Amino [13]-macrodilactones: Synthesis, derivatization, and structural motifs. Issue 48 (26th November 2020)

• Record Type: Journal Article
• Authors: Chen, Chengsheng; Lawrence, Jean-Marc; Peczuh, Mark W.
• Is Part Of: Tetrahedron letters. Volume 61:Issue 48(2020)
• Publication Date: 2020-11-26
• Subjects: Macrocycle -- Conformation -- Synthesis -- X-ray crystallography; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2020.152579
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: The route to [13]-macrodilactones allows diversification of the backbone based on starting diol and pentenoic acids used. The late stage amidation of amino [13]-macrodilactones enables rapid preparation of analogs. A-values were used to rationalize disposition of substituents on [13]-macrodilactone ring. (± ) N -Boc allylglycine was prepared by alkylation and hydrolysis of N -Boc glycine methyl ester. Abstract: 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.