The azaquinone-methide elimination: comparison study of 1,6- and 1,4-eliminations under physiological conditions

Abstract

The azaquinone-methide elimination is a powerful and efficient reaction useful for disassembly of spacers in prodrug systems. We and others have used the spacer-technique to develop dendritic and polymeric self-immolative molecular systems that can disassemble through a domino-like mechanism upon a stimulus event. In this report, we study the disassembly of a system that can disintegrate through para- and ortho-azaquinone-methide eliminations. The disassembly was evaluated with molecules that undergo single 1,6- or 1,4-elimination and with molecules that undergo double 1,6- and 1,4-elimination. The 1,6-elimination was slightly faster than the 1,4-elimination under physiological conditions. This study sheds light on the disassembly-behavior of prodrug systems.