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Professor, Organic and Medicinal Chemistry
E-mail: pcarlier@vt.edu
Office: 1103 HahnHall
Phone: 540-231-9219
e-Fax: 425-984-8099
Group Web Pages: http://www.chem.vt.edu/chem-dept/carlier/
Education
B.S. 1983 Hamilton College
Ph.D. 1988 Massachusetts Institute of Technology
Research Interests
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.
Medicinal Chemistry. Our interests in Medicinal Chemistry encompass the
design of bivalent inhibitors of mammalian acetylcholinesterase (AChE) for use
as memory-enhancing agents for early-stage Alzheimer's Disease (AD). We also use
'Click Chemistry' to design selective bivalent AChE inhibitors that will be potent
only against the enzyme of disease-transmitting insect species. This new collaborative
project is supported by a grant from the Grand Challenges in Global Health Initiative;
see our Group Web page (link above) for details. Finally, we are also synthesizing
inhibitors of BACE1 inhibitors, the enzyme responsible for amyloidogenic processing
of APP. Blood-brain barrier-penetrable BACE1 could be effective preventative/curative
therapeutic agents for AD.
Selected Publications
- "Protonated 2-methyl-1,2-epoxypropane: a challenging problem for density
functional theory" Journal of Organic Chemistry 2006,
71, 1592-1597. http://dx.doi.org/10.1021/jo052303n
- "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
- "The effect of 2,6-disubstituted-aryl groups on acyclic conformation: preference
for an antiperiplanar orientation of the geminal and vicinal hydrogens" Journal
of Organic Chemistry 2006, 71, 8835-8841. http://dx.doi.org/10.1021/jo061495z
- "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
- "The first enantioenriched, metalated nitrile possessing macroscopic configurational
stability" Organic Letters 2007, 9, 1319-1322.
http://dx.doi.org/10.1021/ol070149g
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