Macrocyclization of peptidoarylacetamides with self-assembly properties through late-stage palladium-catalyzed C(sp2)▬H olefination
Macrocyclization of peptidoarylacetamides with self-assembly properties through late-stage palladium-catalyzed C(sp2)▬H olefination
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DOI：
10.1126/sciadv.aaw0323
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发表时间：
2019-03
期刊：
影响因子：
13.6
通讯作者：
J. Tan;Jie Wu;Shu Liu;Hequan Yao;Huan Wang
中科院分区：
文献类型：
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作者：
J. Tan;Jie Wu;Shu Liu;Hequan Yao;Huan Wang
Pd催化的晚期C(Sp2)▬H活化允许自组装环肽的生成。多肽大环通常表现出不同的生物活性和自组装性质，这导致了其在医学和材料科学中的各种应用。过渡金属催化的C▬H活化是氨基酸和多肽的位置选择性功能化以及环多肽的构建的新兴策略。在这里，我们报道了一种由Pd(II)催化的晚期C(Sp2)▬H烯化反应中肽芳基乙酰胺大环化反应的多肽指导法。在该方案中，肽骨架作为内部导向基团，使传统的大内酰胺法难以合成的各种环肽的制备变得容易。此外，我们还发现，在骨架上引入芳基-烯烃交联剂可以将环肽限制在构象上进行自组装。
Pd-catalyzed late-stage C(sp2)▬H activation allows the generation of self-assembling cyclic peptides. Peptide macrocycles often display diverse bioactivities and self-assembly properties, which lead to a variety of applications in medicinal and material sciences. Transition metal–catalyzed C▬H activations are emerging strategies for site-selective functionalization of amino acids and peptides, as well as the construction of cyclic peptides. Here, we report the development of a peptide-directed method for the macrocyclization of peptidoarylacetamides by Pd(II)-catalyzed late-stage C(sp2)▬H olefination. In this protocol, peptide backbones act as internal directing groups and enable facile preparation of diverse cyclic peptides that are difficult to synthesize by conventional macrolactamization. Furthermore, we show that the incorporation of aryl-alkene cross-link in the backbone constrains cyclic peptides into conformations for self-assembly.