Natural products inspired drug discovery

Key Words: Organic Synthesis, Organometallic Chemistry, and 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 isolation/semi-synthesis and method development/total-synthesis to access a library of diverse analogues to study structure-activity relationships (SAR). To advance our synthetic compounds, we are having a multidisciplinary collaboration with leading laboratories at the Vanderbilt University, Bridge Institute (University of Southern California), and Mount Sinai, New York with combined expertise in natural product isolation, organic synthesis, medicinal chemistry, computational chemistry and molecular pharmacology. Our current research includes novel bond forming reactions utilizing diazo synthons, biomimetic approaches, asymmetric catalysis and complex natural product total synthesis along with structural diversification to establish the SAR.

Opportunities


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.


Highschool Students:
Send the following to Arianne Hunter (Arianne.C.Hunter-1@ou.edu) : High School Transcript and a short summary describing why you desire to observe the Sharma Lab and your plans after high school. ​


Undergraduate Students:

Send the following to Dr. Sharma (isharma@ou.edu): Unofficial Undergraduate Transcript, CV​, and a short letter describing why you are interested in joining the Sharma Lab and your future career goals.

Prospective Graduate Students:

Apply to the University of Oklahoma Department of Chemistry and Biochemistry Graduate Program (http://chem.ou.edu/graduate).  Once accepted contact Dr. Sharma to set up a meeting during your visit.

Prospective Post-Doctoral Fellows:

Outstanding candidates will provide the following to Dr. Sharma: Cover letter defining your career goals and scientific interests, CV, and research summary.  All Post-Doctoral Fellows are encouraged to apply for external funding where applicable

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. 

Methods Development


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.




NATURAL PRODUCTS INSPIRED DRUG DISCOVERY