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William Roush, Ph.D.

Professor
Associate Dean of Graduate Studies
Department of Chemistry
Florida Campus
Laboratory Website
roush@scripps.edu
(561) 228-2450

Scripps Research Joint Appointments

Executive Director, Medicinal Chemistry
Faculty, Graduate Program

Research Focus

Over many years the major focus of our research effort has focused on the synthesis of stereochemically complex, biologically active natural products and the development of new synthetic methodology. Significant emphasis is placed on the discovery, development, and/or illustration of new reactions and synthetic methods in this research. Some of these synthesis projects have involved intramolecular cycloaddition reactions. Others make use of acyclic diastereoselective or enantioselective stereochemical techniques.

We are increasingly pursuing research programs in bioorganic chemistry, chemical biology and medicinal chemistry, including the design and synthesis of inhibitors of cysteine proteases isolated from tropical parasites.  Additional projects focus on the develop potent, selective inhibitors of several kinases and proteases, inhibitors of certain epigenetic targets, inhibitors (inverse agonists) or activators of nuclear receptors, the design and synthesis of selective CYP51 inhibitors, and small molecule inhibotors of carboxylic acid transporters as potential therapeutic agents, among others.  Studies focusing on the development of new technology for synthesis of antibody-crug conjugates are also in progress.

Education

B.S., Chemistry, University of California, Los Angeles, 1974
Ph.D., Chemistry, Harvard University, 1977

Professional Experience

1977-78, Postdoctoral research, Harvard University
1978-83, Assistant Professor of Chemistry, Massachusetts Institute of Technology
1983-86, Associate Professor of Chemistry, Massachusetts Institute of Technology
1987-89, Associate Professor of Chemistry, Indiana University
1989-95, Professor of Chemistry, Indiana University
1995-97, Distinguished Professor of Chemistry, Indiana University
1997-2005, Warner Lambert/Parke Davis Professor of Chemistry, University of Michigan
2002-2004, Chair, Department of Chemistry, University of Michigan

Awards & Professional Activities

1982-86, Fellow of the Alfred P. Sloan Foundation
1992, Alan R. Day Award of the Philadelphia Organic Chemist's Club
1994, Arthur C. Cope Scholar Award, American Chemical Society
1996, ACS Akron Section Award 1996 Merit Award, National Institute of General MedicalSciences
1999, Distinguished Faculty Achievement Award, University ofMichigan
2002, Paul G. Gassman Distinguished Service Award, ACS Divisionof Organic Chemistry
2004, ACS Ernest Guenther Award in the Chemistry of NaturalProducts
2006, Fellow, American Association for the Advancement of Science
2009, Fellow, American Chemical Society

1990-93, Secretary-Treasurer, ACS Division of OrganicChemistry
1995, Chairman, ACS Division of Organic Chemistry
1990-02, Alternate Councilor, ACS Division of OrganicChemistry
1990-93, NIH Medicinal Chemistry Study Section, Member
1993-95, Chairman, NIH Medicinal Chemistry Study Section
1991-2002, Editorial Board, Organic Reactions
1995-present, Board of Directors, Organic Reactions
1992-2002, Editorial Board, Encyclopedia of Reagents for OrganicSynthesis
1993-2002, Editorial Board, Organic Syntheses
2003-present, Board of Directors, Organic Syntheses
1996-2002, Consulting Editorial Board, Tetrahedron
1999-present, Editorial Advisory Board, Organic Letters
1999-present, Associate Editor, Journal of the American Chemical Society
2005-present, Editorial Advisory Board, Chemical Biolgy and Drug Design
2005-present, Editorial Advisory Board, Beilstein Journal of Organic Chemistry
2007-2009, Editorial Advisory Board, Accounts of Chemical Research
2008-present, Scientific Advisory Board, Sandler Center for Basic Research in Parasitic Diseases, University of California San Francisco

Selected References

D. J. Mergott, S. A. Frank, and W. R. Roush, "Total Synthesis of (-)-Spinosyn A via Transannular Diels-Alder Reaction/Ring Contraction Sequence," Proc. Natl. Acad. Sci. 2004, 101, 11955.

J. M. Tinsley and W. R. Roush, "Total Synthesis of Asimicin via Highly Stereoselective [3+2] Annulation Reactions of Substituted Allylsilanes," J. Am. Chem. Soc. 2005, 127, 10818.

