UC Berkeley

This dissertation describes our approaches toward a variety of natural products, including the arcutine family and the related diterpenoid atropurpuran. A methodology developed to access several interesting terpenoids is also discussed. Chapter 1 is an introduction to the diterpenoid alkaloids, a large class biologically active natural products possessing highly caged scaffolds. Arcutine is the prototypical member of a small family of these molecules consisting of arcutine, arcutinine, aconicarmicharcutinium and the diterpenoid atropurpuran. This section includes a discussion of the biosynthesis of these molecules as well as our biosynthetic proposal. Previous work toward these molecules, including two total syntheses of atropupuran, is also discussed.

Chapter 2 describes our initial approaches toward arcutine and demonstrates many of the limitations of these approaches. In particular, much of the discussion focuses on synthetic disconnections that build on our groups previous approaches toward the diterpenoid alkaloids.

Chapter 3 describes our current approach toward the arcutines. While this approach has not led to a total synthesis to date, it has led to the first synthesis of the hexacyclic arcutine scaffold. Many of the transformations needed to access the arcutines from this scaffold have been completed and a total synthesis of all of the natural products in this family is well within reach. This approach hinges on an oxopyrrolium Diels–Alder cycloaddition that was developed to improve upon many of the shortcomings of previous approaches. This in turn led to a scalable synthesis of the hexacyclic arcutine framework.

Finally, Chapter 4 describes some previously published work that utilizes carvone derived cyclobutanols as precursors toward a variety of natural product and natural product like scaffolds. This work builds on our groups initial report based on these cyclobutanols, and extends it to allow further C–C bond formation. We use these new C–C bonds to forge a variety of interesting targets as well as a 4 step synthesis of the taxoid core. This work has spawned projects toward various diterpenoid natural products.