Kwok Ryan W, Rutkoski Ryan, Nagorny Pavel, Marianski Mateusz
Department of Chemistry, Hunter College, The City University of New York, 695 Park Ave., New York, NY 10065, USA.
PhD Program in Chemistry, The Graduate Center, The City University of New York, 365th Ave., New York, NY 10016, USA.
Molecules. 2025 Jan 7;30(2):218. doi: 10.3390/molecules30020218.
Using methods of DFT, we investigated the effect of electron withdrawing and electron donating groups on the relative stability of tentative glycosyl donor reaction intermediates. The calculation shows that by changing the stereoelectronic properties of the protecting group, we can influence the stability of the dioxolenium type of intermediates by up to 10 kcal mol, and that by increasing nucleophillicity of the 4--Bz group, the dioxolenium intermediate becomes more stable than a triflate-donor pair. We exploited this mechanism to design galactosyl donors with custom protecting groups on O2 and O4, and investigated the outcome of the reaction with cyclohexanol. The reaction showed no change in the product distribution, which suggests that the neighboring group participation takes precedence over remote group participation due to kinetic barriers.
我们采用密度泛函理论（DFT）方法，研究了吸电子基团和供电子基团对暂定糖基供体反应中间体相对稳定性的影响。计算结果表明，通过改变保护基团的立体电子性质，我们可以将二氧戊环鎓型中间体的稳定性改变高达10千卡/摩尔，并且通过提高4 - Bz基团的亲核性，二氧戊环鎓中间体比三氟甲磺酸酯 - 供体对更稳定。我们利用这一机制设计了在O2和O4上带有定制保护基团的半乳糖基供体，并研究了其与环己醇反应的结果。反应产物分布没有变化，这表明由于动力学障碍，邻基参与优先于远程基团参与。
