Date of Award

5-2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical and Chemical Engineering and Sciences

First Advisor

Nasri Nesnas

Second Advisor

D. Andrew Knight

Third Advisor

Alan B. Brown

Fourth Advisor

David Carroll

Abstract

Retinoids are a class of synthetic and natural molecules that are functionally and structurally related to Vitamin A. They have various biological roles and potential therapeutic values. Providing treatment for eye diseases requires more detailed understanding of the visual process. However, investigating every aspect of the visual phenomenon is constrained by the difficulties involved in the synthesis of pure retinoids with the desired stereochemistry. Therefore, developing a suitable and valuable synthetic route for 11-cis-retinal and its analogues is highly desirable. The first chapter of this dissertation explains new synthetic pathways for 11-cisretinal. In addition, the total synthesis of stereoselectively deuterium-labeled 11- cis-retinal and 9-cis-retinal (an important analogue of 11-cis-retinal) will be discussed. These molecules are critical for biophysical studies on the structure and dynamics of the visual process. Silicon is the second most abundant element on earth. It has unique physiochemical properties and a wide range of applications in materials, synthetic methods, and pharmaceutical products. Installing silicon onto carbon is one of the most challenging areas in silicon chemistry. A discovery made by professor Brian M. Stoltz and professor Robert H. Grubbs at Caltech, which utilizes an abundant base, KOt Bu, for this purpose, is a major breakthrough in the field. In the second chapter of this work, experiments are designed to uncover the mechanism of this discovery and improve the scope of the reaction. Chapter two also includes our work on the preparation of asymmetric silicon-tethered compounds, which are valuable tools for performing site-selective functionalization, and for synthesizing complex molecules. In the last section of this chapter, experiments on site-selective nucleophilic reactions through silylated intermediates based on a deuteration strategy recently reported by Wen-Bo Liu at Wuhan University, that involves silicon species, are described. Caged neurotransmitters are molecules that are temporarily inactivated by connection to a chemical group (the cage). Light is used to break this connection and the active molecule can be released (uncaging). The fact that caged neurotransmitters can be activated by light provides full control over the timing, location and amplitude of the neurotransmitters. In spite of much research that has been done in this field, there are several aspects that require more study, such as GABA receptor inhibition and the need to improve the solubility of relatively hydrophobic designs. In the final section of this dissertation, a caged neurotransmitter linked to polyethylene glycol (PEG) is introduced. Amongst the advantages of this CDNI-Glu-PEG molecule are increased solubility and bulkiness in comparison to the available cages, the presence of two units of CDNI-Glu on each molecule, and biocompatibility of the designed structure.

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