Stereoselective synthesis of photoactivatable Man(01,4)GlcNAc-based bioorthogonal probes

We report an operationally facile protocol to prepare photoactivatable probes of the bioactive mam-malian disaccharide, Man(01,4)GlcNAc. Using conformationally restricted mannosyl hemi-acetal donors in a one-pot chlorination, iodination and glycosylation sequence, 0-mannosides were generated in excel-lent 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(01,4)GlcNAc-based probes. This new synthetic protocol greatly sim-plifies the preparation of this important bioactive disaccharide to enable future work to identify its pro-tein binding partners in cells.(c) 2023 Elsevier Ltd. All rights reserved.