Audran Gérard, Brémond Paul, Marque Sylvain R A, Yamasaki Toshihide
Aix Marseille Université, CNRS, ICR, UMR 7273 , 13397 Marseille Cedex 20, France.
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS , Pr. Lavrentjeva 9, 630090 Novosibirsk, Russia.
J Org Chem. 2016 Mar 4;81(5):1981-8. doi: 10.1021/acs.joc.5b02790. Epub 2016 Feb 15.
A few years ago, Bagryanskaya and colleagues (J. Org. Chem. 2011) showed that protonation of the nitroxyl fragment deactivated the alkoxyamine C-ON bond. Conversely, our group showed that protonation (Chem. Commun. 2011), as well as other chemical reactions such as oxidation or amine quaternization (Org. Lett. 2012), of the pyridyl moiety carried by the alkyl fragment was suitable to activate the homolysis of the C-ON bond. To pursue our goal of applying alkoxyamines as theranostic agents (Org. Biomol. Chem. 2014 and Mol. Pharmaceutics 2014) by activation of the C-ON bond homolysis, we turned our interest to the chemical activation of the nitroxyl fragment by oxidation/reduction of selected functions. Conversion of a hydroxyl group located close to the nitroxyl moiety successively into aldehyde, then acid, and eventually into ester, led to a successive decrease in kd.
几年前，巴格里扬斯卡娅及其同事（《有机化学杂志》，2011年）表明，硝酰基片段的质子化使烷氧基胺的C-ON键失活。相反，我们团队表明，烷基片段携带的吡啶基部分的质子化（《化学通讯》，2011年）以及其他化学反应，如氧化或胺季铵化（《有机快报》，2012年），适合激活C-ON键的均裂。为了通过激活C-ON键均裂来实现我们将烷氧基胺用作诊疗剂的目标（《有机生物分子化学》，2014年和《分子药剂学》，2014年），我们将兴趣转向通过选定官能团的氧化/还原对硝酰基片段进行化学活化。靠近硝酰基部分的羟基依次转化为醛，然后转化为酸，最终转化为酯，导致kd值逐渐降低。
