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K.C. Nicolaou, Ph.D.

Professor Adjunct
Aline W. and L.S. Skaggs Professor of Chemical Biology
and Darlene Shiley Chair in Chemistry
Department of Chemistry
California Campus
Laboratory Website
Scripps VIVO Scientific Profile
kcn@scripps.edu
(858) 784-2400

Scripps Research Joint Appointments

The Skaggs Institute for Chemical Biology

Research Focus

Chemical Synthesis and Chemical Biology

Research in our group focuses on the chemical synthesis and chemical biology of natural and designed compounds. Programs are directed toward the discovery and invention of new synthetic reactions and the development of novel synthetic strategies for the synthesis of complex molecules. Additional aspects of the work include investigations of the biological properties of the synthesized molecules and of the mechanism of action of biologically active compounds, as well as drug design and development.

Specific examples of our past and present projects include the total synthesis of calicheamicin γ1I, (Mylotarg®, anticancer drug), Taxol® (anticancer drug), the epothilones (anticancer agents), brevetoxins A and B, azaspiracids 1−3 and maitotoxin (marine neurotoxins), vancomycin, thiostrepton, abyssomycin, platensimycin, the hirsutellones (antibiotics) and the biyouyanagins (antiviral agents).

Overall, our research programs aim to advance the field of total synthesis and to apply the fundamental knowledge gained to the drug discovery and development process. Education of the next generation of young scientists in the chemical and biological sciences is our other top priority.

For more information on our educational and research activities, see our webpage: http://www.scripps.edu/chem/nicolaou/

Education

B.S., Chemistry, University of London, 1969
Ph.D., Chemistry, University of London, 1972
D.Sc., Chemistry, University of London, 1994

Professional Experience

Research Associate, Columbia University, 1972-1973
Research Associate, Harvard University, 1973-1976
Rhodes-Thompson Professor of Chemistry, University of Pennsylvania,1976-1989
Distinguished Professor of Chemistry, Department of Chemistry & Biochemistry, University of California, San Diego, 1989 - Present
Chairman, Department of Chemistry, Aline W. and L.S. Skaggs Professor of Chemical Biology, and Darlene Shiley Chair in Chemistry, The Scripps Research Institute, 1989 - Present

Awards & Professional Activities

The Humboldt Foundation US Senior Scientist Prize (Germany, 1987), the A.C. Cope Scholar Award, American Chemical Society (1987), the Award for Creative Work in Synthetic Organic Chemistry, American Chemical Society (1993), the Dr. Paul Janssen Prize for Creativity in Organic Synthesis, Janssen Research Foundation (1994), the Rhone-Poulenc Medal, Royal Society of Chemistry (U.K., 1995), the William H. Nichols Medal, New York Section-American Chemical Society (1996), the Inhoffen Medal, Gesellschaft fur Biotechnologische Forschung mbH (GBF) (Germany, 1996), the Ernest Guenther Award in the Chemistry of Natural Products, American Chemical Society (1996), the Chemical Pioneer Award, American Institute of Chemists (1996), the Linus Pauling Award, Oregon, Portland, Puget Sound Sections-American Chemical Society (1996), the Decoration of the Order of the Commander of Honor Medal (bestowed by the President of Greece, 1998), the Esselen Award for Chemistry in the Public Interest, American Chemical Society (1998), the Yamada Prize (Japan, 1999), the first Aspirin Prize for Solidarity through Chemistry (Spain, 1999), the Max Tishler Lecture Prize, Harvard University (2000), the Paul Karrer Gold Medal, Universitat Zurich (Switzerland, 2000), the Centenary Medal, Royal Society of Chemistry (U.K., 2000-2001), the Ernst Schering Prize, Ernst Schering Research Foundation (Germany, 2001), the Nagoya Gold Medal of Organic Chemistry, Nagoya University (Japan, 2001), Tetrahedron Prize for Creativity in Organic Chemistry (2002), the ACS Nobel Laureate Signature Award for Graduate Education in Chemistry (2003), the Aristeio Bodossaki Prize (2004), the ACS A.C. Cope Award (2005) Auburn Section-American Chemical Society Auburn-G. M. Kosolapoff Award (2006), the Burkardt-Helferich Prize (2006), the ISHC Senior Award in Heterocyclic Chemistry (2007), the August-Wilhelm-von-Hofmann-Denkmünze Award (2008), the Chandler Medal, Columbia University (2008), Lampousa Lifetime Achievement Award (Cypriot American Association), 2009; and the Science Award, Ministry of Education and Culture, Cyprus (2010), and the Benjamin Franklin Medal in Chemistry, The Franklin Institute (2011).

