(6S)-Methyl-L-swainsonine [(1R,2S,6S,8S,8aS)- 6-methyloctahydroindolizine-1,2,8-triol]

# 2007 International Union of Crystallography All rights reserved (6S)-Methyl-l-swainsonine, C9H17NO3, together with the 6Repimer, was formed in a synthetic sequence in which there was an ambiguity in configuration at position C-6. This ambiguity was resolved by establishing the relative stereochemistry of the title compound by X-ray crystallographic analysis. The absolute configuration was determined by the use of dglycero-d-gulo-heptono-1,4-lactone as the starting material.

(6S)-Methyl-l-swainsonine, C 9 H 17 NO 3 , together with the 6Repimer, was formed in a synthetic sequence in which there was an ambiguity in configuration at position C-6. This ambiguity was resolved by establishing the relative stereochemistry of the title compound by X-ray crystallographic analysis. The absolute configuration was determined by the use of dglycero-d-gulo-heptono-1,4-lactone as the starting material.

Comment
Imino sugars, in which the ring oxygen of a sugar is replaced, are a class of glycosidase inhibitor with a range of chemotherapeutic targets (Watson et al., 2001;Asano et al., 2000). d-Swainsonine (1), a natural product isolated from Swainsona canescens (Colegate et al., 1979), is a mimic of dmannofuranose (2) and a powerful -mannosidase inhibitor. Potential use of 1 for the chemotherapy of cancer (Lagana et al., 2006;Klein et al., 1999;Goss et al., 1997) has led to the publication of over 40 syntheses (Au & Pyne, 2006;Ceccon et al., 2006;Martin et al., 2005;Heimgaertner et al., 2005;Nemr, 2000). l-Swainsonine (4), the enantiomer of the natural product (1), is the corresponding imino sugar mimic of lrhamnofuranose (3) and is a potent inhibitor of naringinasean -rhamnosidase (Davis et al., 1996). Very few syntheses of 4, with different therapeutic targets, have been reported (Guo & O'Doherty, 2006;Oishi et al., 1995). No carbon-branched swainsonine analogues have been described. In order to determine how such a substitution changes the structure of the swainsonine nucleus, the C6-methyl analogues (5) and (6) were prepared (Hå kansson et al., 2007); in order to firmly establish the relative configuration at C6 of the two epimers, X-ray crystallographic analysis of (6) is reported in this paper. The absolute configuration of (6S)-methyl-l-swainsonine (6) was determined by the use of d-glycero-d-gulo-heptono-1,4lactone as the starting material.
The molecular structure of (6) (Fig. 1) shows no unusual features. The largest differences from the MOGUL norms (Bruno et al., 2004) are C5-O6 (0.01 Å ) and C11-C10-C1 (2.9 ). As is normal in sugar derivatives, all the hydroxyl groups are involved in hydrogen bonding. Each molecule takes part in two different hydrogen-bonded helices ( Fig. 2 and Table 1). The helix around ( 1 3 , 2 3 , z) only involves O12; that at ( 2 3 , 1 3 , z) involves both O7 and N2. The fact that each molecule is involved in two helices leads to a very rigid framework and explains the high melting point (422 K).
In the absence of significant anomalous scattering, Friedel pairs were merged and the absolute configuration assigned from the starting material.
The sample consisted of fine brittle plates which could not be cut without being destroyed. The relatively large ratio of minimum to maximum corrections applied in the multiscan process (1:1.22) reflects changes in the illuminated volume of the crystal. The changes in illuminated volume were kept to a minimum, and were taken into account (Gö rbitz, 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, 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.