Native Chemical Ligation Strategy to Overcome Side Reactions during Fmoc-Based Synthesis of C-Terminal Cysteine-Containing Peptides

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• 作者：Dominique Lelièvre ; Victor P. Terrier ; Agnès F. Delmas ; Vincent Aucagne
• 刊名：Organic Letters
• 出版年：2016
• 出版时间：March 4, 2016
• 年：2016
• 卷：18
• 期：5
• 页码：920-923
• 全文大小：271K
• ISSN：1523-7052

文摘

The Fmoc-based solid phase synthesis of C-terminal cysteine-containing peptides is problematic, due to side reactions provoked by the pronounced acidity of the Cα proton of cysteine esters. We herein describe a general strategy consisting of the postsynthetic introduction of the C-terminal Cys through a key chemoselective native chemical ligation reaction with N-Hnb-Cys peptide crypto-thioesters. This method was successfully applied to the demanding peptide sequences of two natural products of biological interest, giving remarkably high overall yields compared to that of a state of the art strategy.