Substituents on quinone methides strongly modulate formation and stability of their nucleophilic adducts.
Substituents on quinone methides strongly modulate formation and stability of their nucleophilic adducts.
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DOI：
10.1021/ja062948k
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发表时间：
2006-09
影响因子：
15
通讯作者：
Emily E. Weinert;R. Dondi;Stefano Colloredo-Melz;Kristen N Frankenfield;Charles H Mitchell;M. Freccero;S. Rokita
中科院分区：
文献类型：
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作者：
Emily E. Weinert;R. Dondi;Stefano Colloredo-Melz;Kristen N Frankenfield;Charles H Mitchell;M. Freccero;S. Rokita
醌甲基化物 (QM) 的电子扰动极大地影响其稳定性，进而改变 QM 与脱氧核苷反应的动力学和产物谱。与该反应中间体的缺电子性质一致，给电子取代基具有稳定作用，而吸电子取代基则具有不稳定作用。例如，dC N3-QM 加合物在观察过程（7 天）内由于存在抑制 QM 再生的吸电子酯基而变得稳定。相反，具有供电子甲基的相关加合物非常不稳定，并且会重新生成其 QM，半衰期约为 5 小时。这些效应的普遍性通过一系列替代醌甲基化物前体 (QMP) 得到了证明，这些前体含有连接在环外亚甲基不同位置的各种取代基。通过激光闪光光解测量的取代 QM 的亲核加成速率同样跨越 5 个数量级，其中富电子物质反应最慢，缺电子物质反应最快。 QM 反应的可逆性现在可以针对任何所需的应用进行可预测的调整。
Electronic perturbation of quinone methides (QM) greatly influences their stability and in turn alters the kinetics and product profile of QM reaction with deoxynucleosides. Consistent with the electron-deficient nature of this reactive intermediate, electron-donating substituents are stabilizing and electron-withdrawing substituents are destabilizing. For example, a dC N3-QM adduct is made stable over the course of observation (7 days) by the presence of an electron-withdrawing ester group that inhibits QM regeneration. Conversely, a related adduct with an electron-donating methyl group is very labile and regenerates its QM with a half-life of approximately 5 h. The generality of these effects is demonstrated with a series of alternative quinone methide precursors (QMP) containing a variety of substituents attached at different positions with respect to the exocyclic methylene. The rates of nucleophilic addition to substituted QMs measured by laser flash photolysis similarly span 5 orders of magnitude with electron-rich species reacting most slowly and electron-deficient species reacting most quickly. The reversibility of QM reaction can now be predictably adjusted for any desired application.