Stereoselective synthesis of photoactivatable Man(ß1,4)GlcNAc-based bioorthogonal probes.

We report an operationally facile protocol to prepare photoactivatable probes of the bioactive mammalian disaccharide, Man(ß1,4)GlcNAc. Using conformationally restricted mannosyl hemi-acetal donors in a one-pot chlorination, iodination and glycosylation sequence, ß-mannosides were generated in excellent diastereoselectivities and yields. Upon accessing the disaccharide, we generated the corresponding photoactivatable probes by appending a diazirine-alkyne equipped linker via a condensation reaction between a diazirine-containing linker and C-1 and C-2 derivatized mannosylamines to furnish the desired C-1 and C-2 modified Man(ß1,4)GlcNAc-based probes. This new synthetic protocol greatly simplifies the preparation of this important bioactive disaccharide to enable future work to identify its protein binding partners in cells.