Iterative Assembly of Macrocyclic Lactones using Successive Ring Expansion Reactions

Macrocyclic lactones can be prepared from lactams and hydroxyacid derivatives via an efficient 3- or 4-atom iterative ring expansion protocol. The products can also be expanded using amino acid-based linear fragments, meaning that macrocycles with precise sequences of hydroxy- and amino acids can be assembled in high yields by 'growing' them from smaller rings, using a simple procedure in which high dilution is not required. The method should significantly expedite the practical synthesis of diverse nitrogen containing macrolide frameworks.