A Computational Experimental Approach to Heterobiaryl Atropismerism
Subject Area
Chemistry
Description
Emily Orloff ’22, Major: Chemistry
Colby Agostino ’22, Majors: Biochemistry and Computer Science
Faculty Mentor: Dr. Kristen Baker, Chemistry and Biochemistry
Atropisomers have barriers to rotation, Grot, that prevent racemization. We used computational modeling to develop a suite of 30 configurationally stable, bio-inspired 1-aryl-β-carbolines with varying Grot, from which a strong structure-activity relationship was observed for 2-substituted-1-naphthyl substituents. We then synthesized two of these atropisomers, 1s and 1t, and resolved the enantiomers via chiral chromatography. Racemization studies revealed experimental Grot values of 39.5 and 33.0 kcal/mol for 1s and 1t, respectively, which were consistent with our computational results. These atropisomers exhibited long half-lives, which allowed for their full physicochemical characterization and stereochemical assignment via electronic and vibrational circular dichroism.
Publisher
Providence College
Date
4-28-2022
Type
Poster
Language
English
