Physical Sciences and Mathematics Commons^™

Total Synthesis Of Cytotoxic Mansouramycins From Amino Acids, Beatriz Gamez

Theses and Dissertations

Natural products produced by plants, animals, and microorganisms are of significant importance in chemistry for being major sources of molecular scaffolds essential for new drug discovery. Mansouramycins are cytotoxic bioactive compounds containing isoquinoline skeletons with substituents on the quinone and pyridine rings that may be difficult to synthesize. Synthetic processes exist for compounds B and D, however, there exists an absence of simple synthetic approaches to all four alkaloids.

This project aims to provide a general total synthetic pathway to Mansouramycins A—D from amino acids for possible use in cancer treatment via these isoquinolinequinones. Preliminary experimentation suggests there may be …

Aryne-Guided C-H Functionalization Of Benzenoid Rings Using Diaryliodonium Salts, Aleksandra Nilova

Dissertations and Theses

The benzenoid core is a frequent and irreplaceable component of biologically active molecules. Structure function relationship of these compounds has been broadly analyzed and presented in numerous literature reports. Herein, we augmented existing knowledge by a broad analysis of the benzenoid substitution patterns in small molecule active pharmaceutical ingredients approved by the FDA. Our findings reveal a strong correlation that the most represented substitution patterns are those achieved via S_EAr. Despite the rapid development of methods to functionalize benzenoid rings, the lack of synthetic methodologies to access sterically and electronically unfavorable positions is highlighted. We sought to establish …

Isolation, Structure Elucidation, And Synthesis Of Natural Products From Marine Cyanobacteria, Keren Solomon

Electronic Theses and Dissertations

This thesis describes the isolation, structure elucidation, and synthesis of natural products from marine cyanobacteria. A crude extract from a cyanobacterium collected in Curacao showed selective affinity for the dopamine D₅ receptor in a screen against a panel of CNS receptors. Due to the high similarity of the D₅ and D₁ receptor, to date there are no known ligands that differentiate them. Attempts to purify the compound responsible for this affinity led to the isolation of the known compound caylobolide A. A second extract from a cyanobacterium collected in Panama underwent bioassay-guided fractionation and yielded the novel …

Development Towards An Ethylene Sensing Artificial Metalloenzyme, Mitchell Lee Ellinwood

Electronic Theses and Dissertations

Ethylene (ethene) is the essential ripening hormone for climacteric plants, and consequently its detection and quantification is of considerable interest to the horticulture industry. Its detection however is a non-trivial pursuit, traditionally requiring expensive and inaccessible instrumentation that fail to provide in vivo information about ethylene. A ruthenium based fluorescent probe for the selective detection of ethylene has recently been developed, and it was envisioned that this probe could be made biocompatible by encasing it within a protein scaffold making it an artificial metalloenzyme. To this end biotinylated N-heterocyclic carbenes (NHCs) were synthesized, which can be appended onto the ruthenium …

Studies On The Size And Non-Planarity Of Aromatic Stacking Moiety On Conformation Selectivity And Thermal Stabilization Of G-Quadruplexes, Mandeep Singh

University of the Pacific Theses and Dissertations

Targeting DNA has the advantage over proteins for cancer remediation because of the fewer copies of the ligands required for the desired therapeutic effect. Traditionally, covalent DNA binders like alkylating agents have been used to induce genetic instability through the formation of DNA lesions and strand breaks, leading to cellular apoptosis. The primary drawback of this treatment is the non-specific binding that affects both cancerous and non-cancerous cells. G-quadruplexes are the DNA secondary structures that are present in abundance near the promoter regions of the oncogenes and are involved in the regulation of their activities. A ligand-mediated stabilization of G-quadruplexes …