Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
Sci Adv. 2023 Sep 15;9(37):eadj3090. doi: 10.1126/sciadv.adj3090. Epub 2023 Sep 13.
Since the initial report in 1975, the Shono oxidation has become a powerful tool to functionalize the α position of amines, including proline derivatives, by electrochemical oxidation. However, the application of electrochemical Shono oxidations is restricted to the preparation of simple building blocks and homogeneous Shono-type oxidation of proline derivatives remains challenging. The late-stage functionalization at proline residues embedded within peptides is highly important as substitutions about the proline ring are known to affect biological and pharmacological activities. Here, we show that homogenous copper-catalyzed oxidation conditions complement the Shono oxidation and this general protocol can be applied to a series of formal C-C coupling reactions with a variety of nucleophiles using a one-pot procedure. This protocol shows good tolerance toward 19 proteinogenic amino acids and was used to functionalize several representative bioactive peptides, including captopril, enalapril, Smac, and endomorphin-2. Last, peptide cyclization can also be achieved by using an appropriately positioned side-chain hydroxyl moiety.
自 1975 年首次报道以来，Shono 氧化已成为通过电化学氧化官能化胺的α位的有力工具，包括脯氨酸衍生物。然而，电化学 Shono 氧化的应用仅限于简单构建块的制备，并且脯氨酸衍生物的均相 Shono 型氧化仍然具有挑战性。在肽中嵌入脯氨酸残基的后期功能化非常重要，因为已知脯氨酸环的取代会影响生物和药理学活性。在这里，我们表明，均相铜催化氧化条件补充了 Shono 氧化，并且该一般方案可以通过一锅法应用于一系列与各种亲核试剂的形式 C-C 偶联反应。该方案对 19 种蛋白质氨基酸具有良好的耐受性，并用于功能化几种代表性的生物活性肽，包括卡托普利、依那普利、Smac 和内吗啡肽-2。最后，通过使用适当定位的侧链羟基部分也可以实现肽环化。
