Year of Publication
Master of Science (MS)
Dr. Steven G. Van Lanen
Dr. Jurgen Rohr
Despite over a century of advancement, tuberculosis remains a grave threat to world health. In particular, third world countries continue to struggle with the crushing weight of the disease. Furthermore, the emergence of drug resistance in TB strains poses a significant threat to the first world where incidence and mortality is low. The dwindling efficacy of current drug regimens necessitates research into new small molecules capable of arresting the growth and spread of TB. The capuramycin family of nucleoside antibiotics shows strong potential to become part of this new generation of anti-TB small molecules. Indeed, their ability to inhibit Translocase I, a key enzyme in the biosynthesis of bacterial cell walls, makes them exciting targets for medicinal chemistry efforts.
The synthesis of the family focused on dividing the molecules into three congruent, synthetically separate parts: the variable amide linked tail, the hexauronic acid linker, and the uridine "head". Construction of the ubiquitous core structure comprised of the hexauronic acid and uridine would allow rapid diversification while the variable tail would allow SAR studies and development of novel new members of the family.
Jacobsen, Jesse M., "TOWARDS THE TOTAL SYNTHESIS OF THE CAPURAMYCIN FAMILY OF NATURAL PRODUCTS" (2011). University of Kentucky Master's Theses. 162.