Lup-20(29)-en-28-ol-3-one (betulone)

The asymmetric unit of the title compound, C30H48O2, contains two independent molecules, the main difference between them being that the isopropenyl group is rotated by approximately 180°. In each molecule, the fused six-membered rings have chair–chair–chair–chair conformations and the cyclopentane ring adopts an envelope conformation with the C atom bearing the hydroxymethyl group as the flap. All ring junctions are trans-fused. With the exception of one of the methyl groups adjacent to the C=O group, all the methyl groups are in axial positions. The isopropenyl group is equatorial and the hydroxymethyl group is in an axial orientation. In the crystal, weak C—H⋯O interactions link the molecules into chains along [010]. Weak intramolecular C—H⋯O hydrogen bonds are also observed but the hydroxy groups are not involved in hydrogen bonds.

The asymmetric unit of the title compound, C 30 H 48 O 2 , contains two independent molecules, the main difference between them being that the isopropenyl group is rotated by approximately 180 . In each molecule, the fused sixmembered rings have chair-chair-chair-chair conformations and the cyclopentane ring adopts an envelope conformation with the C atom bearing the hydroxymethyl group as the flap. All ring junctions are trans-fused. With the exception of one of the methyl groups adjacent to the C O group, all the methyl groups are in axial positions. The isopropenyl group is equatorial and the hydroxymethyl group is in an axial orientation. In the crystal, weak C-HÁ Á ÁO interactions link the molecules into chains along [010]. Weak intramolecular C-HÁ Á ÁO hydrogen bonds are also observed but the hydroxy groups are not involved in hydrogen bonds. H atoms treated by a mixture of independent and constrained refinement Á max = 0.55 e Å À3 Á min = À0.50 e Å À3 Table 1 Hydrogen-bond geometry (Å , ). Data collection: CrysAlis CCD (Oxford Diffraction, 2008); cell refinement: CrysAlis RED (Oxford Diffraction, 2008); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: Mercury (Macrae et al., 2006); software used to prepare material for publication: publCIF (Westrip, 2010). This work was supported by the Medical University of Silesia in Katowice, Poland (grant No. KNW-1-006/P/2/0).
The structure of betulone is based on the 30-carbon skeleton comprising of four 6-membered rings and one cyclopentane ring. It has three available sites for simple chemical modification, namely: keto group at C3, primary hydroxy group at C28 and isopropenyl side chain at C19. These groups and their positions, mutual distances and orientation with respect to the rings can influence hydrogen bonding and the interactions of betulone with other active sites of surrounding species.
Betulone is also known as a derivative of betulin, which is one of the most plentiful triterpenes comprising up to 30% dry weight of the outer bark of the white birch. In comparison to betulin, the content of betulone in the outer bark of different tree species is very low, e.g. about of 0.03% in Betula platyphylla (Fuchino et al., 1996) and for this reason the isolation from raw plant material is poorly profitable. A more effective method to obtain betulone with high yield is to carry out synthesis from betulin (Hase et al., 1981). The crystal structure of betulone has not been reported until now.
However, the crystal structures of betulonic acid-DMSO and betulonic acid-DMF solvates (Boryczka et al., 2012b) were earlier described. In addition, the structure of betulinic acid-DMSO solvate (Boryczka et al., 2012a) has also been reported. In the present work, we describe the crystal structure of betulone in order to gain a better understanding of the structure-activity relationships of this important molecule. Betulonic alcohol was obtained by oxidation of naturally occurring betulin in a one-step reaction utilizing Jones-oxidation (CrO 3 /H 2 SO 4 in acetone-water solution) as the side product.
The asymmetric unit contains two independent molecules (IA and IB). A schematic drawing of the ring and atom labeling is shown in Fig. 1  respectively. The methyl groups C24, C25, C26, C27 occupy axial positions, but the methyl group C23 and isopropenyl group at C19 are equatorial. Fig. 4 shows the different orientations of the isopropenyl groups in the two independent molecules, (IA and IB). The value of the C21-C19-C20-C29 torsion angle describes the orientation of the isopropenyl group is equal to 92.3 (4)° (IA) and -98.8 (4)° (IB). The value of the C21-C19-C20-C29 torsion angle for betulin-DMSO and betulin-ethanol solvates are -96.8 (5)° and 88.6 (5)°, respectively. The hydroxymethyl group is attached to atom C17 of ring D in an axial orientation. No classical hydrogen bonding involving the hydroxy groups is observed. In the crystal, weak intermolecular C-H···O interactions link molecules into chains along [010]. Weak intramolecular C-H···O hydrogen bonds are also observed.

Refinement
The aromatic hydrogen atoms were treated as riding on their parent carbon atoms with d(C-H) = 0.95 Å and assigned isotropic atomic displacement parameters equal to 1.2 times the value of the equivalent atomic displacement parameters of the parent carbon atom [U iso (H)= 1.2U eq (C)]. The methylene H atoms were constrained to an ideal geometry with d(C -H) = 0.99 A° or d(C-H) = 0.95 Å (for terminal methylene group) and U iso (H) = 1.2U eq (C). Methyl H atoms were constrained as riding atoms, fixed to the parent atoms with distance of 0.98 A° and U iso (H) = 1.5U eq (C). hydroxy H atoms were constrained as riding atoms with d(O-H) = 0.84 Å and U iso (H) = 1.5U eq (O). Hydrogen atoms involved in weak hydrogen bonds were refined freely with U iso (H) equal to 1.2U eq of the parent atom. In the absence of significant anomalous dispersion effects the Friedel pairs were merged.    The asymmetric unit of the title compound. Displacement ellipsoids are drawn at the 50% level.  View of the unit cell along the crystallographic a axis.

Lup-20 (29)-en-28-ol-3-one
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 > σ(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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
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