Glenn C. Micalizio
New Hampshire Professor of Chemistry
Professor Micalizio trained as a Fellow of the Helen Hay Whitney Foundation in the laboratories of Professor Stuart L. Schreiber at Harvard University (2001-2003), received his PhD at the University of Michigan (2001) after graduate studies in the laboratories of Professor William R. Roush, and completed undergraduate studies at Ramapo College of NJ (1996). Prior to joining the Dartmouth Faculty in 2013, Professor Micalizio was an Associate Professor in the Department of Chemistry at The Scripps Research Institute (2008-2013), and an Assistant Professor in the Department of Chemistry at Yale University (2003-2008).
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Department(s)
Chemistry
Selected Publications
A. R. Bucknam, G. C. Micalizio, “Asymmetric De Novo Synthesis of a Cucurbitane Triterpenoid: Total Synthesis of Octanorcucurbitacin B” J. Am. Chem. Soc. 2022, 144, accepted.
L. E. Markham, J. D. Tolbert, F. J. Kull, C. R. Midgett, G. C. Micalizio, “An Enantiodefined and Conformationally Constrained Fatty Acid Mimetic and Potent Inhibitor of ToxT” ACS Med. Chem. Lett. 2021,12, 1493-1497.
K. Du, M. A. Kier, Z. D. Stempel, V. Jeso, A. Rheingold, G. C. Micalizio, “Synthesis of Anhydroryanodol”, J. Am. Chem. Soc. 2020, 142, 12937-12941.
R. Karmakar, A. Rheingold, G. C. Micalizio, “Studies Targeting Ryanodol Result in an Annulation Reaction for the Synthesis of a Variety of Fused Carbocycles” Org. Lett. 2019, 21, 6126-6129.
R. M. Leon, D. Ravi, J. S. An, C. L. del Genio, A. Rheingold, A. B. Gaur, G. C. Micalizio, “Synthesis of C14-Desmethylene Corialactone D and the Discovery of Inhibitors of Nerve Growth Factor-Mediated Neurite Outgrowth” Org. Lett. 2019, 21, 3193-3197.
W. S. Kim, Z. A. Shalit, S. Nguyen, E. Schoepke, A. Eastman, T. P. Burris, A. B. Gaur, G. C. Micalizio, “A Synthesis Strategy for Tetracyclic Terpenoids Leads to Agonists of ERb” Nature Commun. 2019, 10, article #2448 (DOI: 10.1038/s41467-019-10415-6).
A. B. Millham, M. J. Kier, R. M. Leon, R. Karmakar, Z. D. Stempel, G. C. Micalizio, “A Complementary Process to Pauson–Khand-type Annulation Reactions for the Construction of Fully Substituted Cyclopentenones” Org. Lett. 2019, 21, 567-570.
K. Du, M. J. Kier, A. Rheingold, G. C. Micalizio, “Toward the Total Synthesis of Ryanodol via Oxidative Alkyne–1,3-Diketone Annulation: Construction of a Ryanoid Tetracycle” Org. Lett. 2018, 20, 6457-6461.
W. S. Kim, K. Du, A. Eastman, R. P. Hughes, G. C. Micalizio “Synthetic nat- or ent-steroids in as few as five chemical steps from epichlorohydrin” Nat. Chem. 2018, 10, 70-77.
N. F. O’Rourke, G. C. Micalizio “Function-Oriented Studies Targeting Pectenotoxin 2: Synthesis of the GH-Ring System and a Structurally Simplified Macrolactone” Org. Lett. 2017, 19, 5154-5157.
M. J. Kier, R. M. Leon, N. F. O’Rourke, G. C. Micalizio “Synthesis of Highly Oxygenated Carbocycles by Stereoselective Coupling of Alkynes to 1,3- and 14,-Dicarbonyl Systems” J. Am. Chem. Soc. 2017, 139,12374-12377.
