Modular synthesis of nonadecasaccharide motif from Psidium guajava polysaccharides with potent antidiabetic activity through orthogonal one-pot glycosylation strategy.

Carbohydrates are important biomolecules with numerous crucial roles in a variety of biological processes. Due to the issues of microheterogeneity, isolation of pure and sufficient amounts of glycans from nature is a formidable task. Chemical synthesis is an efficient and scalable method to obtain well-defined and pure glycans for developing therapeutic agents and deciphering their functions. So far, synthesis of long, branched and complex carbohydrate sequences remains one of the most challenging tasks in chemical synthesis. Here, we report an efficient modular one-pot synthesis of nonadecasaccharide and shorter sequences from Psidium guajava polysaccharide with potent a-glucosidase inhibitory activity. Our synthetic strategies have the following features: (1) several one-pot glycosylation reactions on the basis of PTFAI glycosylation and Yu glycosylation to streamline the chemical synthesis of oligosaccharides, (2) the successful and efficient assembly sequences (first O-3', second O-5', final O-2') toward the challenging 2, 3, 5-branched Ara f motif, (3) the stereoselective 1,2- cis -glucosylation by reagent control, and (4) the convergent [6 + 6 + 7] one-pot coupling reaction for the final assembly of the target nonadecasaccharide. Our results demonstrate that one-pot glycosylation strategy using PTFAI glycosylation and Yu glycosylation can streamline the chemical synthesis of long, branched and complicated carbohydrate chains.