Ynamide-Mediated Macrolactonization
Ming Yang, Xuewei Wang, Junfeng Zhao
Abstract
Macrolactonization represents a long-standing challenge for organic chemists. Herein, an ynamide-mediated macrolactonization of seco-acids with the assistance of an acid catalyst is described. Various macrolactones ranging in ring size from medium to large can be prepared by using this method. The notorious issues associated with conventional macrolactonization reactions, such as the racemization/epimerization of seco-acids containing an α-chirality center, and the E/Z isomerization of α,β-unsaturated seco-acids can be avoided using this method. In addition, the ynamide-mediated two-step macrolactonization reaction can be performed in a one-pot manner, thus offering a user-friendly protocol. Cyclodepsipeptides containing both amide and ester bonds can also be constructed using this method as the key step to facilitate the ring closure. The total synthesis of dehydroxy LI-F04a, which contains a cyclic hexadepsipeptide core, has been accomplished using this method.