Studies toward the synthesis of ( - ) agelastatin a and mechanistic investigations of the uncatalyzed chlorocyclization of 4-phenyl-4-pentenoic acid

This thesis presents an investigation into efforts towards the total synthesis of agelastatin A, as well as a mechanistic study of the uncatalyzed chlorocyclization reaction of 4-phenyl-4-pentenoic acid. Chapter 1 introduces all the prior total syntheses completed to date of agelastatin A. This chapter details the benefits, and similarities between each synthesis, as well as serves as an introduction into why a different, and novel route to the molecule is beneficial. Chapter 2 presents the current studies towards synthesizing the molecule utilizing chemistry that was developed in the Borhan lab. Within this chapter, different synthetic routes to access the molecule are described. Chapter 3 focuses on the mechanistic studies to determine the molecularities that lead to the syn- and anti-chlorolactonization. Chemical kinetics were a central part of this investigation, as well as concentration studies. This information provided key insights into the postulated transition states that lead either the syn-addition or anti-addition product.