Crystal structure of racemic 2-[(β-arabinopyranosyl)sulfanyl]-4,6-diphenylpyridine-3-carbonitrile

In the racemic title compound, the sulfur atom is attached equatorially to the sugar ring with unequal S—C bonds. The dihedral angles between the pyridine ring and its attached phenyl groups are 42.24 (8) and 6.37 (14)°. In the crystal, a system of classical O—H⋯O and O—H⋯(O,O) hydrogen bonds links the molecules to form tube-like assemblies propagating parallel to the c-axis direction.


Chemical context
In recent years, nucleoside analogues of pyrimidines and purines have been shown to be effective as chemical therapeutic agents against cancer cells (Yoshimura et al., 2000;Elgemeie et al., 2016Elgemeie et al., , 2017a. Recently, heterocyclic thioglycosides have been used as antimetabolic agents in medicinal chemistry (Dinkelaar et al., 2006;Kananovich et al., 2014;Elgemeie & Abu-Zaied, 2017). We and others have designed new syntheses for pyridine thioglycosides, which have shown strong cytotoxicity against various human cancer cell lines and block proliferation of various cancer cell lines (Komor et al., 2012;Elgemeie et al., 2015). It has also been shown that thioglycosides involving pyridine and dihydropyridine groups exert inhibitory effects on both DNA-containing viruses and inhibitors of protein glycosylation (Agrawal et al., 2017;Elgemeie et al., 2010;Masoud et al., 2017). Based on these significant biological findings and with the aim of identifying new potent chemotherapeutics as new anticancer agents with improved pharmacological and safety profiles, we have prepared several new non-classical thioglycosides containing the pyridine ring.

Structural commentary
The crystal structure determination indicated unambiguously the formation of the pyridine-2-thioarabinoside (4) as the only product in the solid state. We suggest that the 2,3,4-tri-Oacetyl--d-arabinopranosyl bromide (2) interacts via a simple S N 2 reaction to give the -glycoside product (3), which after deprotection leads to the free 2-(-d/l-arabinopyranosylthio)pyridine-3-carbonitrile (4). This separates as a racemic mixture, presumably because of thermodynamic racemization during synthesis or crystallization (Brands & Davies, 2006).
The molecular structure of (4) is shown in Fig. 1. The sulfur atom is attached equatorially to the sugar ring. Similarly to the structure of a related glucose derivative (Masoud et al., 2017), the C-S bond lengths are unequal, with S-C s 1.808 (2) and S-C p 1.770 (2) Å (s = sugar, p = pyridyl). The phenyl ring at C31 is approximately coplanar with the pyridyl ring, but the ring at C21 is significantly rotated (interplanar angles = 6.4 (2) and 42.24 (8) , respectively). The relative orientation of the pyridyl ring and the sugar moiety is defined by the torsion angles N1-C2-S1-C11 9.7 (2) and C2-S1-C11-C12 162.73 (12) . The intramolecular contact O1-H01Á Á ÁS1, with HÁ Á ÁS 2.79 (4) Å and an angle of 109 (3) , is probably too long and has too narrow an angle to be considered a hydrogen bond.

Figure 1
Structure of the title compound (4) in the crystal. Ellipsoids represent 50% probability levels.

Synthesis and crystallization
To a solution of the pyridine-2-(1H)-thione (1) (2.88 g, 0.01 mol) in aqueous potassium hydroxide (6 ml, 0.56 g, 0.01 mol) was added a solution of 2,3,4-tri-O-acetyl--darabinopyranosyl bromide (2) (3.73 g, 0.011 mol) in acetone (30 ml). The reaction mixture was stirred at room temperature until the reaction was judged complete by TLC (30 min to 2 h). The mixture was evaporated under reduced pressure at 313 K and the residue was washed with distilled water to remove the potassium bromide. The solid was collected by filtration and crystallized from ethanol to give compound ( Packing diagram of (4) viewed parallel to the a axis. Dashed lines indicate classical hydrogen bonds. Phenyl rings are represented by the ipso carbon atoms only.

Figure 2
Packing diagram of (4) projected parallel to the c axis. Dashed lines indicate classical hydrogen bonds.

2-[(β-Arabinopyranosyl)sulfanyl]-4,6-diphenylpyridine-3-carbonitrile
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. Least-squares planes (x,y,z in crystal coordinates) and deviations from them (* indicates atom used to define plane) 9.6921 (