Synthesis and characterization of carbohydrate mimics

Abstract

The synthesis of N-acetyl-D-fucosamine and N-((2R,3R,4R)-2,4-dihydroxy-6-methylene-5-oxo-tetrahydro-2H-pyran-3-yl)acetamide will be pursued from the inexpensive starting material N-acetyl-D-glucosamine. These carbohydrates are mimics of intermediates used by Staphylococcus aureus in the construction of its protective capsular polysaccharide, which allows the bacteria to evade both the host immune system and antibiotics in current use. Synthesis of these molecules allows for carbohydrate mimics to be developed which can be used as targeted antibiotics needed for use against antibiotic-resistant Staphylococcus aureus strains. Characterization by nuclear magnetic resonance spectroscopy will allow determination of structural conformation, of structures' dependence on solvent while in solution, and presence of the desired product. These studies will be carried out to be compared with other structural determination techniques in wide use today. Knowledge of the solution state structure of a molecule is necessary to understand the possible interactions in biological systems which must be understood in pharmaceutical development. Recent developments in NMR techniques allow for multi-dimensional spectra which can relate interconnected atoms in a molecule to provide information on the relative spatial orientation of atoms within a molecule.