MY Ngai Group
Chemistry-Biology-Imaging
The Ngai lab focuses on (i) developing novel and practical synthetic methodologies to address unmet challenges in organic synthesis and medicinal chemistry, and (ii) identifying and developing new radiotracers for Positron Emission Tomography (PET) imaging to elucidate disease mechanisms, identify drug targets, assess treatment efficacy, and accelerate drug discovery and development. Our research programs are multidisciplinary, covering organic and organometallic chemistry, photochemistry, radiochemistry, and biomedical imaging.
C–C and C–heteroatom bond forming reactions are vital to a broad range of areas including fine chemicals, pharmaceuticals, and materials. Therefore, the development of new catalysts for general, efficient, practical, and stereoselective C–C and C–heteroatom bond forming reactions stands as a critical goal in chemical synthesis. Although a considerable number of existing synthetic methods aim toward such goals, processes that streamline organic synthesis, minimize byproduct waste, and maximize atom economy are highly desired. Enzymes catalyze numerous chemical transformations under ambient conditions. Such mild reaction conditions are made possible through multiple cooperative activations of substrates in enzyme active sites. Drawing inspiration from such activation modes, one of our research programs is directed toward designing and synthesizing easily assembled multifunctional catalysts to enable direct regio-, chemo-, diastereo-, and enantioselective conversion of C–H and/or C–OH to C–C and C–heteroatom with H2 or H2O as the only byproduct. In specific, we focus upon direct stereospecific alcohol activation through the use of bifunctional catalysts, which comprises a Lewis acidic component and a nucleophilic component. Our goal is to facilitate the direct catalytic conversion of chirally pure alcohols to various chiral C–heteroatom bonds with retention of stereochemistry and water as the only byproduct.
Bio-Inspired Catalysis for Organic Synthesis
Visible-Light Photoredox Catalysis
Development of greener and milder reaction conditions for both known and new transformations poses a continuous challenge for synthetic organic chemists. is very appealing. Although the first use of light as a renewable energy source for chemical reactions occurred more than a century ago, only recently has there been a surge of interest in applying visible light photoredox catalysis to organic transformations. This mode of catalysis relies on the general property that a photoredox catalyst has enhanced reducing and oxidizing power in its excited state as compared to its ground state. Our goal is to apply this general property to transition metal catalysis to enable new modes of chemical reactivity and unlock the potential of photoredox catalysis in organic chemistry. More specifically, we will merge photoredox catalysis with transition metal-mediated dearomatization reactions to enable catalytic dearomatization reactions and apply these transformations to the total synthesis of various cyclic natural products.
Positron Emission Tomography (PET) Tracers for the Study of Human Diseases
Chronic inflammation is a common feature of numerous severe human diseases, including cancer, diabetes, Alzheimer's disease, and various neurological disorders. Understanding the mechanisms that govern inflammation in tissues and diseases should provide new strategies for therapeutic intervention, and accelerate drug discovery and development. Glycogen synthase kinase 3 (GSK-3) is a key protein kinase regulating numerous cellular functions, which has been implicated in governing inflammatory processes. Our research program aims at developing GSK-3b imaging probes for positron emission tomography (PET), a non-invasive in vivo imaging technology using radioactive tracers to visualize, characterize, and quantify physiological processes at the cellular level. This in vivo imaging technology will enable researchers to directly study GSK-3b. Our ultimate goal is to translate this technology to human PET imaging to elucidate disease mechanisms, identify drug targets, assess treatment efficacy, and accelerate drug discovery and development.