UCLA

This dissertation describes studies on the use of solid-state photochemistry to construct challenging carbon–carbon bonds in alkaloid natural products, as well as a novel methodology to synthesize peripherally functionalized pentiptycenequinones. Solid-state photochemistry represents a promising but underutilized method to assemble the synthetically daunting vicinal quaternary stereocenter motif. This dissertation details the use of this methodology to forge the vicinal quaternary stereocenters present in cyclotryptamine and bis(cyclotryptamine) alkaloids. Additionally, a separate study focusing on the modular construction of pentiptycenequinones with promising materials applications is described.

Chapter One is a perspective on the solid-state Norrish type I photodecarbonylation to assemble vicinal quaternary stereocenters. This chapter describes early, proof-of-concept studies that demonstrate the feasibility of the transformation and details the thermochemical and structural parameters required for ketone substrates. The reaction scope, scalability, and applications in total synthesis are also discussed.

Chapter Two focuses on the evaluation of the solid-state photodecarbonylation reaction to install reverse prenyl moieties on the pyrrolidinoindoline scaffold. These studies include progress toward the total synthesis of debromoflustramine A. Furthermore, a workflow to optimize the physical state of ketone substrates for the photodecarbonylation reaction is also discussed.

Chapters Three and Four describe the use of the solid-state photodecarbonylation reaction to synthesize the bis(cyclotryptamine) alkaloid psychotriadine. These efforts culminated in an understanding of how crystalline substrate conformation influences the success or failure of the photodecarbonylative reaction. Furthermore, this work allowed for the first total synthesis of “psychotriadine”, bearing the elusive piperidinoindoline framework. This alkaloid was subsequently identified in the extracts of the flower Psychotria colorata suggesting that it is a previously overlooked natural product.

Chapter Five focuses on a modular route to synthesize diverse, octakis-substituted pentiptycenequinone molecules. Our strategy was enabled by a sequential iron-mediated bromination reaction followed by a high-yielding palladium-catalyzed cross-coupling to form eight new C–C bonds. These endeavors enabled the construction of diverse pentiptycenequinone-based structures that could be promising candidates for materials science applications.