Stereoselective β-Mannosylation by Neighboring-Group Participation

The stereoselective synthesis of glycosidic bonds is the main challenge of oligosaccharide synthesis. Neighboring-group participation (NGP) of C2 acyl substituents can be used to provide 1,2-trans-glycosides. Recently, the application of NGP has been extended to the preparation of 1,2-cis-glycosides with the advent of C2 chiral auxiliaries. However, this methodology has been strictly limited to the synthesis of 1,2-cis-gluco-type sugars. Reported herein is the design and synthesis of novel mannosyl donors which provide 1,2-cis-mannosides by NGP of thioether auxiliaries. A key element in the design is the use of (1) C4 locked mannuronic acid lactones to enable NGP of the C2 auxiliary. In addition to C2 participation a new mode of remote participation of the C4 benzyl group was identified and provides 1,2-cis-mannosides.