Physical Sciences and Mathematics Commons^™

Part I. The Development Of Non-Secosteroidal Vitamin D Receptor Modulators Part Ii. The Development Of A Universal Gtp-Ase Assay, Kelly Ann Teske

Theses and Dissertations

The vitamin D receptor is a nuclear hormone receptor that regulates cell proliferation, cell differentiation, calcium homeostasis and immunomodulation. The receptor is activated by the vitamin D metabolite, 1,25-dihydroxyvitamin D3, which induces a cascade of events including the recruitment of coactivators that activate transcription of specific VDR target genes. Thousands of VDR agonists have been synthesized based on the secosteroid scaffold of 1,25-dihydroxyvitamin D3. However, most of these ligands are metabolically unstable, have sub-optimal drug-like properties, and induce hypercalcemia in vivo. The limited numbers of VDR antagonists reported bear the same secosteroid scaffold and thus exhibit similar problems encountered by …

Enantiospecific Stereospecific Strategy For The Total Synthesis Of Sarpagine And Macroline Related Oxindole Alkaloids: First Total Synthesis Of Affinisine Oxindole, Isoalstonisine, Alstofoline, Macrogentine, N(1)-Demethylalstonisine, Alstonoxine A And Second Generation Synthesis Of Alstonisine, German Oscar Fonseca Cabrera

Theses and Dissertations

The (7R)-sarpagine/macroline related oxindole alkaloids (-)-isoalstonisine (27) and (-)-macrogentine (31) together with the (7S)-sarpagine/macroline related oxindole alkaloids (-)-affinisine oxindole (24), (-)-alstonoxine A (19), (+)-alstonisine (8, second generation total synthesis), (+)-Na-demethylalstonisine (17) and (+)-alstofoline (18) were concisely synthesized during these studies.

These oxindole alkaloids were isolated from plants of the genus Alstonia which is characterized by the preponderance of sarpagine/macroline-type indole and oxindole alkaloids. Plants that belong to this genus are mainly distributed over tropical regions of Central America, Africa, and Asia where they are used locally in traditional medicine, for example, in the treatment of malaria and dysentery. The main …

Asymmetric Synthesis Of Tryptophan Driviatives And Its Application To Streamlined Synthesis Of Tryprosatain A And B, Matthew Huisman

Theses and Dissertations

Tryprostatins have been shown to be potential antitumor antimitotic agents. Tryprostatins have been isolated from the fermentation broth of marine fungal strain Aspergillus fumigatus in trace amounts. Our lab has developed a phase-transfer-catalyzed asymmetric alkylation reaction to produce protected tryptophans (Trp) with high enantioselectivity (90-95% ee) as synthetic precursors to Tryprostatins. Studies of Tryprostatins indicate that manipulation of ring-A may cause enhanced activity. We propose a general synthetic route to several new tryprostatins that may be tolerant to ring-A analogues of gramine utilizing achiral reactants. The synthesis of Tryprostatin B has been completed with 20% overall yield in 7 steps. …

Synthesis, Surface Functionalization, And Biological Testing Of Iron Oxide Nanoparticles For Development As A Cancer Therapeutic, Stanley E. Gilliland Iii

Theses and Dissertations

Iron oxide nanoparticles are highly researched for their use in biomedical applications such as drug delivery, diagnosis, and therapy. The inherent biodegradable and biocompatible nanoparticle properties make them highly advantageous in nanomedicine. The magnetic properties of iron oxide nanoparticles make them promising candidates for magnetic fluid hyperthermia applications. Designing an efficient iron oxide nanoparticle for hyperthermia requires synthetic, surface functionalization, stability, and biological investigations. This research focused on the following three areas: optimizing synthesis conditions for maximum radiofrequency induced magnetic hyperthermia, designing a simple and modifiable surface functionalization method for specific or broad biological stability, and in vitro and in …