Research Mission
Modern medicine has been one of the major beneficiaries of advancements in the field of synthetic organic chemistry over the last several decades, and a seemingly infinite number of challenges and opportunities still exist in both fields. Our mission is to make fundamental contributions to synthetic organic chemistry, biology and medicine. To accomplish this, we seek out problems in medicinal chemistry and chemical biology that are in need of new synthetic organic chemistry developments. Thus, primary studies carried out by lab members range from reaction discovery and mechanism investigations to multi-step synthetic strategy developments. We simultaneously partner with experts in complementary fields in order to leverage these advancements in a broad range of interdisciplinary projects devoted to lead drug discovery and development.
Publications
2023
58. Bejcek, L. P.^; Eli, O.^ ; Lyubimova, A.; Kapkayeva, D. M.; Nafie, J.; Beutler, J. A.; Gallicchio, E.; Sackett, D.; Murelli, R. P. "Studies on a Type III Atropisomeric Colchicine Analog Enabled by an Intermolecular Oxidopyrylium (5 + 2) Cycloaddition/Reductive Ring-Opening Sequences" ChemRxiv, 2023 . (^contributed equally) (link)
57. Baucom, J-C.; Agyemang, N. B.; Trelles, T.; Gallicchio, E.; Murelli, R. P. "Studies on the Configurational Stability of Tropolone-Ketone, -Ester, and Aldehyde-Based Chiral Axess" J. Org. Chem. 2023 , Accepted. (link)
56. Woodson, M. E.; Mottaleb, M. A.; Murelli, R. P.; Tavis, J. E. "In vitro evaluation of tropolone absorption, metabolism, and clearance" Antiviral Res., 2023 , 220, 105762. (link)
55. Schiavone, D. V; Gallardo, J.; Kapkayeva, D. M.; Baucom, J-C.; Murelli, R. P. "Lactam-Fused Tropolones: A New Tunable, Environmentally Sensitive Fluorophore Class" Org. Biomol. Chem. 2023 , 21, 7900-7907. (link)
54. Gazquez Casals, A.; Berkowitz, A. J.; Yu, A. J.; Waters, H. E.; Schiavone, D. V.; Kapkayeva, D. M.; Morrison, L. A.; Murelli, R. P. "Antiviral Activity of Amide-Appended α-Hydroxytropolones against Herpes Simplex Virus-1 and -2" RSC Advances, 2023 , 13, 8743-52. (link)
53. Murelli, R. P.; Berkowitz, A. J.; Zuschlag, D. W. "Carbocycloaddition strategies for troponoid synthesis" Tetrahedron, 2023 , 130, 133175. (link)
2022
52. Geerling, E.; Murphy, V.; Mai, M. C.; Stone, E. T.; Casals, A. G.; Hassert, M.; O'Dea, A. T.; Cao, F.; Donlin, M. J.; Elagawany, M.; Elgendy, B.; Pardali, V.; Giannakopoulou, E.; Zoidis, G.; Schiavone, D. B.; Berkowitz, A. J.; Agyemang, N. B.; Murelli, R. P.; Tavis, J. E.; Pinto, A. K.; Brien, J. D. "Metal coordinating inhibitors of Rift Valley fever virus replication" Plos One 2022,17, e0274266. (link)
51. Berkowitz, A. J.; Murelli, R. P. "Synthesis of α-Tropolones through Autoxidation of Dioxole-Fused Cycloheptatrienes" J. Org. Chem. 2022,87, 4499-4705. (link)
See also Journal Cover.
