CyClick Chemistry for the Synthesis of Cyclic Peptides
CyClick Chemistry for the Synthesis of Cyclic Peptides
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DOI：
10.1002/anie.201911900
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发表时间：
2019-11-07
影响因子：
16.6
通讯作者：
Raj, Monika
中科院分区：
文献类型：
--
作者：
Adebomi, Victor;Cohen, Ryan D.;Raj, Monika
在这里，我们报告了一种新的“CyClick”策略的大环化的肽，其工作在一个专门的分子内的方式，从而排除通过分子间反应形成的二聚体和低聚物。CyClick化学对具有C-末端醛的肽的N-末端具有高度化学选择性。在该方案中，肽构象在内部指导骨架酰胺键的活化，从而促进形成具有高非对映选择性（> 99%）的稳定的4-咪唑烷酮-稠合环肽。这种方法是宽容的各种肽醛，并已被应用于在温和的反应条件下，在一锅合成12至23元环的不同氨基酸组成。该反应生成肽大环，其特征在于在其支架中的4-咪唑烷酮，其作为内环控制元件，促进分子内氢键结合并导致具有构象刚性转弯结构的大环。
Here, we report a novel "CyClick" strategy for the macrocyclization of peptides that works in an exclusively intramolecular fashion thereby precluding the formation of dimers and oligomers via intermolecular reactions. The CyClick chemistry is highly chemoselective for the N-terminus of the peptide with a C-terminal aldehyde. In this protocol, the peptide conformation internally directs activation of the backbone amide bond and thereby facilitates formation of a stable 4-imidazolidinone-fused cyclic peptide with high diastereoselectivity (>99 %). This method is tolerant to a variety of peptide aldehydes and has been applied for the synthesis of 12- to 23-membered rings with varying amino acid compositions in one pot under mild reaction conditions. The reaction generated peptide macrocycles featuring a 4-imidazolidinone in their scaffolds, which acts as an endocyclic control element that promotes intramolecular hydrogen bonding and leads to macrocycles with conformationally rigid turn structures.