期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 143, 期 30, 页码 11811-11819出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.1c05718
关键词
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资金
- Australian Research Council [DE180100092]
- Australian Research Council [DE180100092] Funding Source: Australian Research Council
The efficient synthesis of designer C-terminal peptide amides without epimerization is achieved by utilizing the inherent reactivity of C-terminal carboxylates. This method is compatible with most functional groups and overcomes major limitations associated with conventional coupling-based approaches. The utility of this approach is demonstrated through the synthesis of various bioactive compounds, showcasing its broad applicability.
Designer C-terminal peptide amides are accessed in an efficient and epimerization- free approach by pairing an electrochemical oxidative decarboxylation with a tandem hydrolysis/reduction pathway. Resembling Nature's dual enzymatic approach to bioactive primary a-amides, this method delivers secondary and tertiary amides bearing high-value functional motifs, including isotope labels and handles for bioconjugation. The protocol leverages the inherent reactivity of C-terminal carboxylates, is compatible with the vast majority of proteinogenic functional groups, and proceeds in the absence of epimerization, thus addressing major limitations associated with conventional coupling-based approaches. The utility of the method is exemplified through the synthesis of natural product acidiphilamide A via a key diastereoselective reduction, as well as bioactive peptides and associated analogues, including an anti-HIV lead peptide and blockbuster cancer therapeutic leuprolide.
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