Department of Chemistry, Indian Institute of Technology Palakkad; Environmental Sciences and Sustainable Engineering Center, Indian Institute of Technology Palakkad, Palakkad, Kerala, 678557, India.
Sci Rep. 2022 Mar 21;12(1):4815. doi: 10.1038/s41598-022-08775-z.
The design and synthesis of a versatile class of macrocycles with tunable functional groups and ring size are unfolded. Herein, a synthetic strategy is reported to furnish a new class of macrocycles in multi-gram scale in a two-step reaction. The total time taken for synthesizing a macrocycle is 1.5 h. Dithiocarbamates, an important functional group in biomedical and material sciences, is strategically incorporated in the macrocyclic backbone without metal for the first time. It is noteworthy that when state-of-the-art macrocycle synthesis is in millimolar concentration, this work employs the reaction in molar concentration (0.2-0.4 M). As proof-of-principle, a library of macrocycles was synthesized, varying the functional groups and ring size. The physicochemical properties of macrocycles revealed their druggable nature and are affirmed by protein (serum albumin) interaction study theoretically and experimentally. Diverse functional groups and ring sizes of macrocycles brought about twenty-five-fold difference in binding constant with the model protein.
本文展开了一类具有可调功能基团和环大小的多功能大环的设计和合成。在此，报道了一种在两步反应中以多克规模提供新大环的合成策略。合成大环的总时间为 1.5 小时。二硫代氨基甲酸盐是生物医学和材料科学中的一个重要功能基团，首次在大环骨架中没有金属的情况下被战略性地引入。值得注意的是，当最先进的大环合成处于毫摩尔浓度时，这项工作采用摩尔浓度（0.2-0.4 M）的反应。作为原理验证，合成了一系列具有不同功能基团和环大小的大环文库。大环的物理化学性质揭示了它们的成药性，并通过理论和实验上的蛋白质（血清白蛋白）相互作用研究得到证实。大环的不同功能基团和环大小导致与模型蛋白的结合常数有二十五倍的差异。
