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

ABSTRACT: 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.

SUBMITTER: Stone EA 

PROVIDER: S-EPMC8513768 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature