Presentation description

Polycyclic heteroaromatic structural motifs are commonly found in bioactive natural products, especially in plant-produced secondary metabolites. To address limitations in known strategies to access these important motifs, the Roberts group developed a strategy to synthesize substituted pyridyl-bearing polycyclic aromatic molecules from commercially available aromatic building blocks. The blocks are assembled and transformed in three steps that can be described as tertiary amine formation ('build'), reductive cyclization ('cyclize'), and deaminative contraction ('contract') events.
To show further access to polycyclic heteroaromatics utilizing the build, cyclize, contract method, this project prepared and studied synthetic methods to generate a substrate scope of various phenanthrenes, and efforts toward two bioactive natural products, santiagonamine and (-)-artapilosine A. First, a multi-step synthesis to build substituted phenanthrenes was explored to gage functional group toleration. Synthetic knowledge leveraged will be applied towards a concise total synthesis of santiagonamine in eight total steps. Total synthesis of (-)-artapilosine A will then be explored via a [1,2]-Steven's rearrangement, double Hoffmann elimination cascade. The utilization of the build, cyclize, contract method toward phenanthrenes and complex natural products expands upon previous efforts in the Roberts laboratory, and emphasizes the broader impact of a standardized synthesis route for a collection of more complex polycyclic compounds.