UC Berkeley

Marine bryozoans continue to provide architecturally fascinating halogenated alkaloids that pose unique challenges for chemical synthesis. This dissertation documents the evolution of a synthetic program aimed at accessing the trihalogenated alkaloid caulamidine A.In Chapter 1, we provide an introduction to the caulamidine alkaloids, detailing their isolation, structural elucidation, and synthetic challenges. In our discussion, we compare and contrast the caulamidine alkaloids to the well-studied and topologically homologous C20 bis(cyclotryptamine) alkaloids, highlighting how the caulamidine alkaloids require the development of new synthetic strategies. In Chapter 2, we describe our efforts in developing a synthetic strategy toward caulamidine A. Initially, we proposed to install the challenging neopentylic chloride motif leveraging an alkene chlorination strategy, which culminated in a 16-step racemic synthesis of caulamidine A. To achieve an asymmetric synthesis and to optimize the formation of key stereogenic centers, we truncated the synthetic route to an 11-step sequence featuring a rapid, diastereoselective ketoneamidine annulation reaction facilitated by glycol bistriflate and a highly diastereoselective hydrogen atom transfer that correctly established the key chlorine-bearing stereogenic center.