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Chemistry

Faculty

Karl Sharpless, PhD

W.M. Keck Professor of Chemistry
Professor
Department of Chemistry
California Campus
Laboratory Website

Scripps Research Joint Appointments

The Skaggs Institute for Chemical Biology
Faculty, Graduate Program

Research Focus

Designing Man-Made Catalysts

The Sharpless Lab pursues useful new reactivity and general methods for selectively controlling chemical reactions. Though the focus has progressed from regio- to stereo- to asymmetric and, now, to connectivity control, the core chemistry remains unchanged: the oxidation of olefins, that single most versatile, powerful and reliable (KBS argues) chemical transformation. The Sharpless Lab was the first academic chemistry group with robotics, and the lesson from the combinatorial numbers game was the primacy of reliability. "Click" chemistry was the Sharpless Lab's response: a set of powerful, virtually 100% reliable, selective reactions for the rapid synthesis of new compounds via heteroatom links (C-X-C). Click chemistry is integral now to all research within the Sharpless Lab.

In 2002, the Sharpless group discovered CuAAC (the copper-catalyzed azide-alkyne cycloaddition), now known as a quintessential “click chemistry”.  Recently the Sharpless group discovered SuFEx, another near-perfect click reaction. In concert with the thiol-ene reaction, these three make click chemistry a far-reaching method for drug discovery, chemical biology and materials science.

Education

B.A., Chemistry, Dartmouth College, 1963
Ph.D., Chemistry, Stanford University, 1968

Awards & Professional Activities

ACS Award for Creative Work in Synthetic Organic Chemistry, 1983
Dr. Paul Janssen Prize for Creativity in Organic Synthesis, 1986
AIC Chemical Pioneers Award, 1988
ETH Prelog Medal, 1988
Scheele Medal, 1991
ACS Arthur C. Cope Award, 1992
Tetrahedron Prize for Creativity in Organic Chemistry, 1993
The King Faisal International Prize for Science, 1995
ACS Roger Adams Award in Organic Chemistry, 1997
Member, National Academy of Sciences, 1985
Nobel Prize in Chemistry (with W. Knowles and R. Noyori), 2001
Chirality Medal, Italian Chemical Society, 2001
Rhone Poulenc Medal, Royal Society of Chemistry, United Kingdom, 2001
Benjamin Franklin Medal in Chemistry, Franklin Institute, Philadelphia, Pennsylvania, 2001
Wolf Prize in Chemistry, Wolf Foundation, Herzlia Bet, Israel, 2001
Nobel Prize in Chemistry (with M. Meldal and C. Bertozzi), 2022

Editorial Boards: Tetrahedron Publications, Catalysis Technology, Enantiomer, Advanced Synthesis and Catalysis, Chirality, Topics in Stereochemistry, Current Opinion in Drug Discovery and Development, Organic Letters, Synlett.

Selected References

A Heck-Matsuda Process for the Synthesis of β-Arylethenesulfonyl Fluorides: Selectively Addressable Bis-electrophiles for SuFEx Click Chemistry. Qin HL, Zheng Q, Bare GA, Wu P, Sharpless KB.  Angew Chem Int Ed Engl. 2016 Oct 10. doi: 10.1002/anie.201608807.

Arylfluorosulfates Inactivate Intracellular Lipid Binding Protein(s) through Chemoselective SuFEx Reaction with a Binding Site Tyr Residue. Chen W, Dong J, Plate L, Mortenson DE, Brighty GJ, Li S, Liu Y, Galmozzi A, Lee PS, Hulce JJ, Cravatt BF, Saez E, Powers ET, Wilson IA, Sharpless KB, Kelly JW. J Am Chem Soc. 2016 Jun 15;138(23):7353-64. doi: 10.1021/jacs.6b02960. Epub 2016 Jun 2.

