Amide Bonds Meet Flow Chemistry: A Journey into Methodologies and Sustainable Evolution. Issue 6 (1st February 2022)

• Record Type: Journal Article
• Authors: Alfano, Antonella Ilenia; Lange, Heiko; Brindisi, Margherita
• Is Part Of: ChemSusChem. Volume 15:Issue 6(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-01
• Subjects: amide bonds -- flow chemistry -- green chemistry -- peptides -- sustainable synthesis; Green chemistry -- Periodicals; Sustainable engineering -- Periodicals; Chemistry -- Periodicals; Chemical engineering -- Periodicals; 660
• DOI: 10.1002/cssc.202102708
• Languages: English
• ISSNs: 1864-5631

Abstract

Abstract: Formation of amide bonds is of immanent importance in organic and synthetic medicinal chemistry. Its presence in "traditional" small‐molecule active pharmaceutical ingredients, in linear or cyclic oligo‐ and polypeptidic actives, including pseudopeptides, has led to the development of dedicated synthetic approaches for the formation of amide bonds starting from, if necessary, suitably protected amino acids. While the use of solid supported reagents is common in traditional peptide synthesis, similar approaches targeting amide bond formation in continuous‐flow mode took off more significantly, after a first publication in 2006, only a couple of years ago. Most efforts rely upon the transition of traditional approaches in flow mode, or the combination of solid‐phase peptide synthesis principles with flow chemistry, and advantages are mainly seen in improving space‐time yields. This Review summarizes and compares the various approaches in terms of basic amide formation, peptide synthesis, and pseudopeptide generation, describing the technological approaches and the advantages that were generated by the specific flow approaches. A final discussion highlights potential future needs and perspectives in terms of greener and more sustainable syntheses. Abstract : Find your flow : This Review summarizes and compares flow‐aided methodologies for basic amide formation, peptide synthesis, and peptidomimetic framework generation. Beyond describing the technological approaches and showcasing advantages generated by the specific flow protocols, it offers a critical point of view on future needs and perspectives towards greener and more sustainable syntheses of amide bond‐containing compounds.