Novel (homo-)Nazarov approaches to complex polycycles and application to bioactive targets

Abstract

Complex carbocycles and heterocycles make up a large majority of natural product scaffolds and active pharmaceutical ingredient cores. As a result of this, developing methods to obtain such scaffolds in new, greener, and more modular ways remains an invaluable objective within the synthetic organic community. In this thesis, a number of exciting new methodologies have been developed to access some of these scaffolds, and significant progress is shown toward the application of these methodologies to access pharmaceutically-relevant cores: (1) a chemodivergent and catalytic interrupted, formal homo-Nazarov cyclization to access densely functionalized carbocycles, (2) the application of homo-Nazarov methodology toward the anticancer natural product, Propolisbenzofuran B, and (3) the application of Nazarov-like, Friedel- Crafts methodology toward the antimalarial natural product, Flinderole A. These methodological transformations are tolerant of a variety of functionalities, thus giving broad substrate scope. These syntheses seek to have modular key transformations that will allow formation of a wide variety of non-natural analogs, thus providing rapid access to a compound library useful in the study of structure-activity relationships.