Synthesis of Novel Antimycobacterials and a Fluorescent Sensor for Simple Carbohydrates

• Main Author: Walker, Brian Thomas
• Format: Others
• Published: VCU Scholars Compass 2006
• Subjects: mannose receptor; infection; mycobacteria; tuberculosis; synthesis; macrophage; tetrasaccharide; Chemistry; Physical Sciences and Mathematics
• Online Access: http://scholarscompass.vcu.edu/etd/1340; http://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=2339&context=etd

Cell surface carbohydrates play an important role in a wide variety of biological processes such as inflammation, tumor metastasis, and viral and bacterial infection. The goal of our research has been two-fold. The first objective was the synthesis of antimycobacterial compounds. A mannose containing tetrasaccharide from the mannan core of lipoarabinomannan (LAM) of Mycobacterium tuberculosis has been synthesized using α-D-methylmannopyranoside as starting material and Koeings-Knorr reactions to couple saccharides. The synthesis was completed in nine steps and in 14% total yield. This compound should be useful in competitive inhibition studies with macrophages or as an immunological marker. We have successfully synthesized nonsulfated mimics of the aminosterol antibiotic from 5α-cholestan-3-one in two steps in 40-70% total yield. The critical step in this synthesis is the addition of the boronic acid functional group using 2-o-formylphenylboronic acid. It is hypothesized that the addition of boronic acids will improve the antibacterial and anti-angiogenic activity of these compounds. The second objective was the synthesis of a simple fluorescent receptor for simple carbohydrates. A receptor using anthracene as the fluorophore has been completed demonstrating an improved yield over previous methods. This receptor is the first to show selectivity for myo-inositol over other saccharides.