TITLE New Methods for the Synthesis and Study of Bioactive Nitrogen-Containing Molecules PROJECT SUMMARY/ABSTRACT The ubiquitous presence of nitrogen atom in small-molecule probes and drugs highlights the significance of nitrogen-containing molecules in biomedical research and drug discovery. Rapid and efficient synthesis of structurally diverse nitrogen-containing skeletons is of the utmost importance, as is the ability to understand their biology, pharmacology and potential as chemical probes and drug candidates. Thus, developing new methods for the synthesis and study of novel nitrogen-containing molecules is significant and necessary to advance our understanding of human disease and the discovery of new therapies. The broad availability of drugs is directly dependent on the existence of cost-efficient methods that can reliably build such novel molecular structures and uncover their biological activity and therapeutic promise. The long-term goal of our research is to establish a chemical platform for designing and developing novel small-molecule probes and tools to advance the understanding and treatment of human disease. The objective of this proposal is to develop new methods that offer rapid and efficient access to valuable nitrogen-containing building blocks for the synthesis and study of relevant biologically active molecules and pharmaceuticals. Toward this, the proposed strategy innovatively exploits the unique and diverse reactivity of heteroatom-nitrogen bonds?? readily available yet traditionally underutilized nitrogen precursors??to design powerful C?N bond formation reactions that are new and different but complementary to existing methods, through the following three specific aims:
aim 1) Direct arene C?H amination and amidation via H?Zn exchange and electrophilic amino trapping;
aim 2) selective difunctionalization of alkenes by electrophilic amino activation;
and aim 3) new methods for constructing diverse azaheterocycles with facile installation of imaging tags. Successful implementation of these studies will greatly facilitate the synthesis and study of a wide range of nitrogen- containing molecules that are difficult or impossible to access with current technologies. With the importance of nitrogen-containing molecules in biomedical research, new methods developed in this application and the products generated from these transformations will have broad impact on developing novel chemical probes and lead compounds for the understanding and treatment of disease.
The ubiquitous presence of nitrogen atom in small-molecule probes and drugs highlights the significance of nitrogen-containing molecules in biomedical research and drug discovery. This project will develop new methods that exploits the unique reactivity of heteroatom-nitrogen bonds to design powerful C?N bond formation reactions to advance the synthesis and study of novel nitrogen-containing molecules. Such ability to prepare structurally diverse nitrogen-containing skeletons in the most rapid and efficient way possible is of the utmost importance, as is the ability to understand their biology, pharmacology and potential as chemical probes and drug candidates.
|Liu, Chuan; Wang, Qiu (2018) Alkenylation of C(sp3 )-H Bonds by Zincation/Copper-Catalyzed Cross-Coupling with Iodonium Salts. Angew Chem Int Ed Engl 57:4727-4731|
|Shen, Kun; Wang, Qiu (2017) Copper-catalyzed aminoalkynylation of alkenes with hypervalent iodine reagents. Chem Sci 8:8265-8270|
|Shen, Kun; Wang, Qiu (2017) Copper-Catalyzed Alkene Aminoazidation as a Rapid Entry to 1,2-Diamines and Installation of an Azide Reporter onto Azahetereocycles. J Am Chem Soc 139:13110-13116|
|Ortiz Jr, Gerardo X; Hemric, Brett N; Wang, Qiu (2017) Direct and Selective 3-Amidation of Indoles Using Electrophilic N-[(Benzenesulfonyl)oxy]amides. Org Lett 19:1314-1317|
|Hendrick, Charles E; Bitting, Katie J; Cho, Seoyoung et al. (2017) Site-Selective Copper-Catalyzed Amination and Azidation of Arenes and Heteroarenes via Deprotonative Zincation. J Am Chem Soc 139:11622-11628|