Physical Sciences and Mathematics Commons^™

Design Of Ruthenium(Ii) Polypyridyl Complexes For Effectively Caging Nitriles And Aromatic Heterocycles, Ao Li

Wayne State University Dissertations

ABSTRACT

DESIGN OF RUTHENIUM(II) POLYPYRIDYL COMPLEXES FOR EFFECTIVELY CAGING NITRILES

AND AROMATIC HETEROCYCLES

by

AO LI

May 2018

Advisor: Dr. Jeremy Kodanko

Major: Chemistry

Degree: Doctor of Philosophy

Ru(II) polypyridyl complexes have been frequently employed in the caging and photorelease of biologically active compounds. Traditional photocaging groups derived from Ru(II) have been largely based on bi- or tridentate ancillary ligands, and those bearing ancillary ligands with high-denticities are yet to be developed. Exploring Ru(II) polypyridyl complexes possessing ancillary ligands with high-denticities provides insight into the photophysical and photochemical properties of ruthenium complexes, which creates novel prospects in the design of …

Design And Synthesis Of Oligo-(3,5-Dithio-Β-D-Glucopyranoside) As Β-(1→3)-Glucan Mimetics, Xiaoxiao Liao

Wayne State University Dissertations

This dissertation presents the design and synthesis of oligo-(3,5-dithio-β-D-glucopyranoside) as β-(1 → 3)-D-glucan mimetics. The synthesized dimeric, trimeric and tetrameric mimetics were tested for their binding affinities to Dectin-1 and CR3 and their abilities to activate phagocytosis and pinocytosis.

The first chapter gives an introduction of β-(1 → 3)-D-glucan. It gives an introduction about the structure and origin of β-(1 → 3)-D-glucan as well as the immunostimulating effect of natural β-(1 → 3)-D-glucan. The study of interaction between β-(1 → 3)-D-glucan and the receptors leads to a conclusion that the hydrophobicity of β-(1 → 3)-D-glucan is crucial to its immunostimulating …

Modification Of 4,5- Aminoglycosides To Overcome Drug Resistance Bacteria And Toxic Side Effect, Guanyu Yang

Wayne State University Dissertations

ABSTRACT

MODIFICATION OF 4,5- AMINOGLYCOSIDES TO OVERCOME DRUG RESISTANCE BACTERIA AND TOXIC SIDE EFFECT

by

Guanyu Yang

September 2018

Advisor: Professor David Crich

Major: Chemistry

Degree: Doctor of Philosophy

Infectious diseases causing by antibiotic resistant pathogen are one of the major threat to human health and society today. Many researchers tried to develop next generation of antibiotics by reinvesting the existing antibacterial drugs. Aminoglycosides have long been used as highly potent and broad-spectrum antibiotics for treating bacterial infections. But their side effect, especially the irreversible ototoxicity, and the fast-growing resistant problem limit their application. The goal of this research was …

Stereoselective Synthesis Of Legionaminic Acid And Pseudaminic Acid Glycosides, Bibek Dhakal

Wayne State University Dissertations

Legionaminic acid (Leg) and pseudaminic acid (Pse) are deoxy acetamido analogues of the most common sialic acid, N-acetylneuraminic acid (NeuAc) that are found in microorganisms. Leg and Pse are rare but important class of sialic acids, as their glycosides are found in lipopolysaccharides and glycoproteins of several pathogenic Gram-negative bacteria including Pseudomonas aeruginosa, Legionella pneumophila serogroup 1, Campylobacter jejuni, and Campylobacter coli. As such, the stereoselective glycosylation of the equatorial Leg and Pse donors, and the role played by their side chain conformations in anomeric reactivity and selectivity are the focus of this thesis.

Chapter two describes the synthesis of …

Addressing The Threat Of Multidrug Resistant Infectious Diseases By Synthesis Of Novel Aminoglycoside Antibiotics, Girish Chandra Sati

Wayne State University Dissertations

The ever-growing increase in multidrug resistant infectious diseases is one of the major cause of human mortality, and there is an inherent need for the development of new antibiotics. Since the discovery of streptomycin, AGAs have been playing a very important role in human therapy as highly potent broad-spectrum antibiotics and are listed as one of the critically important antimicrobials by WHO. AGAs act by inhibiting the bacterial protein synthesis and by targeting the A-site present in the small subunit of bacterial ribosome. The clinical use of AGAs is somewhat restricted due to their toxic effects (ototoxicity and nephrotoxicity) and …

Cation Clock Reactions For The Determination Of Relative Reaction Kinetics In Glycosylation Reactions, Philip Adero

Wayne State University Dissertations

This dissertation presents the development of cyclization reactions as clocks for the determination of the molecularity of glycosylation reactions in individual pyranoside systems and extends it to the arabinofuranoside systems. It also describes the development of selective hydrogenolytic cleavage of naphthylmethyl ethers in the presence of sulfides.

The first part of chapter one gives an overview of the significance of glycochemistry and the challenges involved. The second part describes some selected glycosylation methods and extends this to the general mechanistic studies of glycosylation. This is followed by the discussion of the general clock reactions in literature which initiates a further …

Progress Toward Controlled Disulfide Formation To Access Neuroactive Conotoxins, Thilini Kondasinghe

Wayne State University Dissertations

"Conotoxins are mini proteins isolated from marine snails of the Conus family. They have shown activity in the selective inhibition of various ion channels. Therefore, they present an opportunity as possible therapy for a myriad of neurological ailments. The synthesis of conotoxins would enable both biological studies and evaluation of these structures as lead targets for therapeutics. However, establishing a reliable method to consistently folding disulfide rich proteins, including conotoxin, into their native structure has been challenging over few decades. In this research project, it is shown the progress towards a mild, efficient, and broadly applicable methods to generate the …

Harnessing Radical Reactivity For The Construction Of Natural Product Frameworks And Transition Metal Catalyst Stability In A Modified Kochi Coupling Reaction, Mathes Hewage Hansamali Sakuntala Sirinimal

Wayne State University Dissertations

Polycyclic N-containing heterocycles play an important role in therapeutic

applications and as molecular tools in studying biological processes, making them

important synthetic targets. Current synthetic approaches are too lengthy, use toxic

reagents or are limited to accessing a particular framework and hence, their synthesis

warrant further study. We have recently developed conditions to avoid both reduction and

slow addition in aminyl radical cyclizations in our venture to access the constrained ABC

core of calyciphilline A, a Daphniphyllum alkaloid. An electron deficient enone with a

pendent internal alkyne as the neutral aminyl radical precursor was used for radical

cyclization. Based on …