Development of more efficient glycosyl donors and kinetic study of glycosylation reactions.

摘要

Carbohydrates and glycocconjugates play important roles in biological and pharmaceutical sciences, and received much attention in past decades. Since oligosaccharides were found to compose the major blood group antigens, the interest into the wider roles of carbohydrates within biological systems was triggered. It is not surprising that scientists then discovered a great structural variety of complex oligosaccharides are used as ligands and attend a number of key biological processes, like cell growth and differentiation, immune responses, fertilization, embryogenesis, hormone activities, viral and bacterial infections, and cancer cell metastasis.;Biological important target carbohydrates are insufficient amount required in order to study the glycobiology. However, it is very difficult to obtain the target carbohydrates from natural sources or molecular biology methods, so the chemical synthesis is the better approach. The chemical synthesis of oligosaccharides is hampered by challenges such as controlling the stereoselectivity, so the study of the glycosylation reaction, the key step in oligosaccharide synthesis, is therefore of great interest. The major objective of our research is to develop efficient glycosyl donors in order to supply good reaction yield and high stereoselectivity as expected. Meanwhile, the mechanism study of glycosylation reactions are launched to understand the process of glycosylation, so that the development could be benefit from this study.;A study on the glycosyl carbonates as glycosyl donors is described. A series of glycosyl carbonates and carbonothioates were prepared and were tested in glycosylation reactions. The conditions of synthesis the glycosyl carbonates and the conditions of glycosylation reactions were discussed.;High alpha-selective galactosyl donor and glucosyl donors were designed based on the previous studies in our group. This part of the study focused on the synthesis of those glycosyl donors and the glycosylation reactions with them to testify their stereoselectivity. The results verified our previous studies and indicated that the acetyl groups at 3 and 4- positions are important for high alpha-selectivity of galactosyl donors and 3 and 6- positions are important for high alpha-selectivity of glucosyl donors.;The final part of our study investigated the glycosylation mechanism of alpha and & beta galactosyl pentaacetates by kinetic means. Our results determined the overall reaction orders of two glycosylation reactions and analysis the processes, which implied the neighboring acetyl group could assist the leaving of beta acetyl group on anomeric center and accelerate the reaction.