Member of the New York Academy of Sciences (1987), Fellow of the American Academy of Arts and Sciences (1993), Member of the National Academy of Sciences (USA, 1996), Fellow of the American Association for the Advancement of Science (1999), Foreign Member, Academy of Athens (Greece, 2001), Honorary Fellow, Indian Academy of Sciences (2007), Honorary Member, Israel Chemical Society (2009), Member, German Academy of Sciences Leopoldina (2009), and 12 honorary degrees from universities around the world.

Selected References

All Publications

Below are selected references as author or co-author from over 700 scientific articles, reviews, and book chapters. For a full listing of publications please see our webpage:  http://www.scripps.edu/chem/nicolaou/       

Selected Original Articles

  1. The Endiandric Acid Cascade.  Electrocyclizations in Organic Synthesis.  4. "Biomimetic" Approach to Endiandric Acids A-G.  Total Synthesis and Thermal Studies, K.C. Nicolaou, N.A. Petasis, R.E. Zipkin, J. Am. Chem. Soc. 1982, 104, 5560–5562.
  2. Total Synthesis of Amphotericin B, K.C. Nicolaou, R.A. Daines, T.K. Chakraborty, Y. Ogawa, J. Am. Chem. Soc. 1987, 109, 2821–2822.
  3. The Total Synthesis of Calicheamicin g1I. K.C. Nicolaou, C.W. Hummel, E.N. Pitsinos, M. Nakada, A.L. Smith, K. Shibayama, H. Saimoto, J. Am. Chem. Soc. 1992, 114, 10082–10084.
  4. Total Synthesis of Taxol, K.C. Nicolaou, Z. Yang, J.J. Liu, H. Ueno, P.G. Nantermet, R.K. Guy, C.F. Claiborne, J.B. Renaud, E.A. Couladouros, K. Paulvannan, E.J. Sorensen, Nature 1994, 367, 630–634.
  5. Total Synthesis of Brevetoxin B.  2: Completion, K.C. Nicolaou, F.P.J.T. Rutjes, E. Theodorakis, J. Tiebes, M. Sato, E. Untersteller, J. Am. Chem. Soc. 1995, 117, 1173–1174.
  6. Synthesis of Epothilones A and B in Solid and Solution Phase, K.C. Nicolaou, N. Winssinger, J. Pastor, S. Ninkovic, F. Sarabia, Y. He, D. Vourloumis, Z. Yang, T. Li, P. Giannakakou, E. Hamel, Nature 1997, 387, 268–272.
  7. Total Synthesis of Brevetoxin A, K.C. Nicolaou, Z. Yang, G.-Q. Shi, J.L. Gunzner, K.A. Agrios, P. Gärtner, Nature 1998, 392, 264–269.
  8. Total Synthesis of Vancomycin, K.C. Nicolaou, H.J. Mitchell, N.F. Jain, N. Winssinger, R. Hughes, T. Bando, Angew. Chem. Int. Ed. 1999, 38, 240–245.
  9. Total Synthesis of the CP Molecules CP-263,114 and CP-225,917 - Part 2: Evolution of the Final Strategy, K.C. Nicolaou, P.S. Baran, Y.-L. Zhong, K.C. Fong, Y. He, W.H. Yoon, H.-S. Choi, Angew. Chem. Int. Ed. 1999, 38, 1676–1678.
  10. Total Synthesis of Diazonamide A, K.C. Nicolaou, M. Bella, D.Y.-K. Chen, X. Huang, T. Ling, S.A. Snyder, Angew. Chem. Int. Ed. 2002, 41, 3495–3499.
  11. Structural Revision and Total Synthesis of Azaspiracid-1. Part 2: Definition of the ABCD Domain and Total Synthesis, K.C. Nicolaou, T.V. Koftis, S. Vyskocil, G. Petrovic, T. Ling, Y.M.A. Yamada, W. Tang, M.O. Frederick, Angew. Chem. Int. Ed. 2004, 43, 4318–4324.