50. Schiavone, D. V.; Kapkayeva, D. M.; Li, Q.; Woodson, M. E.; Gazquez Casals, A.; Morrison, L. A.; Tavis, J. E.; Murelli, R. P. "Synthesis of Polyoxygenated Tropolones and their Antiviral Activity Against Hepatitis B Virus and Herpes Simplex Virus-1" Chem. Eur. J. 2022, 28, e202104112. (link)
2021
49. Murelli, R. P. "Intermolecular Oxidopyrylium [5+2] Cycloaddition Chemistry and its Application Towards the Synthesis and Study of Highly Oxygenated Troponoids" In Strategies and Tactics in Organic Synthesis, Vol. 15, Harmata, M., Ed; Elsevier, 2021 (Invited Research Account) (link)
48. Bradley, D. P.; O’Dea, A. T.; Woodson, M. E.; Li, Q.; Ponzar, N. L.; Knier, A.; Rogers, B. L.; Murelli, R. P.; Tavis, J. E. "Effects of troponoids on mitochondrial function and cytotoxicity" Antimicrob. Agents Chemother., 2021, 01617-21 (link)
47. Swain, M. Ageeli, A. A.; Kasprzak, W. K.; Mi L.; Miller, J. T.; Sztuba-Solinska, J.; Schneekloth, J. S.; Koirala, D.; Piccirili, J.; Fraboni, A. J.; Murelli, R. P.; Wlodawer, A.; Shapiro, B. A.; Baird, N.; Le Grice, S. F. J. "Dynamic bulge nucleotides in the KSHV PAN ENE triple helix provide a unique binding platform for small molecule ligands"Nucleic Acids Res. 2021, 39, 13179-13193. (link)
46. Schiavone, D. V.; Kapkayeva, D. M.; Murelli, R. P. "Investigations into a Stoichiometrically Equivalent, Intermolecular Oxidopyrylium [5+2] Cycloaddition Reaction Leveraging 3-Hydroxy-4-Pyrone-Based Oxidopyrylium Dimers" J. Org. Chem. 2021, 86, 3826-3835.(link)
2020
45. Bak, E.; Miller, J. T.; Noronha, A.; Tavis, J.; Gallicchio, E.; Murelli, R. P.; Le Grice, S. F. J. "3,7-Dihydroxytropolones Inhibit Initiation of Hepatitis B Virus Minus-Strand DNA Synthesis" Molecules, 2020, 25, 4434.(link)
44. Li, Q.; Lomonosoca, E.; Donlin, M.; Cao, F.; O'Dea, A.; Milleson, B.; Berkowitz, A. J.; Baucom, J-C.; Stasiak, J. P.; Schiavone, D. V.; Abdelmessih, R. G.; Lyubimova, A.; Fraboni, A. J.; Bejcek, L. P.; Villa, J. A.; Gallicchio, E.; Murelli, R. P.; Tavis, J. E. "Amide-containing α-hydroxytropolones as inhibitors of hepatitis B virus replication " Antiviral Res. 2020, 177, 104777. (link)
43. Bejcek, L. P.; Murelli, R. P. "Synthesis of Aryl-Substituted 2-Methoxyphenol Derivatives from Maltol-Derived Oxidopyrylium Cycloadducts through an Acid-Mediated Ring-Contraction Cascade" Chem. Comm. 2020, 56, 3203-3205. (link)
42. Lanave, G.; Martella, V.; Tempesta, M.; Catella, C.; Murelli, R. P.; Morrison, L. A.; Lucenta, M. S.; Buinavoglia, C.; Camero, M. "Antiviral Activity of α-Hydroxytropolones on Caprine Alphaherpesvoris 1 in Vitro" Res. Vet. Sci. 2020, 129, 99-102. (link)
________________
2019
41. Agyemang, N. B.; Murelli, R. P. "Synthesis of 5-Hydroxy-4-methoxy-2-methylpyrylium Trifluoromethanesulfonate from Kojic Acid" Org. Synth. 2019, 96, 494-510. (link)
40. Bejcek, L. P.; Garimallaprabhakaran, A. K.; Suyabatmaz, D. M.; Greer, A.; Hersh, W. H.; Greer, E. M.; Murelli, R. P. "Maltol- and Allomaltol-Derived Oxidopyrylium Ylides: Methyl Substitution Pattern Kinetically Influences [5+3] Dimerization versus [5+2] Cycloaddition Reactions" J. Org. Chem., 2019, 84, 14670-14678. (link).
