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

• Synthesis of four monodeoxy Calreticulin/Calnexin-recognizing trisaccharides.
• Efficient formation of 2-deoxy-α-d-arabino-linkages using a 1,2-di-bromo-mannosyl donor.
• The α-directing effect of a donor 3-O-acetyl group is dependent on acceptor/donor structure.

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.

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