Natural Products Diversification/Total Synthesis
Is Nature still the best chemist to provide unique structural scaffolds for drug discovery? Well, the answer in many ways is still yes, as natural products have proven to be an excellent source of clinical agents and have provided the basis for countless biologically important molecules in drug discovery. However, natural products are not drugs and therefore have to be structurally modified to identify leads compounds for drug development. We are engaged in a two-pronged approach; first diversifying readily available bioactive natural products, and second developing an efficient synthetic route to natural product scaffolds that are not easily available either by isolation or total synthesis. The resulted natural products-inspired libraries are then screened for a wide range of promising new therapeutic targets in collaborations with other laboratories or through the NIMH-Psychoactive Drug Screening program. Target molecules include alkaloids, spiro heterocycles, macrocyles and terpenoids.
The pursuit of natural products-inspired drug discovery requires innovative approaches to novel scaffolds, and development of asymmetric methods to install complex stereocenters. For natural scaffolds, we take inspiration from the Mother Nature to design our synthetic route mimicking the biosynthesis. In addition, we are focusing on the development of novel methods utilizing ambiphilicity of diazo synthons through synergistic metal-catalysis to access spiro-heterocycles, macrocyclic scaffolds and core structure of terpenoids.
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 and chemical biology. With these skill-sets, students will be prepared well for a career in either academia or industry.