Fred Eshelman Distinguished Professor, Jointly Appointed with the School of PharmacyMarsico Hall 3012
New Synthetic Techniques, Total Synthesis, Study of Peptidomimetics
The Aubé group has a continuing interest in the development of new reactions that complement existing methods for the preparation of biologically relevant molecules. This interest has been especially directed toward nitrogen-insertion reactions because of the ubiquity of nitrogen in pharmaceutical products.We have used such ring expansion reactions in syntheses of alkaloids, amino acid bioisosteres, and various classes of peptidomimetics.
A useful reaction discovered in the Aubé laboratories is the intramolecular Schmidt reaction. This beautifully simple reaction involves the acid-promoted combination of a carbonyl compound with an alkyl azide. The result of this process is an amide, one of the most versatile nitrogen-containing functional groups known. As part of an active program in total synthesis, the group has used this new reaction in synthetic approaches to compounds such as the indolizidine alkaloids of South American poison frogs, sparteine, aspidospermidine, and stenine.
Another aspect of our overall research program is concerned with how novel molecules can be designed as peptide mimics, enzyme inhibitors, or as probes of cellular transport processes. Peptide mimics are compounds designed to inhabit the naturally occurring recognition sites of biologically important peptide hormones, eventually resulting in the synthesis of small-molecule antagonists or agonists of the endemic peptides. This project involves aspects of NMR, CD, and computational methods in addition to organic synthesis. In collaborative work, we have also been heavily involved in the synthesis of protease inhibitors and the study of cellular transport mechanisms.
University of Kansas, Department of Medicinal Chemistry, University Distinguished Professor, 2012 - present, Professor, 1996 - 2012; Associate Professor, 1992 - 1996; Assistant Professor, 1986 - 1992; Leader, Drug Discovery, Development, and Experimental Therapeutics division, KU Cancer Center, 2012 – present; Full member, KU Masonic Cancer Center, 2008 – present; Director, Synthesis Core, KU Center for Cancer Experimental Therapeutics, 2009 – present; Director, KU Specialized Chemistry Center, 2008 – present; Director and co-PI, Atlantis Dual Degree Program, 2006 – 2011; Member, Kansas Masonic Cancer Research Institute, 2005 - present; Director, KU Chemical Methodologies and Library Design Center, 2003-present; Innovatec lecturer, University of Regensburg, Germany, 2003; Center for Teaching Excellence, Interim Director, 2001 - 2002; Visiting Professor, University of Innsbruck, Innsbruck, Austria, 1997; Invited Professor, University of Rennes I, Rennes, France, 1993; NIH Postdoctoral Fellow, 1984-1986, Yale University with Professor Samuel Danishefsky; Research Assistant, 1980-1983, Duke University. Research director: Professor Steven W. Baldwin. Dissertation title: "Asymmetric Synthesis with Chiral Hydroxylamines."; Undergraduate Research, 1979-1980, University of Miami, with Professor Robert E. Gawley
Midwest Award, St. Louis Section of the American Chemical Society, 2012; ACS Fellow, American Chemical Society, selected 2012; Arthur C. Cope Scholar, American Chemical Society, 2012; Leading Light Award, University of Kansas, 2012; Sato International Award, Pharmaceutical Society of Japan, 2011; Abbott Lecturer, Massachusetts Institute of Technology, 2010; Nikolai N. Khaladjan International Award for Innovation in Higher Education, American Association of University Administrators, 2008; Fellow, American Association for the Advancement of Science, 2004; Olin Petefish Award for Research in the Basic Sciences, Higuchi/Endowment Research Achievement Award, University of Kansas, 2001; Fellow, Japanese Society for the Promotion of Science, 1996; Phi Beta Kappa, honorary member, 1996; American Cyanamid Faculty Award in Organic Chemistry, 1993; Alfred P. Sloan Research Fellow, 1993-1995; Eli Lilly Grantee, 1989-1991.
News & Publications
In this review, following a brief history of HFIP in organic synthesis and an overview of its physical properties, literature examples of organic reactions using HFIP as a solvent or an additive are presented, emphasizing the effect of solvent of each reaction.
Here, we characterize a monomodular NRPS, PvfC, encoded by the Pseudomonas virulence factor (pvf) gene cluster that is essential for virulence and signaling in different bacterial species.