Sulfur(VI) Fluoride Exchange (SuFEx): Another Good Reaction for Click Chemistry. Dong, J.; Krasnova, L.; Finn, M.G.; Sharpless K. B. Angew. Chem. Int. Ed. Accepted.

Aromatic sulfonyl fluorides covalently kinetically stabilize transthyretin to prevent amyloidogenesis while affording a fluorescent conjugate. Grimster, N. P.; Connelly, S.; Baranczak, A.; Dong, J.; Krasnova, L. B.; Sharpless, K. B.; Powers, E. T.; Wilson, I. A.; Kelly, J. W. J. Am. Chem. Soc. 2013, 135, 5656.

Observation of the controlled assembly of preclick components in the in situ click chemistry generation of a chitinase inhibitor. Hirose, T.; Maita, N.; Gouda, H.; Koseki, J.; Yamamoto, T.; Sugawara, A.; Nakano, H.; Hirono, S.; Shiomi, K.; Watanabe, T.; Taniguchi, H.; Sharpless, K. B.; Omura, S.; Sunazuka, T. Proc. Natl. Acad. Sci. U.S.A. 2013, 110, 15892.

Expanded therapeutic potential in activity space of next-generation 5-nitroimidazole antimicrobials with broad structural diversity. Miyamoto, Y.; Kalisiak, J.; Korthals, K.; Lauwaet, T.; Cheung, D. Y.; Lozano, R.; Cobo, E. R.; Upcroft, P.; Upcroft, J. A.; Berg, D. E.; Gillin, F. D.; Fokin, V. V.; Sharpless, K. B.; Eckmann, L. Proc. Natl. Acad. Sci. U.S.A. 2013, 110, 17564.

Iterative in situ click chemistry assembles a branched capture agent and allosteric inhibitor for Akt1. Millward, S. W.; Henning, R. K.; Kwong, G. A.; Pitram, S.; Agnew, H. D.; Deyle, K. M.; Nag, A.; Hein, J.; Lee, S. S.; Lim, J.; Pfeilsticker, J. A.; Sharpless, K. B.; Heath, J. R. J. Am. Chem. Soc.  2011, 133, 18280.

Copper(I)-Catalyzed Cycloaddition of Organic Azides and 1-Iodoalkynes. Hein, J. E.; Tripp, J. C.; Krasnova, L. B.; Sharpless, K. B.; Fokin, V. V. Angew. Chem., Int. Ed., 2009, 48, 8018.

Multivalent, Bifunctional Dendrimers Prepared by Click Chemistry. Wu, P.; Malkoch, M.; Hunt, J. N.; Vestberg, R.; Kaltgrad, E.; Finn, M. G.; Fokin, V. V.; Sharpless, K. B.; Hawker, C. J. Chem. Comm. 2005, 5775.

A Stepwise Huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective "Ligation" of Azides and Terminal Alkynes". Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem. Int. Ed. 2002, 41, 2596.

"Click Chemistry in situ: Aceytlcholinesterase as a Molecular-Scale Reaction Vessel for the Selective Assembly of a Femtomolar Inhibitor from an Array of Building Blocks". Lewis, W. G.; Green, L. G.; Grynszpan, F.; Radic, Z.; Carlier, P. R.; Taylor, P.; Finn, M. G.; Sharpless, K. B. Angew. Chem. Int. Ed. 2002, 41, 1053.

"Click Chemistry: Diverse Chemical Function From a Few Good Reactions". Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem. Int. Ed. 2001, 40, 2004.

Links

Scripps Research professor K. Barry Sharpless receives 2022 Nobel Prize in Chemistry

K. Barry Sharpless Steps into the Spotlight

K. Barry Sharpless is Awarded the 2001 Nobel Prize in Chemistry

The Skaggs Institute for Chemical Biology

Tricking Diseases into Synthesizing Their Own Worst Enemies: A Revolutionary Strategy for Drug Discovery at The Scripps Research Institute (TSRI) Succeeds on an Enzyme

Sharpless Addresses National Science Teachers Convention