Chemistry Department

Thomas E. Smith

Organic Chemist

My research interests lie within the broad category of organic synthesis. Synthesis plays a central role in organic chemistry, and advances in this area impact upon a wide variety of investigations at the molecular level including those relating to biology, pharmacology, materials science, and reaction mechanism. My current focus is on the development of new methods for increased efficiency in organic synthesis and their application to molecules of biological significance. Organotransition metal systems, in particular, are utilized extensively in this endeavor due to their versatile selectivity profiles and catalytic possibilities.

In one project, we are exploring a general asymmetric synthesis of the kavalactones. These natural products are the biologically active constituents of kava root, which has been used ceremonially in South Pacific cultures for centuries and has attracted recent attention in the Western world as an “alternative” anti-anxiety remedy. We are also investigating the asymmetric total synthesis of the myxobacterial antibiotic, jerangolid D, wherein both the δ-lactone and cis-dihydropyran rings are assembled using an extension of the methods developed for the kavalactone syntheses. In another project we are probing the scope and limitations of a new method for the thermodynamic deprotonation of readily available heterocyclic systems, thus allowing for the assembly of more complex molecular architectures from simple building blocks.

This technique was successfully applied to a novel synthesis of the antiviral marine natural product, hennoxazole A.  Studies on other complex pyran-based anticancer natural products such as enigmazole A, tedanolide C, and aplyronine are currently underway and are supported by grants from the National Cancer Institute and the Camille & Henry Dreyfus Foundation.