Reengineering Chemical Glycosylation: Direct, Metal-Free Anomeric O-Arylation of Unactivated Carbohydrates.

Abstract

To sustain innovation in glycobiology, effective routes to well-defined carbohydrate probes must be developed. For over a century, glycosylation has been dominated by the formation of the anomeric Csp3 -O acetal junction in glycostructures. A dissociative mechanistic spectrum spanning SN 1 and SN 2 is frequently operational thereby reducing the efficiency. By reengineering this fundamental process, an orthogonal disconnection allows the acetal to be formed directly from the reducing sugar without the need for substrate pre-functionalisation. The use of stable aryliodonium salts facilitates a formal O-H functionalisation reaction. This allows lactols to undergo mild, metal-free O-arylation at ambient temperature. The efficiency of the transformation has been validated using a variety of pyranoside and furanoside monosaccharides in addition to biologically relevant di- and trisaccharides (up to 85 %). Fluorinated mechanistic probes that augment the anomeric effect were employed. It is envisaged that this strategy will prove expansive for the construction of complex acetals under substrate-based stereocontrol.