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...
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...
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...
The sea offers a wide variety of potentially useful resources. Marine algae have been a rich source of structurally unique natural products showing diverse biological properties. The current need to develop new antifungal, antibiotic, anticancer and antiviral drugs has prompted intense research efforts into the discovery, isolation and structure determination...
This thesis is an account of investigation on the natural products deriving from various marine algae and has resulted in the discovery of eleven novel bioactive metabolites. Isolation and characterization of these new molecules were carried out using different chromatographic techniques and by analyses of different spectroscopic data, respectively. Using...
Molecular genetic and enzymological techniques have been employed to study secondary metabolite biosynthesis. These investigations have focused on two projects: the cloning and heterologous expression of biosynthetic gene clusters from unculturable marine organisms and the characterization of individual enzymes involved in the biosynthesis of the antifungal agent blasticidin S. The...
This thesis details my investigations of marine cyanobacterial natural products that resulted in the discovery of eighteen new secondary metabolites. Isolation and characterization of these unique molecules were carried out using different chromatographic techniques and by careful analyses of 1D and 2D NMR data, respectively. Preliminary bioassays of the crude...
Among the myriad of naturally occurring bioactive compounds are the aminocyclopentitol-containing natural products that represent a family of sugar-derived microbial secondary metabolites, such as the antibiotics pactamycin, allosamidin, and trehazolin. Pactamycin, a structurally unique aminocyclitol antibiotic isolated from Streptomyces pactum, consists of a 5-membered ring aminocyclitol (cyclopentitol) unit, two aromatic...
Ascorbic acid, or vitamin C, is well known as a co-factor for proline-hydroxylase and as an anti-oxidant. However, it is also capable of forming covalent bonds, particularly in the role of a nucleophile, henceforth termed 'ascorbylation'.
The ascorbylation of electrophiles can occur under physiological conditions. Furthermore, there are a number...