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.