The Skaggs Institute for Chemical Biology
Faculty, Graduate Program
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.
B.A., Chemistry, Dartmouth College, 1963
Ph.D., Chemistry, Stanford University, 1968
1987-1990 Arthur C. Cope Professor, Massachusetts Institute of Technology
1980-1990 Professor of Chemistry, Massachusetts Institute of Technology
1977-1980 Professor of Chemistry, Stanford University
1970-1977 Assistant Professor of Chemistry, Massachusetts Institute of Technology
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, 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 W. Knowles and R. Noyori), 2002. 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.
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.