Abstract:

C-N bonds are prevalent in biologically active natural products and the installation of new C-N bonds continues to be highly desirable. Silver, gold catalyzed aziridinations of olefins were introduced in this thesis. Commercially available sulfonamides could be directly used as nitrene precursor. Silver, gold and platinum catalyzed direct C-N bond formations from C-H bonds are also developed.

MgrA is a global regulator in Staphylococcus aureus and was first discovered in 2003. A series of both in vitro and in vivo experiments were then performed and showed that the alkylation of Cys12 will dissociate MgrA from DNA and initiate the signaling pathways that turn on antibiotic resistance and influence virulence-related genes. Then we tested the validity of this high throughput screening method on library of 3000 compounds and screened 100, 000 compounds at NSRB (The National Screening Laboratory for the Regional Centers of Excellence in Biodefense and Emerging Infectious Diseases), Harvard Medical School.