39. Agyemang, N. B.; Kukla, C. R.; Edwards, T. C.; Li, Q.; Langen, M. K.; Schaal, A.; Franson, A. D.; Gazquez Casals, A.; Donald, K. A.; Yu, A. J.; Donlin, M. J.; Morrison, L. A.; Tavis, J. E.; Murelli, R. P. "Divergent Synthesis of a Thiolate-Based α-Hydroxytropolone Library with a Dynamic Bioactivity Profile" RSC Advances, 2019, 9, 34227-34234. (link).
38. Berkowitz, A. J.; Franson, A. D.; Gazquez Cassals, A.; Donald, K. A.; Yu, A. J.; Garimallaprabhakaran, A. K.; Morrison, L. A.; Murelli, R. P. "Importance of Lipophilicity for Potent Anti-Herpes Simplex Virus-1 Activity of α-Hydroxytropolones"Med. Chem. Commun., 2019, 10, 1173-1176. (link).
37. Stasiak, J. P.; Grigoryan, A.; Murelli, R. P. "Spectrophotometric Determination of α-Hydroxytropolone pKa values: A Structure-Acidity Relationship Study" Tetrahedron Lett. 2019, 60, 1643-5. (link)
36. Hirsch, D. R.; Metrano, A. J.; Stone, E. A.; Storch, G.; Miller, S. J.; Murelli, R. P. "Troponoid Atropisomerism: Studies on the Configurational Stability of Tropone-Amide Chiral Axes" Org. Lett. 2019, 21, 2412-5. (link)
35. Tavis, J. E.; Zoidis, G.; Meyers, M. J.; Murelli, R. P. "Chemical Approaches to Inhibiting the Hepatitis B Virus Ribonuclease H" ACS. Infect. Dis. 2019, 5, 655-8. (link)
________________
2018
34. Cao, F.; Orth, C.; Donlin, M. J.; Adegboyega, P.; Meyers, M. J.; Murelli, R. P.; Elagawany, M.; Elgendy, B.; Tavis, J. E. "Synthesis and evaluation of troponoids as a new class of antibiotics" ACS Omega, 2018, 3, 15125-33. (link)
33. Miller, J. T.; Zhao, H.; Masaoka, T.; Varnado, B.; Cornejo Castro, E. M.; Marshall, V. A.; Kouhestani, K.; Lynn, A. Y.; Aron, K. E.; Xia, A.; Beutler, J. A.; Hirsch, D. R.; Tang, L.; Whitby, D.; Murelli, R. P.; Le Grice, S. F. J. "Sensitivity of the C-Terminal Nuclease Domain of Kaposi's Sarcoma-Associated Herpesvirus ORF29 to Two Classes of Active Site Ligands" Antimicrob. Agents Chemother. 2018, 62, e00233-18. (link)
32. Berkowitz, A. J.; Abdelmessih, R. G.; Murelli, R. P. "Amidation Strategy for Final-Step α-Hydroxytropolone Diversification" Tetrahedron Lett. 2018, 59, 3026-8. (link)
31. Bejcek, L. P.; Murelli, R. P. "Oxidopyrylium [5+2] Cycloaddition Chemistry: Historical Perspective and Recent Advances (2008-2018)" Tetrahedron, 2018, 74, 2501-2521. (link)
30. D'Erasmo, M. P.; Murelli, R. P. "Fluorous-Phase Approach to α-Hydroxtropolone Synthesis" J. Org. Chem. 2018, 83, 1478-1485. (link)
29. Dehghanpir, S. D.; Birkenheuer, C. H.; Yang, K.; Murelli, R. P.; Morrison, L. A.; Le Grice, S. F. J.; Baines, J. D. "Broad Anti-Herpesviral Activity of α-Hydroxtropolones" Vet. Microbiol. 2018 214, 125-131. (link)
