Betulin 3,28-di-O-tosylate

The title compound, C44H62O6S2 {systematic name: (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-[(tosyloxy)methyl]icosahydro-1H-cyclopenta[a]chrysen-9-yl 4-methylbenzenesulfonate}, was obtained by tosylation of naturally occurring betulin. All the cyclohexane rings adopt chair conformations and the cyclopentane ring adopts a twisted envelope conformation, with the C atom bearing the tosylmethyl substituent forming the flap. In the crystal, molecules form a three-dimensional network through multiple weak C—H⋯O hydrogen bonds.


S1. Comment
The crystal and molecular structure of the betulin has not been previously reported, however, Drebushchak et al. (2013) have indexed X-ray powder diffraction pattern and calculated lattice parameters. The bond lengths (Allen et al., 1987) and angles in the molecule are close to standard values. All the cyclohexane rings adopt chair conformations and the cyclopentane ring adopts a twisted envelope conformation with the isopropenyl group equatorially attached to C19. The torsion angle C21-C19-C20-C29, which describs the conformation of the isopropenyl group, is equal to -102.1 (5)°. This conformation is variable among the structures disscused in this section.

S2. Experimental
Single crystals of betulin 3,28-di-O-tosylate were grown from a hexanes/dichloromethane (15/1) solution by slow evaporation at ambient temperature. 1 H-NMR and 13 C-NMR spectra were recorded at 400 MHz and at 100. the residue and the resulting mixture was evaporated under reduced pressure. Additional amount of toluene (2 × 10 mL) was added and the evaporation was repeated. This process removes the residual pyridine via azeotrope distillation. The resulting residue was directly transferred to silica gel column and chromatographed with EtOAc/hexanes (3/97). The fraction corresponding to R f =0.40 (EtOAc/hexanes 1:5) was collected and the obtained colorless powder (0.25 g, 15%) was crystallized from the hexanes/dichloromethane (15/1) solution by slow evaporation at ambient temperature to provide single crystals of betulin 3,28-di-O-tosylate. Other fractions (1.10 g) contained the title product together with its mono-tosyl congeners.

S3. Refinement
All non-hydrogen atoms were refined anisotropically. All hydrogen atoms were positioned geometrically with C-H distances ranging from 0.93 Å to 0.98 Å and refined as riding on their parent atoms with U iso (H) = 1.5U eq (C) for methyl groups and U iso (H) = 1.2U eq (C) for others.
There are 21 reflections with intensities affected by the beamstop; these were removed from the final refinement since they are in systematic error. The asymmetric unit of the title compound showing 50% probability displacement ellipsoids and the atom-numbering.

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.