Easy Access to Configurationally Controlled C-Glycofuranoside-Based Building Blocks by Means of Formyl C-Glycofuranosides

Abstract

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