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The stereoselective synthesis of new 3,4-dihydroxypyrrolidine derivatives starting from D-mannose, D-ribose and L-fucose is presented. Two synthetic strategies employing organometallic addition to hemiacetalic sugars followed by selective nucleophilic displacement or conjugate addition of ammonia to conjugate aldonic esters as key steps, are used. The new compounds were assayed for their inhibitory activity towards 13 commercially available glycosidases. Compounds that share the absolute configuration at C(2,3,4,5) of L-fucopyranosides and incorporate aromatic moieties are potent and selective inhibitors of alpha-L-fucosidases in the nM range.

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A general approach to enantiopure C-glycofuranosidebased hybrid a/b-amino acids and nitrones, among other valuable building blocks, has been established via formyl C-glycofuranosides, easily available from hexose-derived equatorial-2-OH-glycopyranosides by DAST-promoted ring contraction.The replacement of the exocyclic carbon-oxygen or carbon-nitrogen bond of native glycoconjugates with a carbon-carbon bond creates compounds which are resistant to chemical and enzymatic degradation with minimal loss or enhancement in biological activity with respect to the parent O-or N-glycosides. 1 Therefore the ready access to C-glycosides is of great interest in carbohydrate chemistry. 2 A major problem to prepare functionalized C-glycosides relies on the few available anomeric carbon-carbon bondforming reactions endowed with both chemical efficiency and stereocontrol. This problem could be avoided by the use of C-functionalized carbohydrate derivatives bearing an a-or b-linked highly reactive carbon functionality at the anomeric center. Following this idea, we have developed by means of formyl C-glycofuranosides 1, a widescope method for the synthesis of configurationally controlled C-glycofuranoside-based building blocks containing the substructures 2-4 (Scheme 1), from which an easy access to biologically relevant more complex C-glycofuranoside-based molecules (C-oligosaccharides and Cglycoconjugates) is provided. The key step in this strategy is clearly a DAST-mediated rearrangement reaction that involves ring contraction of hexose-derived equatorial 2-OH-glycopyranosides, and leads to formyl C-glycofuranosides under remarkably mild conditions. This methodology allowed us to prepare a series of formyl Cglycofuranosides, 3 and from the point of view of atom economy 4 it can be considered in the carbohydrate field as a greener formylation methodology than those strategies that are based on the use of formyl anion equivalents. 5 We have employed formyl C-glycofuranosides 1 as key intermediates via reductive amination of the formyl group for the synthesis of enantiopure N-substituted 1-C-aminomethyl glycofuranosides 5 (Figure 1). 6