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Student Research Projects

Conjugate Addition of Active Methylene Carbon Nucleophiles to Quinoline Vinylacetylenes and Addition of Ethylene Glycol to Pyrrolo [1,2-a] Quinoxaline

Student Rachel Fancher, Shannon Cassatt
Faculty Mentor(s) Dr. Anthony Hayford
Department Chemistry

Abstract

Benzoindolizines and heterocyclic-containing bridgehead nitrogen compounds are valuable because they have been proven in applications in pharmecuticals and biomedicine. Specifically, they have been synthesized, isolated and tested in the areas of cancer, HIV, and tuberculosis research. A number of pyrroloquinoline containing compounds, known as PQQs, are currently used for the enzyme inhibition of aldose reductase, glyoxalase, and reverse transcriptase. Pyrroloquinoxalines are structurally similar to pyrroloquinolines and also have applications in many of the same fields, especially as selective 5-HT3 receptors. However, quinoxaline derivatives and polypeptide drugs tend to have issues with solubility and proteolytic enzyme degradation. Therefore, pyrroloquinoxaline compounds would benefit from PEGylation with ethylene glycol monomers to remedy these issues. This could potentially increase the effectiveness of their delivery although no synthesis schemes for ethylene glycol addition to pyrroloquinoxalines presently exist.

The synthesis of the pyrrolo[1, 2-a]quinoline and pyrrolo[1,2-a]quinoxaline heterocycles were performed in three relatively simple steps. Both 2-quinoline aldehyde and quinoxaline-2-carbaldehyde starting products were converted into respective vinyl bromide intermediates via Wittig Olefination with a Wittig salt.3,4,7 The Wittig salt was made by allowing triphenylphosphine, dibromomethane and toluene to reach reflux overnight. The quinoline and quinoxaline vinyl bromides were then subjected to Sonogashira Cross-Coupling to produce enyne TMS intermediates. The final and most essential step involved the novel flouride anion heterocyclization of the silylated quinoline vinylacetylene and silylated quinoxaline vinylacetylene intermediate to yield the desired functionalized benzoindolizine derivative and the pyrrolo[1,2-a]quinoxaline derivative with attached ethylene glycol unit.

Grants

VWC Undergraduate Research Conference Travel Grant

Conferences

Gamma Sigma Epsilon, February 27 – March 1, 2009 in New York City

 

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