  12. Total Synthesis of Thiostrepton, Part 2: Construction of the Quinaldic Acid-Containing Macrocycle and Completion of the Synthesis, K.C. Nicolaou, M. Zak, B.S. Safina, S.H. Lee, A.A. Estrada, Angew. Chem. Int. Ed. 2004, 43, 5092–5097.
  13. Total Synthesis of Platensimycin, K.C. Nicolaou, A. Li, D.J. Edmonds, Angew. Chem. Int. Ed. 2006, 45, 7086–7090.
  14. Molecular Design and Chemical Synthesis of a Highly Potent Epothilone, K.C. Nicolaou, B.A. Pratt, S. Arseniyadis, M. Wartmann, A. O’Brate, P. Giannakakou, ChemMedChem 2006, 1, 41–44.
  15. Asymmetric Synthesis and Biological Properties of Uncialamycin and 26-epi-Uncialamycin, K.C. Nicolaou, J.S. Chen, H. Zhang, A. Montero, Angew. Chem. Int. Ed. 2008, 47, 185–189.
  16. Total Synthesis of (+)-Cortistatin, K.C. Nicolaou, Y.-P. Sun, X.-S. Peng, D. Polet, D.Y.-K. Chen, Angew. Chem. Int. Ed. 2008, 47, 7310–7313.
  17. A Concise Asymmetric Total Synthesis of Aspidophytine, K.C. Nicolaou, S.M. Dalby, U. Majumder, J. Am. Chem. Soc. 2008, 130, 14942–14943.
  18. Total Synthesis of Hopeahainol A and Hopeanol, K.C. Nicolaou, R.T. Wu, Q. Kang, D.Y.-K. Chen, Angew. Chem. Int. Ed. 2009, 48, 3440–3443.
  19. Total Synthesis of Sporolide B, K.C. Nicolaou, Y. Tang, J. Wang, Angew. Chem. Int. Ed. 2009, 48, 3449–3453.
  20. Total Synthesis of (+)-Haplophytine, K.C. Nicolaou, S.M. Dalby, S. Li, T. Suzuki, D.Y.-K. Chen, Angew. Chem. Int. Ed. 2009, 48, 7616–7620.
  21. Total Synthesis and Biological Evaluation of (+)- and (–)-Bisanthraquinone Antibiotic BE-43472B and Related Compounds, K.C. Nicolaou, J. Becker, Y.H. Lim, A. Lemire, T. Neubauer, A. Montero, J. Am. Chem. Soc. 2009, 131, 14812–14826.
  22. Cortistatin A Is a High-Affinity Ligand of Protein Kinases ROCK, CDK8, and CDK11, V.J. Cee, D.Y.-K. Chen, M.R. Lee, K.C. Nicolaou, Angew. Chem. Int. Ed. 2009, 47, 8952–8957.
  23. Synthesis of the ABCDEFG Ring System of Maitotoxin, K.C. Nicolaou, R.J. Aversa, J. Jin, F. Rivas, J. Am. Chem. Soc. 2010, 132, 6855–6861.
  24. Total Synthesis and Structural Revision of Vannusals A and B. Synthesis of the Originally Assigned Structure of Vannusal B, K.C. Nicolaou, A. Ortiz, H. Zhang, P. Dagneau, A. Lanver, M.P. Jennings, S. Arseniyadis, R. Faraoni, D.E. Lizos, J. Am. Chem. Soc. 2010, 132, 7138–7152.
  25. Total Synthesis and Structural Revision of Vannusals A and B. Synthesis of the True Structures of Vannusals A and B, K.C. Nicolaou, A. Ortiz, H. Zhang, G. Guella, J. Am. Chem. Soc. 2010, 132, 7153–7176.
  26. Synthesis of the QRSTU Domain of Maitotoxin and Its 85-epi- and 86-epi-Diastereomers, K.C. Nicolaou, C.F. Gelin, J.H. Seo, Z. Huang, T. Umezawa, J. Am. Chem. Soc. 2010, 132, 9900–9907.

