Modular Synthesis and Hydroalkylation of Vicinally Functionalized Ketopiperazines: A solution to the Piperazine Problem

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.

Name thesis:degree_name

Master of Science (MS)

Discipline thesis:degree_discipline

Chemistry

Year dc:date.available

2019

Author dc:creator

• Moreno, Antonio

Contributors dc:contributor

• Timothy K. Beng
• JoAnn Peters
• Levente Fabry-Asztalos

• Castagnoli-Cushman Reaction
• lactamoyl ester
• piperazine
• trifluoroacetyl group
• [3.3.1]-azabicycle
• Chemistry
• Organic Chemistry

Language dc:language

English

Repository record dc:identifier

https://digitalcommons.cwu.edu/etd/1215

OAI identifier oai:identifier

oai:digitalcommons.cwu.edu:etd-2193