Sialic acids are a diverse family of naturally occurring 2-keto-3-deoxy-nononic acids, amongst which N-acetylneuraminic acid (Neu5Ac) is the most common, that are involved in a wide range of biological processes.
Sialic acids normally appear at terminal positions of oligosaccharides of glycoproteins and glycolipids where they are a(2,3) or a(2,6) linked to galactosides or a(2,6) linked to 2-acetamido-galactosides. The disialosyl structures Neu5Aca(2-8)Neu5Ac and Neu5Aca(2-9)Neu5Ac have also been found as constituents of oligosaccharides of glycoproteins and lipids.
As components of sugar-protein and sugar-lipid compounds (glycoconjugates), sialic acids cover all cells of higher animals and man with an negatively charged coat and exert a variety of different biological functions. In fact, in this exposed position sialic acids are important regulators of cellular and molecular interactions, where they can either act as recognition determinants or masking agents. For the latter, sialic acid 'masks' the oligosaccharide chain by the action of hormone receptors or antigens. As recognition determinant sialic acids modulate cell growth, differentiation and cell adhesion. Another interesting aspect of the biological proprieties of sialic acid is its involvement in certain diseases: sialic acid-specific adhesion of bacteria and viruses is a phenomenon drawing an increasing level of interest, as a critical step in infectious diseases. It has been known for many years that microbial pathogens, i.e., viruses, mycoplasma, bacteria, and protozoa, take advantage of cell surface sialic acids to adhere to their respective host cell. In addition, sialo-conjugates have been related to diseases such as atherosclerosis, asthma as well as oncogenesis.
Although extensively explored, the chemical synthesis of sialosides in high yield and stereoselectivity is still a challenge.
In our group we are investigating new methodologies for the stereocontrolled synthesis of a sialosides, studying different novel leaving groups as well as conformationally modified sialyl donors and acceptor