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Research

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: 

  • Huh, S.; Saunders, G. J.; Yudin, A. K. “Single Atom Ring Contraction of Peptide Macrocycles Using Cornforth Rearrangement,” Angew. Chem. Int. Ed. 2022, 134, https://doi.org/10.1002/ange.202214729
  • Saunders, G. J.; Yudin, A. K. “Property-Driven Development of Passively Permeable Macrocyclic Scaffolds Using Heterocycles,” Angew. Chem. Int. Ed. 2022, 134, e202206866
  • 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:

  • Tien, C.-H., Lough, A.J., Yudin, A. K. “Iminologous epoxide ring-closure,” Chem. Sci. 2022, 13, https://doi.org/10.1039/D2SC04496J
  • 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: 

  • 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:

  • Trudel, V.; Brien, C.; Tan, J.; Yudin, A. K. “Towards depeptidized aminoboronic acid derivatives through the use of borylated iminium ions,” ChemComm 2022, 58, 5033-5036
  • 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

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