Enantioselective synthesis of 3-arylquinazolin-4(3H)-ones via peptide-catalyzed atroposelective bromination.

ABSTRACT: We report the development of a tertiary amine-containing β-turn peptide that catalyzes the atroposelective bromination of pharmaceutically relevant 3-arylquinazolin-4(3H)-ones (quinazolinones) with high levels of enantioinduction over a broad substrate scope. The structure of the free catalyst and the peptide-substrate complex were explored using X-ray crystallography and 2D-NOESY experiments. Quinazolinone rotational barriers about the chiral anilide axis were also studied using density functional theory calculations and are discussed in light of the high enantioselectivities observed. Mechanistic studies also suggest that the initial bromination event is stereodetermining, and the major monobromide intermediate is an atropisomerically stable, mono-ortho-substituted isomer. The observatio

SUBMITTER: Diener ME 

PROVIDER: S-EPMC5134330 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature