PROJECT SUMMARY/ABSTRACT Nitrogen-containing heterocycles are of considerable interest in medicinal chemistry, often responsible for key non-bonding interactions that contribute to a molecule’s overall pharmacological activity. The zoanthamine alkaloids are an example of natural products that display a variety of biological activities mostly attributed to the heterocyclic portion of their structures. Notable examples include norzoanthamine with potent anti-osteoporotic properties, and zoanthenol, which is a selective collagen receptor antagonist for inhibiting platelet aggregation. The difficulties in synthesizing these architecturally complex alkaloids are apparent in the relative dearth of total syntheses: since their initial isolation in 1984, only two total syntheses have been reported for norzoanthamine and one for zoanthenol, all of which are considerably lengthy (40+ steps). This project proposes a total synthesis for zoanthenol using an aza-Heck/C–C cleavage/cross coupling cascade process to provide an overall convergent approach to the natural product. The proposed methodology builds upon precedent established by the Sarpong group in utilizing C–C cleavage/cross coupling as a strategy for rapidly generating complexity from simple, hydroxylated pinenes. The addition of an aza-Heck reaction to this overall sequence should provide an avenue for introducing N- heterocycles onto natural product-like structures. Specific Aim I outlines key considerations for introducing an aza-Heck reaction to the C–C cleavage/cross coupling sequence, and identifying O-acyl oximes as a versatile precursor for N-heterocycle formation using transition metal catalysis. Specific Aim II then details a total synthesis of the natural product zoanthenol using the cascade process developed in Specific Aim I as the key coupling step. This approach should also enable preparations of related derivatives for potential structure-activity relationship (SAR) studies to fully elucidate the unique bioactivities displayed by the zoanthamine alkaloids.