Research in the Yudin lab
Research in the Yudin lab addresses contemporary problems in synthetic organic chemistry. We care as much about how we make our molecules as we do about their functional significance. Aside from purely fundamental aspects of synthesis that we find exciting, sustainable practice of organic chemistry is influencing what we do in an ever-increasing manner.
In our research endeavours we typically start by defining a project with well-articulated and clear goals. This involves careful formulation of scientific questions and risk assessment. During their studies in the Yudin lab, students polish scientific reasoning skills at weekly group meetings and during personal meetings with Andrei. At our group meetings we discuss long-term goals of our ongoing projects, dwell on the short-terms objectives, and solve problem sets.
Our students progress through their PhD, MSc, undergraduate, or postdoctoral studies by learning the fundamentals of teamwork. They get to present their findings, write scientific papers, and defend their arguments at conferences. The goal of any post-graduate study is to secure appropriate employment. Upon acquiring state-of the art synthetic skills, our graduates find employment in big pharmaceutical companies, biotech companies, universities, and government agencies.
The following areas are representative of our current research directions
Macrocycles and peptides
We develop and apply new methods for making complex macrocycles. This effort involves discovery of new cyclization reactions and careful spectroscopic characterization of our molecules with the goal of understanding their conformation.
Representative examples:
Širvinskas, M. J.; Saunders, G. J.; Mitrache, M.; Yudin, A. K. “Stabilization of 310-Helices in Cyclic Peptides Using Dominant Rotor Methodology,” J. Am. Chem. Soc. 2024, 146, 24085–24093.
Appavoo, S. D.; Heller, N. W.; van Campenhout, C. T.; Saunders, G. J.; Yudin, A. K. “Identification of “Structural Pin” Interactions and Their Significance for the Conformational Control of Macrocyclic Scaffolds,” Angew. Chem. Int. Ed. 2024, e202402372.
Huh, S.; Saunders, G. J.; Yudin, A. K. “Single Atom Ring Contraction of Peptide Macrocycles Using Cornforth Rearrangement,” Angew. Chem. Int. Ed. 2022, 134,
Diaz, D. B.; Appavoo, S. D. Bogdanchikova, A. F.; Lebedev, Y.; McTiernan, T. J.; Gomes, G.; Yudin, A. K. “Illuminating the Dark Conformational Space of Macrocycles Using Dominant Rotors,” Nat. Chem. 2021, 13, 218-225
Reaction discovery
Our hypothesis is that new chemical transformations can arise from combinations of half-reactions, which can be either endothermic or exothermic. Several ongoing projects tackle this area and seek to discover new transformations by combining the elements of existing processes in entirely new ways.
Representative examples:
Trofimova, A.; Diamandas, M.; Brien, C.; Khasanzode, N.; Lough, A. J.; Yudin, A. K. “Terpenoid Cyclophanes with Planar Chirality,” J. Am. Chem. Soc. 2024, 146, 23365–23375
Tien, C.-H., Lough, A.J., Yudin, A. K. “Iminologous epoxide ring-closure,” Chem. Sci. 2022, 13,
Yudin, A. K. “Space, Energy, and Synthetic Half-Reactions,” Chem. World 2021, 18, 5
Yudin, A. K. “Synthetic Half-Reactions,” Chem. Sci. 2020, 11, 12423-12427
Amphoteric molecules
Bifunctional structures that combine seemingly incompatible reactivity centers (e.g. a nucleophile and an electrophile) are a long-standing research area in our group. Over the years we have developed synthetic reagents that are broadly used in chemical synthesis.
Representative examples:
Trofimova, A.; White, B.; Diaz, D. B.; Širvinskas, M. J.; Lough, A. J.; Dudding, T.; Yudin, A. K. “A Boron Scan of Ethyl Acetoacetate Leads to Versatile Building Blocks,” Angew. Chem. Int. Ed. 2024, e202319842.
Soor, H. S.; Diaz, D. B.; Burton, K. I.; Yudin, A. K. “Synthesis of Fluorinated Aminoboronic Acids from Amphoteric α-Boryl Aldehydes,” Angew. Chem. Int. Ed. 2021, 60, 16366-16371
Tien, C.-H.; Trofimova, A.; Holownia, A.; Kwak, B. S.; Larson, R. T.; Yudin, A. K. “Carboxyboronate as a Versatile In Situ CO Surrogate in Palladium-Catalyzed Carbonylative Transformations,” Angew. Chem. Int. Ed. 2021, 60, 4342-4349
Lee, C. F.; Diaz, D. B.; Holownia, A.; Kaldas, S. K.; Liew, S. K.; Garrett, G. E.; Dudding, T.; Yudin, A. K. “Amine Hemilability Enables Boron to Mechanistically Resemble Either Hydride or Proton,” Nat. Chem. 2018, 10, 1062-1070
Chemical biology
The main objective of this effort is to apply complex macrocycles and boron-containing molecules to interrogate biological targets. We collaborate with many labs all over the world who use our molecules in order to perform biochemical assays and cell-based work.
Representative examples:
Huh, S.; Batistatou, N.; Wang, J.; Saunders, G. J.; Kritzer, J. A.; Yudin, A. K. “Cell Penetration of Oxadiazole-Containing Macrocycles,” RSC Chem. Biol. 2024, 5, 328-334
Tan, J; Cognetta, A. B. III, Diaz, D. B.; Lum, K. M.; Adachi, S.; Kundu, S.; Cravatt, B. F.; Yudin, A. K. “Multicomponent Mapping of Boron Chemotypes Furnishes Selective Enzyme Inhibitors,” Nat. Commun. 2017, 8, 1760
Lee, C. F.; Holownia, A.; Bennett, J. M.; Elkins, J. M.; St. Denis, J. D.; Adachi, S.; Yudin, A. K. “Oxalyl Boronates Enable Modular Synthesis of Bioactive Imidazoles”, Angew. Chem. Int. Ed. 2017, 56, 6264-6267