Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań, Poland.
Department of Organic Chemistry, Faculty of Pharmacy, Poznań University of Medical Sciences, Poznań, Poland.
PLoS One. 2018 Sep 20;13(9):e0203604. doi: 10.1371/journal.pone.0203604. eCollection 2018.
1D and 2D NMR investigations as well as computational studies, including static quantum-mechanics calculations, density function theory formalism, and classical molecular dynamics, were applied to determine the protonation sites in the thermolabile protecting group (TPG) containing a 2-pyridynyl moiety within its structure. This protecting group has three possible sites for protonation: an azomethine (pyridinic) atom (N1), 2-aminoethanol residue (N2), and 4-amino substituent (N4). Our investigations showed that the protonation mainly occurs on the N1 atom. Such protonation seems to be a major inhibitory factor in the thermal removal of 2-pyridynyl TPG by the "chemical switch" approach and decreases the aromaticity of the pyridine ring. We also discussed possible participation of N2 nitrogen in irreversible intramolecular cyclization under acidic conditions.
我们采用一维和二维核磁共振技术以及计算研究手段，包括静态量子力学计算、密度泛函理论形式和经典分子动力学，以确定含有 2-吡啶基部分的热不稳定保护基团（TPG）中的质子化部位。该保护基团有三个可能的质子化部位：亚甲胺（吡啶基）原子（N1）、2-氨基乙醇残基（N2）和 4-氨基取代基（N4）。我们的研究表明，质子化主要发生在 N1 原子上。这种质子化似乎是通过“化学开关”方法热去除 2-吡啶基 TPG 的主要抑制因素，并降低吡啶环的芳香性。我们还讨论了在酸性条件下 N2 氮原子可能参与不可逆的分子内环化。
