Publication Date

April 2019

Advisor(s)

Michael Calter

Major

Chemistry

Language

English (United States)

Abstract

The National Cancer Institute estimated that in the United States in 2018, ~24,000 people would die of leukemia and ~60,000 new cases would be detected.1 Thus, discovering and synthesizing new antileukemic compounds is essential to allow treatment of this disease. Therefore, this thesis describes a novel, faster, cheaper, and greener route for synthesizing an antileukemic natural product found in low levels in the roots and stems of Aglia elliptifolia in southeast Asia.2 Rocaglamide’s significant anti-cancer activity relies heavily on its structural complexity, containing five stereocenters. While total syntheses of (-)-rocaglamide have been developed, all of the current total syntheses are long, have poor yields, and utilize expensive and very toxic compounds.2 Through an asymmetric organocatalytic Interrupted Feist-Bénary-like synthesis, the enantioselectivity of two substituted cinchona alkaloid-derived pyrimidine catalysts have been tested under various reaction conditions. After the reaction conditions were optimized, the phenyl-phenyl derived catalyst proves to be the most effective with an enantioselectivity of 45-51% enantiomeric excess at room temperature. Though high enantioselectivity has not yet been achieved, the phenyl-phenyl derived catalyst proves to be effective at room temperature independently of the solvent used to run the IFB-like reaction. Once a potential chiral organocatalyst yields an enantiomer at greater excess of rocaglamide’s core structure, we will have two controlled stereocenters that will facilitate the total enantioselective synthesis of rocaglamide. In developing this new synthetic pathway for the total synthesis of rocaglamide, we will not only provide new insight into green, synthetic chemistry but also enable sufficient quantities of potential low-cost therapeutic treatments.

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