Chemical reactivity
at the biological
interface
Elucidating the emergent properties
of natural products
Research in our group is centered in the synthesis and study of complex secondary metabolites, with an emphasis on metabolites that interact with DNA. We use chemical synthesis to enable detailed elucidation of the mode of action of these compounds (ideally, with atomic-level precision).
One of the most exciting aspects of complex secondary metabolites is that they often do not follow first-order principles of chemical structure, bonding, and reactivity. Instead, many of the targets we have made or are pursuing contain a rich, and often unique, profile of chemical reactivity encoded in their structures. Stated another way, secondary metabolites often possess emergent properties that are difficult if not impossible to predict a priori. Elucidating these properties in both abiological and biological contexts advances basic organic chemistry, and our findings can be leveraged to impact adjacent fields, such as chemical synthetic methods, biosynthesis, and therapeutic development.
The concept of emergence is well-known and accepted in biology (e.g., a cell is more than the sum of its organelles), but it has not gained the same level of traction in chemistry. We ultimately seek to formalize the study of emergence in complex secondary metabolites, with the ultimate goal of connecting the modular, evolved chemical reactivity within a metabolite structure with cellular phenotype.
A detailed discussion of emergence in chemistry can be found here.
A discussion framed in the context of our own work can be found here
Selected Publications:
- Herzon, S. B.; Lu, L.; Woo, C. M.; Gholap, S. L. “11-Step Enantioselective Synthesis of (–)-Lomaiviticin Aglycon.” J. Am. Chem. Soc. 2011, 133, 7260.
- King, S. M.; Calandra, N. A.; Herzon, S. B. “Total Syntheses of (–)-Acutumine and (–)-Dechloroacutumine.” Angew. Chem., Int. Ed. 2013, 52, 3642.
- Colis, L. C.; Woo, C. M.; Hegan, D. C.; Li, Z.; Glazer, P. M.; Herzon, S. B. “The Cytotoxicity of (–)-Lomaiviticin A Arises from Induction of Double-strand Breaks in DNA.” Nat. Chem. 2014, 6, 504.
- Parr, B. T.; Economou, C.; Herzon, S. B. “A concise synthesis of (+)-batzelladine B from simple pyrrole-based starting materials.” Nature 2015, 525, 507.
- Healy, A. R.; Nikolayevskiy, H.; Patel, J. R.; Crawford, J. M.; Herzon, S. B. “A Mechanistic Model for Colibactin-induced Genotoxicity.” J. Am. Chem. Soc. 2016, 138, 15563.
- Ma, X.; Herzon, S. B. “Intermolecular hydropyridylation of unactivated alkenes.” J. Am. Chem. Soc. 2016, 138, 8718.
- Murphy, S. K.; Zeng, M.; Herzon, S. B. “A Modular and Enantioselective Synthesis of the Pleuromutilin Antibiotics.” Science 2017, 356, 956.
- Economou, C.; Tomanik, M.; Herzon, S. B. “Synthesis of Myrocin G, the Putative Active Form of the Myrocin Antitumor Antibiotics.” J. Am. Chem. Soc. 2018, 140, 16058.
- Hoang, K. M.; Lees, N. R.; Herzon, S. B. “Programmable Synthesis of 2-Deoxyglycosides.” J. Am. Chem. Soc. 2019, 141, 8098.
- Xue, M., et al. “Structure elucidation of colibactin and its DNA cross-links.” Science 2019, 365, eaax2685.
- Tomanik, M.; Xu, Z.; Herzon, S. B. “Enantioselective Synthesis of Euonyminol.” J. Am. Chem. Soc. 2021, 143, 699.
- Lin, K.; Gueble, S. E.; Sundaram, R. K.; Huseman, E. D.; Bindra, R. S.; Herzon, S. B. “Mechanism-based design of agents that selectively target drug-resistant glioma.” Science 2022, 377, 502.
- Alexander, B. W.; Bartfield, N. M.; Gupta, V.; Mercado, B. Q.; Del Campo, M.; Herzon, S. B. “An oxidative photocyclization approach to the synthesis of securiflustra securifrons alkaloids.” Science 2024, 383, 849.
