| Complex carbohydrates and their conjugates in biological systems are either structural or informational molecules. On the cell surface many carbohydrates of glycoconjugates are involved in various types of biochemical recognition processes, including growth, development, immune responses, infection, cell adhesion, metastasis, and numerous signal transduction events. This dissertation is focusing on the synthesis and screening of sugar analogs with high therapeutic potential, preparation of the disaccharide structural component of bacterial cell wall lipid A and finding new glycosyl donors, to facilitate oligosaccharide synthesis.; The first part of this dissertation (chapters 2 & 3) describes new synthesis and screening procedures for glycosidase inhibitors, especially 1,5-iminoalditols and aldono δ-lactones. These two classes of compounds have high inhibitory activity and they constitute viable candidates for cancer, AIDS and diabetes treatment. A new, general method for the preparation of such compounds with the D-gluco and D-galacto configuration starting from β-glycosides is presented. The procedure stands out among the preexisting methods due to its generality, straightforwardness, high yield and stereoselectivity. This methodology has been used in the one pot synthesis of a library of compounds belonging to 4 classes of substances: methyl glycosides, aldonic acid lactams, aldonic acid lactones and 1,5-dideoxy-1,5-iminosugars. These have been screened for activity against glucosidases. The approach provides a facile and rapid route towards the synthesis and screening of a multitude of potential glycosidase inhibitors.; Chapter 4 discusses an improvement and new application of the chromium trioxide oxidation of glycosides, while chapter 5 describes a novel protecting/activating group for N-acetylglucosamine. o-Nitrophenyl 2-acetamido-2-deoxy-β-D-glucopyranoside can be activated with ZnCl2 to afford, in the presence of an alcohol, high yields of N-acetamide β-D-glucosides.; The last chapter presents various attempts towards the total synthesis of the disaccharide headgroup of lipid A from Rhizobium trifolii. Lipid A is a component of lipopolysaccharides (LPS), which are a unique class of glycolipids found on the surface of Gram-negative bacteria. LPS are capable of eliciting a wide array of biological responses when they interact with cellular systems of animals. Determination of their structure can help in the elucidation of their physiologic activity. |
