Stereoselective Construction of β-, γ-, and δ-Lactam Rings via Enzymatic C-H Amidation.

ABSTRACT: Lactam rings are found in many biologically active natural products and pharmaceuticals, including important classes of antibiotics. Methods for the asymmetric synthesis of these molecules are therefore highly desirable, particularly through the selective functionalization of unreactive aliphatic C-H bonds. Here we show the development of a strategy for the asymmetric synthesis of β-, γ-, and δ-lactams via hemoprotein-catalysed intramolecular C-H amidation reaction with readily available dioxazolone reagents. Engineered myoglobin variants serve as excellent biocatalysts for this transformation yielding the desired lactam products in high yields, high enantioselectivity, and on preparative scale. Mechanistic and computational studies elucidate the nature of the C-H amination and enantiodete

SUBMITTER: Roy S 

PROVIDER: S-EPMC10997382 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature