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Alex Huszagh

Alex Huszagh

Major: 

Chemistry

University: 

Macalester University

Mentor(s): 

Donald Wenz

Faculty Sponsor(s): 

Javier Read de Alaniz

Faculty Sponsor's Department(s): 

Chemistry and Biochemistry

Project Title: 

HYPOTHETICAL DESIGN OF SMALL CHIRAL CENTRES BY FRAGMENTATION OF 4-AMINOCYCLOPENTENONE

Project Description: 

Due to the chirality of most biologically active molecules, small functionalizable chiral centres are an important scaffold in the synthesis of pharmaceuticals. We propose a mechanistic pathway that proceeds via the fragmentation of 4-aminocyclopentenones, producing differing relative reactivity at the termini.  Cyclopentenones are frequently found in biologically active molecules with burgeoning varying methodologies for their synthesis. Synthetic methodologies now include the use of low cost, renewable starting materials in the aza-Piancatelli rearrangement, which ends in a 4p Nazarov cyclization. These rearrangements afford 5-substituted 4-aminocyclopentenones in high yields under Lewis acidic catalytic conditions with a 2-furylcarbinol; these 2-furylcarbinols can be synthesized in high yield by nucleophilic addition to furfural, an agricultural byproduct. By epoxidizing the double bond and proceeding with an Eschenmoser-Tanabe fragmentation, these 4,5-substituted cyclopentenones can form short 5 carbon chain molecules with substituted carbons 4,5 in the center, useful as possible intermediates in pharmaceutical synthesis. We predict the fragmentation products to be racemic in this instance owing to the undefined stereochemistry following the 4p electro cyclization. Via an enone transposition, we should be able to access all racemic isomers of our 4,5 aryl- amino- compounds. In other substrates, the trans- selectivity of the rearrangement could be partitioned into an anti-substituted product. Therefore, we hope to synthesize low cost functionalizable chiral molecules as intermediates in the synthesis of biologically active molecules.