Intramolecular palladium-catalyzed alkene carboamination is a particularly atom-efficient reaction, which allows in a single step the concomitant formation of a C-N bond, a C-C bond and up to two stereocenters from a protected aminoalkene with a high degree of regio- and diastereoselectivity. This reaction involves a combination of an air-stable palladium complex with a commercially available phosphine ligand in the presence of a base and an aryl, alkenyl or alkynyl halide . This intramolecular reaction has mainly been employed for the synthesis of five-membered nitrogen heterocycles, but it has never been used for the synthesis of highly functionalized heterocycles such as iminosugar C-glycosides .
Iminosugars are glycomimetics known for inhibiting carbohydrate processing enzymes, in which the endocyclic oxygen is replaced by a nitrogen atom . As anomeric configuration is fundamental to the biological activity of carbohydrates, incorporating this information in the structure of glycomimetics is crucial and makes iminosugar C-glycosides more interesting, as they can exist in the form of two different pseudo anomers, even if their synthesis is much more challenging .
This new methodology will allow in a few steps the synthesis of iminosugar libraries with a high degree of molecular diversity, which will be achieved by the use of different commercially available sugars as starting materials (aldoses/ketoses, pentoses/hexoses, furanose/pyranose forms) and by the use of different commercially available aryl, alkenyl or alkynyl halides. Biological evaluation of the synthesized compounds towards a panel of enzymes will be realized.
The synthesis of various sugar-derived aminoalkenes will be presented, as well as the optimization of carboamination reaction conditions leading to a diversity of novel iminosugar C-glycosides in a highly diastereoselective process.
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