Expanding the Chemical Space of Non-Proteinogenic N-4-Substituted Asparagine: Racemic, Enantioenriched, and Deuterated Derivatives

A site-selective carbamoylation strategy to access non-proteinogenic N-4-modified asparagines has been described. The protocol is characterized by mild reaction conditions, high functional group compatibility, and a wide diversity of functionalized carbamoyl radicals making possible the access to peptides, pharmaceuticals, and natural N-4-asparagine conjugates, as well as enantioenriched unnatural N-4-asparagines. Besides that, deuterated analogues were achieved with the insertion of D2O and enantioenriched derivatives could be obtained in 15 min in continuous-flow conditions.