Progess Toward The Total Synthesis of Ammocidin D

Abstract

The dissertation contained herein describes the synthetic efforts towards the total synthesis of the cytotoxic macrolide ammocidin D. Ammocidin D, isolated by Hayakawa and coworkers in 2009 from the culture broth of Saccharothrix sp. AJ9571 exhibited anti-proliferative activity against the human cancer line MCF7 (IC50. 5.0 µM). Chapter 1 discusses the structural features for the ammocidin class of macrolides, a structural comparison to the related family of apoptolidins and their respective synthetic efforts. Chapter 2 highlights the early approaches towards the pyranose ring system contained within the southern hemisphere. Chapter 3 describes the mechanistic labeling studies and succesful synthesis of the southern hemisphere. Chapter 4 details the synthetic efforts towards the unification between the northern and southern fragments and outlines the final pertinent operations towards the synthesis of ammocidin D.