Patrick Dussault, Charles Bessey Professor
Charles Bessey Professor
University of Nebraska–Lincoln
809B Hamilton Hall
Lincoln, Nebraska 68588-0304
1) Organic synthesis (natural products as well as functionalized materials)
2) New oxidation methods
3) Chemistry of peroxide explosives
4) Chemical biology
Peroxide natural products: There are very few synthetic methods with which to approach the growing number of peroxide-containing natural products. Our group is a leader in the development of new methods for peroxide synthesis, as illustrated by the first syntheses of plakinic acids (J. Org. Chem. 2006, 71, 2283) and the peroxyacarnoates (Org. Lett. 2005, 7, 2509). Current research explores organometallic approaches to the peroxyplakorates.
Antimalarials: Peroxides are of interest as therapeutic agents for drug-resistant malaria. As part of a collaboration with Prof. Jon Vennerstrom (UNMC) and the Swiss Tropical Institute, we recently discovered that spiro-bisperoxyketals are stable and easily prepared compounds demonstrating promising activity in antimalarial assays (Org. Lett., 2008, 10, 2401).
New Oxidation Chemistry:
Although alkene ozonolysis has been known for over a century, we have discovered that the textbook chemistry of the intermediate carbonyl oxides can be strongly perturbed by the presence of Lewis acids and/or nucleophiles, offering a significant expansion in the utility of this oxidation, a process requiring only oxygen and electricity. (J. Org. Chem. 2008, 73, 4688); Tetrahedron, 2006, 62, 10747) Outgrowths of this project resulted in the discovery of the Re(VII)-catalyzed synthesis of 1,1-dihydroperoxides and 1,2,4,5-tetraoxanes; the latter are of major interest as potential antimalarials. (Org. Lett., 2008 10, 4577)
Triacetone triperoxide (TATP) is an easily prepared explosive of great concern as a weapon of terrorism. As part of a DoD-funded collaboration with five other departmental research groups, we are investigating the fundamental chemistry of TATP and related compounds in order to determine improved conditions for their detection and decomposition.
A long-term collaboration with Prof. Ken Nickerson (UNL School of Biological Sciences) uncovered the first examples of fungal quorum sensing, in which a released chemical signal (farnesol) controls population dependent cell-cell communication. Ongoing efforts in this area seek to explore the therapeutic consequences of synthetic enhancement of or interference with this pathway. (Bioorg. Med. Chem. 2008, 16, 1842) A collaboration with Prof. Tim Carr (UNL Nutrition Sciences) is exploring the relationship of molecular structure with dietary uptake and processing of plant sterols (J. Nutr. 2006, 136, 2722). Other ongoing collaborations target the preparation of bacterial quorum sensing molecules, enzyme inhibitors, and unnatural fatty acids.
- "Tandem application of C-C bond-forming reactions with reductive ozonolysis” Willand-Charnley, R.; Dussault, P. H., J. Org. Chem, 2012, 78, 42-47.DOI: 10.1021/jo3015775 (special issue in honor of Robert E. Ireland).
- "In vitro and in vivo activity of 3-alkoxy-1,2-dioxolanes against Schistosoma mansoni" Ingram, K.; Schiaffo, C.; Sittiwong, W.; Benner, E.; Dussault, P. H.; Keiser, J.* Journal of Antimicrobial Chemotherapy, 2012, 67, 1979-86.
- "Pyridine as an organocatalyst for the reductive ozonolysis of alkenes" R. Willand-Charnley, T. Fisher, B. Johnson, and P. H. Dussault Org. Lett. 2012, 14, 2242.
- "Regioselective Synthesis of tetralkynylarenes via Consecutive Dual Sonogashira Couplings of the bistriflate of 1,2-Dihydroxy-4,5-diodobenzene", Fisher T.; Dussault, P. H. Eur. J. Org. Chem. 2012, 2831-4. *NANO-relevant
- "Generation of singlet oxygen from fragmentation of monoactivated 1,1-dihydroperoxides" Hang, J.; Ghorai, P.; Finkenstaedt-Quinn, S.; Findik, I; Sliz, E.; Kuwata, K. T, Dussault, P. H.*, J. Org. Chem, 2012, 77(3), 1233–1243; Feature article.
- "A Mild One-pot Conversion of Alkenes to Amines through Tandem Ozonolysis and Reductive Amination" by Kyasa, S-K.; Fisher, T. J.; Dussault, P. H. Synthesis, 2011, 3475-3481.
- "Phytosterol stearate esters elicit similar responses on plasma lipids and cholesterol absorption but different responses on fecal neutral sterol excretion and hepatic free cholesterol in male Syrian hamsters" Ash, M. M.; Hang, J.; Dussault, P. H. Carr. T. P. Nutr. Res. 2011, 31(7), 537-543.
- "N5-phosphonoacetyl-L-ornithine (PALO): a convenient synthesis and investigation of influence on regulation of amino acid biosynthetic genes in Saccharomyces cerevisiae." Johnson, B.; Steadman, R.; Fager, K.; Bunker, J.; Atkin, A.*, Dussault, P. H.* Biorg. Med. Chem. Lett. 2011, 21, 2351-3.
- "3-Alkoxy-1,2-Dioxolanes: Synthesis and Evaluation as Potential Antimalarial Agents" Schiaffo, C. E.; Rottman, M.; Wittlin, S.; Dussault, P. H.* ACS Med. Chem. Lett. 2011, 2, 316-319. DOI: 10.1021/ml100308d
- Roman Shchepin (PhD, December 2006). Investigation of quorum sensing in C. albicans Postdoc, Department of Chemistry, Vanderbilt University (Porter)
- Chunping Xu (PhD., August 2006); Total synthesis of peroxyacarnoic acids and peroxyplakoric acids Postdoc, Cell Biology, The Scripps Research Institute
- Peng Dai, PhD, December 2004; Synthetic Approches to the Plakinic Acids; Albany Molecular Research Institute.
Recent Graduates (MS)
- Kyle Mott, In-situ capture of carbonyl oxides : direct ozonolytic conversion of alkenes to carbonyls MS, August 2004, Siegwerks, (Des Moines, IA)
- Tony Trullinger; Ph.D.; NIH postdoc at University of Michigan
- Qiang Han, MS; Graduate student at Penn
- Jeff Schultz, Ph.D.; NIH postdoc at UC Irvine; Arena Pharm. (San Diego)
- Su Cho-Schultz, MS; Scientist, Pfizer, La Jolla, CA
- Bridget Miller, MS; Scientist, Pharmacia-Upjohn
- Todd Eary, Ph.D.; NIH postdoc at Univ. of Texas; Array-Biopharma (CO)
- Don Davies, Ph.D.; Assistant Professor at Weber State University (UT)