B.S. 1983 Hamilton College
Ph.D. 1988 Massachusetts Institute of Technology

Medicinal Chemistry. Our interests in Medicinal Chemistry encompass three areas. First, we have prepared species-selective inhibitors of acetylcholinesterase (AChE) targeting the malaria mosquito (Anopheles gambiae). Such compounds could be deployed on insecticide treated nets to prevent malaria transmission in sub-Saharan Africa. Second, we use click-chemistry based discovery methods to identify BACE1 (beta-secretase) inhibitors; such compounds could be to useful to prevent Alzheimer's disease. Finally, we have prepared novel triple reuptake inhibitors to treat SSRI-resistant depression. Our work in these areas has been supported by the Grand Challenges in Global Health Initiative (Gates/Foundation, Foundation for the National Institutes of Health); the Alzheimers' and Related Disease Research Award Fund; the Georgetown-Virginia Tech Consortium for Drug Discovery; and the Research Division of Virginia Tech.

Enantioselective Synthetic Methods. Organolithium reagents are ubiquitous in organic synthesis. We are interested in developing new stereoselective reactions of organolithium compounds and enolates, and in using computation and multinuclear NMR spectroscopy to determine structures and reaction pathways. Recently we have developed an enantioselective alkylation route to a new class of (so-called "quaternary") benzodiazepines. A key feature of this work is the intermediacy of transiently non-racemic ("dynamically chiral") intermediates. Our work in this area is supported by the National Science Foundation, the Petroleum Research Fund of the ACS, and the Jeffress Memorial Trust.

1. "Towards a Species-Selective Acetylcholinesterase Inhibitor to Control the Mosquito Vector of Malaria, Anopheles gambiae" Chemico-Biological Interactions 2008, 175, 368-375. http://dx.doi.org/10.1016/j.cbi.2008.04.037
2. "Antidepressant-like pharmacological profile of a novel triple re-uptake inhibitor, PRC200" Journal of Pharmacology and Experimental Therapeutics 2008, in press. http://dx.doi:10.1124/jpet.108.143610
3. "The first enantioenriched, metalated nitrile possessing macroscopic configurational stability" Organic Letters 2007, 9, 1319-1322. http://dx.doi.org/10.1021/ol070149g
4. "Complexes of Alkylene-Linked Tacrine Dimers with Torpedo californica Acetylcholinesterase: Binding of bis(5)-Tacrine Produces a Dramatic Rearrangement in the Active-Site Gorge Journal of Medicinal Chemistry 2006, 49, 5491-5500 (Joel Sussman, corresponding author). http://dx.doi.org/10.1021/jm060164b
5. "Enantioselective Synthesis of Diversely Substituted Quaternary 1,4-Benzodiazepine-2-ones and 1,4-Benzodiazepin-2-,5-diones" Journal of the American Chemical Society, J. Am. Chem. Soc. 2006, 128, 15215-15220. http://dx.doi.org/10.1021/ja0640142