Title: Synthetic Explorations and Expeditions in the Resveratrol Class
Description: Research interest in resveratrol, a structurally simple plant metabolite, has increased exponentially in the last two decades. Since its isolation from red wine it has been hypothesized that this structure may account for the so-called "French Paradox," the notion that despite a diet high in cholesterol one can enjoy a relatively healthy lifestyle through moderate red wine consumption. The biological implications of these claims are presented. Concurrently isolated along with resveratrol are hundreds of oligomeric natural products with structures varying in both size and complexity. The discovery, biosynthesis, and previous synthetic studies towards these natural products will be presented to frame the landscape of the field and its current limitations. Heimiol A and hopeahainol D are oxidized, resveratrol dimers characterized by their [3.2.2] bicyclic framework with a bridging ether. The total synthesis of these epimeric natural products was accomplished by the development of a halolactonization/Friedel-Crafts cascade to construct the bicyclic core.

Subsequently, a steric bias inherent in the molecule was doubly exploited to synthesize both targets with complete selectivity. During the course of these studies, a number of unexpected results were observed which have led, or may potentially lead, to alternate courses of investigation. These results and their potential impact are also presented. Well-established in the synthetic community are the challenges associated with medium-sized ring construction. Of particularly rarity are solutions addressing all carbon 9-membered rings. Seeing this motif present in a subclass of resveratrol oligomers, we sought to investigate this challenging substructure. Our efforts to achieve this end are detailed with the successful development of two unique methods to construct the requisite 9-membered ring core. One succeeded in the first ever reported 9-exo-dig cyclization while the other enabled the robust total synthesis of caraphenol A. [1.1.1]-orthocyclophanes have received considerable attention of late due to their numerous applications in the field of supramolecular chemistry.

Owing to their rigid, bowl shape, these scaffolds are capable of engaging in numerous guest-host complexes. The previous syntheses of [1.1.1]-orthocyclophanes as well as a survey of their applications are presented. In the course of our synthetic studies toward caraphenol A, we accomplished the synthesis of a unique [1.1.1]-orthocyclophane as well as the successful oxidation to its corresponding triketone. These results are presented noting that despite many efforts, no other [1.1.1]-orthocyclophane triketone has ever been successfully synthesized with our work constituting the first such report.