Isolating Conformers to Assess Dynamics of Peptidic Catalysts Using Computationally Designed Macrocyclic Peptides

Studying the relationship between
catalyst conformational dynamics
and selectivity in an asymmetric reaction is a challenge. In this
study, cyclic peptides were computationally designed to stabilize
different ground state conformations of a highly effective, flexible
tetrapeptide catalyst for the atroposelective bromination of N-aryl quinazolinones. Through a combination of computational
and experimental techniques, we have determined that dynamic movement
of the lead catalyst plays a crucial role in achieving high enantioselectivity
in the reaction of study. This approach may also serve as a valuable
method for investigating the mechanism of other peptide-catalyzed
transformations.