Dissertation/Thesis Abstract

Access to Diverse Scaffolds by Modification of Ugi-Smiles Couplings
by Harris, Aubrey, M.S., Southern Illinois University at Edwardsville, 2016, 96; 10125667
Abstract (Summary)

Being able to create diverse compounds efficiently is essential for drug development research. Multicomponent coupling reactions (MCRs) are one-pot reactions that combine several reactive components to form complex products. By changing substituents on the initial components, the reactions are readily applied to produce libraries of structurally-similar compounds. The Ugi-Smiles 4CR is an MCR that uses a phenol, amine, aldehyde and isocyanide to produce drug-relevant scaffolds in one step. Prior to the work reported by the Luesse group, heterocyclic and conjugated aldehydes were considered unsuccessful for Ugi-Smiles couplings. However, use of 2-furaldehyde and allyl amine as components led to a tandem Ugi-Smiles intramolecular Diels-Alder process (US-IMDA), with a Diels-Alder cycloaddition following the traditional Ugi-Smiles coupling, to produce epoxyisoindolines.

The goal for this project was to modify both the Ugi-Smiles reaction and its products. Initially, this project aimed to modify the US-IMDA specifically by reversing the roles of the amine and aldehyde components to result in a similar system for Diels-Alder cyclization. However, upon using α,β-unsaturated aldehydes, a new Ugi-Smiles related, five-component coupling was discovered. Initial mechanistic and optimization studies were completed as well as component variations. Additionally, a group of epoxyisoindolines created via the US-IMDA reaction were altered at the oxabicyclic core via aromatization, ring-opening, and ring-forming reactions.

Indexing (document details)
Advisor: Luesse, Sarah B.
Commitee: DeMeo, Cristina, Dixon, Robert
School: Southern Illinois University at Edwardsville
Department: Chemistry
School Location: United States -- Illinois
Source: MAI 55/05M(E), Masters Abstracts International
Subjects: Biochemistry, Organic chemistry
Keywords: Epoxyisosindoline, Five component reaction, Multicomponent coupling reactions, Oxy-michael, Synthesis, Ugi-smiles
Publication Number: 10125667
ISBN: 978-1-339-83739-0
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