Stereoselective synthesis of pseudoglycosides catalyzed by TeCl4 under mild conditions
Graphical abstract
Introduction
In addition to their role in energy metabolism, carbohydrates are also responsible for several functions in cells and organisms.1 For instance, carbohydrates can be found in intra- and extracellular media bound to proteins and lipids.2 They are also present as free polysaccharides on cell surfaces and in intercellular space, which are used by bacteria and virus as attachment sites.3
Pseudoglycosides can also be used as building blocks in the synthesis of natural products,4 glycopeptides,5 sugars,6 oligosaccharides,7 and nucleosides.8 Besides, carbohydrates are present as units in several natural products such as salicin,9 catalpol,10 and macrolactin O11 (Fig. 1), which present a wide range of biological activities.
2,3-Unsaturated-O-glycosides are useful intermediates in carbohydrate chemistry. They can be easily obtained from the glycosylation reaction or through a Ferrier rearrangement, which involves a nucleophilic substitution reaction combined with an allylic shift in a glycal.12 The orientation of the formed glycoside bond, α or β depends on some combination of control elements, being the most important the ‘kinetic anomeric effect’.13
A number of Lewis acids and oxidizing agents can promote this reaction14 with some caveats in generality, yields, and selectivity. In addition, the use of strong acidic or oxidizing conditions, as well as the cost of the reagents led to a search for a milder procedure for the preparation of this class of compounds.
Tellurium tetrahalides (TeCl4, TeBr4, and TeI4) are versatile compounds, since they can react with both Lewis bases and Lewis acids,15 and this amphoteric behavior can be understood in terms of the partially ionic Te–X bonding, which can be controlled by the electronegativity of the halide.
Recently, we described the use of tellurium tetrabromide (IV) to promote the O-glycosylation of glycals to yield the corresponding 2,3-unsaturated-O-glycosides.14b We describe herein the results obtained by using tellurium tetrachloride, a less expensive and more electrophilic Lewis acid choice to promote the O-glycosylation of 3,4,6-tri-O-acetyl-d-glucal, 1. The method may be useful as an alternative to the previously described ones, particularly for the synthesis of glycopyranosides with rigid or flexible linkers, compounds of great interest in chemistry and biology (Fig. 2).16
Section snippets
Results and discussion
For preliminary optimization of the reaction conditions, 1 (1.0 mmol) and propargyl alcohol (1.2 mmol) in dichloromethane (10 mL) were treated at room temperature with different amounts of TeCl4 and the progress of the reaction was monitored by TLC. The results are depicted in Table 1.
In all cases the reaction proceeded smoothly leading to the complete conversion of 1 into the corresponding 2,3-unsaturated O-glycoside 2a in high yield and with excellent α selectivity (Table 1, entries 1–5). It is
Conclusion
In summary, we have demonstrated that a catalytic amount of tellurium(IV) tetrachloride can efficiently promote the O-glycosylation of glycals. The approach is complementary to the previously described methods for the synthesis of O-glycosides and a comparison of the use of a catalytic amount of TeCl4 with literature methods is described in Table 8. Although the available methods gave 2a in good yields and selectivities in some cases, our method gave similar results using shorter reaction times
Material
All reagents and solvents used were previously purified and dried in agreement with the literature.36 Tellurium(IV) tetrachloride was purchased from Aldrich Chemical Co. and used as received. All other commercially available reagents and solvents were used as received. Reactions were monitored by thin-layer chromatography on 0.25 mm E. Merck silica gel 60 plates (F254) using UV light, vanillin, and p-anisaldehyde as visualizing agents. Column chromatography purification was performed using
Acknowledgements
The authors gratefully acknowledge CNPq (484778/2011-0), FACEPE (APQ-1402-1.06/10), CAPES and INCT-INAMI for financial support. P.H.M, J.C.R.F., and T.R.C. are thankful to CNPq for their fellowships.
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