Activation of the amide group by acylation : Hydroxy- and aminoacyl incorporation in peptide systems

Abstract A new reaction, the hydroxy- and aminoacyl incorporation in aliphatic and alicyclic N-hydrox-(amino)acl amides is described in detail. The reaction affording linear or cyclic peptides and depsipeptides proceeds via formation of cyclols. Its course depends on the nucleophilicity of the HO- and NH 2 -groups, the electrophilicity of the amide carbonyl and, with cyclic amides, on the size of the ring. The cyclols which sometimes can be isolated display a number of unique properties, in particular, a tendency to undergo transformation into acylamides or macrocycles. Hydroxy- and aminoacyl incorporation is significant in the synthesis of peptides and depsipeptides. For example, it has been utilized in the synthesis of the antibiotic serratomolide and its analogues. A discussion of the biochemical and biogenetic implications of the reaction is given.