Document Type

Thesis

Date of Degree Completion

Spring 2019

Degree Name

Master of Science (MS)

Department

Chemistry

Committee Chair

Timothy K. Beng

Second Committee Member

JoAnn Peters

Third Committee Member

Levente Fabry-Asztalos

Fourth Committee Member

Gil Belofsky

Abstract

The stereocontrolled synthesis of functionalized piperazines is of great interest to pharmaceutical companies owing to their multiple biological activities such as antidepressant, antiparasitic, anticancer and antiretroviral. Current methods towards functionalized piperazines include intramolecular cyclization of appropriately tethered on acyclic precursors as well as α-C–H functionalization of intact piperazine rings. Although effective for the most part, these methods suffer from drawbacks such as the use of expensive catalysts, potentially toxic reagents, limited scope and functional group compatibility. Seeking to side-step some of the aforementioned limitations, we herein describe a step-economical-, cost-effective-, transition metal-free-, and mild approach to highly functionalized piperazines, including [3.3.1]-bicyclic piperazines. The success of a novel enolate hydroalkylation methodology hinges on a cascade reaction triggered by the addition of allyl magnesium bromide to a vicinally functionalized piperazinonate. Furthermore, we have successfully synthesized fluorinated ketopiperazine, in hopes of potentially modulating biological properties such as pharmacokinetic and physicochemical properties. The [3.3.1] azabicyclic piperazinols and fluorine-containing 2-oxopiperazines are subsequently engaged in structure-activity-relationship (SAR) studies on neglected tropical diseases (NTDs), including leishmaniasis.

Language

English

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