Süli-Vargha Helga, Schlosser Gitta, Ilas Janez
Research Group for Peptide Chemistry, Hungarian Academy of Sciences, Eötvös Loránd University, Budapest, Hungary.
J Pept Sci. 2007 Nov;13(11):742-8. doi: 10.1002/psc.885.
The Fmoc-based SPPS of H-Xaa-Asp(OBzl)-Yaa-Gly-NH(2) sequences results in side reactions yielding not only aspartimide peptides and piperidide derivatives, but also 1,4-diazepine-2,5-dione-peptides. Evidence is presented to show that the 1,4-diazepine-2,5-dione derivative is formed from the aspartimide peptide. The rate of this ring transformation depends primarily on the tendency to aspartimide and piperidide formation, which is influenced by the nature of the amino acid following the aspartic acid beta-benzyl ester (Xaa). However the bulkiness of the amino acid side chain preceeding the aspartic acid beta-benzyl ester (Yaa) is also important. Under certain conditions the 1,4-diazepine-2,5-dione peptide derivative may even be formed dominantly, which is a highly undesirable side reaction in peptide synthesis, but which provides a new way for the synthesis of diazepine peptide derivatives with targeted biological or pharmacological activity.
基于Fmoc的H-Xaa-Asp(OBzl)-Yaa-Gly-NH(2)序列固相肽合成会产生副反应，不仅生成天冬酰胺肽和哌啶衍生物，还会生成1,4 - 二氮杂卓 - 2,5 - 二酮肽。有证据表明1,4 - 二氮杂卓 - 2,5 - 二酮衍生物是由天冬酰胺肽形成的。这种环转化的速率主要取决于形成天冬酰胺和哌啶的倾向，这受到天冬氨酸β - 苄酯（Xaa）之后氨基酸性质的影响。然而，天冬氨酸β - 苄酯（Yaa）之前氨基酸侧链的体积大小也很重要。在某些条件下，1,4 - 二氮杂卓 - 2,5 - 二酮肽衍生物甚至可能占主导形成，这在肽合成中是一种非常不受欢迎的副反应，但为合成具有靶向生物或药理活性的二氮杂卓肽衍生物提供了一种新方法。
