Dow Mark, Marchetti Francesco, Abrahams Katherine A, Vaz Luis, Besra Gurdyal S, Warriner Stuart, Nelson Adam
School of Chemistry, University of Leeds, Leeds, LS2 9JT, UK.
Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
Chemistry. 2017 May 29;23(30):7207-7211. doi: 10.1002/chem.201701150. Epub 2017 May 2.
A modular synthetic approach was developed in which variation of the triplets of building blocks used enabled systematic variation of the macrocyclic scaffolds prepared. The approach was demonstrated in the synthesis of 17 diverse natural product-like macrocyclic scaffolds of varied (12-20-membered) ring size. The biological relevance of the chemical space explored was demonstrated through the discovery of a series of macrocycles with significant antimycobacterial activity.
开发了一种模块化合成方法，其中通过改变所用构建块的三联体，能够系统地改变所制备的大环支架。该方法在合成17种不同的、具有不同环大小（12至20元）的天然产物样大环支架中得到了验证。通过发现一系列具有显著抗分枝杆菌活性的大环化合物，证明了所探索化学空间的生物学相关性。
