Synthesis Of Neu5Ac Glycan Receptors And Neu5Ac Derivatives

One part of this thesis is the synthesis of oligosaccharide receptors.The influenza virus infects host cell through a vital step that mediated by the specific interaction of viral hemagglutinin (HA) with host surface glycan receptors.Thus we synthesize three kinds of typical oligosaccharide receptors. three representative glycan receptors containing propargyl group which could be further applied in the detection of influenza virus receptor-binding properties with glycan-functionalized gold nanoparticles.The other part of this thesis is the synthesis of NeuSAc dericatives, Efficient and large-scale synthesis of N-acetyl neuraminic acid (Neu5Ac),CMP-Neu5Ac and their derivative is very important because of the biological and pharmacological significance.The whole-cell catalysis is well studied and presents a new potential tool in industrial production of Neu5Ac.Convenient enzymatic synthesis of CMP-Neu5Ac is also recently well established by use of CMP-Neu5Ac synthase NeuA.However,the preparation of derivatives of Neu5Ac and CMP-Neu5Ac remains challenging due to their diverse and complex structures.Here we present an efficient synthetic strategy of the derivatives based on the conbined use of whole-cell catalysis and a chemoenzymatic approach.The proposed process contains (ⅰ) chemical modification of N-acetyl glucosamine(GlcN Ac) to produce a set of GlcNAc derivatives;(ⅱ) whole-cell-catalyzed transformations of the GlcNAc derivatives to Neu5Ac derivatives using a genetically engineered Escherichia coli strain we developed previously;and (ⅲ) enzymatic preparation of the corresponding CMP-NeuSAc derivatives from the GlcNAc by a recombinant NeuA overexpressed and purified from the another engineered E.coli strain.In this study,we will increase the possibility of the strategy to synthesis further derivates with various substituents on gram-scale.Our study may generate sufficient and appropriate library compounds for the future biological and pharmacological research.