N‐Terminal Selective C−H Azidation of Proline‐Containing Peptides: a Platform for Late‐Stage Diversification. Issue 17 (23rd February 2022)

• Record Type: Journal Article
• Authors: Allouche, Emmanuelle M. D.; Simonet‐Davin, Raphaël; Waser, Jerome
• Is Part Of: Chemistry. Volume 28:Issue 17(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-23
• Subjects: amino acids -- azidation -- C−H functionalization -- peptides -- selectivity; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202200368
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: A methodology for the C−H azidation of N ‐terminal proline‐containing peptides was developed employing only commercially available reagents. Peptides bearing a broad range of functionalities and containing up to 6 amino acids were selectively azidated at the carbamate‐protected N ‐terminal residue in presence of the numerous other functional groups present on the molecules. Post‐functionalizations of the obtained aminal compounds were achieved: cycloaddition reactions or C−C bond formations via a sequence of imine formation/nucleophilic addition were performed, offering an easy access to diversified peptides. Abstract : A selective C−H azidation of up to 6 amino acids long proline‐containing peptides is reported. In each example, the N ‐terminal residue was selectively functionalized even in presence of amino acids bearing tertiary aliphatic, benzylic and α to heteroatoms C−H bonds. The azidated products were used in cycloaddition reactions and as masked imines for new C−C bond formations, allowing an easy access to diversified peptide scaffolds.