Division of Organic Chemistry and Biochemistry, Ruder Bosković Institute, Zagreb, 10000-HR Croatia.
J Org Chem. 2010 Sep 17;75(18):6219-28. doi: 10.1021/jo101302n.
Enediyne-peptide conjugates are recently recognized as useful tools in targeting various proteins, while the mechanism underlying the observed activity remains somewhat unclear. Addressing these issues, we have prepared acyclic amino acid derived enediynes and disclosed a novel thermally induced cyclization-elimination pathway. Initial formation of 1,4-benzene diradical and H-atom abstraction from an external donor is followed by S(N)2 substitution leading to 2,3-dihydrobenzo[f]isoindoles. The proposed mechanism is supported by experimental and computational data. Additionally, we showed that amino acid side chains, although placed three bonds away from acetylene terminuses, have an appreciable influence on the reactivity of studied enediynes. These results demonstrate that amino acid or peptide parts of enediyne-peptide conjugates cannot be considered as recognition elements exclusively but may also participate in various reactions through amine functionality.
烯二炔-肽缀合物最近被认为是靶向各种蛋白质的有用工具，而观察到的活性的机制仍有些不清楚。为了解决这些问题，我们已经制备了无环氨基酸衍生的烯二炔，并揭示了一种新的热诱导环化-消除途径。最初形成 1,4-苯二自由基和从外部供体中提取 H 原子，然后进行 S(N)2 取代，生成 2,3-二氢苯并[f]异吲哚。所提出的机制得到了实验和计算数据的支持。此外，我们表明，氨基酸侧链尽管离乙炔末端三个键，但对研究的烯二炔的反应性有明显的影响。这些结果表明，烯二炔-肽缀合物的氨基酸或肽部分不能仅被视为识别元件，而且还可以通过胺官能团参与各种反应。
