2-Acetamido-N-benzyl-1,4-imino-1,2,4-trideoxy-l-xylitol (N-benzyl-l-XYLNAc)

X-ray crystallography defines the relative configuration at the three-stereogenic centres in the title compound N-benzyl-l-XYLNAc, C14H20N2O3. The five-membered pyrrolidine ring adopts an envelope conformation with the N atom lying out of the plane of the other four atoms. In the crystal structure, intermolecular O—H⋯O, N—H⋯O and O—H⋯N hydrogen bonds link the molecules into chains along [100]. The carbonyl group O atom acts as an acceptor for a bifurcated hydrogen bond. The absolute configuration is determined by the use of l-glucuronolactone as the starting material for the synthesis.

X-ray crystallography defines the relative configuration at the three-stereogenic centres in the title compound N-benzyl-l-XYLNAc, C 14 H 20 N 2 O 3 . The five-membered pyrrolidine ring adopts an envelope conformation with the N atom lying out of the plane of the other four atoms. In the crystal structure, intermolecular O-HÁ Á ÁO, N-HÁ Á ÁO and O-HÁ Á ÁN hydrogen bonds link the molecules into chains along [100]. The carbonyl group O atom acts as an acceptor for a bifurcated hydrogen bond. The absolute configuration is determined by the use of l-glucuronolactone as the starting material for the synthesis.
Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: LH5029).

Comment
Iminosugars in which the oxygen of a sugar ring is replaced by nitrogen comprise a large family of inhibitors of carbohydrate processing enzymes (Asano et al., 2000;Watson et al., 2001). Specific inhibition of individual hexosaminidases may allow the investigation of a number of diseases including osteoarthritis (Liu, Numa et al., 2004), allergy (Reese et al., 2007), Alzheimer's disease (Liu, Iqbal et al., 2004), and cancer (Woynarowska et al., 1992). Inhibition of N-acetylgalactosaminyltransferases  and protection of macrophage activating factor (Greco et al., 2009) may provide new strategies for the treatment of cancer. There are many piperidine hexosaminidase inhibitors, such as naturally occurring nagstatin (Tatsuta et al., 1997) and DNJNAc (Fleet et al., 1986;Fleet et al., 1987;Steiner et al., 2009), some with picomolar inhibition (Ho et al., 2010). Until very recently, potent furanose analogue inhibitors of hexosaminidases have been unknown.
In a study of the hexosaminidase inhibition of diastereomers of LABNAc 2 (Fig. 1), the L-xylo-epimer L-XYLNAc 4 has been prepared from L-glucuronolactone 6, a common constituent of the chiral pool for the preparation of imino sugars . The lactone 6 may be efficiently converted to the diol 5 (Best, Chairatana et al., 2010) which has been further transformed to 4 via the N-benzyl L-XYLNAc 3 of L-XYLNAc. This paper reports the crystal structure of 3 which establishes the relative configuration and will allow modelling studies to rationalize enzyme inhibition by the diastereomeric 2-acetamido-pyrrolidine sugar mimics; the absolute configuration is determined by the use of L-glucuronolactone 6 as the starting material.
The pyrrolidine ring of the title compound adopts an envelope conformation with the nitrogen lying out of the plane (Fig.   2). The compound exists as chains of hydrogen-bonded molecules lying parallel to the a-axis (Fig. 3). Each molecule is a donor and acceptor for 3 hydrogen bonds and the hydrogen bond involving O19 is bifurcated. Only classical hydrogen bonding is considered.

Refinement
In the absence of significant anomalous scattering, Friedel pairs were merged and the absolute configuration was assigned from the use of L-glucuronolactone as the starting material.
supplementary materials sup-2 The relatively large ratio of minimum to maximum corrections applied in the multiscan process (1:1.29) reflect changes in the illuminated volume of the crystal. Changes in illuminated volume were kept to a minimum, and were taken into account (Görbitz, 1999) by the multi-scan inter-frame scaling (DENZO/SCALEPACK, Otwinowski & Minor, 1997).
The H atoms were all located in a difference map, but those attached to carbon atoms were repositioned geometrically.
The H atoms were initially refined with soft restraints on the bond lengths and angles to regularize their geometry (C-H in the range 0.93-0.98, N-H in the range 0.86-0.89 N-H to 0.86 O-H = 0.82 Å) and U iso (H) (in the range 1.2-1.5 times U eq of the parent atom), after which the positions were refined with riding constraints.