Our Research
Medicinal Chemistry
We specialize in medicinal chemistry which is a key part of the discovery and development of new medicines. We synthesize small organic molecules with drug-like structural features. Working closely with biological collaborators who evaluate these compounds, we modify their structures to achieve optimal biological properties and pharmaceutical potential with the goal of advancing promising "drug candidates" into clinical trials. Our research home is the Boris Family Medicinal Chemistry Laboratory.
Synthetic Methods
We develop new reactions and synthetic strategies that enhance the capacity of chemists to produce valuable speciality compounds from simpler inexpensive building blocks. We focus mainly on three areas: 1) leveraging organosulfur functionalities like sulfoxides and vinyl sulfides as versatile synthetic intermediates, 2) using environmentally benign heterogeneous reagents to simplify reactions and 3) efficiently synthesizing natural products that are of biomedical interest.
Our Publications
A platform for predicting mechanism of action based on bacterial transcriptional responses identifies an unusual DNA gyrase inhibitor
S. French, A. B. Y. Guo, M.J. Ellis, J.P. Deisinger, J.W. Johnson, K.Rachwalski, Z. A. Piquette, T. Lluka, M. Zary, S. Gamage, J. Magolan, E.D. Brown.
Cell Reports 2024, 43(4), 114053
doi.org/10.1016/j.celrep.2024.114053
Magolan Lab members Jarrod Johnson and Zoe Piquette made synthetic chemistry contributions to this collaborative investigation led by the lab of Prof. Eric Brown.
2024
Allosteric inhibition of tRNA synthetase Gln4 by N-pyrimidinyl-β-thiophenylacrylamides exerts highly selective antifungal activity
E. Puumala, D. Sychantha, E.Lach, S. Reeves, S. Nabeela, M. Fogal, A.K. Nigam, J. W. Johnson, A. Aspuru-Guzik, R.S. Shapiro, P. Uppuluri, S. Kalyaanamoorthy, J.Magolan, L. Whitesell, N. Robbins, G. D. Wright, L. E. Cowen.
Cell Chem. Biol. 2024, 31(4), 760-775.e17 doi.org/10.1016/j.chembiol.2024.01.010
Magolan Lab member Elizabeth Lach and Jarrod Johnson made synthetic chemistry contributions to this collaborative investigation led by the lab of Prof. Leah Cowen at the University of Toronto.
2024
Bioactivity of the Cannabigerol Cannabinoid and its Analogues – the role of 3-Dimensional Conformation
M. Salha, H. Adenusi, J. Dupuis, E. Bodo, B. Botta, I. Mckenzie, R. Yada, D. Farrar, J. Magolan, K. V. Tian, G. Chass.
Org. Biomol. Chem. 2023, 21, 4683-4693.
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2023
Deep learning-guided discovery of an antibiotic targeting Acinetobacter baumannii
G. Liu, D. B. Catacutan, K. Rathod, K. Swanson, W. Jin, J. C. Mohammed, A. Chiappino-Pepe, S. A. Syed, M. Fragis, K. Rachwalski, J. Magolan, M. G. Surette, B. K. Coombes, T. Jaakkola, R. Barzilay, J. J. Collins, J. M. Stokes *
Nat. Chem. Biol. 2023 (ASAP, online May 25, 2023)
doi.org/10.1038/s41589-023-01349-8
Magolan Lab member Meghan Fragis made synthetic chemistry contributions to this collaborative investigation led by the lab of Prof. Jonathan Stokes.
2023
Genetic and Chemical Screening Reveals Targets and Compounds to Potentiate Gram-Positive Antibiotics against Gram-Negative Bacteria
K. Klobucar, E. Jardine, M. A. Farha, M. R. MacKinnon, M. Fragis, B. Nkonge, T. Bhando, L. Borrillo, C. N. Tsai, J. W. Johnson, B. K. Coombes, J. Magolan, E. D. Brown*
ACS Infect. Dis. 2022 8(10), 2187-2197
doi.org/10.1021/acsinfecdis.2c00357
Magolan Lab members Marc MacKinnon, Meghan Fragis, Brenda Nkonge, Louis Borrillo, and Jarrod Johnson made synthetic chemistry contributions to this collaborative investigation led the lab of Prof. Eric Brown.
2022
QSAR Models Reveal New EPAC-Selective Allosteric Modulators
H. Mohamed, H. Shao, M. Akimoto, P. Darveau, M. R. MacKinnon, J. Magolan, G. Melacini*
RSC Chem. Biol. 2022 ,3, 1230-1239
doi.org/10.1039/D2CB00106C
Magolan Lab members Patrick Darveau and Marc MacKinnon made synthetic chemistry contributions to this collaborative investigation led the lab of Prof. Giuseppe Melacini
2022
Use of Vinyl Sulfides in Fischer Indole Reactions
P. Pal, M. Fragis, S. Dharavath, J. W. Johnson, J. Magolan
Synthesis. 2022, 54, 4917-4931
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Highlight on Organic Chemistry Portal.
