Wednesday, January 15, 2025
1/15/2025
PROJECT SUMMARY/ABSTRACT Chemical synthesis has long benefited public health through the discovery and preparation of pharmaceuticals, the synthesis and study of natural products, and the development of new methods for drug delivery among many others. The continuation and acceleration of such contributions requires the development of new chemical methods with a focus on increasing selectivity, efficiency, practicality and scalability, and the ability to access diverse and novel chemical space. Our laboratory focuses on the creation of new chemical methods, novel reagents, and the total synthesis of bioactive natural products. Each project focuses on filling a key gap in the literature while delivering end products that will be of immediate and practical use to the scientific community, both in the context of fundamental chemistry and translational drug discovery. This proposal combines two distinct, but thematically linked, programs that share the overarching goal of developing novel methods and reagents to enable new chemical transformations and explore new chemical space with direct applications to medicinal chemistry, natural product synthesis, and drug discovery. The first section of the proposed work will develop new methods that allow for the efficient installation of sulfonimidoyl moieties onto both simple and complex scaffolds and the use of sulfonimidoyl-containing reagents for the syntheses of otherwise difficult-to-access chemical space including pharmaceutically relevant spirocycles and natural products. Among the methods in this proposal are the synthesis and applications of sulfoximines as asymmetric molecular transfer reagents, the use of sulfoximines as chiral anion stabilizing groups for anion relay chemistry, the development of modular syntheses of sulfonimidoyl fluorides and chiral bifunctional sulfonimidoyl linchpin reagents. In the second section, diazirines are developed as unique nitrogen transfer reagents, which react with a wide variety of chemical handles including carboxylic acids, unactivated C–H bonds, alcohols, and α-positions. The products of these reactions, diaziridines, are versatile heterocycles that are easily transformed in one step to high-value amines, hydrazines, and nitrogen-containing heterocycles. This chemistry will be applied in the target-oriented synthesis of hydrazine, hydrazide, and piperazic acid- containing natural products, asymmetric transformations, and the synthesis of novel probes for proteomics. The chemistry developed throughout this proposal will enhance the discovery and development of new small molecule therapeutics across disease states in both academic and industry.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).