Synthesis of four (4"-, 2"-, 2'-, and 6-) monodeoxy analogs of the trisaccharide α-D-Glcp-(1 → 3)-α-D-Manp-(1 → 2)-α-D-ManpOMe recognized by Calreticulin/Calnexin.

Routes for efficient synthesis of four (4"-, 2"-, 2'-, and 6-) monodeoxy analogs of the trisaccharide α-D-Glcp-(1 → 3)-α-D-Manp-(1 → 2)-α-D-ManpOMe have been developed. For the introduction of the 2'- and 2"-deoxy motifs the most efficient way was to use a 1,2-di-bromo-mannosyl donor in silver triflate-promoted couplings to construct the α-glycosidic linkage followed by reduction of the 2-bromo-function to a 2-deoxy motif at the di- or trisaccharide level. In contrast, the 4"- and 6-deoxy functions were introduced already at the monosaccharide stage. The most challenging part of the syntheses was the stereoselective formation of the non-reducing end cis-α-D-glucosidic linkages. The established α-directing effect of a 3-O-acetyl group in glucosyl donors was explored but the magnitude of the effect was variable and dependent on donor/acceptor structure and nature of promoter and an optimization had to be made for each individual glycosylation.