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2022
Caffeine blocks SREBP2-induced hepatic PCSK9 expression to enhance LDLR-mediated cholesterol clearance
P. F. Lebeau, J. H. Byun, K. Platko, P. Saliba, M. Sguazzin, M. E. MacDonald, G. Paré, G. R. Steinberg, L. J. Janssen, S. A. Igdoura, M. A. Tarnopolsky, S. R. W. Chen, N. G. Seidah, J. Magolan, R. C. Austin
Nat. Commun. 2022, 13, 770
doi.org/10.1038/s41467-022-28240-9
Magolan Lab members Paul Saliba and Matthew Sguazzin made synthetic chemistry contributions to this collaborative investigation led the lab of Prof. Richard Austin
2022
Hexafluoroisopropyl Sulfamate
J. W. Johnson, M. A. Sguazzin, J Magolan
Encyclopedia of Reagents for Organic Synthesis 2022 (online Jan 23, 2022)
doi.org/10.1002/047084289X.rn02436
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2022
Antibacterial Activity of Metergoline Analogues: Revisiting the Ergot Alkaloid Scaffold for Antibiotic Discovery
J. W. Johnson, M. J. Ellis, Z. A. Piquette, C. MacNair, L. Carafrae, T. Bhando, N. E. Ritchie, P. Saliba, E. D. Brown, J. Magolan
ACS Med. Chem. Lett. 2022 (online Jan 21, 2022)
doi.org/10.1021/acsmedchemlett.1c00648
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2022
2022
Exploration of BAY 11-7082 as a novel antibiotic
V. E. Coles, P. Darveau, X. Zhang, H. Harvey, B. D. Henriksbo, A. Yang, J. D. Schertzer, J. Magolan, L. L. Burrows
ACS Infect. Dis. 2022, 8(1), 170-182.
(first published online December 3, 2021)
doi.org/10.1021/acsinfecdis.1c00522
Magolan Lab members Patrick Darveau and Dr. Xiong Zhang made synthetic chemistry contributions to this collaborative investigation led by Victoria Coles and the lab of Prof. Lori Burrows.
Bibenzyl synthesis in Cannabis sativa L
K. Boddington, E. Soubeyrand, K. Van Gelder, J. A. Casaretto, C. Perrin, T. J.B. Forrester, C. Parry, M. S.Al-Abdul-Wahid, N. G. Jentsch, J. Magolan, G. G. Bozzo, M. S. Kimber, S. J. Rothstein, T. A. Akhtar
The Plant Journal, 2022, 109(3), 693-707
(first published online November 17, 2021)
Magolan Lab member Dr. Nicholas Jentsch made synthetic chemistry contributions to this collaborative investigation led by the lab of Prof. Tariq Akhtar at the University of Guelph.
2022
Aldehyde to Ketone Homologation Enabled by Improved Access to Thioalkyl Phosphonium Salts
M. Fragis, J. L. Deobald, S. Dharavath, J. Scott, J. Magolan
Org. Lett. 2021, 23(12), 4548-4452
doi.org/10.1021/acs.orglett.1c01189
This article received an Editor's Choice Award from Organic Letters and was featured in Prof. Taber's Org. Chem. Highlights: "Carbon-Carbon Bond Construction", Jan. 31, 2022 (link)
2021
Chemical Screen for Vancomycin Antagonism Uncovers Probes of the Gram-Negative Outer Membrane
K. Klobucar, J-P Côté, S. French, L. Borrillo, A.B.Y. Guo, M. H. Serrano-Wu, K.K. Lee, B.K. Hubbard, J.W. Johnson, J.L. Gaulin, J. Magolan, D.T. Hung, E.D. Brown
ACS Chem. Bio. 2021, 16(5), 929-942
doi.org/10.1021/acschembio.1c00179
Magolan Lab members Louis Borrillo and Dr. Jarrod Johnson made synthetic chemistry contributions to this collaborative investigation led by the lab of Prof. Eric Brown.
2021
Targeting SUMOylation dependency in human cancer stem cells through a unique SAE2 motif revealed by chemical genomics
Y.D. Benoit, R.R. Mitchell, W. Wang, L. Orlando, A.L. Boyd, B. Tanasijevic, L. Aslostovar, Z. Shapovalova, M. Doyle, C.J. Bergin, K. Vojnits, F.L. Casado, J.D. Lu, D.P. Porras, J.L. Garcı´a-Rodriguez, J. Russell, A. Zouggar, A.N. Masibag, C. Caba, K. Koteva, L.K. Kinthada, J.S. Patel, S.N. Andres, J. Magolan, T.J. Collins, G.D. Wright, M. Bhatia.
