Use of onium salt-based coupling reagents in peptide synthesis
Use of onium salt-based coupling reagents in peptide synthesis
复制标题
DOI：
10.1021/jo980807y
复制
发表时间：
1998-12-25
影响因子：
3.6
通讯作者：
Kates, SA
中科院分区：
文献类型：
--
作者：
Albericio, F;Bofill, JM;Kates, SA
衍生自基于1-羟基苯并三唑（HOBt）和1-羟基-7-氮杂苯并三唑（HOAt）的鎓盐的肽偶联方法正变得比经典的碳二亚胺方法更频繁地并入合成策略中。我们已经将HOXt（X = A，B）衍生的各种鎓盐的反应性与所讨论的试剂的结构相关联。因此，我们证实，氮杂衍生物比母体苯并三唑衍生物在活化和偶联方面更具反应性。此外，活化步骤由碳骨架的结构决定。因此，吡咯烷基衍生物似乎是相对于哌啶基类似物或衍生自三烷基胺的那些的选择试剂。此外，尽管鏻盐的反应性略低于相应的铵/脲盐，但前者应用于活化受阻物质，因为后者可能导致胍基衍生物的形成。
Peptide coupling methods derived from onium salts based on 1-hydroxybenzotriazole (HOBt) and 1-hydroxy-7-azabenzotriazole (HOAt) are becoming incorporated in synthetic strategies more frequently than the classical carbodiimide methods. We have correlated the reactivity of various onium salts derived from HOXt (X = A, B), with the structure of the reagents in question. Thus, we confirmed that the aza derivatives are more reactive than the parent benzotriazole derivatives in both activation and coupling. In addition, the activation step is determined by the structure of the carbon skeleton. Thus, pyrrolidino derivatives appear to be reagents of choice relative to the piperidino analogues or those derived from trialkylamines. Furthermore although phosphonium salts are slightly less reactive than the corresponding aminium/uronium salts, the former should be used for the activation of hindered species, since the latter may lead to the formation of guanidino derivatives.