个人简介

BS Hamilton College, 1983 PhD Massachusetts Institute of Technology, 1988 Scientist, Polaroid Corporation, 1988-1991 Assistant to Associate Professor of Chemistry, Hong Kong University of Science of Technology, 1991-2000 Associate Professor of Chemistry, Virginia Tech, 2000-2007 Professor of Chemistry, Virginia Tech, 2007-present

研究领域

Organic/Medicinal

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 have used 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 is supported by the National Institutes of Health and the International Vector Control Consortium (Liverpool, UK); previous support was gratefully received from the Grand Challenges in Global Health Initiative (Gates Foundation/FNIH); AstraZeneca; 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 and organomagnesium reagents are ubiquitous in organic synthesis. We are interested in developing new stereoselective reactions of group 1 and 2 organometallics and enolates, and in using computation and kinetic methods spectroscopy to determine structures and reaction pathways. Of particular interest to us are benzodiazepine enolates and metalated nitriles. A key feature of these intermediates is stereolability; thus the challenge is to generate them in enantiopure form and react them before they racemize. Our work in this area is supported by the National Science Foundation. Previous support was gratefully received from the Petroleum Research Fund of the ACS, and the Jeffress Memorial Trust

近期论文

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"Stereochemical inversion of a cyano-stabilized Grignard reagent: remarkable effects of the ethereal solvent structure and concentration" Ming Gao, Neeraj N. Patwardhan, and Paul R. Carlier*, Journal of the American Chemical Society 2013, 135, 14390-14400. DOI: 10.1021/ja407348s "Aryl methylcarbamates: potency and selectivity towards wild-type and carbamate-insensitive (G119S) Anopheles gambiae acetylcholinesterase, and toxicity to G3 Strain An. gambiae", Dawn M. Wong, Jianyong Li, Polo C.H. Lam, Joshua A. Hartsel, James M. Mutunga, Maxim Totrov, Jeffrey R. Bloomquist, and Paul R. Carlier*, Chemico-Biological Interactions, 2013, 203, 313-318. PMID: 22989775. DOI: 10.1016/j.cbi.2012.09.001 "Select small core structure carbamates exhibit high contact toxicity to "carbamate-resistant" strain malaria mosquitoes, Anopheles gambiae (Akron)", PLoS ONE 2012, 7, e46712. DOI: http://dx.plos.org/10.1371/journal.pone.0046712 "Re-engineering aryl carbamates to confer high selectivity for inhibition of Anopheles gambiae vs human acetylcholinesterase" Bioorganic & Medicinal Chemistry Letters 2012, 22, 4593-4598. DOI: 10.1016/j.bmcl.2012.05.103 "Access to ‘Friedel-Crafts-restricted’ tert-alkyl aromatics by activation/methylation of tertiary benzylic alcohols" Journal of Organic Chemistry 2012, 77, 3127-3133. DOI: 10.1021/jo202371c