28. Hirsch, D. R.; Schiavone, D. V.; Berkowitz, A. J.; Morrison, L. A.; Masaoka, T.; Wilson, J. A.; Lomonosova, E.; Zhao, H.; Patel, B. S.; Dalta, S. H.; Majidi, S. J.; Pal, R.; K.; Gallicchio, E.; Tang, L.; Tavis, J. E.; Le Grice, S. F. J.; Beutler, J. A.; Murelli, R. P. "Synthesis and Biological Assessment of 3,7-Dihydroxytropolones" Org. Biomol. Chem. 2018, 16, 62-69. (link)
See also: Journal Cover
27. Long, K. R.; Lomonosova, E.; Li, W.; Ponzar, N. L.; Villa, J. A.; Touchette, E.; Rapp, S.; Liley, R. M.; Murelli, R. P.; Grigoryan, A.; Buller, R. M.; Wilson, L.; Bial, J.; Sagartz, J. E.; Tavis, J. E. "Efficacy of Hepatitis B Virus Ribonuclease H Inhibitors, a New Class of Replication Antagonists, in FRG Human Liver Chimeric Mice" Antiviral Res. 2018, 149, 41-47. (link)
________________
2017
26. Fuhr, K. N.; Hirsch, D. R.; Murelli, R. P.; Brenner-Moyer, S. E. "Catalytic Enantioselective Intermolecular [5+2] Dipolar Cycloadditions of a 3-Hydroxy-4-Pyrone-Derived Oxidopyrylium Ylide", Org. Lett., 2017, 19, 6356-9. (link)
25 Grady, L. M.; Szczepaniak, R.; Murelli, R. P.; Masaoka, T.; Le Grice, S. F. J.; Wright, D. L.; Weller, S. K. "The exonuclease activity of HSV-1 UL12 is required for the production of viral DNA that can be packaged to produce infectious virus" J. Virol. 2017, 91, e01380-17 (link)
24. Lomonosova, E.; Daw, J.; Garimallaprabhakaran, A. K.; Agyemang N. B.; Ashani, Y.; Murelli, R. P.; Tavis, J. E. "Efficacy and cytotoxicity in cell culture of novel α-hydroxytropolone inhibitors of hepatitis B virus ribonuclease H" Antiviral Res. 2017, 144, 164-172. (link)
23. Donlin, M. J.; Zunica, A.; Lipnicky, A; Garimallaprabhakaran, A. K.; Berkowitz, A. J.; Grigoryan, A.; Meyers, M. J.; Tavis, J. E.; Murelli, R. P. "Troponoids can inhibit growth of the human fungal pathogen Cryptococcus neoformans" Antimicrob. Agents Chemother., 2017, 61, e02574-16. (link)
________________
2016
22. Zhang, B.; D'Erasmo, M. P.; Murelli, R. P. Gallicchio, E. "Free Energy-Based Virtual Screening and Optimization of RNase H Inhibitors of HIV-1 Reverse Transcriptase" ACS Omega, 2016, 1, 435-47. (link)
21. D'Erasmo, M. P.; Masaoka, T.; Wilson, J. A.; Hunte, E. M. Jr.; Beutler, J. A.; Le Grice, S. F. J.; Murelli, R. P. 'Traceless Solid-Phase α-Hydroxtropolone Synthesis' Med. Chem. Commun. 2016, 9, 1793-92. (link)
20. Murelli, R. P.; D'Erasmo, M. P.; Hirsch, D. R.; Meck, C.; Masaoka, T.; Wilson, J. A.; Zhang, B.; Pal, R. K.; Gallicchio, E.; Beutler, J. A.; Le Grice, S. F. J. 'Synthetic α-Hydroxytropolones as Inhibitors of HIV Reverse Transcriptase Ribonuclease H Activity' Med. Chem. Commun. 2016, 9, 1783-8. (link)
19. D'Erasmo, M. P.; Meck, C.; Lewis, C. A.; Murelli, R. P. "Discovery and Development of a 3-Component Oxidopyrylium [5+2] Cycloaddition Reaction" J. Org. Chem. 2016, 81, 3744-51. (link).
