(1S,2R,6R,7aS)-1,2,6-Trihydroxyhexahydro-1H-pyrrolizin-3-one

In the title compound, C7H11NO4, prepared via a Morita–Baylis–Hillman adduct, the five-membered ring bearing three O atoms approximates to a twisted conformation, whereas the other ring is close to an envelope, with a C atom in the flap position. The dihedral angle between their mean planes (all atoms) is 23.11 (9)°. The new stereocenters are created in a trans-diaxial configuration. In the crystal, O—H⋯O and O—H⋯(O,O) hydrogen bonds link the molecules, generating a three-dimensional network. A weak C—H⋯O interaction also occurs.


Comment
Crystallographic data of the title polyhydroxylated pyrrolizidinone are disclosed. Compounds of this class can be used as glycosidase inhibitors and present a huge therapeutical potential for the treatment of a number of diseases such as cancer, diabetes, and lysosomal storage disorders (Baumann, 2007). The title compound has been prepared, for the first time, using a synthetic strategy based on a Morita-Baylis-Hillman adduct, easily obtained from a reaction between N-Boc-4(R)hydroxy-2(S)-prolinal and methyl acrylate in 70% yield, as a mixture of diastereoisomers. After chromatographic separation, the minor isomer was transformed into the title compound. This compound was synthesized in five steps and 5.2% overall yield.
The asymmetric pyrrolizidinone, C 7 H 11 NO 4 , a new molecule with four stereocenters from a Morita-Baylis-Hillman adduct is shown in Fig. 1

Experimental
A solution of pyrrolizidinone (II) (0.10 g, 0.59 mmol) in MeOH/CH 2 Cl 2 (3:7, 15 mL) was cooled to -72°C. After that a stream of oxygen/ozone was bubbled into it for 8-10 min (the reaction evolution was followed by TLC). Then, NaBH 4 (0.112 g, 4.45 mmol) was added at -72°C and the resulting mixture was stirred for 6 h at room temperature. The reaction medium was initially acidified to pH 2-3 with a solution of HCl in methanol, then it was neutralized to pH 6-7 with solid Na 2 CO 3 . The resulting mixture was filtered over a pad of Celite (R) and the solid was washed with methanol. The filtrates were combined and the solvents were removed under reduced pressure. The residue was purified by flash silica gel column chromatography (CH 2 Cl 2 :MeOH 95:05) to afford pyrrolizidinone I (0.08 g), as a white solid, in 80% yield. The

Refinement
The calculated Flack parameter was F=0.20 (17) (Flack, 1983). Analysis of the absolute structure was also performed using likelihood methods (Hooft et al., 2008) as implemented in PLATON (Spek, 2009). The resulting value for the Hooft parameter was y=0.12 (4), with a corresponding probability for an inverted structure smaller than 1 × 10 -100 . Taken togheter, these results indicate that the absolute structure has been determined correctly.   Title compound involved into hydrogen bonds. The presence of several hydroxyl groups in its structure leads this compound to behave as a sugar.

Figure 3
The conversion of (I) to pyrrolizidinone (II).

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.