Decarboxylative Peptide Macrocyclization through Photoredox Catalysis.
Decarboxylative Peptide Macrocyclization through Photoredox Catalysis.
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DOI：
10.1002/anie.201608207
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发表时间：
2017-01-16
期刊：
影响因子：
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通讯作者：
MacMillan DW
中科院分区：
文献类型：
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作者：
McCarver SJ;Qiao JX;Carpenter J;Borzilleri RM;Poss MA;Eastgate MD;Miller MM;MacMillan DW
提出了一种含n端Michael受体肽的脱羧大环化方法。该合成方案能够有效地合成含有γ-氨基酸的环肽，并且能够耐受天然和非蛋白质原氨基酸的功能。线性前体范围从3到15个氨基酸在这种光氧化还原协议下有效地环化。为了证明该方法在生物活性分子制备中的实用性，我们已经生成了一种目前处于临床试验中的生长抑素类似物COR-005。提出了一种含n端Michael受体肽的脱羧大环化方法。该合成方案能够有效地合成含有γ-氨基酸的环肽，并且能够耐受天然氨基酸中的功能。线性前体范围从3到15个氨基酸在这种光氧化还原协议下有效地环化。
A method for the decarboxylative macrocyclization of peptides bearing N-terminal Michael acceptors has been developed. This synthetic protocol enables the efficient synthesis of γ-amino acid-containing cyclic peptides and is tolerant of functionality present in both natural and non-proteinogenic amino acids. Linear precursors ranging from 3 to 15 amino acids cyclize effectively under this photoredox protocol. To demonstrate the preparative utility of this method in the context of bioactive molecules, we have generated COR-005, a somatostatin analog currently in clinical trials. A method for the decarboxylative macrocyclization of peptides bearing N-terminal Michael acceptors has been developed. This synthetic protocol enables the efficient synthesis of γ-amino acid-containing cyclic peptides and is tolerant of functionality present in natural amino acids. Linear precursors ranging from 3 to 15 amino acids cyclize effectively under this photoredox protocol.