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K.C. Nicolaou

Harry C. and Olga K. Wiess Professor of Chemistry

The advent of organic synthesis and the understanding of the structure of the molecule stand as two of the most profound developments of all time. Their advancement and exploitation led to the development of the molecular sciences including chemistry, biology and medicine. Total synthesis—the art of constructing the molecules of living nature in the laboratory—has played a crucial role in these developments by challenging and driving forward organic synthesis, thereby facilitating the drug discovery and development process, material sciences, biotechnology and nanotechnology, among other disciplines.

Today the synthesis of biologically active molecules—natural or designed—is at the center of biomedical research, manifesting itself as a creative art and a precise science that enables biology and medicine as well as striving to advance itself to higher levels of sophistication and efficiency.

In our laboratories we are pursuing both the advancement of synthesis and its application to chemical biology and pharmaceutical research. Thus, we strive to discover and develop new synthetic strategies and technologies and employ them in the synthesis of molecular complexity and diversity relevant to biology and medicine. Emphasis is placed on collaborative biomedical research with academic and industrial laboratories around the world.

Current research programs include the synthesis and investigation of biologically active substances, including antitumor, antibacterial and antiviral agents, and marine neurotoxins, among others. Examples of past accomplishments from the group include the synthesis of the endiandric acids (plant secondary metabolites), amphotericin B (antifungal drug), calicheamicin γ1I (anticancer drug), rapamycin (immunosuppressive and anticancer drug), Taxol® (anticancer drug), brevetoxins B and A (marine neurotoxins), epothilones A and B (anticancer agents), vancomycin (antibiotic of last resort), azaspiracids (marine neurotoxins), and thiostrepton (veterinary antibiotic). We have also produced educational tools for graduate and undergraduate students such as the Classics in Total Synthesis series (I, II, and III) and Molecules That Changed the World.


K. C. Nicolaou, P. Heretsch, A. ElMarrouni, C. R. H. Hale, K. K. Pulukuri, A. K. Kudva, V. Narayan, K. S. Prabhu Total Synthesis of Δ12-Prostaglandin J3, a Highly Potent and Selective Antileukemic Agent.  Angew. Chem. Int. Ed., 53: 10443-10447

K. C. Nicolaou, M. Lu, P. Chen, A. A. Shah Practical Synthesis of p- and o-Amino- and Methoxyphenolic Anthraquinones.  Angew. Chem. Int. Ed., 54 2015: 12687-12691

K. C. Nicolaou, C. Nilewski, C. R. H. Hale, C. F. Ahles, C. A. Chiu, C. Ebner, A. ElMarrouni, L. Yang, K. Stiles, D. Nagrath Synthesis and Biological Evaluation of Dimeric Furanoid Macroheterocycles: Discovery of New Anticancer Agents.  J. Am. Chem. Soc., 137 2015: 4766-4770

K. C. Nicolaou, D. Rhoades, Y. Wang, S. Totokotsopoulos, R. Bai, E. Hamel Synthesis and Biological Evaluation of Novel Epothilone B Side Chain Analogues, .  ChemMedChem 2015: 10.1002/cmdc.201500401

K. C. Nicolaou, D. Vourloumis, S. Totokotsopoulos, A. Papakyriakou, H. Karsunky, H. Fernando, J. Gavrilyuk, D. Webb, A. F. Stepan Synthesis and Biopharmaceutical Evaluation of Imatinib Analogues Featuring Unusual Structural Motifs.  ChemMedChem 2015: 10.1002/cmdc.201500510

K. C. Nicolaou, A. A. Shah, H. Korman, T. Khan, L. Shi, W. Worawalai, E. A. Theodorakis Total Synthesis and Structural Revision of Antibiotic CJ-16,264.  Angew. Chem. Int. Ed., 54 2015: 9203-9208

K. C. Nicolaou, Z. Lu, R. Li, J. R. Woods, T. Sohn Total Synthesis of Shishijimicin A.  J. Am. Chem. Soc., 137 2015: 8716-8719

K. C. Nicolaou, Q. Cai, B. Qin, M. T. Peterson, R. J. T. Mikkelsen, P. Heretsch Total Synthesis of Trioxacarcin DC-45-A2.  Angew. Chem. Int. Ed., 53 2015: 3074–3078

K. C. Nicolaou Academic–Industrial Partnerships in Drug Discovery and Development.  Angew. Chem. Int. Ed., 53 2014: 4730–4731

K. C. Nicolaou Advancing the Drug Discovery and Development Process.  Angew. Chem. Int. Ed., 53 2014: 9128–9140

S. F. Ferreiro, N. Vilariño, M. C. Louzao, K. C. Nicolaou, M. O. Frederick, L. M. Botana In Vitro Chronic Effects on hERG Channel Caused by the Marine Biotoxin Azaspiracid-2.  Toxicon, 78 2014: 69-75

