Tang Jian, He Yadong, Chen Hongfei, Sheng Wangjian, Wang Huan
State Key Laboratory of Coordination Chemistry , School of Chemistry and Chemical Engineering , Nanjing University , Nanjing 210093 , China . Email:
Chem Sci. 2017 Jun 1;8(6):4565-4570. doi: 10.1039/c6sc05530c. Epub 2017 Apr 19.
Cyclic peptides have attracted increasing attention in recent years due to their ability to inhibit protein-protein interactions. Current strategies to prepare cyclic peptides often rely on functional amino acid side chains or the incorporation of unnatural amino acids, thus limiting their structural diversity. Here, we describe the development of a highly versatile peptide macrocyclization strategy through a palladium-catalyzed C(sp)-H activation and the synthesis of cyclic peptides featuring unique hydrocarbon linkages between the β-carbon of amino acids and the aromatic side chains of Phe and Trp. We demonstrate that such peptides exhibit improved biological properties compared to their acyclic counterparts. Finally, we applied this method in the synthesis of the natural product celogentin C.
近年来，环肽因其抑制蛋白质 - 蛋白质相互作用的能力而受到越来越多的关注。目前制备环肽的策略通常依赖于功能性氨基酸侧链或非天然氨基酸的掺入，从而限制了它们的结构多样性。在此，我们描述了一种高度通用的肽大环化策略的开发，该策略通过钯催化的C(sp)-H活化以及氨基酸β-碳与苯丙氨酸和色氨酸芳香侧链之间具有独特烃连接的环肽的合成。我们证明，与它们的非环类似物相比，此类肽表现出改善的生物学性质。最后，我们将该方法应用于天然产物塞洛金汀C的合成。
