Despite its promise as a potentially beneficial new source of energy, the ocean-based renewable energy industry is still in its infancy, and like any new idea there are many unknowns with the potential to affect both people and our natural environments. A permit for marine renewable energy (MRE) must cut...
Our quest for pharmaceutically important marine natural products led to re-isolation of known mandelalides A-D and identification of new congeners E-L from re-collected South African Lissoclinum tunicate specimens. Mandelalides A, B, and L were characterized as selective cancer cell toxins, with an unusual activity profile influenced by their glycosylation /...
In this report, three studies are presented that aid in the development of drug discovery and their synthesis. In each, the importance of the marriage between computations and experiments is highlighted. Continued efforts in this vein are essential for future efforts towards improving human health.
The first case study investigated...
This dissertation describes the racemic and enantioselective synthesis cavicularin. Cavicularin is a macrocyclic bisbibenzyls family member natural product. It has been an attractive synthetic target due to its intriguing structure: the macrocyclic core imparts sufficient strain on the system to force one benzene rings to adopt a boat-shaped conformation, out...
The discovery of new antibiotics reached its peak during the golden era of antibiotics in the mid 20th century and continued to thrive until the 1980s. However, after more than 50 years of fruitful exploration and exploitation of microbial natural products the discovery rate of new antibiotics has dropped drastically...
Pactamycin, a potent antitumor antibiotic produced by the soil bacterium Streptomycespactum, is a structurally unique aminocyclopentitol-containing natural product. Itconsists of a highly functionalized cyclopentitol core unit, two aromatic rings [3-aminoacetophenone (3AAP) and 6-methylsalicylic acid (6MSA)], and a 1,1-dimethylurea moiety. Despite its potent biological activity, the development of thisantibiotic was hampered...
This thesis describes an investigation of the molecular basis of the substrate specificity and catalytic mechanism of a unique pseudoglycosyltransferase (PsGT) enzyme, VldE. PsGTs are a newly discovered group of glycosyltransferase (GT)-like proteins that catalyze the transfer of a pseudosugar to an acceptor molecule via a C-N bond formation. This...
Aminal radical intermediates were generated by the method of radical translocation and reacted in C-C bond forming reactions with electronically deficient alkenes (Schiedler et al. Org. Lett. 2012, 14, 6092). Aminal radical intermediates can participate in inter- and intra-molecular reactions using both Bu3SnH and (TMS)₃SiH as hydride donors. Carbon–carbon bonds...
Microbial natural products represent a massive repository of unique chemical scaffolds with corresponding diverse biological functions. However, in the past decade the development of natural products into new therapeutics has dwindled, in part due to the challenges posed by high rediscovery rates and low throughput associated with classical bioassay-guided fractionation...
Organic compounds which contain one or more nitrogen atoms are especially important as they are disproportionately represented among biologically active molecules. As a result, significant effort has been focused on the development of methods for the synthesis of nitrogenous molecules. We identified the aminal as an under-explored functional group. Despite...