P. Va and W. R. Roush, "Total Synthesis of Amphidinolide E," J. Am. Chem. Soc. 2006, 128, 15960.

M. Tortosa, N. A. Yakelis, and W. R. Roush, "Total Synthesis of Superstolide A," J. Am. Chem. Soc. 2008, 130, 2722.

J. R. Dunetz, L. D. Julian, J. Newcom and W. R. Roush, "Total Synthesis of (+)-Tedanolide and (+)-13-Deoxytedanolide," J. Am. Chem. Soc. 2008, 130, 16407.

Y. T. Chen, L. S. Brinen, I. D. Kerr, E. Hansell, P. S. Doyle, J. H. McKerrow, and W. R. Roush, “In Vitro and In Vivo Studies of the Trypanocidal Properties of WRR-483 against Trypanosoma cruzi”, PLoS Neglected Tropical Diseases 2010, 4, e825.

Y. Wang, N. Kumar, P. Nuhant, M. D. Cameron, M. A. Istrate, W. R. Roush, P. R. Griffin and T. P. Burris, "Identification of SR1078, a Synthetic Agnoist for the Orphan Nuclear Receptors RORa and RORg," ACS CHem. Biol. 2010, 5, 1029.

M. Chen and W. R. Roush, “Enantioconvergent Hydroboration of a Racemic Allene: Enantioselective Synthesis of (E)-d-Stannyl-anti-Homoallylic Alcohols via Aldehyde Crotylboration,” J. Am. Chem. Soc. 2011, 133, 5744.

L. A. Solt, N. Kumar, P. Nuhant, Y. Wang, J. L. Lauer, J. Liu, M. Istrate, T. M. Kamenecka, W. R. Roush, D. Vidovic, S. C. Schürer, J. Xu, G. Wagoner, P. D. Drew, P. R. Griffin, and T. P. Burris, “Suppression of TH17 Differentiation and Suppression of Autoimmunity by a Selective Synthetic ROR Ligand,” Nature 2011, 472, 491.

M. Chen and W. R. Roush, “Highly Stereoselective Synthesis of Anti, Anti-Steriotriads:  A Solution to the Long-Standing Problem of Challenging Mismatched Double Asymmetric Crotylboration Reactions,” J. Am. Chem. Soc., 2012, 134, 3925

P. Nuhant and W. R. Roush, “Enantio- and Diastereoselective Synthesis of N-Acetyl Dihydrotetrafibricin Methyl Ester,” J. Am. Chem. Soc. 2013, 135, 5340.

M. Bibian, R. J. Rahaim, J. Y. Choi, Y. Noguchi, S. Schürer, W. Chen, S. Nakanishi, K. Licht, L. H. Rosenberg, L. Li, Y. Feng, M. D. Cameron, D. R. Duckett, J. L. Cleveland and W. R. Roush, “Development of Highly Selective Casein Kinase 1d/1e (CK1d/e) Inhibitors with Potent Antiproliferatve Properties,” Bioorg. Med. Chem. Lett2013, 23, 4374.

P. Nuhant, C. Allais and W. R. Roush, “(Diisopinocampheyl)borane-Mediated Reductive Aldol Reactions:  Highly Enantio- and Diastereoselective Synthesis of Syn-Aldols from N-Acryloylmorpholine,” Angew. Chem. Int. Ed. 2013, 52, 8703.

J. Y. Choi, C. M. Calvet, S. S. Gunatilleke, C. Ruiz, M. D. Cameron, J. H. McKerrow, L. M. Podust, and W. R. Roush, “Rational development of 4-aminopyridyl-based inhibitors targeting Trypanosoma cruzi CYP51 as anti-Chagas agents,” J. Med. Chem., 2013, 56, 7651.

J. R. Doherty, C. Yang, K. E. N. Scott, M. D. Cameron, M. Fallahi, W. Li, M. A. Hall, A. L. Amelio, J. K. Mishra, F. Li, M. Tortosa, H. M. Genau, R. J. Rounbehler, Y. Lu, C. V. Dang, K. G. Kumar, A. A. Butler, T. D. Bannister, A. Hooper, K. Unsal-Kacmaz, W. R. Roush and J. L. Cleveland, “Blocking lactate export by inhibiting the Myc target Mct1 Disables Glycolysis and Glutathione Metabolism,” Cancer Res. 201474, 908.

J. Y. Choi, C. M. Calvet, D. R. Vieira, S. S. Gunatilleke, M. D. Cameron, J. H. McKerrow, L. M. Podust and W. R. Roush, “The R-Configuration of 4-Amniopyridyl-Based Inhibitors of CYP51 Confers Superior Efficacy Against Trypanosoma cruzi”, ACS Med. Chem. Lett. 2014, 5, 434.

Links

Renowned University of Michigan Chemist Joins Scripps Florida Faculty

Roush Joins Scripps Florida