W. S. Kim, K. Du, R. P. Hughes, G. C. Micalizio “Synthetic nat- or ent- steroids in as few as five chemical steps from epichlorohydrin” Nat. Chem. 2017, 9, DOI: 10.1038/nchem.2865.
H. Mizoguchi, G. C. Micalizio “Convergent Synthesis of Angularly Substituted Trans-Decalins by a Metallacycle-mediated Cross-Coupling Reaction Cascade” Angew. Chem. Int. Ed. 2016, accepted.
G. C. Micalizio, N. F. O’Rourke, M. J. Kier “Metallacycle-mediated Cross-Coupling in Natural Product Synthesis” invited Report – Tetrahedron, 2016, accepted.
C. Aquino, S. N. Greszler, G. C. Micalizio “Access to the Cortistatin Pentacyclic Core by Alkoxide-Directed Metallacycle-Mediated Annulative Cross-Coupling” Org. Lett. 2016, 18, 2624-2627.
N. F. O'Rourke, G. C. Micalizio, "Cyclopropenes in Metallacycle-Mediated Cross-Coupling with Alkynes: Convergent synthesis of highly substituted vinylcyclopropanes" Org. Lett. 2016, 18, 1250-1253.
X. Cheng, G. C. Micalizio, "Synthesis of Neurotrophic Seco-prezizaane Sesquiterpenes (1R,10S)-2-oxo-3,4-dehydroneomajucin, (2S)-hydroxy-3,4-dehydroneomajucin, and (–)-jiadifenin" J. Am. Chem. Soc. 2016, 138, 1150-1153.
H. Mizoguchi, G. C. Micalizio “Synthesis of Highly Functionalized Decalins via Metallacycle-Mediated Cross-Coupling” J. Am. Chem. Soc. 2015, 137, 6624-6628.
X. Cheng, G. C. Micalizio “An Annulation Reaction for the Synthesis of Cross-Conjugated Triene-containing Hydroindanes from Acyclic Precursors” Org. Lett. 2014, 16, 5144-5147.
V. Jeso, C. Aquino, X. Cheng, H. Mizoguchi, M. Nakashige, G. C. Micalizio, “Direct Synthesis of Angularly Substituted Trans-fused Hydroindanes by Convergent Coupling of Acyclic Precursors” J. Am. Chem. Soc. 2014, 136, 8209-8212.
V. Jeso, S. Iqbal, P. Hernandez, M. D. Cameron, H. Park, P. V. LoGrasso, G. C. Micalizio “Synthesis of Benzoquinone Ansamycin-Inspired Macrocyclic Lactams from Shikimic Acid” Angew. Chem. Int. Ed. 2013, 52, 4800-4804.
D. Yang, G. C. Micalizio “Synthesis of Alkaloid (–)-205B via Stereoselective Reductive Cross-Coupling and Intramolecular [3+2] Cycloaddition” J. Am. Chem. Soc. 2012, 134, 15237-15240.
S. Greszler, H. A. Reichard, G. C. Micalizio, “Asymmetric Synthesis of Dihydroindanes by Convergent Alkoxide-Directed Metallacycle-Mediated Bond Formation” J. Am. Chem. Soc. 2012, 134, 2766-2774.
M. Z. Chen, G. C. Micalizio “Three-Component Coupling Sequence for the Regiospecific Synthesis of Substituted Pyridines” J. Am. Chem. Soc. 2012, 134, 1352-1356.
C. Aquino, M. Sarkar, M. J. Chalmers, K. Mendez, T. Kodadek, G. C. Micalizio “A Biomimetic Polyketide-Inspired Approach to Small Molecule Ligand Discovery” Nature Chem. 2012, 4, 99-104.
D. Yang, G. C. Micalizio, “Convergent and Stereodivergent Synthesis of Complex 1-Aza-7-Oxabicyclo[2.2.1]heptanes” J. Am. Chem. Soc. 2011, 133, 9216-9219.
