Programmable selective acylation of saccharides mediated by carbene and boronic acid

Chemical synthesis or modification of saccharides remains a major challenge largely because site-selective reactions on their many similar hydroxyl groups are difficult. The lack of efficient chemical synthetic tools has therefore become a main obstacle to understanding saccharide-related biological processes and developing saccharide-based pharmaceuticals. Here, we disclose a programmable multilayered selectivity-amplification strategy enabled by boronic acids and N-heterocyclic carbene (NHC) catalysts for site specific acylation of unprotected monoglycosides. The boronic acids provide transient shielding on certain hydroxyl groups (while simultaneously promoting reactions of other hydroxyl units) via dynamic covalent bonds to offer the first sets of selectivity controls. The NHC catalysts provide further layers of control by mediating selective acylation of the unshielded hydroxyl moieties. Multiple activating and deactivating forces can be easily modulated to yield programmable selectivity patterns. Structurally diverse monosaccharides and their analogs can be precisely reacted with different acylating reagents, leading to quick construction of sophisticated saccharide-derived products.

Automated summary

Chemical synthesis or modification of saccharides is difficult due to the challenge of site-selective reactions on their similar hydroxyl groups. The lack of efficient tools hinders the understanding of saccharide-related biological processes and the development of saccharide-based pharmaceuticals. In this study, a programmable multilayered selectivity-amplification strategy using boronic acids and N-heterocyclic carbene (NHC) catalysts is presented for site-specific acylation of monoglycosides.