Abstract: Production of molecules with desired functional attributes is the enduring objective of chemical synthesis. As structural complexity of therapeutic agents increases, so is the number of interrelated parameters that need to be controlled. Bioactive macrocycles offer a good example underscoring this notion. Their relatively large polar surface area increases the chance to interrogate extended protein binding sites, but also creates an impediment to achieving favorable drug properties. Synthetic tools that allow one not only to cyclize linear precursors but also to exercise control over conformation-driven cellular permeability are in high demand. This part of the lecture will summarize our ongoing efforts in this area and will highlight key experimental findings obtained in the past few months.
Another active area of our research targets biologically active boron-containing molecules. Boron is an abundant element on earth yet, despite its availability, C-B bonds are not present in the structures of natural products. This, however, does not mean that boron has no utility in chemical biology and drug discovery. On the contrary, there are numerous examples of bioactive molecules that bear C-B bonds. Similar to the synthetic utility of organoboron compounds, the biological activity of boron-containing molecules is based on reversible covalent interactions with nucleophiles. I will present the foundational principles of Boroscan – an enabling technology to construct boron-containing bioactive molecules using amphoteric molecules.
Bio: Andrei K. Yudin received his undergraduate degree at the Moscow State University in 1992. He subsequently worked in the laboratories of G. K. S. Prakash and George A. Olah at USC, where he received his PhD in 1996. Following postdoctoral training in the laboratory of K. Barry Sharpless at the Scripps Research Institute, Professor Yudin started his independent career at the University of Toronto in 1998. He became an associate professor in 2002, which was followed by promotion to the rank of a full professor in 2007. Since January 2015, Professor Yudin has served as the Chair of the Board for Organic and Biomolecular Chemistry (a publication of the Royal Society of Chemistry, U.K.). He is an internationally renowned scholar who has created new molecules that serve as powerful tools used for chemical synthesis. Professor Yudin’s concept of “forced orthogonality” has enabled the development of entirely new classes of compounds, previously thought to be too unstable to be used as practical reagents. Professor Yudin has also been active in translating these fundamental discoveries into applications that impact the fields of chemistry, biology and medicine. Professor Yudin has been recognized with a number of awards. He is a fellow of the Royal Society of Chemistry (UK), and is a Fellow of the Royal Society of Canada.