Amino [13]-Macrodilactones: Synthesis, Derivatization, And Structural Motifs

Macrocycles draw their usefulness from an ability to balance size, shape, and functionality according to general principles. These structural parameters manifest as the conformations of macrocycles and ultimately their functions. Reported here are results of an investigation on [13]-macrodilactones that take up unique folded conformations based on the interplay of multi-atom planar units and sterics. The defining feature of this group of [13]-macrodilactones is the pendant amine group attached to the ring. Amidation of the ring generated analogs that were designed to imitate features of the macrocyclic natural product Teixobactin. We also show that intramolecular interactions, and the A-value of an acylated amine can explain the conformational preferences in macrocycles. (C) 2020 Elsevier Ltd. All rights reserved.