Thursday, November 21, 2024
11/21/2024
Project Summary In accord with the NIH mission statement, the proposed work will seek to gain “knowledge to enhance health, lengthen life, and reduce the burdens of illness and disability.” Among the most often prescribed brand- named drugs, more than 60% contain heterocyclic rings. Organic synthetic methods leading to functionalized N-heterocycles are valuable in the development of new and cost-effective medicines. This proposal describes research developing innovative methods for preparing functionalized N-heterocycles. As a focus of the proposed research, conjugate addition reactions will be explored - specifically those involving alkenyl- substituted N-heteroaromatic compounds. These new reactions will prepare functionalized heterocycles by the utilization of new types of nucleophiles, substrates, electrophilic activation, and reaction cascades. The work itself will invent new synthetic methods, however much of the research will also involve target-driven organic synthesis. Thus, pharmaceutical intermediates, drug substructures, and clinically useful drugs will be synthesized with the new chemistry. Many of the projects are based on preliminary studies, including our own published/unpublished work and the published work of others. We also intend to develop several new methods for preparing single enantiomer N-heterocyclic compounds. Given the importance of N-heterocycles in commercial pharmaceuticals and the continuing need for single enantiomer drugs, it is suggested that this is a particularly important aspect of the proposed work. The proposed work will be ideal training for undergraduate and graduate students in organic chemistry. They will develop skills in executing multi-step organic synthesis, especially in the preparations of biologically active products. Some of the students will also gain expertise in asymmetric synthesis and computations methods. All of the research students will be mentored in their presentation skills, both oral and written, and they will be encouraged to present their work at scientific meetings. These aspects of the research will fulfill the goal of the NIH “to strengthen our nation’s research capacity, broaden our research base, and inspire a passion for science in current and future generations of researchers.”
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