Date of Award
Doctor of Philosophy (PhD)
Amos B. Smith
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.
Melvin, Jason, "Studies Toward the Synthesis of Nodulisporic Acids A and D" (2014). Publicly Accessible Penn Dissertations. 1370.