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.
|Advisor:||Luesse, Sarah B.|
|Commitee:||DeMeo, Cristina, Dixon, Robert|
|School:||Southern Illinois University at Edwardsville|
|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|
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