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

The Journal of Organic Chemistry
André Warnecke, Felix Kratz

Abstract

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.

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Citations

Sep 12, 2015·Chemical Reviews·Michal E RothDoron Shabat
Dec 10, 2015·The Journal of Organic Chemistry·Chiaki KomiyaAkira Otaka
Apr 16, 2014·Medicinal Research Reviews·Laizhong ChenMinyong Li
Sep 4, 2015·Journal of the American Chemical Society·Guhuan LiuShiyong Liu
Mar 10, 2010·Biochimie·Marcelo CalderónRainer Haag
Jun 27, 2008·Chemistry : a European Journal·Roy WeinstainDoron Shabat
Nov 13, 2009·Organic & Biomolecular Chemistry·Rotem Perry-FeigenbaumDoron Shabat
Jan 27, 2011·Organic & Biomolecular Chemistry·Matthew A DeWit, Elizabeth R Gillies
Feb 8, 2019·Scientific Reports·Bradley LukasakAlexander Deiters
Sep 6, 2020·International Journal of Molecular Sciences·Gengqi LiuYumiao Zhang
Mar 19, 2021·Chemical Society Reviews·Yufei XueNicolas Hans Voelcker
Apr 2, 2008·Journal of the American Chemical Society·Amit SagiDoron Shabat
Apr 18, 2009·Organic Letters·Ho Yong LeeDongwhan Lee
Jun 12, 2019·The Journal of Organic Chemistry·Agonist Kastrati, Christian G Bochet
Nov 29, 2012·The Journal of Organic Chemistry·Kaitlyn M MahoneyArthur H Winter

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