Date of Award

2015

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Chemistry

First Advisor

Amos B. Smith

Abstract

The dissertation contained herein presents a total synthesis of (-)-enigmazole A utilizing a late-stage large-fragment Petasis-Ferrier union/rearrangement protocol. Chapter One details the isolation, structural elucidation and subsequent biological studies of (-)-enigmazole A. The previous synthetic studies of (-)-enigmazole A are also introduced. The chapter then outlines the Smith three-step Petasis-Ferrier union/rearrangement protocol, as well as a number of the successful total syntheses achieved over the years by the Smith group utilizing this protocol. Herein, a late-stage large-fragment Petasis-Ferrier union/rearrangement will be utilized as the synthetic cornerstone for the Smith total synthesis of (-)-enigmazole A.

Chapter Two describes the retrosynthetic strategy toward (-)-enigmazole A and subsequent total synthesis. The late-stage large-fragment Petasis-Ferrier union/rearrangement, which generates the entire carbon skeleton of (-)-enigmazole A, is described after the construction of the requisite eastern and western hemispheres. The chapter then describes the subsequent macrolactonization studies and the end game of the total synthesis. In addition to the Smith three-step Petasis-Ferrier union/rearrangement protocol, highlights of the total synthesis includes a Negishi cross-coupling, a dithiane-epoxide union, a Type I ARC multicomponent coupling, a Yamaguchi macrolactonization and chemoselective oxidation/reduction strategies

the details of which are also described in Chapter Two.

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