The pyridinone-methide elimination.
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.
Perry-Feigenbaum
Rotem
R
Department of Organic Chemistry, School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel-Aviv University, Tel Aviv 69978, Israel.
Baran
Phil S
PS
Shabat
Doron
D
D045563:Indolequinones / Q000737:chemistry*; D015394:Molecular Structure; D011728:Pyridones / Q000737:chemistry*
D045563:Indolequinones; D011728:Pyridones