Department of Organic Chemistry, School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel-Aviv University, Tel Aviv 69978, Israel.
Org Biomol Chem. 2009 Dec 7;7(23):4825-8. doi: 10.1039/b915265b. Epub 2009 Oct 5.
The quinone-methide elimination is a common, efficient methodology used in linkers designed to undergo self-fragmentation. Here, for the first time, we demonstrate this elimination in a pyridine ring system. Under physiological conditions, a compound constructed of a pyridine core, a reporter, and an enzymatic trigger underwent significantly faster 1,4-elimination than its parent compound with a benzene core. In addition, an AB(2) self-immolative dendron based on a pyridine core released its two reporter units upon activation through 1,6- and 1,4 pyridinone-methide elimination reactions, again faster than the analogous benzene system. Increased aqueous solubility was observed with compounds based on pyridine relative to those based on benzene. The pyridinone-methide elimination could be applied as an alternative tool in designing self-immolative linkers for release of active target molecules in an aqueous environment.
醌-亚甲醚消除是一种常用且高效的方法，常用于设计能够进行自断裂的连接子。在这里，我们首次在吡啶环系统中证明了这种消除反应。在生理条件下，一个由吡啶核心、报告基团和酶触发子组成的化合物经历 1,4-消除的速度明显快于具有苯核的母体化合物。此外，基于吡啶核心的 AB(2) 自毁型树枝状大分子在通过 1,6-和 1,4 吡啶酮-亚甲醚消除反应被激活后释放其两个报告基团，其速度也快于类似的苯系统。与基于苯的化合物相比，基于吡啶的化合物的水溶解度增加。吡啶亚甲醚消除可作为设计自毁性连接子的替代工具，用于在水相环境中释放活性靶分子。
