molecules in the asymmetric unit. The dotted lines represent the intramolecular hydrogen bonds. Table 1 Hydrogen-bond geometry (Å , ). Symmetry codes: (i) Àx þ 3 2 ; y À 1 2 ; Àz þ 1 2 ; (ii) Àx þ 1 2 ; y þ 1 2 ; Àz þ 1 2 .

Figure 3
A view parallel to the crystallographic b-axis, with intramolecular and intermolecular hydrogen bonds shown as dotted red lines and theinteractions as dashed blue lines. The intermolecular hydrogen bonds link molecules into chains propagating along the crystallographic a-axis direction and theinteractions link the hydrogen-bonded chains into two-dimensional sheets in the crystallographic ac plane. Displacement ellipsoids are plotted at the 50% probability level.

Figure 1
The contents of the asymmetric unit with complete atom labelling of one molecule and selected heteroatom labelling of the second molecule, for clarity. Intramolecular hydrogen bonds are shown as dashed magenta lines. Displacement ellipsoids are plotted at the 50% probability level. adjacent chains. This links the chains into two-dimensional sheets in the ac plane. The plane-to-plane angle between phenyl rings is 4.7 (1) and the distance from plane centroid to plane centroid, as indicated by the blue dashed line in Fig. 3, is 3.821 (2) Å .

Plant Material
Desmos dumosus twigs were collected from Doi Tung, Chiang Rai Province, Thailand, in February 2016. The plant was identified by Mr Matin Van de Bult (Doi Tung Development Project, Chiang Rai, Thailand). The specimen (MFU-NPR0110) was deposited at Mae Fah Luang University's Natural Products Research Laboratory.
Extraction and Isolation Air-dried twigs of D. dumosus (7.00 kg) were extracted for three days at room temperature with EtOAc (20 L). Removal of the solvent under reduced pressure provided the crude extract (92.7 g), which was subjected to column chromatography over silica gel using a gradient of hexanes and EtOAc (100% hexanes to 100% EtOAc) to afford 12 fractions (D1-D12). Fraction D5 (7.70 g) was further fractionated by column chromatography over Sephadex-LH 20 resin eluting with 100% MeOH to provide nine subfractions (D5A-D5I). Subfraction D5E (1.45 g) was further separated by column chromatography over silica gel (1:4, v/v EtOAc/hexanes) to give lawinal (35.5 mg) as a faint yellow-coloured solid.
Crystallization and characterization data

Refinement
The data were collected using Mo K radiation, therefore anomalous dispersion effects are small. The crystal structure itself is pseudo-centrosymmetric. Indeed, a structural solution can be successfully obtained in a centrosymmetric space group, although this results in an unsatisfactory refinement, with apparent disorder about the stereogenic center, as expected. The actual inversion symmetry is, of course, incompatible with the natural origin and optical activity of the compound. Crystal data, data collection and structure refinement details are summarized in Table 2. Tertiary C(H), secondary C(H,H), primary C(H,H,H) and aromatic H atoms were placed in geometrically idealized positions (C-H = 1.00, 0.99, 0.98, and 0.95 Å , respectively) and refined in riding models with U iso (H) = 1.2U eq (C) or 1.5U eq (C). The methyl group attached to C-6 was refined as a rotating body. The hydroxylic H atoms were refined unconstrained in isotropic approximation.

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.