Department of Chemistry

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Kay M. Brummond

Professor and Associate Dean for Faculty Affairs

Contact

807 CHVRN
Chevron Science Center
219 Parkman Avenue

Pittsburgh, PA 15260
412-624-1955

Research Overview

Reaction Discovery, Synthesis of Natural Products and Biologically Relevant Compounds, Reaction Mechanisms and Molecular Sensors.

Reaction Discovery. Research in our lab focuses on the discovery and development of transformations to facilitate and overcome the synthetic challenges posed by molecularly complex bioactive compounds. One example of our approach involves using one allene-containing compound and by using different conditions skeletally unique products are afforded. We were amongst the first to validate this DOS strategy and efforts along these lines continue in our lab.

Synthesis of Natural Products and Other Biologically Relevant Compounds. The allenic-Pauson–Khand reaction (APKR) developed in our group provides rapid access to a bicyclo[5.3.0]decane ring system of the guaianolide family of natural products. Guaianolides are a subclass of sesquiterpene lactones with a rich diversity of bioactivity but remain underrepresented in the drug discovery process. One compound from this class that is particularly exciting is Thapsigargin (Tg), a subnanomolar inhibitor of SERCA and one in which a PMSA-activated prodrug has been developed and is currently in Phase II clinical trials because it successfully kills cancer cells independent of proliferation. Despite Tg’s extraordinary chemotherapeutic promise, access to analogs for SAR studies remains challenging. Using the APKR, our group is preparing analogs of Tg and other densely oxygenated guaianolides and/or analogs in an enantio- and stereoselective way.

Intramolecular Didehydro-Diels–Alder Reaction (IMDDA) and Molecular Sensors. The IMDDA reaction offers a rarely used approach to the synthesis of a variety of naphthalene derivatives and benzofused heterocycles. We have showcased the utility of this method by preparing a series of solvatochromic fluorophores that are structurally related to a state of the art sensor. An understanding of the structure-function relationships was made possible by the de novo construction of the aromatic portion of these sensors. Future studies are directed towards expanding this chemistry-driven approach to the rational preparation of sensors with enhanced photophysical and chemical properties for application in biological systems.

Reaction Mechanism. The reaction discovery thrust of our research program has inspired mechanistic studies both experiment and calculation. Success stories include: explaining the selective reaction of the proximal and distal double bond of an allene when using Mo(0)- or Rh(I)-catalysis for the APKR; establishing the existence of a biradical intermediate in the thermally-induced intramolecular [2 + 2] cycloaddition reaction between an allene and an alkyne to afford alkylidene cyclobutenes; and the formation of aromatic compounds by a unimolecular elimination of hydrogen gas. We continue to work closely with our computational collaborators to understand reaction mechanisms. 

Complete Listing of Published Work in MyBibliography:

http://www.ncbi.nlm.nih.gov/myncbi/browse/collection/50348838/?sort=date...

Awards

  • 2016 Oxide Diversity Catalyst Lecturer
  • 2015 ACS Pittsburgh Award
  • Executive Director of the 45th National Organic Symposium
  • 2011 Visiting Fellow, University of New South Wales, Sydney, Australia.
  • 2010 Visiting Professor, Université Pierre et Marie Curie-Paris 6, Paris, France.
  • 2008 Visiting Professor, Department of Chemistry, MIT, Boston, MA.
  • 2007 Carnegie Science Center Award-Emerging Female Scientist.
  • 2007 American Chemical Society Akron Section Award
  • Alternate Councilor, Division of Organic Chemistry-ACS, Elected, 2006-2008
  • NIH Synthetic and Biological Chemistry Study Section A, Permanent Member
  • Editorial Advisory Board, Journal of Organic Chemistry
  • Board of Editors, Organic Synthesis, 2006-2014
  • The Chancellor's Distinguished Research Award
  • 2010 American Chemical Society Fellow

