Preparation of Chiral Contiguous Epoxyaziridines and Their Regioselective Ring-Opening for Drug Syntheses

Abstract

Synthetically valuable chiral (aziridin-2-yl)oxirane-3-carbaldehydes bearing three consecutive functional groups including aziridine, epoxide, and aldehyde were prepared from the stereoselective epoxidation of (aziridin-2-yl)acrylaldehydes with H₂ O₂ using organocatalyst (2R)- or (2S)-[diphenyl(trimethylsilyloxy)methyl]pyrrolidine as organocatalyst. The regioselective ring opening of aziridines and epoxides enabled us to achieve the highly efficient asymmetric synthesis of the antibiotic edeine D fragment 3-hydroxy-4,5-diaminopenatanoic acid, an intermediate for the formal synthesis of non-proteinogenic amino acid (-)-galantinic acid, and for potent antifungal agent (+)-preussin, and the medicinally important framework 3-hydroxy-2-hydroxymethylpyrrolidine.

Keywords: contiguous epoxyaziridine; drug synthesis; enantioselective epoxidation; regioselective ring-opening; scaffold diversity.