Synthetic efforts toward a total synthesis of (+)-Pelorusdie A.

University of Minnesota Ph.D. dissertation. June 2009. Major: Chemisrty. Advisor: Thomas R. Hoye. 1 computer file (PDF); xi, 342 pages, appendix A.This thesis has been divided into six chapters that describe synthetic efforts toward the cytotoxic marine macrolide (+)-peloruside A, isolated by Northcote and coworkers from the New Zealand marine sponge Mycale hentscheli. Chapter 1 discusses the background of peloruside A and published literature studies relating to its biological activity. Chapter 2 conveys a detailed report of the synthetic efforts by others that have resulted in three total syntheses and multiple efforts toward the total synthesis of peloruside A. Chapter 3 describes the previous synthetic efforts by Hoye group members toward peloruside A. Two different strategies for synthesizing the C13-C20 fragment of (+)-peloruside A have been established using ring-closing metathesis. Synthesis of the C1-C9 fragment of (+)-peloruside A was accomplished using a kinetic lactonization strategy. Chapter 4 reports on my efforts at scaling-up and optimizing the synthesis of the C1-C9 fragment of (+)-peloruside A and modifications to the previous route. Chapter 5 describes the new progress toward synthesizing (+)-peloruside A that was achieved. These efforts culminated in the synthesis of a C1-C11 fragment of (+)-peloruside A along with studies investigating the coupling of late stage segments via a 1,5-anti boron-mediated aldol. Chapter 6 highlights the key features of my synthetic efforts toward (+)-peloruside A