18. Ireland, P. J.; Tavis, J. E.; D'Erasmo, M. P.; Hirsch, D. R.; Murelli, R. P.; Cadiz, M. M.; Patel, B. S.; Gupta, A. K.; Edwards, T. C.; Korom, M.; Moran, E. A.; Morrison, L. A. "Synthetic α-hydroxytropolones inhibit replication of wild-type and acyclovir-resistant herpes simplex viruses" Antimicrob. Agents Chemother., 2016, 60, 2140-9. (link)
17. Masaoka, T.; Zhao, H.; Hirsch, D. R.; D'Erasmo, M. P.; Meck, C.; Varnado, B.; Gupta, A.; Meyers, M. J.; Baines, J. D.; Beutler, J. A.; Murelli, R. P.; Tang,L.; Le Grice, S. F. J. "Characterization the C-terminal nuclease domain of herpes simplex virus pUL15 as a target of nucleotidyltransferase inhibitors."Biochemistry, 2016, 55, 809-19. (link)
________________
2015
16. Zhao, H.; Lin, Z.; Lynn, A. Y.; Varnado, B.; Beutler, J. A.; Murelli, R. P.; Le Grice, S. F. J.; Tang, L. "Two distinct modes of metal ion binding in the nuclease active site of a viral DNA-packaging terminase: insight into the two-metal-ion catalytic mechanism" Nucleic Acids Res. 2015, 43, 11003-16. (link)
15. Lu, G.; Lomonosova, E.; Cheng, X.; Moran, E. A.; Meyers, M. J.; Le Grice, S. F. J.; Thomas, C. J.; Jiang, J-K.; Meck, C.; Hirsch, D. R.; D'Erasemo, M. P.; Suyabatmaz, D. M.; Murelli, R. P.; Tavis, J. E. "Hydroxylated tropolones inhibit hepatitis B virus replication by blocking the viral ribonuclease H activity" Antimicrob. Agents Chemother. 2015, 59, 1070-1079. (link)
________________
2014
14. Hirsch, D. R.; Cox, G. C.; D'Erasmo, M. P.; Shakya, T.; Meck, C.; Mohd, N.; Wright, G. D.; Murelli, R. P. "Inhibition of ANT(2")-Ia resistance enzyme and rescue of aminoglycoside antibiotic activity by synthetic α-hydroxytropolones" Bioorg. Med. Chem. Lett. 2014, 24, 4943-4947. (link)
13. D'Erasmo, M. P.; Smith, W. B.; Munoz, A.; Mohandas, P.; Au, A. S.; Marineau, J.; Quadri, L. E. N.; Bradner, J. E.; Murelli, R. P. "7,9-Diaryl-1,6,8-trioxaspiro[4.5]dec-3-e-2-ones: Readily accessible and highly potent anticancer compounds" Bioorg. Med. Chem. Lett. 2014, 24, 4035-4038. (link)
12. Meck, C.; D' Erasmo, M. P.; Hirsch, D. R.; Murelli, R. P. "The biology and synthesis of α-hydroxytropolones" Med. Chem. Commun. 2014, 5, 842-852. (link)
________________
2013
11. Williams, Y. D.; Meck, C.; Mohd, N.; Murelli, R. P. "Triflic acid mediated rearrangements of 3-methoxy-8-oxabicyclo[3.2.1]octa-3,6-dien-2-ones: Synthesis of methoxytropolones and furans" J. Org. Chem. 2013, 78, 11707-11713. (link)
________________
2012
10. Meck, C.; Mohd, N.; Murelli, R. P. "An oxidopyrylium cyclization/ ring-opening route to polysubstituted α-hydroxytropolones" Org. Lett. 2012, 14, 5988-5991. (link)
9. Munoz, A.; Murelli, R. P. "Acid-mediated coupling of gamma-hydroxybutenolides and aldehydes: Synthesis of a new class of spirocyclic ketal-lactones" Tetrahedron Lett. 2012, 53, 6779-6781. (link)
________________
Ryan's Postdoctoral Publications (Yale University)
8. Nelson, J. W.; Chammessian, A. G.; McEnaney, P. J.; Murelli, R. P.; Kazmiercak, B. I.; Spiegel, D. A. “A Biosynthetic Strategy for Re-engineering the Staphylococcus aureus Cell Wall with Non-Native Small Molecules” ACS ChemBio, 2010, 5 , 1147-1155.(link)
See also: Cell, BioTechniques, Science Daily News and Yale Daily News
7. Zhang, A. X.; Murelli, R. P.; Barinka, C.; Michel, J.; Cocleaza, A.; Jorgensen, W. L.; Lubkowski, J.; Spiegel, D. A. “A Remote Arene Binding Site of Prostate Specific Membrane Antigen Revealed by Antibody-Recruiting Small Molecules” J. Am. Chem. Soc. 2010, 132, 12711-12716.(link)
See also: Chemical & Engineering News Highlight and Nature ChemBio Highlight.