 Selected Review Articles

  1. Chemistry and Biology of the Enediyne Anticancer Antibiotics, K.C. Nicolaou and W.-M. Dai, Angew. Chem. Int. Ed. Engl. 1991, 30, 1387–1416.
  2. Total Synthesis of Brevetoxin B.  A Twelve-Year Synthetic Odyssey in Organic Synthesis, K.C. Nicolaou, Angew. Chem. Int. Ed. Engl. 1996, 35, 589–607.
  3. The CP Molecule Labyrinth: A Paradigm of How Endeavors in Total Synthesis Lead to Discoveries and Inventions in Organic Synthesis, K.C. Nicolaou and P.S. Baran, Angew. Chem. Int. Ed. 2002, 41, 2678–2720.
  4. Perspectives in Total Synthesis: A Personal Account, K.C. Nicolaou, Tetrahedron 2003, 59, 6683–6738.
  5. The Essence of Total Synthesis, K.C. Nicolaou, S.A. Snyder, Proc. Natl. Acad. Sci. USA 2004, 101, 11929–11936.
  6. Joys of Molecules. 1. Campaigns in Total Synthesis, K.C. Nicolaou, J. Org. Chem. 2005, 70, 7007–7027.
  7. Joys of Molecules. 2. Endeavors in Chemical Biology and Medicinal Chemistry, K.C. Nicolaou, J. Med. Chem. 2005, 48, 5613–5638.
  8. Metathesis Reactions in Total Synthesis, K.C. Nicolaou, P.G. Bulger, D. Sarlah, Angew. Chem. Int. Ed. 2005, 44, 4490–4527.
  9. Cascade Reactions in Total Synthesis, K.C. Nicolaou, D.J. Edmonds, P.G. Bulger, Angew. Chem. Int. Ed. 2006, 45, 7134–7186.
  10. The Continuing Saga of the Marine Polyether Biotoxins, K.C. Nicolaou, M.O. Frederick, R.J. Aversa, Angew. Chem. Int. Ed. 2008, 47, 7182–7225.
  11. Inspirations, Discoveries, and Future Perspectives in Total Synthesis, K.C. Nicolaou, J. Org. Chem. 2009, 74, 951–972.
  12. Recent Advances in the Total Synthesis and Biology of Naturally Occurring Antibiotics, K.C. Nicolaou, J.S. Chen, D.J. Edmonds, A.A. Estrada, Angew. Chem. Int. Ed. 2009, 48, 660–719.
  13. Samarium Diiodide-Mediated Reactions in Total Synthesis, K.C. Nicolaou, S.P. Ellery, J.S. Chen, Angew. Chem. Int. Ed. 2009, 48, 7140–7165.
  14. The Art of Total Synthesis Through Cascade Reactions, K.C. Nicolaou, J.S. Chen, Chem. Soc. Rev. 2009, 38, 2993–3009.

 Selected Books

  1. Classics in Total Synthesis, K.C. Nicolaou and E.J. Sorensen, VCH Publishers, Weinheim, Germany, p. 798, 1996.
  2. Classics in Total Synthesis II, K.C. Nicolaou and S.A. Snyder, Wiley-VCH Publishers, Weinheim, Germany, p. 636, 2003.
  3. Classics in Total Synthesis III, K.C. Nicolaou and J.S. Chen, Wiley-VCH Publishers, Weinheim, Germany, 2011.
  4. Molecules That Changed the World, K.C. Nicolaou and T. Montangon, Wiley-VCH Publishers, Weinheim, Germany, p. 366, 2008.

Links

The Skaggs Institute for Chemical Biology

The Skaggs Institute Scientific Report

Total Synthesis and the Creative Process