current members
Brandon Alexander, Ph.D. Student
B.S. Biochemistry, 2017, M.S. Chemistry, 2018, University of Michigan
Zechun Wang, Ph.D. Student
B.S. Chemistry, 2020,
Peking University
Zhi (Zikki) Xu, Ph.D. Student
B.S. Chemical Biology, 2019, Peking University
Noah Bartfield, Ph.D. Student
B.S. Biochemistry, 2021,
Florida State University
Mikaela DiBello, Ph.D. Student
B.S. Chemistry, 2019, Rensselaer Polytechnic Institute
Yougant Airan, Postdoctoral
Ph.D., 2021, Indian Institute of Science (IISc)
Alexandria Palazzo
B.S. Chemistry, 2022, Florida State University
Vaani Gupta
B.A. Chemistry & Neuroscience, 2022, Grinnell College
Ian Tibbals, Ph.D. Student
B.S. Chemistry, 2023, University of Notre Dame
Zhanhao Liang, Postdoctoral
Ph.D., 2022, North Carolina State University
past Members
Ph.D. Graduates
Christina Woo, 2013
Assoc. Prof. of Chemistry, Harvard
Nicholas Calandra, 2013
H3 Biomedicine
Sandra King, 2014
Agios Pharmaceuticals
Maung Kyaw Moe Tun, 2014
University Administrator, Burma
Roman Kats-Kagan, 2015
TCI Chemicals
Miho Kaneko, 2015
Goodwin Law (Patent Law)
Mingzhuo Zeng, 2017
Genentech
Herman Nikolayevskiy, 2017
Asst. Prof. of Chemistry, Univ. of San Francisco
Xiaoshen Ma, 2018
Merck
Christos Economou, 2019
Abbvie
Mengzhao Xue, 2019
Postdoctoral Fellow, Brady Laboratory, The Rockefeller University
Ryan Holmes, 2020
Prelude Therapeutics
John Rose, 2020
Prelude Therapeutics
Martin Tomanik, 2021
Asst. Prof. of Chemistry, NYU
Kevin Hoang, 2022
BMS
Olivia Goethe, 2022
Gilead
Kingson Lin, 2022
Yale MD/PhD Program
Kevin Wernke, 2022
Asst. Prof of Chemistry, Colorado Mesa University
Joshua Combs, 2022
Postdoctoral Fellow, Shokat Laboratory, UCSF
Ian Hsu, 2022
FMC
Maddie Frischling, 2023
Treeline Biosciences
Postdoctorals
P.C. Ravikumar, 2008-2009
Associate Professor of Chemical Sciences, NISER Bhubaneswar
Seann Mulcahy, 2009-2010
Associate Professor of Chemistry, Providence College
Liang Lu, 2009-2011
Medicinal Chemist, Prelude Therapeutics Incorporated
Kaveri Balan Urkalan, 2011-2012
Senior Scientist, Loxo Oncology at Lilly
Le Li, 2010-2013
Senior Research & Technology Chemist, Albemarie Co
Shivajirao Gholap, 2008-2014
Assistant Professor, Indian Institute of Technology Delhi
Matthew Burk, 2012-2014
Director of Chemistry, Nalas Engineering Services
Laureen Colis, 2013-2014
Molecular Assay & Sample Management Lead, Spark Therapeutics, Inc.
Zhenwu Li, 2011-2015
Associate Director of Discovery Chemistry, Proteovant Therapeutics
Brendan Parr, 2014-2015
Principal Scientist II, Schrödinger
Stephen Murphy, 2015-2017
Senior Scientist of Medicinal Chemistry, The Janssen Pharmaceutical Companies of Johnson & Johnson
Seewon Joung, 2016-2017
Associate Professor, Inha University
Michail Tsakos, 2016-2017
Research & Development Scientist, Pharmathen
Alan Healy, 2015-2018
Assistant Professor of Chemistry, New York University, Abu Dhabi
Subham Mahapatra, 2015-2018
Principal Scientist of Medicinal Chemistry, Pfizer
Hester Dang, 2016-2018
Chemical Process Development, Bristol Myers Squibb
Chao Wang, 2017-2019
Scientist of Medicinal Chemistry, Turning Point Therapeutics
Nicholas Lees, 2018-2019
Senior Scientist in Process Chemistry, Pharmaron
Haruka Fujino, 2019-2020
Assistant Professor of Medicinal Chemistry, The University of Tokyo
Xin Li, 2019-2021
Research Investigator, Incyte Corporation
Alina Tirla, 2019-2021
Senior Scientist in Chemical Development, Illumina
Yassin Elbatrawi, 2021-2023
Gilead
Timothy Wright, 2020-2022
Postdoctoral Fellow, University of Toronto
Lei Chen, 2022-2023
Director, Nanjing Gritpharma Co.
Eric Huseman, 2021-2023
Assistant Professor, Marquette University
Anna Lo, 2022-2023
Senior Scientist, AstraZeneca
Bo Qin, 2022-2023
Postdoctoral Fellow, New York University
principal investigator
Milton Harris ’29 PhD Professor of Chemistry, Yale University
Professor of Pharmacology and Therapeutic Radiology,
Yale School of Medicine
Member Yale Cancer Center
Co-Founder, Modifi Biosciences
how to Contact us
Class of 1954 Chemistry Research Building
275 Prospect St., New Haven, CT
Room 201, (203) 432-8725
Room 203, (203) 432-8726
Room 205, (203) 432-8732
Room 207, (203) 432-8756
Room 209, (203) 432-8840