Cell Chem. Biol. 2021 28, 1-13
doi.org/10.1016/j.chembiol.2021.04.014
Magolan Lab member Dr. Lakshmana Kinthada made synthetic chemistry contributions to this collaborative investigation led by the lab of Prof. Mick Bhatia.
2021
Hexafluoroisopropyl Sulfamate: A Useful Reagent for the Synthesis of Sulfamates and Sulfamides
M. Sguazzin, J. Johnson, J. Magolan
Org. Lett 2021, 23(9), 3373-3378
DOI: 10.1021/acs.orglett.1c00855
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2021
2020
Efficient Synthesis of Cannabigerol, Grifolin, and Piperogalin via Alumina-Promoted Allylation
N. G. Jentsch, X. Zhang, J. Magolan
J. Nat. Prod. 2020, 83(9), 2587-2591
DOI: 10.1021/acs.jnatprod.0c00131
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2020
Genetic and chemical screening in human blood serum reveals unique antibacterial targets and compounds against Klebsiella pneumoniae
B. S. Weber, A. M. De Jong, A. B. Y. Guo, S. Dharavath, S. French, A. A. Fiebig-Comyn, B. K. Coombes, J. Magolan, E. D. Brown
Cell Reports 2020, 32(3), 107927
DOI: 10.1016/j.celrep.2020.107927
Magolan Lab member Dr. Srinivas Dharavath made synthetic chemistry contributions to this collaborative investigation led by the lab of Prof. Eric Brown.
Targeting two-component systems uncovers a small molecule inhibitor of Salmonella virulence.
C. N. Tsai, C. R. MacNair, M. P. T. Cao, J. N. Perry, J. Magolan, E. D. Brown, B. K. Coombes
Cell Chem. Bio. 2020, 27(7), 793-805
DOI: 10.1016/j.chembiol.2020.04.005
Magolan Lab member Dr. My Cao made synthetic chemistry contributions to this collaborative investigation led by the lab of Prof. Brian Coombes.
2020
Mechanism of Action of an EPAC1-Selective Competitive Partial Agonist
H. Shao, H. Mohamed, S. Boulton, J. Huang, P. Wang, H. Chen, J. Zhou, U. Luchowska-Stańska, N. Jentsch, A. Armstrong, J. Magolan, Y. Stephen, G. Melacini
J. Med. Chem. 2020, 63(9), 4762-4775
DOI: 10.1021/acs.jmedchem.9b02151
Magolan Lab members Dr. Nick Jentsch and Alison Armstrong made synthetic chemistry contributions to this collaborative protein NMR-based investigation led by the lab of Prof. Giuseppe Melacini.
2020
Isolation and Synthesis of Veranamine, an Antidepressant Lead from the Marine Sponge Verongida rigida
A. J. Kochanowska-Karamyan, H. C. Araujo, X. Zhang, A. El-Alfy, P. Carvalho, M. A. Avery, S. Holmbo, J. Magolan, M. T. Hamann
J. Nat. Prod. 2020, 83(4), 1902-1098
DOI: 10.1021/acs.jnatprod.9b01107
Magolan Lab members Hugo Araujo, Xiong Zhang, and Steven Holmbo completed the first gram scale total synthesis of veranamine as part of this international collaboration co-led by Dr. Magolan and Dr. Hamann.
2020
Uncovering the hidden antibiotic potential of Cannabis
M. A. Farha, O. M. El-Halfawy, R.T. Gale, C. R. MacNair, L. A. Carfrae, X. Zhang, N. G. Jentsch, J. Magolan, E. D. Brown
ACS Infec. Dis. 2020, 6(3), 338-346
DOI: 10.1021/acsinfecdis.9b00419
Magolan Lab members Xiong Zhang and Dr. Nick Jentsch made synthetic chemistry contributions to this collaborative investigation led by Prof. Eric Brown's lab.
2020
Alkylation of indoles with α,β-unsaturated ketones using alumina in hexanes
Zhang, X., Jones-Mensah, E., Deobald J., Magolan J.
Advanced Synthesis and Catalysis 2019, 361, 5548-5551.
2019
A macrophage-based screen identifies antibacterial compounds selective for intracellular Salmonella Typhimurium
Ellis, M.J., Tsai, C.N., Johnson, J.W., French, S., Elhenawy, W., Porwollik, S., Andrews-Polymenis, H., McClelland, M., Magolan, J., Coombes, B.K., Brown, E.D
Nature Communications 2019, 10(1), 197
DOI 10.1038/s41467-018-08190-x
Magolan Lab member Dr. Jarrod Johnson made synthetic chemistry contributions to this collaborative investigation led by the labs of Prof. Eric Brown and Prof. Brian Coombes.
