Department of Chemistry

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Dennis Curran

Distinguished Service Professor of Chemistry and Bayer Professor

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Chevron Science Center
219 Parkman Avenue

Pittsburgh, PA 15260
412-624-8240

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Research Overview

Natural Products Total Synthesis, New Synthetic Methods, and Stereochemistry

The field of synthesis is currently undergoing exciting changes as new methods emerge to make more complex compounds more quickly and efficiently. From the standpoint of efficiency, cascade reactions are valuable, and are highly prized if they have broad scope and occur under mild conditions. A major focus of our research is synthetic radical chemistry, and radical reactions are ideally suited for executing sophisticated cascade processes that build complex products from simple starting materials. For example, our recently developed combinatorial synthesis of the camptothecin class of anti-tumor agents features a cascade radical reaction of an isonitrile in the key final step. Using this route, we have made about 100 known and new camptothecin analogs, and some of the new ones are excellent pre-clinical candidates for the treatment of refractory solid tumors.

In addition to developing new classes of cascade radical reactions directed towards other natural products, our work in the radical field focuses on new methods of stereoselection. Our recent introduction of methods for "stereoselection at the steady state" has open a new branch of kinetic stereocontrol. We have shown for the first time that it is possible to achieve stereoselection, solely by orchestrating reaction pathways and without any traditional stereoselective step such as a face or group selective reaction. In another project, we use traditional strategies for stereocontrol, but implement these with new classes of molecules like axially chiral amides.

Combinatorial Synthesis of Camptothecins by Radical Cascade

A second major focus of our group is the new field of "fluorous chemistry." Fluorous chemistry uses highly fluorinated reagents, catalysts, reactants, or substrates and capitalizes on the ready separation of fluorous reaction components like the tin hydride (C6F13CH2CH2)3SnH from standard organic (and inorganic) molecules. The new techniques are part of an emerging trend for using synthesis design to dictate separation, and we call these "strategy level separations." Fluorous reactions are highly suited for combinatorial chemistry and parallel synthesis. For example, in our Center for Combinatorial Chemistry, we use state-of-the-art technology to conduct parallel reactions, and then separate these by filtration over fluorous reverse phase silica gel. We are also developing several innovative new techniques including fluorous mixture synthesis and fluorous triphasic reactions.

Purification of reaction mixtures by solid-liquid extraction over fluorous phase silica gel

Awards

  • 2011- ISI Highly Cited Researcher since 2000; Visiting Professor, Osaka Prefecture University, Japan, 2011
  • Visiting Professor at Westfälische Wilhelms-Universität, 2011
  • 2010 - Honorary Doctorate, University of Paris; Chaire d’excellence, Agence National de la Recherche (ANR), France;
  • 2009 - Fellow of the American Chemical Society; Provost’s Award for Excellence in Mentoring, University of Pittsburgh
  • 2008 - American Chemical Society Award for Creative Work in Fluorine Chemistry
  • 2007 - University of Pittsburgh Innovator Award; Harry and Carol Mosher Award, Santa Clara Valley Section, ACS
  • 2006 - The Pittsburgh Award, Pittsburgh Section, ACS Morley Medal, Cleveland Section, ACS
  • 2003 - Pittsburgh Magazine, Innovator of the Year Award
  • 1999 - Chancellor’s Distinguished Research Award
  • 1998 - Janssen Prize for Creativity in Organic Synthesis
  • 1988 -American Chemical Society Cope Scholar Award

Publications

“Borenium Ion Catalyzed Hydroboration of Alkenes with N-heterocyclic Carbene-Boranes,” A. Prokofjevs, A. Boussonnière, L. Li, H. Bonin, E. Lacôte, D. P. Curran, E. Vedejs, E., J. Am. Chem. Soc., Vol. 134, 2012, Pages 12281-12288
“Minimal Fluorous Tagging Strategy that Enables the Synthesis of the Complete Stereoisomer Library of SCH725674 Macrolactones,” J. D. Moretti, X. Wang, D. P. Curran, J. Am. Chem. Soc., Vol. 134, 2012, Pages 7963-7970
“A Short Total Synthesis of (±)-Epimeloscine and (±)-Meloscine Enabled by a Cascade Radical Annulation of a Divinylcyclopropane,” H. Zhang and D. P. Curran, J. Am. Chem. Soc., Vol. 133, 2011, Pages 10376-10378
“Electron Paramagnetic Resonance and Computational Studies of Radicals Derived from Boron-Substituted N-Heterocyclic Carbene Boranes,” J. C. Walton, M. Makhlouf Brahmi, J. Monot, L. Fensterbank, M. Malacria, D. P. Curran, E. Lacôte, J. Am. Chem. Soc., Vol. 133, 2011, Pages 10312-10321
“Organocatalysis and C–H Activation Meet Radical- and Electron-Transfer Reactions,” A. Studer, D. P. Curran, Angew. Chem. Int. Ed., Vol. 133, 2010, Pages 115-122
“Radical and Heck Cyclizations of Diastereomeric o-Haloanilide Atropisomers,” D. B Guthrie, S. J. Geib, D. P. Curran, J. Am. Chem. Soc., Vol. 133, 2011, Pages 115-122
“Substitution Reactions of Tetracoordinate Boron: Synthesis of N-Heterocyclic Carbene Boranes with Boron–Heteroatom Bonds,” A. Solovyev, Q. Chu, S. J. Geib, L. Fensterbank, M. Malacria, E. Lacôte, D. P. Curran, J. Am. Chem. Soc., Vol. 132, 2010, Pages 15072-15080
“Memory of Axial Chirality in Aryl Radical Phosphanylations,” A. Bruch, A. Ambrosius, R. Fröhlich, A. Studer, D. B. Guthrie, H. Zhang, D. P. Curran, J. Am. Chem. Soc., Vol. 132, 2010, Pages 11452-11454
“Boryltrihydroborate: Synthesis, Structure, and Reactivity as a Reductant in Ionic, Organometallic, and Radical Reactions,” K. Nozaki, Y. Aramaki, M. Yamashita, S.-H. Ueng, M. Malacria, E. Lacôte, D. P. Curran, J. Am. Chem. Soc., Vol. 132, 2010, Pages 11449-11451
“Streamlined Syntheses of (–)-Dictyostatin, 16-Desmethyl-25,26-dihydrodictyostatin, and 6-epi-16-Desmethyl-25,26-dihydrodictyostatin,” W. Zhu, M. Jiménez, W.-H. Jung, D. P. Camarco, R. Balachandran, A. Vogt, B. W. Day, D. P. Curran, J. Am. Chem. Soc., Vol. 132, 2010, Pages 9175-9187
“EPR Studies of the Generation, Structure, and Reactivity of N-Heterocyclic Carbene Borane Radicals,” J. C. Walton, M. Makhlouf Brahmi, L. Festerbank, E. Lacôte, M. Malacria, Q. Chu, S.-H. Ueng, A. Solovyev, D. P. Curran, J. Am. Chem. Soc., Vol. 132, 2010, Pages 2350-2358