Author

Sayre Weast

Date of Award

5-2019

Degree Type

Honors College Thesis

Department

Chemistry and Biochemistry

First Advisor

Julie Pigza, Ph.D.

Advisor Department

Chemistry and Biochemistry

Abstract

Heterocycles have many applications in the discipline of medicinal chemistry. These structures are found in various natural products with relevant biological activity. Our research group, in collaboration with two others, is particularly interested in one heterocycle, quinoline, as a scaffold for HIV-1 integrase inhibitors. A synthetic route has been developed to produce a derivatized structure on small scale. One goal of this thesis was to expand the scale of this route to provide increased quantities of the quinoline scaffold. Procedures were adapted to accommodate the increase in scale to convert commercially available anthranilic acids to quinolines via the isatoic anhydride. The quinolines could then be further derivatized to be tested as HIV-1 integrase inhibitors. At a later stage in the synthesis, the use of a masked acyl cyanide (MAC) reagent allows installation of an alpha-alkoxyester side chain onto the quinoline that is necessary for HIV inhibition. The second goal of this thesis involves heterocycles more broadly by expanding this reaction to include other heterocycles to test the generality of the method. This reaction also highlights the utility of MAC reagents as an example of umpolung chemistry, which is a reversal of polarity and bond formation compared to what is traditionally accomplished. These exciting strategies open the possibility for new reagents and strategies in organic synthesis. A series of heterocyclic structures were tested in the MAC reaction and the results of the method are discussed.

Share

COinS