New Glycoconjugates Containing Selenium and Polyphenols. Stereoselective Synthesis by Pummerer‐like Rearrangement

In the last 20 years the exploitation of antioxidant activity of selenobased compounds has improved, just due to the use of Ebselen, a selenocompound, as a Glutathione peroxidase (GPx) mimic. However, their clinical use seems to be compromised by the low solubility in water. To deal with this problem, it is possible to take advantage of the new approach including selenosugars in which selenium replaces heterocyclic oxygen. In this frame, to optimize the antioxidant properties of selenosugars, the glycoconjugation with a polyphenolic unit, which is a molecule capable of inhibiting or disabling the action of free radicals, has been considered in this work. The Mitsunobu reaction mechanism links covalently the primary alcoholic function of selenobased glycosyl donors, coming from the commercially available d-mannose, and phenolic moiety acceptors, to obtain the corresponding glycoconjugates, has been exploited affording the products in efficient yields. A density functional theory (DFT) theoretical study is carried out to help understand the possible influence of the seleno donor on the reactivity. Crucially, a new pathway based on Pummerer-like rearrangement followed by a glycosylation, gave a selenosugar with selenium in the ring and bearing an acetal-like functional group at C-1. All compounds are characterized by nuclear magnetic resonance (NMR) spectroscopy confirming their structures and purity.