Publication Date

2024

Document Type

Dissertation/Thesis

First Advisor

Klumpp, Douglas A.

Degree Name

Ph.D. (Doctor of Philosophy)

Legacy Department

Department of Chemistry and Biochemistry

Abstract

The work outlined in this dissertation describes acid-base catalyzed projects facilitating the construction of key synthetic analogs with vast therapeutic applications. Three major projects have been covered demonstrating various synthetic routes developed by our research group to furnish key derivatives of heterocyclic compounds, including coumarins, carbohydrate moieties, and beta-lactams. By their catalytic nature, acids, and bases are known to enhance the reactivities of compounds. This allows synthetic chemists to design or chart new and better reaction pathways leading to the delivery of desired reaction products. The first chapter features a summary of the main concepts underpinning the projects.

Chapter 2 of this dissertation describes how an acid-catalyzed Michael addition has been employed to synthesize an extensive array of 4-hydroxycoumarin derivatives. This chemistry provides a straightforward protocol for linking coumarins, thiocoumarin, and quinolone moieties with alkenyl heterocycles. The heterocycles utilized include 2- and 4-vinylpyridines, vinyl pyrazine, vinyl phenyloxazole, and 1,2-di(pyridine-4-yl) ethene. This work further demonstrates the utility of Michael addition as useful route to functionalized heterocycles.

Chapter 3 discusses sugar chemistry in strong acids. It has two parts: the first part outlines the protection strategy utilized to facilitate the C-glycosylation process, and the second part involves a superacid-catalyzed C-glycosylation pathway, which enabled aromatic moieties to be installed on the anomeric position of the glycosyl donor. The picoloyl protecting group has shown promise in the protection of sugar systems in carbohydrate chemistry. Recently, our group, in a Friedel-Craft-type reaction, demonstrated the successful protection of alcohol by the 6-chloronicotinoyl group, allowing cyclization via the phenyl ring.1 Other studies also indicate the picoloyl group aided a H-bond-mediated Aglycone Delivery (HAD) glycosylation reaction ensuring that high facial α- or β-stereoselectivity is achieved.2 While they have been employed in the selective protection of O-glycoside building blocks, our group has developed an efficient strategy of utilizing the picoloyl-protecting group to facilitate a superacid-catalyzed C-glycosylation. Our C-glycosylation protocol is compatible with various glycosyl units and some aromatic nucleophiles. This reaction is proposed to proceed through an oxycarbenium intermediate. Then a nucleophilic attack at the anomeric carbon affords the desired product.

In chapter 4, we demonstrated a multistep protocol involving amination and acylation to afford a carbamate. The removal of a silyl group, which was used as a carbanion source, was expected to lead to cyclization to afford the β-lactam product. Unfortunately, the desired product was not obtained. Future studies would include the determination of the substrate scope of the protocol.

Extent

295 pages

Language

en

Publisher

Northern Illinois University

Rights Statement

In Copyright

Rights Statement 2

NIU theses are protected by copyright. They may be viewed from Huskie Commons for any purpose, but reproduction or distribution in any format is prohibited without the written permission of the authors.

Media Type

Text

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