Publications

“Covalent Modifiers: A Chemical Perspective on the Reactivity of α,β-Unsaturated Carbonyls with Thiols via Hetero-Michael Addition Reactions,” Paul Jackson, John Widen, Daniel Harki, and Kay Brummond , A contributed perspective to the J. Med. Chem., Revisions submitted, September 15 , 2016,
“Alkyne Ligation Handles: Propargylation of Hydroxyl, Sulfhydryl, Amino and Carboxyl Groups via the Nicholas Reaction,” Sarah M. Wells, John C. Widen, Daniel A Harki, and Kay M. Brummond , Org. Lett., Vol. 18, 2016, Pages 4566-4569
“Synthesis of Allenyl Mesylate by a Johnson-Claisen Rearrangement. Preparation of 3-(((tert-butyldiphenylsilyl)oxy)methyl)penta-3,4-dien-1-yl methansulfonate,” Joseph E. Burchick, Jr., Sarah M. Wells, Kay M. Brummond , Procedure submitted to Organic Syntheses for checking August 15, 2016,
“An Intramolecular Dehydro-Diels–Alder Reaction and Its Impact on the Structure-Function Properties of Environmentally Sensitive Fluorophores,” Kay M. Brummond and Laura S. Kocsis , Acc. Chem. Res., Special Thematic Issue on Synthesis, Design and Molecular Function., Vol. 48, 2015, Pages 2320–2329.
“Mechanistic Insight into the Dehydro-Diels-Alder Reaction of Styrene-ynes,” Laura S. Kocsis, Husain N. Kagalwala, Sharlene Mutto, Bhaskar Godugu, Stefan Bernhard, Dean J. Tantillo, and Kay M. Brummond , J. Org. Chem., JOC special issue entitled “50 Years and Counting: The Woodward–Hoffman Rules in the 21st Century.”, Vol. 80, 2015, Pages 2965-2973.
“Cyclopenta[b]naphthalene Cyanoacrylate Dyes: Synthesis and Evaluation as Fluorescent Molecular Rotors,” Laura S. Kocsis, Kristyna M. Elbel, Billie A. Hardigree, Kay M. Brummond, Mark A. Haidekker and Emmanuel A. Theodorakis , Org. & Biomol. Chem., Paper from themed collection 2015 Hot Articles in Organic and Biomolecular Chemistry, Vol. 13, 2015, Pages 2965-2973.
“Organic Syntheses,” Kay M. Brummond (editor) , Volume 91, 2015, Wiley,
“Functionalized Naphthalene Fluorophores,”  Kay M. Brummond, Laura S. Kocsis, and Erica Benedetti , U.S. Patent No. 9,133,234 B2, Issued September 15, 2015,
“Synthesis, Structure and Use of Functionalized Naphthalenes,” Kay M. Brummond, Laura S. Kocsis, and Erica Benedetti , U.S. Patent No. 9,102,703 B2, Issued August 11, 2015,
“Synthesis, Structure and Use of Functionalized Naphthalenes,” Kay M. Brummond, Laura S. Kocsis, and Erica Benedetti , U.S. Patent Application Serial No. 14/822,858, Filed August 10, 2015,
“Identification of ATR-Chk1 Pathway Inhibitors that Selectively Target p53-Deficient Cells Without Directly Suppressing ATR Catalytic Activity,” Masaoki Kawasumi, James E. Bradner, Nicola Tolliday, Renee Thibodeau, Heather Sloan, Kay M. Brummond and Paul Nghiem , Cancer Research, Vol. 74, 2014, Pages 7534-7545.
“A Redox Economical Synthesis of Bioactive 6,12-Guaianolides,” Bo Wen, Joseph K. Hexum, John C. Widen, Daniel A. Harki and Kay M. Brummond , Org. Lett., Vol. 15, 2013, Pages 2644-1647.
“Synthesis and Photophysical Properties of a Series of Cyclopenta[b]naphthalene Solvatochromic Fluorophores,” Erica Benedetti, Laura S. Kocsis and Kay M. Brummond , J. Am. Chem. Soc., Vol. 134, 2012, Pages 11418-12421.
“A Thermal Dehydrogenative Diels–Alder Reaction of Styrenes for the Concise Synthesis of Functionalized Naphthalenes,” Laura S. Kocsis, Erica Benedetti and Kay M. Brummond , Org. Lett., Vol. 14, 2012, Pages 4430-4433.
“Chemical Methodology as a Source of Small-Molecule Checkpoint Inhibitors and Hsp70 Modulators.,” Donna M. Huryn, Jeffrey L. Brodsky, Kay M. Brummond, Peter G. Chambers, Benjamin Eyre, Alex W. Ireland, Masaoki Kawasumi, Matthew G. LaPorte, Kayla Lloyd, Baptiste Manteau, Paul Nghiem, Bettina Quade, Sandlin P. Seguin, and Peter Wipf , Proceedings of the National Academy of Sciences of the United States of America., Vol. 108, 2011, Pages 6757-6762.
“Differentiating Mechanistic Possibilities for the Thermal, Intramolecular [2+2] Cycloaddition of Allene-Ynes,” Siebert MR, Osbourn JM, Brummond KM, et al. , Journal of the American Chemical Society, Vol. 132, 2010, Pages 11952-11966.