Fresenius Kabi iPSUM Srl, Via San Leonardo 23, 45010 Villadose, Italy.
Institute of Chemistry, St. Petersburg State University, Peterhof, Universitetskij pr. 26, 198504 St. Petersburg, Russia.
Molecules. 2022 Jun 30;27(13):4235. doi: 10.3390/molecules27134235.
The suppression of side reactions is one of the most important objectives in peptide synthesis, where highly reactive compounds are involved. Recently, the violuric acid derivative Oxyma-B was introduced into peptide synthesis protocols as a promising additive to efficiently control the optical purity of the amino acids prone to racemization. However, we discovered a side reaction involving the Beckmann rearrangement of Oxyma-B during the coupling reaction, which compromises the yield and purity of the target peptides. Here, we present the investigation of the mechanism of this rearrangement and the optimization of the coupling reaction conditions to control it. These results can be taken into account for the design of novel efficient oxime-based coupling reagents.
抑制副反应是涉及高反应性化合物的肽合成中最重要的目标之一。最近，噁唑烷酮酸衍生物 Oxyma-B 被引入到肽合成方案中，作为一种很有前途的添加剂，可以有效地控制易外消旋化的氨基酸的光学纯度。然而，我们在偶联反应中发现了涉及 Oxyma-B 的贝克曼重排的副反应，这会影响目标肽的产率和纯度。在这里，我们介绍了对这种重排机制的研究以及优化偶联反应条件来控制它。这些结果可以为设计新型有效的肟类偶联试剂提供参考。
