Theses and Dissertations Collection

Clinical depression is the fourth leading cause of disability and death in the world.1 Although a great number and diversity of antidepressant drugs are already on the market, there remain many problems and much room for improvement in this class of therapeutics. Given the problems of current treatments,2 discovery and development of new and improved antidepressant drugs remains a pressing need. The subject of the first chapter is the recently-accomplished first total synthesis of a new and structurally unique antidepressant natural product called veranamine3. We have completed this synthesis in a total of 7 steps with overall yield of 21 % starting with readily available inexpensive starting materials. The key step is an unprecedented vinylogous Pictet-Gams reaction used to assemble the dihydronaphthyridine core scaffold of the natural product. This marine-derived heterocyclic compound is the first structurally new antidepressant lead of its kind in many years3a. Our synthesis is part of a collaborative effort to further develop this compound as a therapeutic lead.

The second chapter is devoted to an unrelated topic. One branch of research in Dr. Magolan's laboratory aims to develop unique synthetic methods that rely on the use of heterogeneous reagents in one-pot multi-step processes. An important benefit of these methods is the facile separation of catalysts and reagents from reaction products through filtration, generating inexpensive and easy product purification. Here we present our initial investigations on the use of clays as aerobic dehydroaromatization catalysts, including a clay-mediated one-pot Fischer indole synthesis and Povarov reaction.