Biocompatible Synthesis of Macrocyclic Thiazol (in) e Peptides
Abstract: Macrocyclic peptides containing a thiazole or thiazoline in the backbone are considered privileged structures in both natural compounds and drug discovery, owing to their enhanced bioactivity, stability, and permeability. Here, we present the biocompatible synthesis of macrocyclic peptides from N‐terminal cysteine and C‐terminal nitrile. While the N‐terminal cysteine is incorporated during solid‐phase peptide synthesis, the C‐terminal nitrile is introduced during cleavage with aminoacetonitrile, utilizing a cleavable benzotriazole linker. This method directly yields the fully functionalized linear peptide precursor. The biocompatible cyclization reaction occurs in buffer at physiological pH and room temperature. The resulting thiazoline heterocycle remains stable in buffer but hydrolyzes under acidic conditions. While such hydrolysis enables access to macrocyclic peptides with a complete amide backbone, mild oxidation of the thiazoline leads to the stable thiazole macrocyclic peptide. While conventional oxidation strategies involve metals, we developed a protocol simply relying on alkaline salt and air. Therefore, we offer a rapid and metal‐free pathway to macrocyclic thiazole peptides, featuring a biocompatible key cyclization step.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Biocompatible Synthesis of Macrocyclic Thiazol (in) e Peptides ; day:17 ; month:06 ; year:2024 ; extent:6
Chemistry - a European journal ; (17.06.2024) (gesamt 6)
- Creator
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He, Junming
Nitsche, Christoph
- DOI
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10.1002/chem.202401716
- URN
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urn:nbn:de:101:1-2406181405577.209191775393
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 11:00 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- He, Junming
- Nitsche, Christoph
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