Organic Chemistry Seminar: Chemoselective Reactions for Late-Stage Skeletal Editing and Molecular Sensing

Abstract:

Synthetic organic chemistry plays a crucial role in developing advanced technologies that benefit society, from large-scale manufacturing to individualized healthcare. In this lecture, I describe approaches for leveraging chemical design and synthetic strategies to address challenges in drug discovery and live-cell images. 

In this first part of the talk, I discuss an unusual methodology to insert a nitrogen atom into the core skeleton of indoles to afford quinazolines.1 The compatibility of the reaction with many common functional groups makes it a promising route for making various types of quinazolines, which are relevant pharmaceutically targets. Thus, the methodology was applied in the context of late-stage skeletal editing of several commercial drugs, clearly highlighting the reaction’s broad potential for drug discovery. 

In the second part of the talk, I describe the design and synthesis of a new chemical-responsive trigger that recognizes CO2 with exquisite selectivity.2 Based on this discovery, a large family of selective fluorescent CO2 sensors was designed, synthesized, and evaluated. The modularity in reactivity and optical properties of these molecular sensors allows their use in a broad spectrum of multidisciplinary applications, including gas mixtures sensing, chemical reaction monitoring, and enzymatic inhibition assays. Notably, these sensors were compatible with biological systems and could be used in live-cell imaging. 

References:

1)    “Late-stage diversification of indole skeletons through nitrogen atom insertion.”
Julia C. Reisenbauer ¥, Ori Green¥, Allegra Franchino, Patrick Finkelstein, Bill Morandi*  
Science, 2022, 377, 1104-1109.

2)    “Activity-Based Approach for Selective Molecular CO2 Sensing.”
Ori Green¥, Patrick Finkelstein¥, Miguel A. Rivero-Crespo, Marius D. R. Lutz, Michael K. Bogdos, Michael Burger, Jean-Christophe Leroux, Bill Morandi*  
J. Am. Chem. Soc. 2022, 144, 8717-8724. 

Event Organizer: Dr. Roman Dobrovetsky