Synthesis and biological evaluation of dispyrin, synthesis and design of selective M4 muscarinic modulators, and exploration of the total synthesis of piperazimycin A

Abstract

The content described in detail in this dissertation covers natural product guided drug discovery, traditional hit-to-lead medicinal chemistry and advances in total synthesis. The synthesis and biological evaluation of dispyrin will be discussed in detail, as well as the optimization of its binding to a potential therapeutic target. The history and design of selective therapeutic M4 muscarinic modulators based around the thienopyridine core is described, as well as the chemical optimization of the starting lead. Lastly, the exploration of the total synthesis of piperazimycin A is discussed as well as optimization of the key piperazic acid synthesis utilizing microwave assisted organic synthesis. These projects were used to potentially find new drug candidates with therapeutic potential.