2,4-Bis(hydroxymethyl)aniline as a building block for oligomers with self-eliminating and multiple release properties.

Linear self-eliminating (LSE) systems are oligomers of branched self-eliminating linkers that disassemble upon a single triggering event under complete degradation of the linear backbone, accompanied by the release of side-chain bound effector molecules. Enabling a controlled and almost simultaneous release of different effectors (drugs) in defined ratios, LSE systems may gain importance for the development of novel combination therapeutics. On the basis of the well-known self-eliminating p-aminobenzyloxycarbonyl (PABC) linker, 2,4-bis(hydroxymethyl)aniline was considered a suitable branched linker for building LSE systems that degrade by 1,6- and 1,4-benzyl elimination reactions. A first LSE model system based on this linker was prepared in a simple procedure and was shown to release its effector payload efficiently after activation. In addition, elimination model compounds were synthesized to study the release behavior of LSE systems based on 2,4-bis(hydroxymethyl)aniline. It was found that chain degrading 1,6-benzyl elimination occurs much faster than the effector releasing 1,4-elimination.