Browsing by Subject "Photochemistry"
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Item Development of Metal-Catalyzed and Photochemical Approaches to Carbon-Carbon Bond Forming Reactions(2022-05) Nair, Vaishnavi Narayanan; Ready, Joseph M.; De Brabander, Jef K.; Chen, Chuo; Tambar, UttamThe development of methods to construct carbon-carbon bonds is fundamental to synthetic organic chemistry. This transformation provides access to a variety of organic compounds including medicinal and pharmaceutical agents, agrochemicals, and polymers. There is a growing interest in practical and efficient catalytic approaches to construct carbon-carbon bonds allowing access to valuable organic molecules. This manuscript describes a review of catalytic methods for onium ylide rearrangements in aromatic systems, our studies on catalyst-controlled rearrangements of onium ylides in indole systems, and our approaches toward photocatalytic asymmetric coupling of imines and alkylarenes. In the first chapter, an overview of the known synthetic approaches for metal-catalyzed onium ylide rearrangements in aromatic systems is discussed. Various catalytic examples from the recent literature show onium ylides undergoing dearomative [2,3]-rearrangement to give alkylated aromatic compounds as final products. The influence of substrate and solvent effects in the selectivity of rearrangements has been demonstrated through several examples. The second chapter describes our studies in the development of catalytic rearrangements of indole-based onium ylides. Our approach allows regiodivergent rearrangements of oxonium ylides in a catalyst-controlled manner to access substituted indole compounds. This method shows the impact of transition-metal catalysis in governing the selectivity of chemical transformations. We also present various experimental and theoretical studies to analyze the mechanistic pathways involved in the methodology. The development of the methodology has also allowed further functionalization of the products resulting in the total synthesis and structural revision of an indole alkaloid. In the third chapter, we describe our approaches in exploiting photocatalysis to perform the functionalization of feedstock chemicals to access enantioenriched chiral amines. Our synthetic strategy leverages the known photophysical properties of compounds to rationally design and develop a catalytic transformation in an enantioselective fashion. The challenges associated with realizing this transformation and our approaches to solving them are discussed.Item Photochemical Preparation of Salicylate/Resorcylate Esters/Amides: Asymmetric Synthesis of SCH 351448(2006-05-16) Soltani, Omid; De Brabander, Jef K.This body of work is divided into two parts. The first part describes the development and general application of a photochemical based methodology for the preparation of substituted salicylate/resorcylate esters and amides. Substitued salicylate/resorcylate esters and amides are found in a variety of biologically active natural products. Naturally occurring molecules with these structural moieties are of interest to both the chemistry and biology communities due to their unique structures and biological activities. Preparation of these esters and amides is often a non-trivial task due to a combination of electronic and steric effects. To date, a variety of methods have been developed to access salicylate/resorcylate esters and amides, however many of these methods suffer from limitations such as poor substrate scope or they require the use of harsh conditions. The photochemical based method described herein addresses some of these issues and provides a general method for the efficient preparation of these structural units. The second portion of this thesis is concerned with the asymmetric synthesis of the natural product SCH 351448. This synthesis utilizes a highly convergent approach that takes advantage of the dimeric nature of the natural product. A key step in the sequence involves the photochemical coupling of two analogous fragments to provide the complete carbon skeleton of SCH 351448. Also, an optimized and shortened route to the natural product is presented. Finally, preliminary experiments provide insight into the biological function of the natural product.Item Using Light-Activated EFG to Control Cell Behavior with Automated Instrumentation(2008-05-13) Miller, Danielle Suzanne; Luebke, Kevin J.A key interest in cell biology is the ability to control cell behavior, particularly for creating functional assemblies of cells to restore, maintain or enhance tissue and organ function. Success in controlling cell behavior must include techniques that provide signals which influence the organization, growth and activities of cells. Growth factors are naturally occurring proteins that act as external chemical signals and which play a key role in regulation and control of a variety of cellular processes, such as differentiation, proliferation and migration. One of the challenges in controlling these processes using growth factors is the ability to spatially direct their timed release to the cellular environment. Another challenge then becomes the continued ability to influence these processes with the dynamic flexibility to meet the changing cellular demands during tissue development. We have developed a technology that uses light-activated epidermal growth factor (EGF) to influence cell behavior. We used peptide synthesis to incorporate a photolabile caging group on a critical residue. The caged-growth factor was inactive until converted with light, which enabled the management of its effects with the precision with which light could be directed. Since the factor was a soluble, diffusible species, it was not limited to a static pattern or substrate. Thus, dynamic control over its mitogenic and chemotactic effects on cell behavior was achieved. To utilize the light-activated EGF we developed a device for its delivery and activation. The system was a fully automated machine capable of maintaining the strict requirements of cell culture, integrated with components that achieved interchangeable, high resolution patterns, along with an optical system for photo-activating caged growth factors. The instrument was designed, characterized and then used to investigate the effect of light-activated EGF on cell patterning and mobility. Using this device, spatially resolved fibroblast cell patterning and migration were achieved.