Synthetic organic chemistry has matured as a field considerably over the last 100 years, and it is now possible to envision applying the tools of this discipline to address the construction of any number of extremely complex targets – large molecules presenting complex architectures containing many rings, functional groups, and stereocenters, for example. However, one of the central challenges facing modern organic chemistry is the development of new strategies and techniques to rapidly build up molecular complexity. Novel and direct transformations can maximize the complexity generation of each synthetic step while minimizing waste, which increases the overall efficiency of a synthesis. The research envisioned in the Osberger Group broadly aims to address this challenge through the development and application of modern methods in organic synthesis and catalysis to achieve the construction of complex, biologically active molecules in efficient synthetic sequences, with the ultimate aim of collaboratively exploring their function.
Novel Anti-Leishmania Compounds. Leishmaniasis, a group of diseases caused by parasites of the genus Leishmania, represents a significant global health concern, with cases reported in at least 88 countries worldwide placing over 350 million people at risk of infection. An estimated 12 million people are currently suffering from this disease and over 2 million new cases are identified every year leading to 60,000 deaths annually. Despite this urgent threat to global health, the main chemotherapeutic agents currently deployed for treatment of leishmania have been used for over 60 years and remain essentially unchanged despite their declining efficacy, while development of new treatments has lagged. Given these factors, there is a clear and pressing need for continued investigation into sources of novel antileishmanial compounds. We are interested in synthesizing derivatives of the bisbenzylisoquinoline (BBIQ) macrocyclic natural products (like Isotetrandrine) and Acivicin, molecules containing the interesting tetrahydroisoquinoline and dihydroisoxazole heterocycles, respectively. Ultimately, our goal is to investigate the potential of these molecules as treatments against Leishmaniasis.
Synthetic Reaction Methodology: Catalysis. The development of new catalytic reactions is central to modern synthetic chemistry and enables the construction of entirely new chemical entities, while improving the efficiency of compound preparation overall. We are interested in exploring and developing catalysts in the field of C-H functionalization, where a C-H bond is directly converted to a C-C, C-O, C-N, or other bond by action of a transition metal catalyst. We will explore the possibility of creating C-C bonds in a stereoselective manner using Pd-based catalysts. Additionally, we are interested in exploring small molecule catalysts for the Beckmann Rearrangement, an industrially important reaction that converts an oxime to an amide. The Beckmann Rearrangement has the potential to be useful for the synthesis of lactams, which are amide-containing ring structures that are present in many natural products and pharmaceuticals.