Department of Chemistry, Villanova University, Villanova, PA 19085, United States.
Department of Chemistry, Temple University, Philadelphia, PA 19122, United States.
Bioorg Med Chem Lett. 2014 Jan 1;24(1):99-102. doi: 10.1016/j.bmcl.2013.11.070. Epub 2013 Dec 4.
Bis-alkylated derivatives of N,N,N',N'-tetramethylethylenediamine (TMEDA) represent a well-known class of versatile biscationic amphiphiles, owing to their low cost and ease of preparation. Asymmetric TMEDA derivatives, however, have been studied significantly less, particularly in regards to their antimicrobial properties. We have thus prepared a series of 36 mono- and bis-alkylated TMEDA derivatives to evaluate their inhibition of bacterial growth. This series of compounds showed low micromolar activity against a panel of four bacteria. Optimal inhibition was observed when the biscationic amphiphiles possessed modest asymmetry and were composed of between 20 and 24 total carbon atoms in the side chains. These amphiphiles were prepared in a simple two-step procedure, utilizing inexpensive materials and atom-economical reactions, making them practical for further development.
N,N,N',N'-四甲基乙二胺（TMEDA）的双烷基化衍生物是一类众所周知的多功能双阳离子两亲物，因为它们成本低且易于制备。然而，不对称 TMEDA 衍生物的研究要少得多，特别是在其抗菌性能方面。因此，我们已经制备了一系列 36 种单烷基化和双烷基化 TMEDA 衍生物来评估它们对细菌生长的抑制作用。该系列化合物对四种细菌表现出低微摩尔的活性。当双阳离子两亲物具有适度的不对称性并且侧链中含有 20 到 24 个总碳原子时，观察到最佳抑制作用。这些两亲物通过简单的两步法制备，使用廉价的材料和原子经济性反应，使它们更适合进一步开发。
