Harpaz Ziv, Loibl Simon, Seitz Oliver
Institut für Chemie, Humboldt Universität zu Berlin, Brook-Taylor-Straße 2, 12489 Berlin, Germany.
Bioorg Med Chem Lett. 2016 Mar 1;26(5):1434-7. doi: 10.1016/j.bmcl.2016.01.060. Epub 2016 Jan 22.
Native chemical ligation (NCL) proceeds via a S-N acyl shift and, therefore, requires N-terminal cysteine. N(α)-auxiliaries have long been used to enable NCL beyond cysteine. However, the reversibility of the S-N acyl shift under the acidic conditions used to remove the commonly applied N-benzyl auxiliaries limits the scope of this reaction. Herein, we introduce a new class of N(α)-auxiliary which is designed for removal under mild basic conditions. The 3-N-linked 4-mercaptobutyrate auxiliary is readily synthesized in a single step and enables introduction on solid phase by means of reductive amination. The usefulness of the new auxiliary was demonstrated in the synthesis of the anti-microbial C-terminal domain of Dermicidine-1L.
天然化学连接（NCL）通过S-N酰基转移进行，因此需要N端半胱氨酸。长期以来，N（α）辅助基团一直用于实现除半胱氨酸以外的NCL。然而，在用于去除常用的N-苄基辅助基团的酸性条件下，S-N酰基转移的可逆性限制了该反应的范围。在此，我们引入了一类新型的N（α）辅助基团，其设计用于在温和的碱性条件下去除。3-N-连接的4-巯基丁酸酯辅助基团易于一步合成，并能够通过还原胺化在固相上引入。新辅助基团的实用性在抗微生物的皮肤杀菌肽-1L的C端结构域的合成中得到了证明。
