K. Barry Sharpless, PhD
Professor
Department of Chemistry
W.M. Keck Professor of Chemistry
Research Focus
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.
Select Publications
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Qin, H. L.; Zheng, Qinheng; Bare, G. A.; Wu, Peng; Sharpless, Karl B. A Heck-Matsuda process for the synthesis of ß-arylethenesulfonyl fluorides: selectively addressable bis-electrophiles for SuFEx click chemistry. Angewandte Chemie-International Edition 2016, 55, 14155-14158.
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Chen, Wentao; Dong, Jiajia; Plate, Lars; Mortenson, David E.; Brighty, Gabriel J.; Li, Suhua; Liu, Yu; Galmozzi, Andrea; Lee, Peter S.; Hulce, Jonathan J J.; Cravatt, Benjamin F.; Saez, Enrique; Powers, Evan T.; Wilson, I A.; Sharpless, K B.; Kelly, Jeffery W. Arylfluorosulfates Inactivate Intracellular Lipid Binding Protein(s) through Chemoselective SuFEx Reaction with a Binding Site Tyr Residue. 2016, 138, 7353-64.
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Dong, J.; Krasnova, L.; Finn, M. G.; Sharpless, Karl B. Sulfur(VI) fluoride exchange (SuFEx): another good reaction for click chemistry. Angewandte Chemie-International Edition 2014, 53, 9430-9448.
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Grimster, Neil P.; Connelly, Stephen; Baranczak, Aleksandra; Dong, Jiajia; Krasnova, Larissa B.; Sharpless, K B.; Powers, Evan T.; Wilson, I A.; Kelly, Jeffery W. Aromatic sulfonyl fluorides covalently kinetically stabilize transthyretin to prevent amyloidogenesis while affording a fluorescent conjugate. 2013, 135, 5656-68.
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Hirose, T.; Maita, N.; Gouda, H.; Koseki, J.; Yamamoto, T.; Sugawara, A.; Nakano, H.; Hirono, S.; Shiomi, K.; Watanabe, T.; Taniguchi, H.; Sharpless, Karl B.; Omura, S.; Sunazuka, T. Observation of the controlled assembly of preclick components in the in situ click chemistry generation of a chitinase inhibitor. Proceedings of the National Academy of Sciences of the United States of America 2013, 110, 15892-15897.
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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, Valery; Sharpless, Karl B.; Eckmann, L. Expanded therapeutic potential in activity space of next-generation 5-nitroimidazole antimicrobials with broad structural diversity. Proceedings of the National Academy of Sciences of the United States of America 2013, 110, 17564-17569.
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