Title: Strategies and Tactics for the Synthesis of Polycyclic Alkaloids
Description: The myrmicarin family of oligomeric natural products comprises one of the most ornate collections of polycyclic alkaloids known. The structural characterization of their unique scaffolds was accomplished through elegant spectroscopic studies. Furthermore, the synthesis of these alkaloids has attracted the attention of the synthetic community, with several syntheses of the monomeric myrmicarins completed. Significant effort has been put forth toward the synthesis of the higher order structures, though no successful approach has been reported to date. These isolation and characterization studies as well as synthetic approaches toward the family are reviewed. Chapter 2. The Evolution of Efficient, Enantioselective Total Syntheses of Monomeric Myrmicarin Alkaloids. In order to provide a family-level solution to the myrmicarin alkaloids, we adopted a strategy-level approach to their synthesis. Utilizing concepts from retrosynthetic analysis and diversity oriented synthesis, an enantioselective and highly streamlined synthesis of the monomeric myrmicarin alkaloids as well as potential dimerization precursors was established from a common intermediate with late stage diversification.

Chapter 3. Dimerization Studies toward the Synthesis of Myrmicarin 430A. An alternative strategy for the synthesis of myrmicarin 430A is presented using a dienamine precursor. This approach allows for the stereoselective synthesis of the all trans stereotriad of the central cyclopentane moiety of myrmicarin 430A. Mechanistic aspects concerning the final bond closure are presented in light of quantum chemical calculations. Chapter 4. An Introduction to the Securinega Alkaloids and NHC Catalysis The Securinega alkaloids comprise a large family of tetracyclic alkaloids, many of which contain a conjugated butenolide moiety. While many distinct synthetic approaches have appeared for the synthesis of members of this family, only a relatively small number of approaches are applied to the synthesis of the butenolide portion of these natural products. The various synthetic endeavors to accessing this structural motif are presented. NHC catalysis is a growing field of research for its ability to promote unusual chemical transformations.

As this field of research is of relevance to our latter studies, a brief overview of modern NHC catalysis is presented. Chapter 5. Development of an NHC-Catalyzed Cascade Reaction to Access the Core Architecture of the Securinega Alkaloids. In targeting the family of <italic>Securinega</italic> alkaloids, a retrosynthesis was devised that proposes a novel intramolecular cyclization approach of an ynal and ketone to deliver the bridging butenolide moiety of these natural products. The development of this reaction and its application toward the synthesis of various <italic>Securinega</italic> alkaloids is presented.