Total Synthesis of Hypersampsone M and Studies of Related Polycyclic Polyprenylated Acylphloroglucinol Systems

Research in the Stoltz group is primarily focused on the total synthesis of complex, bioactive natural products and on the development of reaction methodologies to enable these synthetic endeavors. This thesis focuses on the homoadamantane polycyclic polyprenylated acylphloroglucinol (PPAP) class of natural products, our efforts toward their synthesis, and discoveries made along the way. Chapter 1 describes the completed synthesis of hypersampsone M, while Chapter 2 describes ongoing efforts toward wilsonglucinol G and hypersampsone A. Appendix 5 presents the culmination of optimization studies and unsuccessful routes toward these natural products. Chapter 3 describes selective fragmentations of a-bromocaranones, reactions that were tailored to the synthesis of PPAPs. Chapter 4 discloses the synthesis and characterization of an unexpected, caged side product isolated during an unsuccessful route to the homoadamantane PPAPs. Chapter 5 discusses the development and scope of the key cyclopentene annulation methodology that enabled the installation of the challenging, hindered 5-membered ring on the homoadamantane PPAPs.