6. Murelli, R. P.; Zhang, A. X.; Michel, J.; Jorgensen, W. L.; Spiegel, D.A. “Chemical Control Over Immune Recognition: A Class of Antibody-Recruiting Small Molecules (ARMs) that Target Prostate Cancer” J. Am. Chem. Soc. 2009, 131, 17090-17092.(link)
See also: ACS ChemBio Spotlight, ChemBioChem Highlight, Faculty of 1000 Biology Highlight, Drug Discovery News Article, Yale Daily News, and Science Daily News.
5. Stern, E.; Jay, S. M.; Demento, S. L.; Murelli, R. P.; Reed, M. A.; Malinski, T.; Spiegel, D. A.; Mooney, D. J.; Fahmy, T. M. “Spatiotemporal Control over Molecular Delivery and Cellular Encapsulation from Electropolymerized Micro and Nanopatterned Surfaces” Adv. Funct. Mater. 2009, 19, 2888-2895.(link)
________________
Ryan's Graduate School Publications (Boston College)
4. Murelli, R. P.; Catalán, S.; Gannon, M. P.; Snapper, M. L. “Ruthenium-Catalyzed Enyne Cross-Metathesis-Cyclopropanation: Three Component Access to Vinyl Cyclopropanes” Tetrahedron Lett., 2008, 49, 5714-5717.(link)
3. Murelli, R. P.; Snapper, M. L. “Ruthenium-Catalyzed Tandem Cross-Metathesis/ Wittig Olefination: Generation of Conjugated Dienoic Esters from Terminal Olefins” Org. Lett. 2007, 9, 1749-1752.(link)
See also: Organic Chemistry Portal
2. Murelli, R. P.; Cheung, A. K.; Snapper, M. L. “Conformationally Restricted (+)-Cacospongionolide B Analogues: Influence on Secretory Phospholipase A2 Inhibition” J. Org. Chem. 2007, 72, 1545-1552.(link)
See also: Journal Cover
1. Cheung, A. K.; Murelli, R.; Snapper, M. L. “Total Syntheses of (+)- and (-)-Cacospongionolide B, Cacospongionolide E, and Related Analogues. Preliminary Study of Structural Features Required for Phospholipase A2 Inhibition” J. Org. Chem. 2004, 69, 5712-5719.(link)
________________
Patent Applications
4. Le Grice, S. F. J.; Sztuba-Solinska, J.; Murelli, R. P.; "Chemical entities for lytic activation of Kaposi's sarcoma herpesvirus and therapeutic targeting of viral enzymes/proteins" " PCT Int. Appli. (2019) No. WO 2019118803 A1 20190620.
3. Donlin, M. J.; Tavis, J. E.; Murelli, R.; Meyers, M. J. "Preparation of substituted cycloheptatrienones as antifungal compounds" PCT Int. Appli. (2017) No. WO 2017-184752.
2. Tavis, J. E; Morrison, L. A.; Murelli, R. P. "Preparation of hydroxylated tropolone inhibitorsof nucleotidyl transferases in treatment of herpesvirus and hepatitis B" PCT Int. Appl. (2016) No. WO 2016-201243.
1. Spiegel, D.; Murelli, R.; Zhang, A. “Chimeric Small Molecules that Recruit Antibodies to Cancer Cells” PCT Int. Appl. (2009) No. WO 2009-US2857. Patent No. WO 2009139863.