Development of Functionalized N-Heterocyclic Scaffolds for Application in the Synthesis of Amphibian Alkaloids

Natural products continue to be a source of lead compounds that can be developed for use as medicinal therapeutic agents or as probes for studying biological functions. Due to difficulties in isolation and low yields, natural products are often scarce, thus full characterization and evaluation of novel compounds cannot be achieved. Synthesis of natural products results in useful quantities of these scarce materials to facilitate structural and biological evaluation. Hundreds of alkaloid compounds have been isolated from poison dart frogs. These compounds are grouped according to structural classes, thus the identification of molecular scaffolds based on common core structures found in these classes of compounds would provide a basis for the rapid construction of target compounds for structural and biological evaluation. With a strategically functionalized scaffold, substituents and stereochemical variability can be introduced along the synthetic route. This work utilizes readily available amino acids that will be derivatized and cyclized to form various functionalized scaffolds. These structural scaffolds will be utilized in the synthesis of amphibian alkaloid targets for structural and biological evaluation