C. Cheng, Y. Liu, M. E. Balasis, T. P. Garner, J. Li, N. L. Simmons, N. Berndt, H. Song, L. Pan, Y. Qin, K. C. Nicolaou, E. Gavathiotis, S. M. Sebti, R. Li Marinopyrrole Derivatives with Sulfide Spacers as Selective Disruptors of Mcl-1 Binding to Pro-Apoptotic Protein Bim.  Mar. Drugs, 12 2014: 4311–4325

K. C. Nicolaou Organic Synthesis: The Art of Replicating the Molecules of Living Nature and Others Like Them in the Laboratory.  Proc. R. Soc. A, 470 2014: 20130690

K. C. Nicolaou, P. Heretsch, T. Nakamura, A. Rudo, M. Murata, K. Konoki Synthesis and Biological Evaluation of QRSTUVWXYZA′ Domains of Maitotoxin.  J. Am. Chem. Soc., 136 2014: 16444-16451

K. C. Nicolaou The Chemistry–Biology–Medicine Continuum and the Drug Discovery and Development Process in Academia.  Chem. Biol., 21 2014: 1039-1045

K. C. Nicolaou, L. Shi, M. Lu, M. R. Pattanayak, A. A. Shah, H. A. Ioannidou, M. Lamani Total Synthesis of Myceliothermophins C, D and E.  Angew. Chem. Int. Ed., 53 2014: 10970-10974

K. C. Nicolaou, C. R. H. Hale, C. Nilewski, H. A. Ioannidou, A. ElMarrouni, L. G. Nilewski, K. Beabout, T. T. Wang, Y. Shamoo Total Synthesis of Viridicatumtoxin B and Analogues Thereof: Strategy Evolution, Structural Revision, and Biological Evaluation.  J. Am. Chem. Soc., 136 2014: 12137–12160

K. C. Nicolaou The Emergence of the Structure of the Molecule and the Art of Its Synthesis.  Angew. Chem. Int. Ed., 52 2013: 131-146

K. C. Nicolaou, C. Nilewski, C. R. H. Hale, H. A. Ioannidou, A. ElMarrouni, and L. G. Koch Total Synthesis and Structural Revision of Viridicatumtoxin B.  Angew. Chem. Int. Ed., 52 2013: 8736-8741

K. C. Nicolaou, C. R. H. Hale, C. Nilewski, and H. A. Ioannidou Constructing Molecular Complexity and Diversity: Total Synthesis of Natural Products of Biological and Medicinal Importance.  Chem. Soc. Rev., 41 2012: 5185-5238

K. C. Nicolaou, M. Lu, S. Totokotsopoulos, P. Heretsch, D. Giguère, Y. Sun, D. Sarlah, T. H. Nguyen, I. C. Wolf, D. F. Smee, C. W. Day, S. Bopp, and E. A. Winzeler Synthesis and Biological Evaluation of Epidithio-, Epitetrathio- and bis-(Methylthio)diketopiperazines: Synthetic Methodology, Enantioselective Total Synthesis of Epicoccin G, 8,8'-epi-ent-Rostratin B, Gliotoxin, Gliotoxin G, Emethallicin E and Haematocin and Discovery of New Antiviral and Antimalarial Agents.  J. Am. Chem. Soc., 134 2012: 17320-17332

K. C. Nicolaou Invigorating Education.  Angew. Chem. Int. Ed., 50 2011: 63-74

K. C. Nicolaou and R. J. Aversa Maitotoxin: An Inspiration for Synthesis.  Isr. J. Chem., 51 2011: 359-377

K. C. Nicolaou, A. Ortiz, H. Zhang, and G. Guella Total Synthesis and Structural Revision of Vannusals A and B: Synthesis of the True Structures of Vannusals A and B.  J. Am. Chem. Soc., 132 2010: 7153-7176

K. C. Nicolaou, J. Wang, Y. Tang, and L. Botta Total Synthesis of Sporolide B and 9-epi-Sporolide B.  J. Am. Chem. Soc., 132 2010: 11350-11363

K. C. Nicolaou Inspirations, Discoveries, and Future Perspectives in Total Synthesis.  J. Org. Chem., 74 2009: 951-972

K. C. Nicolaou, D. Sarlah, T. R. Wu, and W. Zhan Total Synthesis of Hirsutellone B.  Angew. Chem. Int. Ed., 48 2009: 6870-6874

K. C. Nicolaou, J. S. Chen, H. Zhang, and A. Montero Asymmetric Synthesis and Biological Properties of Uncialamycin and 26-epi-Uncialamycin.  Angew. Chem. Int. Ed., 47 2008: 185-189

K. C. Nicolaou, D. J. Edmonds, and P. G. Bulger Cascade Reactions in Total Synthesis.  Angew. Chem. Int. Ed., 45 2006: 7134-7186

K. C. Nicolaou, B. A. Pratt, S. Arseniyadis, M. Wartmann, A. O'Brate, and P. Giannakakou Molecular Design and Chemical Synthesis of a Highly Potent Epothilone.  ChemMedChem, 1 2006: 41-44

