Click Chemistry : A

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Click Chemistry A Click away from discovery.

• David Marcoux
• Charettes Laboratories
• February 6th

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Table of Contents

1. Introduction
2. Concept of Click Chemistry
3. Click Reaction
4. Click Application
5. Click Conclusion

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Table of Contents

1. Introduction
2. Concept of Click Chemistry
3. Click Reaction
4. Click Application
5. Click Conclusion

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Chemistry of Life
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Natures Chemistry
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Chemists Chemistry
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Chemists Chemistry
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Drug Discovery
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Natures Chemistry
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Sharpless Point of View
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Table of Contents

1. Introduction
2. Concept of Click Chemistry
3. Click Reaction
4. Click Application
5. Click Conclusion

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K. Barry Sharpless
BA, Dartmouth College (T. A. Spencer), 1963PhD,
Stanford University (E. E. van Tamelen),
1968postdoctoral, Stanford University (J. P.
Collman), 1968postdoctoral, Harvard University
(K. Bloch), 1969
Massachusetts Institute of Technology, 19707,
198090   Arthur C. Cope Professor,
198790Stanford University, 197780The Scripps
Research Institute, W. M. Keck Prof, 1990Skaggs
Institute for Chemical Biology of TSRI,
1996Kitasato University, Visiting Professor,
2002
1976 Catalytic amino and dihydroxylation 1979
Asymetric dihyroxylation 1980 Catalytic
asymetric epoxydation 1987 Catalytic asymetric
dihydroxylation 1996 Catalytic asymetric
aminodihydroxylation 2001 Click Chemistry 2001
Nobel laureate (with Knowles and Noyori)
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K. Barry Sharpless
Award for Creative Work in Organic Synthesis,
1983Arthur C. Cope Scholar, 1986Harrison Howe
Award, Rochester Section, 1987Remsen Award,
Maryland Section, 1989Arthur C. Cope Award,
1992San Diego Scientist of the Year, San Diego
Section, 1992Roger Adams Award in Organic
Chemistry, 1997Top 75 Contributors to the
Chemical Enterprise, 1998Richards Medal,
Northeastern Section, 1998Carothers Award,
Delaware Section, 1999Allan Day Award,
Philadelphia Organic Chemists Club, 1985Dr. Paul
Janssen Prize, Belgium, 1986 (1st
recipient)Prelog Medal, ETH, Switzerland,
1988Sammet Award, Göthe University,
Frankfurt-am-Main, 1988Chemical Pioneer Award,
American Institute of Chemists, 1988Scheele
Medal, Swedish Academy of Pharma Sciences,
1991Tetrahedron Prize (with Noyori),
1993Centenary Lectureship Medal, Royal Society
of Chemistry, 1993Cliff Hamilton Award,
University of Nebraska, Lincoln, 1995King Faisal
Prize for Science, Saudi Arabia, 1995Microbial
Chemistry Medal, Kitasato Institute, Tokyo,
1997Harvey Science Technology Prize, Israel
Inst of Tech, 1998Rylander Award, Organic
Reactions Catalysis Society, 2000Chemical
Sciences Award, National Academy of Sciences,
2000Chiralty Medal, Italian Chemical Society,
2000Rhone Poulenc Medal, Royal Society of
Chemistry, 2000Benjamin Franklin Medal, Franklin
Institute, Philadelphia, 2001Wolf Prize (with
Kagan Noyori), Weizmann Institute, 2001John
Scott Medal Award, City of Philadelphia, 2001ISI
Highly Cited Researchers Database, original
member, 2001Nobel Prize in Chemistry (with
Knowles Noyori), 2001Distinguished Professor
(Hon), Hong Kong Polytechnic University, Hong
Kong, 2002
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Click Chemistry
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Click Chemistry
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Click Chemistry
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Starting Materials
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Benign Solvent
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CLICK REACTIONS
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Solid-Phase Synthesis
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Table of Contents

1. Introduction
2. Concept of Click Chemistry
3. Click Reaction
4. Click Application
5. Click Conclusion

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Hantzsch Ester Synthesis
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Epoxidation
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Dihydroxylation
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Small Rings Opening
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Small Rings Opening
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Small Rings Opening
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Beta-Lactam
Clavulanic acid
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Small Rings Opening
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Tetrazole
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Tetrazole
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Tetrazole
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Tetrazole
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Tetrazole
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Polyfunctionalized Tetrazole
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Cream of the Crop
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1,4 and 1,5 Triazole
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Sources of Cu(I)
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Mechanism
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1,5 Triazole
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1,5 Triazole
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1,5 Triazole
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Mechanism
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Table of Contents

1. Introduction
2. Concept of Click Chemistry
3. Click Reaction
4. Click Application
5. Click Conclusion

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Multi-Step Click Chemistry
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Multi-Step Click Chemistry
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In Situ Click Chemistry
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In Situ Click Chemistry
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In Situ Click Chemistry
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In Situ Click Chemistry
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In Situ Click Chemistry
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Polymer Chemistry
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Polymer Chemistry
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Biology
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Biology
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Biology
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Column
Wang resin
Immobilised initiator
clickable polymer
click
Multivalent ligand
Lectin conjugate
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Column
Reagent and conditions a) 2-bromo-2-methyl-propio
nyl bromide, triethylamine, DMAP, CH2Cl2, b)
methacrylic acid 3-trimethylsilanyl-prop-2-ynyl
ester, Cu(I)Br/ N-(n-propyl)-2 pyridylmethanimine,
toluene, 60 ºC, c) TBAF3H2O, acetic acid, THF,
-20 to 25 ºC d) (PPh3)3Cu(I)Br,
a-(3-azido-1-propyl)-D-mannose, DIPEA, 60 ºC.
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Click Columns
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Click-Click Chemistry
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Click Conclusion

• Nice concept to facilitate drug discovery
• Revisited Chemistry
• Lots of applications
• We will continue to hear about it

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Click Conclusion

• Click can now be used as
• A noun click
• Verb clicking
• Adverb clickable
• Click-Click