Reinventing Amide Bond Formation

Abstract

The chemical synthesis of peptides and proteins has long relied on inno- vative inventions of amide-forming reactions. Our group has discovered and devel- oped an amide-forming ligation reaction by the coupling of a-ketoacids and hydroxylamine (KAHAligation). This reaction does not require reagents or catalysts, proceeds in the presence of unprotected functional groups, and generates no nonvol- atile by-products. This chapter recounts our discovery of this reaction, our develop- ment of novel methods for the preparation of a-ketoacids and hydroxylamines, and the application of these new methods to the synthesis of peptides and proteins.