转鼓
组合化学
催化作用
发散合成
化学
芳基
不对称氢化
外消旋化
肽
烷基
对映选择合成
有机化学
亲核细胞
生物化学
作者
Xinjian Song,Shan Bai,Yuan Li,Yi Tang,Xinyu Long,Pu Qin,Ting Dang,Mengjie Ma,Qiao Ren,Xurong Qin
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2023-12-22
卷期号:9 (51)
被引量:1
标识
DOI:10.1126/sciadv.adk4950
摘要
The development of a reliable method for asymmetric synthesis of unnatural peptides is highly desirable and particularly challenging. In this study, we present a versatile and efficient approach that uses cobalt-catalyzed diastereoselective umpolung hydrogenation to access noncanonical aryl alanine peptides. This protocol demonstrates good tolerance toward various functional groups, amino acid sequences, and peptide lengths. Moreover, the versatility of this reaction is illustrated by its successful application in the late-stage functionalization and formal synthesis of various representative chiral natural products and pharmaceutical scaffolds. This strategy eliminates the need for synthesizing chiral noncanonical aryl alanines before peptide formation, and the hydrogenation reaction does not result in racemization or epimerization. The underlying mechanism was extensively explored through deuterium labeling, control experiments, HRMS identification, and UV-Vis spectroscopy, which supported a reasonable Co I /Co III catalytic cycle. Notably, acetic acid and methanol serve as safe and cost-effective hydrogen sources, while indium powder acts as the terminal electron source.
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