Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)

Graduate Group


First Advisor

Amos B. Smith


This dissertation describes progress towards the synthesis of spirastrellolide E, a potent cytotoxic marine macrolide. In particular, the synthesis of advanced southern hemisphere fragments is reported. Chapter 1 details the isolation, structural determination, and biological activity of the spirastrellolide family, as well as synthetic efforts towards members of the family. Chapter 2 describes the evolution of the Smith group synthetic strategy towards the spirastrellolides, details the choice of target for a total synthesis effort, and describes a successful first generation approach to a relevant advanced southern hemisphere fragment. Key steps involve a convergent Type I Anion Relay Chemistry (ARC) union and a gold catalyzed directed spiroketalization. Chapter 3 then revises the overall retrosynthetic analysis by proposing a novel strategy for hemisphere union, involving a cross metathesis/epoxidation/epoxide ring opening cascade, and describes the synthesis of more than 500 mg of a revised southern hemisphere fragment. In addition, the mechanism of the key directed gold catalyzed spiroketalization is discussed in detail. A stereochemical rationale for diverging outcomes during spiroketalization is described.

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