CAREER: Stereoselective Carbene Cascade Cyclizations

点击翻译按钮获取中文摘要

With this CAREER Award, the Chemical Synthesis Program of the Division of Chemistry is supporting the research of Professor Indrajeet Sharma at the University of Oklahoma. Professor Sharma is developing new synthetic methods for the construction of the types of bioactive molecules that are frequently used in efforts to identify drug leads for the treatment of cancer, infectious diseases, and neurological disorders. The research described seeks to develop cascade reactions that take advantage of a sequence of carefully timed steps to convert inexpensive, readily accessible compounds into higher-value, complex molecules. To accomplish this, the Sharma group is developing new reaction protocols that involve the use of more than one metal at a time. This research is expected to have broad application in the fields of chemical synthesis, medicinal chemistry, and therapeutics development. Professor Sharma is also pioneering an outreach program, the Synergistic Catalytic Cycle for Education Excellence (SC2E2), that provides crucial hands-on science education for underrepresented students in the State of Oklahoma. The SC2E2 program encourages an increase in school enrollment, retention, and graduation rates of highly qualified STEM students from low-income areas in the State of Oklahoma.Despite dramatic advances in natural product-inspired drug discovery, many bioactive scaffolds (spirocycles, medium-sized rings, and terpene furanolactones) remain underexploited in drug discovery screening owing to the challenges associated with their synthesis. To address these challenges, this research program will utilize metal carbene cascade reactions for the efficient scalable synthesis of such scaffolds. More specifically, this research focuses on the use of diazo-derived metal-carbenes that are ambiphilic in nature in combination with a second metal catalyst to trigger sequential reactions with a nucleophile and an electrophile. The ensuing cascade reactions lead to the rapid generation of molecular complexity. A comprehensive educational plan is also integrated with the research goals to provide an inclusive scientific education experience for students from underrepresented groups in the State of Oklahoma. The proposed SC2E2 program is inspired from developed research involving synergistic catalysis, in which two or more catalysts act simultaneously to improve the efficiency of existing transformations. Likewise, SC2E2 builds upon inclusive educational practices in a cyclic process by providing students training, guidance and leadership opportunities, which ultimately help cultivate a new generation of diverse STEM professionals.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.