Recent Advances in the Synthesis of Trisubstituted Hydroxylamines

In recent years, N,N,O-trisubstituted hydroxylamine motif is gradually asserting its potentials as a novel structural element for drug discovery because of its multiple features, including low basicity, good stability, and an inherent lack of reactivity toward enzymes, which confer mutagenicity on less-substituted hydroxylamines. However, the broad application of this moiety for drug discovery purposes is limited by the paucity of synthetic methods for a series of complex hydroxylamine derivatives. This short review focuses on recent advances in the synthesis of N,N,O-trisubstituted hydroxylamines suitable for fragment-based drug design in medicinal chemistry.