Differentiating the Fine Reactivity Difference of Functional Saccharides

Saccharides are a major class of biomolecules involved in numerous biological activities. Modulation of saccharides or saccharide segments leads to therapeutic agents such as vaccines and antibiotics with billion-dollar commercial success. However, despite of the enormous applications and potentials, understanding of saccharide-related biological processes and development of saccharide-based pharmaceuticals remain challenging. A major problem lies on the lack of efficient chemical synthetic tools for access to saccharides and their derivatives. It is difficult to selectively functionalize the many hydroxyl (OH) groups present in saccharides because the reactivity differences of the various OH groups are very small.

(A) Aims: We seek to integrate the powers of molecular recognitions and N-heterocyclic carbene organic catalysis to create new catalytic technology for precise differentiation and regio-selective functionalization of saccharides, and thus to achieve short-route and scalable access to industrially important saccharide-derived products

(B) Hypotheses: (a) the OH groups on saccharides can be differentiated through molecular recognitions; (b) combined molecular recognition and NHC catalysis can amplify the reactivity differences of OHs to realize regio-selective reactions.

(C): Methodology: We will introduce three driving forces (e.g., tunable substrates, catalysts, and supramolecular receptors) to amplify these otherwise small reactivity differences and thus to realize selective reactions. The overall objectives will be achieved through three interlinked subprojects, concerning selective functionalization of monosaccharides, oligosaccharides, and short-route synthesis of saccharides conjugates and derivatives.

(D: Feasibility: The proposed research is supported by our preliminary studies (showing that with different NHC catalysts/conditions, acylation reactions can selectively occur on specific OH group) and earlier studies by the PIs.

(E) Importance: Our concise synthetic routes will make saccharide-based medicines more accessible, and provide crucial research tools to investigate biological processes for developing new medical solutions. Our research will generate new knowledge in understanding chemical moieties with similar reactivities, molecular recognitions, and saccharides.