Crystal structure and absolute configuration of (4S,5R,6S)-4,5,6-trihydroxy-3-methylcyclohex-2-enone (gabosine H)

The absolute configuration of the title compound, determined as 4S,5R,6S on the basis of the synthetic pathway, was confirmed by single-crystal X-ray diffraction. The molecule is formed by a substituted six-membered cyclohexene ring adopting an envelope conformation and substituted by carbonyl, methyl and hydroxyl groups. The supramolecular structure is mainly built by a combination of O—H⋯O and weaker C—H⋯O hydrogen bonds.


Chemical context
Gabosines are regarded as secondary metabolites and were first isolated in 1974 from Streptomyces strains (Tsushiya et al., 1974). These compounds are closely related to carbasugars and exhibit DNA binding properties (Tang et al., 2000). To date, 15 gabosines have been isolated, of which 14 have been synthesized. Gabosine H is one of such kind, whose total synthesis has recently been achieved by our research group (Tibhe et al., 2017), starting from a biotransformation of toluene that introduces chirality. A further sequence of reactions, including Mitsunobu and final removal of the acetyl protective group, led to the title compound. Fig. 1 shows the molecule of the title compound. The absolute configuration of gabosine H with the carbonyl, methyl and hydroxyl groups in equatorial positions, determined as 4S,5R,6S on the basis of synthetic pathway, was confirmed by X-ray diffraction on the basis of anomalous dispersion of light atoms only. The six-membered ring (C1-C6) in the molecule ISSN 2056-9890 adopts an envelope conformation with atom C5 as the flap [deviating from the plane through the other ring atoms by 0.639 (2) Å ] and puckering parameters Q = 0.4653 (19) Å , = 129.5 (2) and ' = 66.7 (3) .

Figure 1
The molecular structure of the title compound, showing the anisotropic displacement ellipsoids drawn at the 50% probability level. [001]. Between these neighboring [001] sheets, weak dipolar or van der Waals forces stabilize the assembly along the c-axis direction.

Synthesis and crystallization
The synthesis of gabosine H was achieved by inversion of the allylic -OH group using Mitsunobu conditions followed by deprotection. (4R,5R,6S)-5-Acetoxy-4,5-dihydroxy-3-methylcyclohex-2-enone (2, Fig. 4; 0.149 mmol, 0.030 g) was dissolved in 1 ml of benzene and TPP (0.283 mmol, 0.078 g) was added along with p-nitrobenzoic acid (0.299 mmol, 0.050 g) and diisopropyl azodicarboxylate (DIAD; 0.297 mmol, 0.060 g). The reaction mixture was stirred at room temperature for 6 h. The solvent was evaporated and the crude mass was used for the next reaction without further purification. The crude product was dissolved in MeOH (3.4 mL), a catalytic quantity of K 2 CO 3 was added and the reaction mixture was stirred at room temperature for 5 min and filtered. Evaporation of the solvent from the filtrate afforded crude gabosine H, which was purified by column chromatography (CH 2 Cl 2 /MeOH Reaction scheme.

Figure 3
Partial crystal packing of the title compound connected into a nearly orthogonal assembly along [001] through C-HÁ Á ÁO and O-HÁ Á ÁO hydrogen bonds (dotted lines).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. H atoms bonded to C were placed in calculated positions (C-H = 0.93-0.98 Å ) and included as riding contributions with isotropic displacement parameters set to 1.2-1.5 times the U eq of the parent atom. Hydroxy H atoms were located in difference density maps and were refined with U iso (H) = 1.5 U eq (O). The absolute structure parameter y was calculated using PLATON (Spek, 2009). The resulting value of 0.07 (7) indicates that the absolute structure was determined correctly (Hooft et al., 2008). Crystal structure and absolute configuration of (4S,5R,6S)-4,5,6-trihydroxy-3-

(4S,5R,6S)-4,5,6-Trihydroxy-3-methylcyclohex-2-enone
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.