Nature synthesizes many diverse polycyclic, stereodense natural products. Such molecules are also often the targets of laboratory syntheses. We are exploring the mechanisms of key cascade reactions used both in biosyntheses and biomimetic laboratory syntheses of many complex natural products - representative examples are shown above and representative papers are listed below.
Ho, G. A.; Nouri, D. Tantillo, D. J. J. Org. Chem. 2005, 70, 5139-5143: "The Cationic Cascade Route to Longifolene"
Nouri, D. H.; Tantillo, D. J. Curr. Org. Chem. 2006, 10, 2055-2074: "They Came from the Deep: Syntheses, Applications, and Biology of Ladderanes"
Gutta, P.; Tantillo, D. J. J. Am. Chem. Soc. 2006, 128, 6172-6179: "Theoretical Studies of Farnesyl Cation Cyclization: Pathways to Pentalenene"
Gutta, P.; Tantillo, D. J. Org. Lett. 2007, 9, 1069-1071: "A Promiscuous Proton in Taxadiene Biosynthesis?"
Willenbring, D.; Tantillo, D. J. Russ. J. Gen. Chem. 2008, 78, 723-731 (Rossiiskii Khimicheskii Zhurnal 2007, 51, 49-55): "Mechanistic Possibilities for Oxetane Formation in the Biosynthesis of Taxol's D Ring"
Wang, S. C.; Tantillo, D. J. J. Org. Chem. 2008, 73, 1516-1523: "Theoretical Studies on Synthetic and Biosynthetic Oxidopyrylium–Alkene Cycloadditions. Pericyclic Pathways to Intricarene"
Tantillo, D. J. J. Phys. Org. Chem. 2008, 21, 561-570: "Recent Excursions to the Lands between Concerted and Stepwise: From Natural Products Biosynthesis to Reaction Design"
Wang, S. C.; Tantillo, D. J. Org. Lett. 2008, 10, 4827-4830: "Prediction of a New Pathway to Presilphiperfolanol"
Ho, G. A.; Nouri, D. H.; Tantillo, D. J. Tetrahedron Lett. 2009, 50, 1578-1581: "Carbocation Rearrangements in Aspernomine Biosynthesis"
Hong, Y. J.; Tantillo, D. J. J. Am. Chem. Soc. 2009, 131, 7999-8015: "Consequences of Conformational Preorganization in Sesquiterpene Biosynthesis. Theoretical Studies on the Formation of the Bisabolene, Curcumene, Acoradiene, Zizaene, Cedrene, Duprezianene, and Sesquithuriferol Sesquiterpenes"
Hong, Y. J.; Tantillo, D. J. Nature Chem. 2009, 1, 384-389: "A Potential Energy Surface Bifurcation in Terpene Biosynthesis"
Sio, V.; Harrison, J. G.; Tantillo, D. J. Tetrahedron Lett. 2012, 53, 6919-6922: "Theoretical Assessment of the Viability of Thermal [2+2] Processes for Formation of Plumisclerin A"
Hudson, B. M.; Harrison, J. G.; Tantillo, D. J. Tetrahedron Lett. 2013, 54, 2952-2955: "Assessing the Viability of Biosynthetic Pathways for Calophyline A Formation - Are Pericyclic Reactions Involved?"
Painter, P. P.; Pemberton, R. P; Wong, B. M.; Ho, K. C; Tantillo, D. J. J. Org. Chem. 2014, 79, 432-435: "The Viability of Nitrone-Alkene (3+2) Cycloadditions in Alkaloid Biosynthesis"
Yoneda, H.; Tantillo, D. J.; Atsumi, S. ChemSusChem 2014, 7, 92-95: "Biological Production of 2-Butanone in Escherichia coli"
Larson, R. T.; Pemberton, R. P.; Franke, J. M.; Tantillo, D. J.; Thomson, R. J. J. Am. Chem. Soc. 2015, 137, 11197-11204: "Total Synthesis of the Galbulimima Alkaloids Himandravine and GB17 using Biomimetic Diels–Alder Reactions of Double Diene Precursors"
Williams, D. R.; Klein, J. C.; Kopel, L. C.; Tantillo, D. J.; Nguyen, Q. N. Org. Lett. 2016, 18, 424-427: "Studies Toward Australifungin. A Synthesis Dilemma of Regioselective Keto-Enol Tautomerization"
Hare, S. R.; Farnham, J. M.; Tantillo, D. J. Tetrahedron 2017, 73, 4227-4232: "Putative Biosynthetic Cycloadditions en route to the Diterpenoid (+)-Chatancin," invited contribution to a Symposium-in-Print on "New Advances in Pericyclic Reactions."
Xu, G.; Elkin, M.; Tantillo, D. J.; Newhouse, T. R.; Maimone, T. J. Angew. Chem. Int. Ed. 2017, 56, 12498-12502: "Traversing Biosynthetic Carbocation Landscapes in the Total Synthesis of Andrastin and Terretonin Meroterpenes"
Tantillo, D. J. WIREs Comp. Molec. Sci. 2020, 10, e1453: "Interrogating Chemical Mechanisms in Natural Products Biosynthesis Using Quantum Chemical Calculations," invited.
Cen-Pacheco, F.; Santiago-Benítez, A. J.; Tsui, K. Y.; Tantillo, D. J.; Fernández, J. J.; Hernandez Daranas, A. J. Org. Chem. 2021, 86, 2437-2446: "Structure and Computational Basis for Backbone Rearrangement in Marine Oxasqualenoids"
Balo, A. R; Carusio, A.; Tao, L.; Tantillo, D. J.; Seyedsayamdost, M. R.; Britt, R. D. Proc. Natl. Acad. Sci. USA, 2021, 118, e2101571118: "Trapping a Crosslinked Lysine-Tryptophan Radical in the Catalytic Cycle of the Radical SAM Enzyme SuiB"
Prasad, S.; Tantillo, D. J. ACS Omega 2021, 6, 29685-29691: "Substituent Effects on the Basicity of Patriscabrin A and Lettucenin A: Evolution Favors the Aromatic?"
Soysal, E. N.; Findik, V.; Dedeoglu, B.; Aviyente, V.; Tantillo, D. J. ACS Omega 2022, 7, 31591-31596: "Theoretical Investigation of the Biogenetic Pathway for Formation of Antibacterial Indole Alkaloids from Voacanga africana"
