Date of Award

2014

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Chemistry

First Advisor

Amos B. Smith

Abstract

The dissertation herein presents efforts toward the synthesis of the potent insecticidal indole diterpenes, nodulisporic acids A and D. Chapter one details the isolation of the nodulisporic acid family of compounds by Merck, as well as the efforts at Merck to utilize (+)-nodulisporic acid A as a veterinary medicine lead structure. Further, chapter one reviews the previous strategies employed by the Smith group toward the syntheses of the nodulisporic acid family. Lastly, the development of a modular and highly convergent strategy to access the nodulisporic acids exploiting a one-pot tandem Buchwald-Hartwig/Heck cascade to generate a common central indole core is described.

Chapter 2 will describe the development of a revised synthetic strategy to access the required western hemisphere chloroindoline for the synthesis of nodulisporic acid A.

Chapter 3 outlines the synthesis of the eastern hemisphere common to both nodulisporic acids A and D. The development of a new strategy for the construction of the C-3 and C-12 stereocenters now allow for the synthesis of sufficient quantity of the eastern hemisphere for coupling studies.

Chapter 4 describes the development and implementation of an Enders alkylation and a Stille-Kelly coupling to generate the western hemisphere of nodulisporic acid D.

Chapter 5 disclosed our results attempting to implement the one-pot tandem Buchwald-Hartwig/Heck cascade to access nodulipsoric acids A and D. Furthermore, future plans for the further development of the Buchwald-Hartwig/Heck(Barluenga) cascade tactic are described.

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