Synthesis of Novel Antimycobacterials and a Fluorescent Sensor for Simple Carbohydrates

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.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Year dc:date.available

2006

Author dc:creator

• Walker, Brian Thomas

Contributors dc:contributor

• Dr. Todd A. Houston

• mannose receptor
• infection
• mycobacteria
• tuberculosis
• synthesis
• macrophage
• tetrasaccharide
• Chemistry
• Physical Sciences and Mathematics

Statement dc:rights

• © The Author

Identifier

https://scholarscompass.vcu.edu/etd/1340

OAI identifier oai:identifier

oai:scholarscompass.vcu.edu:etd-2339