PhD
Distinguished Professor, Center for Integrative Chemical Biology and Drug Discovery
Professor, UNC Department of Chemistry
Eshelman School of Pharmacy
UNC-Chapel Hill
Molecular Therapeutics
Area of Interest
The Aubé laboratory pursues an agenda that mixes innovation in basic chemistry (methodology, total synthesis, and physical organic chemistry) with a commitment to chemical biology and drug discovery.
Our interests in organic chemistry encompass organic synthesis methodology with a dash of natural product total synthesis, especially focusing on alkaloids. One of our signature accomplishments was the discovery of the intramolecular Schmidt reaction of alkyl azides, which has proved of enduring practical utility and evolving theoretical interest. We have devised variations of the process, including intermolecular versions of simple alkyl, “in situ tethering” of hydroxyalkyl azides, an asymmetric version, and domino variations.
In addition to our program in azide chemistry, we have maintained a sustained interest in other aspects of heterocyclic synthesis, with a strong emphasis on stereochemistry and mechanistic detail. Some highlights include an in-depth stereochemical analysis of stereochemistry of the oxaziridine to lactam rearrangement reaction, and study of single-electron transfer reactions of oxaziridines to generate nitrogen radicals. We seek to uncover new principles of physical organic chemistry through the in-depth study of our reactions.
Although not a major effort of our group, we have regularly pursued alkaloid synthesis in our project portfolio to test our chemistry in a challenging environment or to explore questions of reaction control. Targets have included yohimbine, indolizidine 223A, and stenine.
We also leverage our interest in making functional molecules to inform projects in chemical biology and medicinal chemistry, often in close collaboration with leading scientists with complementary expertise. Since many programs in modern drug discovery begin with screening, we have sought to design and construct small molecule libraries that provide alternatives to store-bought compound collections. Specific interests in this area include natural-product inspired libraries, collections that optimize stereochemical diversity in drug-like molecules, and new approaches to providing fragments for screening approaches informed by structural biology.
Our current portfolio of medicinal chemistry projects include the development of probe compounds and drug candidates for neuroscience applications, mostly focusing on agents designed to shed light on the intracellular signaling pathways at the kappa opioid receptor, and the evaluation of these pathways as targets of new drugs for addiction and depression (with Laura Bohn and Thomas Prisinzano). Several projects are devoted to the development of novel chemotherapeutic agents, such as:
- Androgen biosynthesis inhibitors (with Emily Scott)
- Inhibitors of protein–RNA interactions (with Liang Xu and Kristi Neufeld)
- Several approaches to arrest tumor metastasis in a targeted fashion.
Finally, we collaborate with a consortium led by Carl Nathan of the Weill–Cornell Medical College dedicated to the discovery of new cures for Mycobacterium tuberculosis.