M. A. Tarselli, K. M. Raehal, A. K. Brasher, C. Groer, M. D. Cameron, L. M. Bohn, G. C. Micalizio, “Synthesis of Conolidine, a Potent Non-Opioid Analgesic for Tonic and Persistent Pain” Nature Chem. 2011, 3, 449-453.
V. Jeso, G. C. Micalizio, “Total Synthesis of Lehualide B by Allylic Alcohol–Alkyne Reductive Cross-Coupling” J. Am. Chem. Soc. 2010, 132, 11422-11424.
D. P. Canterbury, G. C. Micalizio, “Polyketide Assembly by Alkene–Alkyne Reductive Cross-Coupling: Spiroketals Through the Union of Homoallylic Alcohols” J. Am. Chem. Soc. 2010, 132, 7602-7604.
T. K. Macklin, G. C. Micalizio, “Convergent and Stereospecific Synthesis of Skipped Polyenes and Polyunsaturated Fatty Acids” Nature Chem. 2010, 2, 638-643.
D. Yang, G. G. Micalizio, “A Convergent Stereoselective Synthesis of Quinolizidines and Indolizidines: Chemoselective Coupling of 2-Hydroxymethyl Substituted Allylic Silanes with Imines” J. Am. Chem. Soc. 2009, 131, 17548-17549.
Selected Works & Activities
Research Interests
A central focus of modern synthetic organic chemistry is the design of new reactions and synthesis strategies that facilitate the construction of complex molecules. With such contributions, classes of molecules that have been outside the realm of medicinal exploration (due to challenges associated with their synthesis) can be included in pursuits that seek to identify the next generation of pharmaceutical agents. In this way, opening doors to explore the medicinal value of molecules that could not have easily been investigated previously, advances in synthetic organic chemistry can have a profound impact on medicine and human health. We are inspired by the substantial molecular complexity and structural diversity of natural products (small molecules that have played a prominent role in the pharmaceutical industry) and aim to develop chemical reactions and synthesis strategies that allow for facile assembly of architecturally complex and rare natural products as well as structurally related unnatural analogs.
With these goals in mind, scientists in my laboratory pursue three broad research topic areas:
Reaction Methodology/Synthesis Strategy: This area of research is focused on defining enabling techniques for the facile synthesis of complex molecules. We pursue this course of study to define science that can be employed to allow medicinal exploration of molecules that are currently quite challenging/costly to prepare. Such contributions can have a broad impact with potential to shape the future of medicinal chemistry and drug discovery.
We are particularly concerned with advancing reaction methods and synthesis strategies that solve challenging problems associated with stereo- and regiocontrol in new carbon-carbon bond-forming reactions.
Natural Product Synthesis: In concert with our efforts directed at new synthetic methods, we are actively engaged in research aimed at demonstrating the utility of these methods in the synthesis of biologically important natural products. These pursuits often do not end with the completed laboratory synthesis of a rare natural product. Rather, the chemical solution defined serves as a scientific foundation to enable collaborative pursuits to explore the biology of the target and closely related synthetic analogs.
Natural Product-Inspired Function-Oriented Synthesis: Our approach to the design, discovery, and development of new reaction methods and strategies of utility for complex molecule synthesis has the potential of providing enabling technologies suitable to drive efforts targeting the discovery of new biologically relevant small molecules. We are actively involved in such programs, and focus on developing the basic organic chemistry necessary to drive such pursuits. To date, these efforts take the form of targeting synthetic variants of natural products with potential therapeutic value, as well as an unbiased diversity-oriented approach, where common natural product motifs provide inspiration for the synthesis of large and diverse small molecule compound collections from which novel biological probes and/or therapeutics can be discovered. In each case, our efforts are soundly grounded in organic synthesis while our goals target interdisciplinary and collaborative pursuits at the interface between chemistry, biology and medicine.