Stereoselective Synthesis of Nojirimycin α- C -Glycosides from a Bicyclic Acyliminium Intermediate: A Convenient Entry to N , C -Biantennary Glycomimetics.

A simple and efficient method for the stereoselective synthesis of nojirimycin α- C -glycoside derivatives has been developed using a bicyclic carbamate-type sp 2 -iminosugar, whose preparation on a gram scale has been optimized, as the starting material. sp 2 -iminosugar O -glycosides or anomeric esters serve as excellent precursors of acyliminium cations, which can add nucleophiles, including C -nucleophiles. The stereochemical outcome of the reaction is governed by stereoelectronic effects, affording the target α-anomer with total stereoselectivity. Thus, the judicious combination of C -allylation, carbamate hydrolysis, cross-metathesis, and hydrogenation reactions provides a very convenient entry to iminosugar α- C -glycosides, which have been transformed into N , C -biantennary derivatives by reductive amination or thiourea-forming reactions. The thiourea adducts undergo intramolecular cyclization to bicyclic iminooxazolidine iminosugar α- C -glycosides upon acid treatment, broadening the opportunities for molecular diversity. A preliminary evaluation against a panel of commercial glycosidases validates the approach for finely tuning the inhibitory profile of glycomimetics.