UC Berkeley

One of the many goals of natural product total synthesis, is to leverage modern chemicalmethods to develop strategic paradigms which result in increasingly efficient synthesis routes. The work described in this dissertation explores the development of strategies enabled by skeletal remodeling tactics and C–H functionalization. Chapters 1 and 2 provide background for the work discussed in the subsequent chapters. Chapter 1 discusses the development of skeletal remodeling tactics by the Sarpong Group. Chapter 2 introduces a theoretical framework for application of C–H oxidation in complex molecule synthesis. It utilizes that framework in comparative analysis of previous syntheses which have employed C–H oxidation reactions, to highlight the strategies which they enable. Chapter 3 discusses our progress toward a total synthesis of the diterpenoid natural product sordaricin. An efficient synthesis of sordaricin might enable the development of novel an- tifungal lead compounds. We proposed the use of a “camphor-first” strategy to synthesize sordaricin. This strategy would utilize several C–H oxidations to enable construction of the core around a [2.2.1]bicyclic fragment, an approach distinct from previous strategies. Several potential routes are discussed which culminated in the successful synthesis of intermediates in which the western portion of the molecule. Chapters 4 and 5 discuss our synthetic studies of the longiborneol family of sesquiterpenoids. Chapter 4 discusses how a “camphor-first” strategy, similar to that proposed for sordaricin, enabled a succinct synthesis of the parent natural product, longiborneol. Chapter 5 discusses how we extensively employed C–H oxidation chemistry to develop divergent syntheses of nine additional natural products. Overall, this work demonstrates that strategies utilizing both skeletal remodeling tactics and C–H oxidation can enable exceedingly efficient syntheses, and may have further merit in complex molecule synthesis.