Solid-phase synthesis of N-formylhydroxylamines (reverse/retro-hydroxamates).

Abstract

N-Formylhydroxylamines, also known as reverse- or retro-hydroxamates, have become of significant interest in the recent past as inhibitors of metalloenzymes. Although solution-phase synthetic routes to such compounds have been reported, these are often lengthy and involve purification at each stage. Herein, novel three-step solid-phase synthetic approaches are described that enable libraries of such compounds to be produced in a convergent and efficient manner using commercially available starting materials. [reaction: see text]