Associate Professor
Research Areas: Inorganic, Organic
Email: isharma@ou.edu
Office: SLSRC 2160
Education:
B.S., 2004, University of Delhi, India
M.S., 2006, Indian Institute of Technology Kharagpur, India
Ph.D., 2011, Wayne State University, Detroit, Michigan
Postdoc, 2011-2014, Memorial Sloan-Kettering Cancer Center, New York, New York
Research Keywords:
synergistic catalysis, metal carbenes, carbohydrate chemistry, nitrous oxide, drug discovery, organic synthesis, natural products, laughing gas
Natural Product-Inspired Drug Discovery
As a part of the Institute for Natural Products Applications and Research Technologies (INPART) at the University of Oklahoma (OU), the Sharma laboratory engages in the synthesis, assessment, and modification of potential therapeutic leads derived from natural products for the treatment of cancer, bacterial infections, and neurological disorders. We use two complementary approaches, targeted total synthesis and method development, to access a library of diverse analogues to study structure-activity relationships (SAR). Our focus is primarily on method development (the creation of novel chemical transformations by synthetic organic means), as well as studying the mechanisms of these new reactions. We then apply these reactions to synthesize traditionally difficult natural products through total synthesis to develop potential leads for pharmaceutical applications. Our current research includes novel bond-forming reactions utilizing Earth-abundant (Fe/Cu/Zn) metal carbenes, carbohydrate methodology, asymmetric catalysis, complex natural product total-synthesis, and structural diversification.
Method Development
Cascade Reactions: The pursuit of natural products-inspired drug discovery requires innovative approaches to novel scaffolds and the development of asymmetric methods to install complex stereocenters. We take inspiration from Mother Nature to design cascade reactions for bioactive scaffolds. We harness the ambiphilicity of Earth-abundant (Fe/Cu/Zn) metal carbenes to access spiro-heterocycles, macrocyclic scaffolds, and complex natural product cores.
Mitigating Potent Greenhouse Gases by Converting Them to Benign and Valuable Chemicals: Coupling of Methane and Nitrous Oxide: Nitrous oxide (N2O) is an important long-lived greenhouse gas (GHG), 300 times more potent than carbon dioxide. Another potent GHG is the hydrocarbon methane (CH4). In this project, we are working on the grand challenge of converting potent GHGs (N2O and CH4) and other hydrocarbons to value-added chemicals (CH3OH, alcohols) and harmless nitrogen (N2).
Development of non-addictive painkillers: Mother Nature remains the greatest inspiration for chemists designing new drug molecules. Over half of all new drugs approved by the FDA in recent years have either come directly from or have been inspired by natural products. In the Sharma Lab, we focus on the total synthesis of bioactive natural products using chiral building blocks of Mother Nature. One such example is Collybolide, a natural product isolated from the mushroom Collybia Maculata, which has analgesics properties without the side effects seen in well-known analgesics such as morphine, due to its selectivity for the kappa-opioid receptor. Upon successful completion of a total-synthesis, we pursue Structural Activity Relationship (SAR) for further optimization of lead compounds to identify potential drug candidates.
The Sharma Laboratory welcomes motivated individuals, who are willing to work as a team to pursue groundbreaking research. Students will gain outstanding training in synthetic organic chemistry applied to drug design, together with a breadth of experience in medicinal chemistry. With these skills, students will be well prepared for a career in either academia or industry.
