4-Methoxyphenyl 2,3,4,6-tetra-O-acetyl-1-thio-α-d-mannopyranoside

The title compound, C21H26O10S, was synthesized in a single step from mannose pentaacetate. The molecular structure confirms the α configuration of the anomeric thioaryl substituent. Spectroscopic and melting-point data obtained for the title compound are in disagreement with those previously reported, indicating the previously reported synthesis [Durette & Shen (1980 ▶). Carbohydr. Res. 81, 261–274] to be erroneous. The crystal structure is stabilized by weak intermolecular C—H⋯O hydrogen bonds.

The title compound, C 21 H 26 O 10 S, was synthesized in a single step from mannose pentaacetate. The molecular structure confirms the configuration of the anomeric thioaryl substituent. Spectroscopic and melting-point data obtained for the title compound are in disagreement with those previously reported, indicating the previously reported synthesis [Durette & Shen (1980). Carbohydr. Res. 81, 261-274] to be erroneous. The crystal structure is stabilized by weak intermolecular C-HÁ Á ÁO hydrogen bonds.

Comment
Thioglycosides are extremely useful and versatile glycoside donors for the synthesis of oligosaccharides, which may be activated by a wide range of electrophiles and also by electrochemical methods (France et al., 2004). The nature of an aromatic substituent of an aryl thioglycoside has a strongly modulating effect on the reactivity of such a thioglycoside; strongly electron donating substituents greatly increase their reactivity towards electrophiles (Roy et al., 1992), and also decrease their oxidation potentials so that they may be electrochemically activated at relatively low externally applied potentials (Drouin et al., 2007). Such 'armed' (Mootoo et al., 1988) thioglycosides may therefore be used as donors for the glycosylation of less reactive 'disarmed' thioglycoside acceptors. The title compound was obtained in a single step from mannose penta-acetate by treatment with 4-methoxythiophenol and boron trifluoride etherate in dichloromethane ( Fig. 1). Spectroscopic data obtained for this compound was in disagreement with that previously reported in the only reported synthesis (Durette et al., 1980). Moreover the anomalous optical rotation reported therein had also been highlighted in a subsequent paper (Poh, 1982). Single crystal X-ray analysis was therefore undertaken to confirm the authenticity of our material, and this indeed demonstrated the correctness of our structural assignment (Fig. 2), and in particular the α-anomeric configuration of the thioaryl group. We conclude that the previous report (Durette et al., 1980) in fact probably details the synthesis of the corresponding β-anomer, formed by an S N 2 substitution reaction on the α-glycosyl bromide, which was incorrectly assigned the α-anomeric configuration by the authors.
After 22 h, t.l.c. (petroleum ether/ethyl acetate, 1:1) indicated the formation of a major product (R f 1/2) and the complete consumption of the starting material (R f 0.4; 1/2). The reaction was then quenched by the addition of triethylamine and the resulting mixture was partitioned between dichloromethane (240 ml) and water (240 ml). The organic extracts were washed with a saturated aqueous solution of sodium hydrogencarbonate (240 ml), a saturated aqueous solution of sodium chloride (240 ml), and were then dried over MgSO 4 , and concentrated in vacuo. The residue was purified by flash column chromatography (petroleum ether/ethyl acetate, 6:4) to give the desired 4-methoxyphenyl 2,3,4,6-tetra-O-acetyl-1-thio-α-D-mannopyranoside (13.31 g, 88%) which crystallized from cyclohexane as a white crystalline solid, m.p. 335-337K (cyclohexane); a sample suitable for X-ray analysis was then re-crystallized from a solution in pentane

Refinement
A polycrystalline aggregate was divided to give a fragment having dimensions approximately 0.2 x 0.32 x 0.44 mm, which was mounted on a glass fibre using perfluoropolyether oil. The sample was cooled rapidly to 150 K in a stream of cold N 2 using an Oxford Cryosystems Cryostream unit (Cosier and Glazer, 1986). Diffraction data were measured using an Bruker-Nonius KappaCCD diffractometer (graphite-monochromated Mo Kα radiation, λ = 0.71073 Å). Intensity data were processed using the DENZO-SMN package (Otwinowski and Minor, 1997).
Examination of the systematic absences of the intensity data showed the space group to be P2 1 2 1 2 1 and the structure was solved using the direct-methods program SIR92 (Altomare et al., 1994), which located all ordered non-hydrogen atoms.
Subsequent full-matrix least-squares refinement was carried out using the CRYSTALS program suite (Betteridge et al., 2003).
Coordinates and anisotropic thermal parameters of all non-hydrogen atoms were refined. The relatively large thermal parameters of some of the acetate carbon and carbonyl oxygen atoms (Figure 1) suggest that there may be unresolved disorder of these groups. Attempts to model this did not lead to any improvement in the agreement with the X-ray data and were abandoned.
Refinement of the Flack x parameter (Flack, 1983) gave a value of -0.063 (63) and examination of the Bijvoet Pairs gave the Hooft y parameter as -0.016 (29) (G=1.031 (59)) and giving the probability that the absolute configuration is correct as 1.000, using either a two or three-hypothesis model (Hooft et al., 2008).
The hydrogen atoms were all visible in the difference map, but were repositioned geometrically. Initially they were refined with soft restraints on the bond lengths and angles to regularize their geometry (C-H in the range 0.93-0.98), 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.