Szaniszló Szebasztián, Csizmadia Imre G, Jákli Imre, Farkas Viktor, Láng András, Sulyok-Eiler Máté, Harmat Veronika, Pintér István, Perczel András
Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Pázmány Péter sétány. 1/A, H-1117, Budapest, Hungary.
Hevesy György PhD school of Chemistry, Institute of Chemistry, Eötvös Loránd University, Pázmány Péter sétány. 1/A, H-1117, Budapest, Hungary.
Chemistry. 2025 Mar 12;31(15):e202403319. doi: 10.1002/chem.202403319. Epub 2025 Feb 5.
The present study reveals an unexpected anomaly observed in the acid-catalyzed hydrolysis of the 5,6-O-isopropylidene group in 3-O-protected D-gluco- and D-allofuranose derivatives. Although the removal of the 5,6-O-isopropylidene protecting group is typically rapid and quantitative under acidic conditions, an unexpected inhibition of this reaction is observed for the two C3-epimers, 3-O-imidazole sulfonyl moiety. X-ray data show a two-faced imidazole ring orientation in the crystal, while solution state NOE data reveal a critical interaction type between the isopropylidene and the imidazole rings. Advanced conformational searches coupled with ab initio molecular modeling illuminate and explain the NMR and kinetic data and lay the groundwork for the most plausible mechanism of this unprecedented inhibition. These results provide valuable insights into the cross-coupling of carbohydrate O-protecting groups and shed light on how specific ring orientations and steric effects can trigger the inhibition of an otherwise easily feasible reaction, such as an acid-catalyzed hydrolysis.
本研究揭示了在3 - O - 保护的D - 葡萄糖和D - 阿洛呋喃糖衍生物中5,6 - O - 异亚丙基基团的酸催化水解过程中观察到的意外异常现象。虽然在酸性条件下5,6 - O - 异亚丙基保护基团的去除通常迅速且定量，但对于两种C3 - 差向异构体（3 - O - 咪唑磺酰基部分），观察到该反应出现意外的抑制。X射线数据显示晶体中咪唑环呈双面取向，而溶液状态的NOE数据揭示了异亚丙基与咪唑环之间的关键相互作用类型。先进的构象搜索结合从头算分子建模阐明并解释了NMR和动力学数据，并为这种前所未有的抑制作用最合理的机制奠定了基础。这些结果为碳水化合物O - 保护基团的交叉偶联提供了有价值的见解，并揭示了特定的环取向和空间效应如何能够触发对原本容易进行的反应（如酸催化水解）的抑制。
