2-Acetamido-N-benzyl-1 , 4-imino-1 , 2 , 4-trideoxy-L-arabinitol 0 . 33-hydrate

-N-Acetylglucosaminidases (NAGs) have attracted considerable research interest as therapeutic targets for some lysosomal storage diseases (Tropak et al., 2004), cancer (Woynarowska et al., 1992) and osteoarthritis (Liu et al., 2001), and as antifungal agents (Horsch et al., 1997) and catalysts for biomass degradation (Kato, Uno et al., 2005). Monosaccharides in which the ring oxygen has been replaced by nitrogen constitute a general class of glycosidase inhibitors (Watson et al., 2001; Asano et al., 2000). All potent inhibitors of NAGs in this class have hitherto been pyranose analogues of NAG such as the piperidine (1) (Fleet et al., 1986) and NAG-thiazoline (Knapp et al., 1996); other heterocyclic compounds containing a pyranose ring (Terinek & Vasella, 2005; van den Berg et al., 2004) also show promise as potential chemotherapeutic agents. In contrast few five-ring pyrrolidine analogues, none of which are potent, have been reported (Croucher et al., 1994; Liessem et al., 1993; Liu et al., 2004).

The solid-state conformation of the title compound, C 14 H 20 N 2 O 3 Á0.33H 2 O, a potent hexosaminidase inhibitor, prepared from d-lyxonolactone, has been established by X-ray crystallography. The asymmetric unit contains three molecules, which have very similar conformations, together with a molecule of water.
A systematic study of the stereoisomers of a set of pyrrolidine analogues, (3), as potential NAG inhibitors (Harding et al., 2005) is in progress. Both enantiomers of imino sugars are frequently inhibitors of the same enantiospecific enzyme Asano et al., 2005;Yu et al., 2004). Solid-state and solution studies of the conformations of the diastereomers of (3) may yield an understanding of this phenomenon; this paper reports the crystal structure of the title compound, (4), which is a potent inhibitor of a number of hexosaminidases, prepared from d-lyxonolactone (5).
The asymmetric unit of (4) contains three sugar molecules (Figs. 1 and 2), together with a solvent water molecule. The water molecule is involved in the hydrogen bonding, and forms part of a hydrophilic layer which is surrounded by the hydrophobic benzyl groups (Figs. 3 and 4). The three independent molecules differ only slightly in conformation from each other, the main difference being that the hydroxyl group of the middle molecule in Fig. 2 points almost in the opposite direction from that of its counterparts in the other two molecules.

Experimental
A solution of the title compound was dissolved in acetonitrile. The vial was placed inside another vial containing cyclohexane and closed to the atmosphere. This system was then left to undergo competitive diffusion for two weeks. Small amounts of water also found their way into the system. This yielded small plate-like clear crystals of the hydrated title compound. The full experimental method will be published separately .  The structure of one molecule, with displacement ellipsoids drawn at the 50% probability level.
H atoms were observed in difference electron density maps. They were initially refined with soft restraints on the bond lengths and angles to regularize their geometry [C-H = 0.93-98 Å , N-H = 0.86-0.89 Å and O-H = 0.82 Å , and with U iso (H) in the range 1.2-1.5U eq of the parent atom], after which they were refined with riding constraints. In the absence of significant anomalous scattering effects, Friedel pairs were merged. The absolute configuration is known from the synthesis. Several low-angle reflections were omitted from the refinement because they appeared to be obscured by the beam-stop.