people
|Faculty
|Dennis Curran
 |
Dennis Curran Department of Chemistry |
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.
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.
Awards
Dreyfus Young Investigator Award, 1981-1986; Alfred P. Sloan Foundation Fellow, 1985-1987; Eli Lilly Grantee, 1985-1987, Dreyfus Teacher Scholar, 1985-1991; National Institutes of Health Research Career Development Award, 1987-1992; ACS Cope Scholar Award, 1988; President's Research Award, University of Pittsburgh, 1989; ICI Award for Excellence in Chemistry, 1990; Japan Society for the Promotion of Science Fellow, 1994; Alexander von Humboldt Research Fellow, 1998-2000; Janssen Prize for Creativity in Organic Chemistry, 1998; American Associate Editor, Tetrahedron: Asymmetry and Tetrahedron Letters; American Chancellor's Distinguished Research Award (Univ. of Pittsburgh), 1999; Chairman, American Chemical Society Division of Organic Chemistry, 2000; American Chemical Society Award for Creativity in Organic Synthesis, 2000; 2000 Boston College Alumni Achievement Award in Science.
Selected Publications
"Synthesis, reaction, and recycle of light fluorous Grubbs-Hoveyda catalysts for alkene metathesis.," Matsugi, M.; Curran, D. P., J. Org. Chem., 2005, 70, (5), 1636-1642
"Stereochemistry of hexenyl radical cyclizations with tert-butyl and related large groups: Substituent and temperature effects.," Tripp, J. C.; Schiesser, C. H.; Curran, D. P., J. Am. Chem. Soc., 2005, 127, (15), 5518-5527
"Total synthesis of (–)-dictyostatin: Confirmation of relative and absolute configurations.," Shin, Y.; Fournier, J. H.; Fukui, Y.; Bruckner, A. M.; Curran, D. P., Angew. Chem. Int. Ed., 2004, 43, (35), 4634-4637
"Handbook of Fluorous Chemistry.," Gladysz, J. A.; Curran, D. P.; Horvath, I. T., Wiley-VCH: Weinheim, 2004, 595
"Stereoisomer libraries: Total synthesis of all 16 stereoisomers of the pine sawfly sex pheromone by a fluorous mixture-synthesis approach.," Dandapani, S.; Jeske, M.; Curran, D. P., Proc. Nat. Acad. Sci, 2004, 101, 12,008-12,012
"Synthesis and reactions of fluorous carbobenzyloxy ((F)Cbz) derivatives of alpha-amino acids," D. P. Curran, M. Amatore, D. Guthrie, M. Campbell, E. Go, Z. Y. Luo, J. Org. Chem., 2003, 68, 4643
"Discodermolide/dictyostatin hybrids: Synthesis and biological evaluation," Y. Shin, N. Choy, R. Balachandran, C. Madiraju, B. W. Day, D. P. Curran, Org. Lett., 2002, 4, 4443
"Asymmetric total synthesis of (20R)-homocamptothecin, substituted homocamptothecins and homosilatecans," A. E. Gabarda, W. Du, T. Isarno, R. S. Tangirala, D. P. Curran, Tetrahedron, 2002, 58, 6329
"Synthesis of Enantioenriched Axially Chiral Anilides from Atropoisomerically Enriched Tartarate Ortho-Anilides," A. Ates and D. P. Curran, J. Am. Chem. Soc., 2001, 123, 5130
"Fluorous Mixture Synthesis: A Fluorous-Tagging Strategy for the Synthesis and Separation of Mixtures of Organic Compounds," Z. Luo, Q. Zhang, Y. Oderaotoshi, and D. P. Curran, Science, 2001, 291, 1766