OUR GENERAL APPROACH 

We are chemists who consider catalysis and synthesis as our core specialty. We view ourselves as molecular designers keen on learning more about catalysis and how it might be used to generate functional molecules of all sizes. Our approach is multidisciplinary and collaborative.

Catalytic transformations that deliver stereochemically defined fragments, necessary to the function of a molecule, regardless of its size, is one central tenet of our research. For instance, we have developed catalysts that can be used to prepare a range of otherwise difficult-to-access E– or Z-trisubstituted alkenes in high stereoisomeric purity. Another example are catalytic strategies for forming C–prenyl bonds. We have taken on the task of designing catalysts that can be used to synthesize readily alterable tetrasubstituted olefins in either stereoisomeric form – processes that are of value to drug discovery and development. We introduce new multicomponent transformations, involving one or perhaps more catalysts, capable of delivering products that are densely functionalized and are easy to modify. Mechanistic understanding is central to our studies, and with each advance we hope to enrich this foundation.

Our search is not only for a practical way of synthesizing natural products, it is also to develop strategies for securing, through networks of shared transformations, precisely re-modelled skeletal analogs. We recently put forward a catalytic multicomponent diastereo- and enantioselective process that generates a multi-functional and chemoselectively modifiable platform that can be used for concise synthesis of a rare polycyclic indole alkaloid. What is more, it facilitates access to several scaffolds that have been expanded, contracted or distorted by one-two methylene units. Together with the Hergenrother group (UIUC) we established that a doubly-expanded skeletal analog of the aforementioned weakly anti-malarial natural product – but not itself or the other exactly altered frameworks – is cytotoxic against the four cancer cell lines screened (3 mM). Molecular dynamics and AI-accelerated docking studies performed by the Liu group (Pittsburgh) and Accutar Biotech (Shanghai) helped us gain insight regarding what differentiates various scaffolds and what might be the origins of their marked proclivity for binding to various biological receptors. On an associated front, we are keen on developing efficient ways of surgically altering scaffolds of complex bioactive molecules; this would facilitate drug discovery by making it possible to explore rarely visited regions in the diversity space.

We favor investigating catalytic approaches that can expedite access to new molecules, small (bioactive) and large (functional polymers). We have had great fun designing a link-and-modify strategy that is orthogonal to CuAAC and SuFEx. By merging these three catalytic processes, one can quickly fabricate site-selectively modifiable and/or cleavable macromolecules. The strategy can be used for concise synthesis of multi-drug conjugates that also have fluorescent linkages.

What we will be searching for in five to ten years we do not know. What we can tell you is that, if you join us, you will have something to say about it.