Natural products with complex molecular architectures often serve as valuable leads for therapeutic agents. This thesis focuses on the synthesis and characterization of biologically significant natural products, with an emphasis on the pyrrolopiperazinone scaffold—a structural motif frequently found in bioactive compounds. Chapter 1 provides a comprehensive review of the pyrrolopiperazinone scaffold, highlighting its occurrence in natural products, synthetic methodologies, and biological significance. This foundational overview informs the subsequent research efforts. Chapter 2 describes efforts toward the synthesis of Aspidazide A, a natural product with a distinct framework. Although the total synthesis was not completed, significant progress was made, including the successful construction of the phenyl pyrrolopiperazinone scaffold in six steps with an overall yield of 11%. Efforts toward electrochemical N-N oxidative coupling are also discussed. Chapter 3 focuses on the efforts toward the total syntheses of Aspidostomides D, E, and F, showcasing the successful construction of the indole pyrrolopiperazinone scaffold in eight steps with a 49% yield. Progress was made in late-stage bromination and α-methoxylation, addressing challenges in regioselectivity and functional group compatibility to produce advanced intermediates. Future directions highlight the potential to further decorate phenyl and indole pyrrolopiperazinone scaffolds via regioselective bromination or enantioselective α-methoxylation, enabling the synthesis of novel analogues. These derivatives offer promising opportunities for exploration in medicinal chemistry, paving the way for the discovery of new therapeutic agents.
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