1,2,3-Tri-O-acetyl-5-deoxy-d-ribofuranose

The title compound, C11H16O7, was obtained from the breakage reaction of the glycosidic bond of 5′-deoxy-2′,3′-diacetylinosine. The ribofuranose ring has a C2-exo, C3-endo twist configuration. No alteration of the relative configuration compared with d-(−)-ribose is observed.


Related literature
For possible catalytic mechanisms at the anomeric carbon centre in the cleavage of glycosidic linkages, see: Vocadlo et al. (2001). For the synthesis of the title compound from d-ribose, see: Sairam et al. (2003). For a 5-deoxy-ribofuranoid active as an antitumour drug, see: Shimma et al. (2000).

Experimental
Crystal data

Comment
During the last decades there has been considerable interest in the chemical synthesis of the nucleoside analogues for their biological evaluation of the anti-tumor activity (Sairam et al., 2003). 1,2,3-O-Triacetyl-5-deoxy-D-ribofuranose, as one of the important intermediates, was used to synthesize some anti-cancer drugs such as Doxifluridine, Capecitabine (Shimma et al., 2000), and so on. There were different synthetic routes available in literature for the synthesis of this intermediate.
We obtained this compound from inosine as starting material in a linear synthetic route. Possible formation mechanisms of the title compound are shown in Fig. 1. To know the relative stereochemistry of the anomeric position in the ribose, it is therefore necessary to gain the well defined structure of the 1,2,3-O-triacetyl-5-deoxy-D-ribofuranose by X-diffraction method (Fig. 2).
We observed that the ribofuranose ring has a C2-exo, C3-endo twist configuration and the anomeric carbons are always β configuration in the crystal packing. We suppose that the mechanism of the breakage reaction of the glycosidic bond is similar to that of the glycoside hydrolase (Vocadlo et al., 2001). Firstly, the nucleophilic group of the cation resin attacks the anomeric centre of the 5'-deoxy-2',3'-diacetyl-inosine, resulting in the formation of a glycosyl intermediate. Then a nucleophilic acetic anhydride as a base acts the glycosyl intermediate by acetolysis, giving the title product. In another way, the product obtained with sulfuric acid as catalyst is a α/β anomeric mixture and the yield is much lower. This difference may be because the intermediate produced using strong acid is a carbocation and the furan ring may be decomposed to some byproducts.

Experimental
The title compound was prepared from the reaction of the breakage of the glycosidic bond of 5'-Deoxy-2',3'-diacetyl-inosine, which was gained from inosine by halogenation, hydrogenization and acetylation in turn. 5'-Deoxy-2',3'-diacetyl-inosine (6.72 g, 20 mmol) and cation-exchange resin (6 g) were added to a solution of acetic anhydride/acetic acid (60 ml, 9: 1), was heated to 358 K and reacted under stirring for 8 h. The reacting mixture was filtered and the filtrate was concentrated in vacuo. The residue was resolved in ethyl acetate, then the precipitate was filtered and the filtrate was washed by the saturated solution of NaHCO 3 . The organic layer was dried with anhydrous Na 2 SO 4 , filtered, and concentrated in vacuo.
The residue was recrystallized from methanol/water. The purified title compound was subsequently dissolved in methanol and added water to the solution until it turned cloudy. Upon standing at room temperature, a colorless block appeared and was separated from the solvent by decantation.

Refinement
All H atoms were positioned geometrically and refined using a riding model, with C-H distances of 0.98 Å (methyl), with U iso (H) = 1.2U eq (C) and 1.5U eq (C-methyl).
In the absence of significant anomalous scattering effects, Friedel pairs were averaged.

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.
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 Rfactors(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.