K. C. Nicolaou Joys of Molecules. 1. Campaigns in Total Synthesis.  J. Org. Chem., 70 2005: 7007-7027

K. C. Nicolaou Joys of Molecules. 2. Endeavors in Chemical Biology and Medicinal Chemistry.  J. Med. Chem., 48 2005: 5613-5638

K. C. Nicolaou, T. V. Koftis, S. Vyskocil, G. Petrovic, T. Ling, Y. M. A. Yamada, W. Tang, and M. O. Frederick Structural Revision and Total Synthesis of Azaspiracid-1. Part 2: Definition of the ABCD Domain and Total Synthesis.  Angew. Chem. Int. Ed., 43 2004: 4318-4324

K. C. Nicolaou and S. A. Snyder The Essence of Total Synthesis.  Proc. Nat. Acad. Sci. USA, 101 2004: 11929-11936

K. C. Nicolaou, M. Zak, B. S. Safina, S. H. Lee, and A. A. Estrada Total Synthesis of Thiostrepton, Part 2: Construction of the Quinaldic Acid-Containing Macrocycle and Completion of the Synthesis.  Angew. Chem. Int. Ed., 43 2004: 5092-5097

K. C. Nicolaou and P. S. Baran The CP Molecule Labyrinth: A Paradigm of How Endeavors in Total Synthesis Lead to Discoveries and Inventions in Organic Synthesis.  Angew. Chem. Int. Ed., 41 2002: 2678-2720

K. C. Nicolaou, M. Bella, D. Y.-K. Chen, X. Huang, T. Ling, and S. A. Snyder Total Synthesis of Diazonamide A.  Angew. Chem. Int. Ed., 41 2002: 3495-3499

K. C. Nicolaou, H. J. Mitchell, R. M. Rodríguez, K. C. Fylaktakidou, and H. Suzuki Total Synthesis of Everninomicin 13,384-1. Part 3. Synthesis of the DE Fragment and Completion of the Total Synthesis.  Angew. Chem. Int. Ed., 38 1999: 3345-3350

K. C. Nicolaou, H. J. Mitchell, N. F. Jain, N. Winssinger, R. Hughes, and T. Bando Total Synthesis of Vancomycin.  Angew. Chem. Int. Ed., 38 1999: 240-245

K. C. Nicolaou, P. S. Baran, Y.-L. Zhong, K. C. Fong, Y. He, W. H. Yoon, and H.-S. Choi Total Synthesis of the CP Molecules CP-263,114 and CP-225,917 - Part 2: Evolution of the Final Strategy.  Angew. Chem. Int. Ed., 38 1999: 1676-1678

K. C. Nicolaou, Z. Yang, G.-Q. Shi, J. L. Gunzner, K. A. Agrios, and P. Gärtner Total Synthesis of Brevetoxin A.  Nature, 392 1998: 264-269

K. C. Nicolaou, N. Winssinger, J. Pastor, S. Ninkovic, F. Sarabia, Y. He, D. Vourloumis, Z. Yang, T. Li, P. Giannakakou, and E. Hamel Synthesis of Epothilones A and B in Solid and Solution Phase.  Nature, 387 1997: 268-272

K. C. Nicolaou, F. P. J. T. Rutjes, E. Theodorakis, J. Tiebes, M. Sato, and E. Untersteller Total Synthesis of Brevetoxin B. 2. Completion.  J. Am. Chem. Soc., 117 1995: 1173-1174

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, and E. J. Sorensen Total Synthesis of Taxol.  Nature, 367 1994: 630-634

K. C. Nicolaou, T. K. Chakraborty, A. D. Piscopio, N. Minowa, and P. Bertinato Total Synthesis of Rapamycin.  J. Am. Chem. Soc., 115 1993: 4419-4420

K. C. Nicolaou, C. W. Hummel, E. N. Pitsinos, M. Nakada, A. L. Smith, K. Shibayama, and H. Saimoto The Total Synthesis of Calicheamicin γ1I.  J. Am. Chem. Soc., 114 1992: 10082-10084

K. C. Nicolaou, R. A. Daines, and T. K. Chakraborty, Y. Ogawa Total Synthesis of Amphotericin B.  J. Am. Chem. Soc., 109 1987: 2821-2822

K. C. Nicolaou, N. A. Petasis, and R. E. Zipkin The Endiandric Acid Cascade. Electrocyclizations in Organic Synthesis. 4. 'Biomimetic' Approach to Endiandric Acids A-G. Total Synthesis and Thermal Studies.  J. Am. Chem. Soc., 104 1982: 5560-5562

K.C. Nicolaou's Research Group Website

  • Ph.D. (1972) University College, University of London
  • B.Sc. (First Class Honors) (1969) Bedford College, University of London
  • D.Sc. Chemistry (1994) University College, University of London
  • Department of Chemistry
  • Institute of Biosciences and Bioengineering
  • Research Areas: Total Synthesis of Natural and Designed Molecules, Chemical Biology, Bioorganic, Organic, Pharmaceutical
Email: kcn@rice.edu
Phone: (713) 348-8860
Office: BioScience Research Collaborative, Suite 363