Isocyanide-based consecutive Bargellini/Ugi reactions: an efficient method for the synthesis of pseudo-peptides containi
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ORIGINAL ARTICLE
Isocyanide‑based consecutive Bargellini/Ugi reactions: an efficient method for the synthesis of pseudo‑peptides containing three amide bonds Hassan Farhid1 · Mohammad Taghi Nazeri1 · Ahmad Shaabani1 · Mahsa Armaghan2 · Christoph Janiak2 Received: 8 September 2019 / Accepted: 13 November 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020
Abstract Isocyanide-based consecutive Bargellini/Ugi multicomponent reactions as a combinatorial strategy have been developed for the synthesis of new class of pseudo-peptides. Via Bargellini reaction 3-carboxamido-isobutyric acids are prepared using acetone, chloroform, sodium hydroxide, and isocyanides. Then, using Ugi multicomponent reaction strategy, pseudo-peptides containing three amide bonds are synthesized using the Bargellini reaction product, aldehydes, amines, and isocyanides. This is an efficient and eco-friendly approach for easy access to wide variety of structurally diverse, drug-like pseudo-peptides from cheap and readily available precursors in high yields. Keywords Consecutive multicomponent reaction · Pseudo-peptide · Bargellini reaction · Ugi reaction · Isocyanide
Introduction Peptides and proteins perform essential task in both unicellular and multicellular organisms and living without them would be impossible (Avan et al. 2014). Among them, short peptides are sorely significant bioactive compounds and exhibiting an extensive variety of biological activities. For example, glutathione operates as an antioxidant, detoxificant, and anti-aging agent. Other examples of short peptides are endomorphin-2 and tetrapeptide GE81112A, which act as natural inhibitor of stress and antibiotic, respectively (Fig. 1) (Jürjens et al. 2018; Vorobyeva et al. 2012).
Handling editor: P. Meffre. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00726-020-02917-1) contains supplementary material, which is available to authorized users. * Ahmad Shaabani a‑[email protected] 1
Faculty of Chemistry, Shahid Beheshti University, G.C., P.O. Box 19396‑4716, Tehran, Iran
Institut Für Anorganische Chemie und Strukturchemie, Heinrich-Heine-Universität Düsseldorf, 40204 Düsseldorf, Germany
2
Accordingly, drug discovery based on peptides is an extensively investigated area in biomedical research and peptides synthesis has been very much considered in organic chemistry (Comegna et al. 2015). The therapeutic utilization of peptides and proteins is limited by their short-time life, nonselective receptor binding and low absorption (Rabong et al. 2010). Amide bonds are typically provided from the reaction between carboxylic acids and amines; however, these reactions do not proceed spontaneously at ambient temperature because of formation the stable salts. The direct condensation of the salt can occur at high temperature (160–180 °C). For this reason, it is usually necessary to activate the carboxylic acid via a coupling reagent prior to treatment with the amine (Montalbetti and Falque 2005; Valeur and Brad
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