2019
One-pot carbonyl reduction and carbonate formation using sodium borohydride in dialkyl carbonate solvents
Osumah, A., Magolan J., Waynant, K.
Tetrahedron Letters. 2019, 60(44), 151203
2019
Magolan Lab research done at the University of Idaho (2010-2017)
Biaryl Ketones via Suzuki-Miyaura Cross-Coupling of Organotrifluoroborates and Acid Chlorides.
Frobes, A. M.; Meier, G. P.; Jones-Mensah, E.; Magolan J.
Eur. J. Org. Chem. 2016, 17, 2983-2987.
2016
Dimethylsulfoxide as a Synthon in Organic Chemistry.
Jones-Mensah, E.; Karki, M.; Magolan, J.
Synthesis 2016, 48(10), 1421-1436.
2016
Cerium-Free Luche Reduction Directed by Rehydrated Alumina.
Jones-Mensah, E.; Nickerson, L. A.; Deobald, J. L.; Ertel, A. B.; Knox, H. L.; Magolan. J.
Tetrahedron 2016, 72(26) 3748-3753.
DOI:10.1016/j.tet.2016.03.017
2016
Evaluation of Synthetic Coumarins for Antiausterity Cytotoxicity against Pancreatic Cancers.
Farley, C. M.; Dibwe, D.F.; Ueda, J.; Hall, E.A.; Awale, S. Magolan, J.
Bioorg. Chem. Med. Lett. 2016, 26(5), 1471-1474.
DOI:10.1016/j.bmcl.2016.01.054
2016
Bromination of Olefins with HBr and DMSO.
Karki, M.; Magolan, J.
J. Org. Chem. 2015, 80(7) 3701-3707.
DOI: 10.1021/acs.joc.5b00211
2015
Aryl methyl sulfides via SNAr using DMSO as the source of the thiomethyl moiety.
Jones-Mensah, E.; Magolan, J.
Tetrahedron Lett. 2014, 55(38), 5323-5326.
DOI: 10.1016/j.tetlet.2014.07.058
2014
2013
Dehydroaromatization with V2O5.
Karki, M.; Araujo, H. C.; Magolan, J.
Synlett 2013, 24(13), 1675-1678.
DOI: 10.1055/s-0033-133927
2012
Combined Pd/C and Montmorillonite Catalysis for Efficient One-Pot Synthesis of Benzimidazoles.
Weires, N.A.; Boster, J.; Magolan, J.
Eur. J. Org. Chem. 2012, 33, 6508-6512
DOI: 10.1002/ejoc.201201101
highlighted: Snieckus V.; Singh S.P. SYNFACTS 2013, 9(3), 254
Publications from Dr. Magolan's graduate and postdoctoral research
Tilly, D.; Magolan, J.; Mortier, J.
Directed Remote Aromatic Metalations: Mechanisms and Driving Forces.
Chemistry a European Journal 2012, 18(13), 3804-3820. (link)
Magolan, J.; Adams, N.B.P.; Onozuka, H.; Esumi, H.; Hugerford, N.L.; Coster, M.J.
Synthesis and biological evaluation of analogues of the natural product angelmarin for anti-pancreatic cancer activity.
ChemMedChem 2012, 7(5), 766-770. (link)
Magolan, J.; Coster, M.J.
Targeting the resistance of pancreatic cancer cells to nutrient deprivation: anti-austerity compounds.
Current Drug Delivery 2010, 7(5), 355-369. (link)
Magolan, J.; Coster M.J.
Total Synthesis of (+)-Angelmarin.
Journal of Organic Chemistry 2009, 74(14), 5083–5086. (link)
Magolan, J.; Carson, C.; Kerr, M.A.
Total Synthesis of (±)-Mersicarpine.
Organic Letters 2008, 10(7), 1437-1440. (link)
Li, L.; Jones, C.D.; Magolan, J.; Lemieux, R.P.
Siloxane-terminated phenylpyrimidine liquid hosts.
Journal of Materials Chemistry 2007, 17, 2313-2319. (link)
Magolan, J.; Kerr, M.A.
Expanding the Scope of Mn(OAc)3-Mediated Cyclizations: Synthesis of the Tetracyclic Core of Tronocarpine.
Organic Letters 2006, 8(17), 3777-3779. (Link)
England, D.B.; Magolan, J.; Kerr, M.A.
Synthesis of the Western Half of the Lolicines and the Lolitrems.
Organic Letters 2006, 8(11), 2209-2212. (link)