Friday, March 14, 2025
3/14/2025
PROJECT SUMMARY/ABSTRACT Natural products have long held societal value as folk medicines, and even in this modern era, many FDA-approved drugs are still being derived from terpenes and alkaloids found in nature. Biomedical research has also benefited from natural products, as previously unknown mechanisms of action have been discovered while studying the unique biochemical pathways that these compounds undergo in the human body. Furthermore, endeavors in the total synthesis of these architecturally diverse compounds have continuously provided chemists with challenges, which in turn have led to the establishment of research programs in both academic and industrial environments. Ever since its inception, our laboratory has been pursuing, and has succeeded in, the total synthesis of iconic natural products in both the terpene and alkaloid families. These syntheses have identified gaps in the chemical literature, which we have subsequently addressed. The products of this research program—new synthetic strategies, unprecedented transformations and novel reagents—have in turn enabled the synthesis of even more natural products and pharmaceutically relevant motifs, thus completing a catalytic cycle of discovery. We seek to replicate this success with the current proposal: the described projects will target complex natural products to identify shortcomings in chemical methodology, while simultaneously devising methods of widespread interest, followed by the assessment of their practicality in the synthesis of complex molecules. For the next five years our laboratory will generate chemical knowledge that transcends the original objective of natural product synthesis. We will focus on efficiently synthesize complex natural products aiming for ideality. We will also develop of useful methods for synthesis and medicinal chemistry. The resulting procedures will be utilized in the construction of complex pharmaceutical motifs, which will serve to expand chemical space and accelerate discovery in drug discovery. Notably, we have already established numerous collaborations to study the biological properties of the products that will be synthesized, to validate and field-test new methods, and to commercialize reagents for widespread adoption in both academic and industrial settings. Lastly, we will focus on strategic applications and development of synthetic organic electrochemical methods, wherein the development of oxidative mediators for C-H functionalization, desaturation of carbonyls, and reductive cross-couplings are presented.
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