One‐pot peptide cleavage and macrocyclization through direct amidation using triazabicyclodecene. Issue 4 (24th March 2020)

• Record Type: Journal Article
• Authors: Hickey, Jennifer L.; Lin, Songnian
• Other Names: Gierasch Lila guestEditor.; Albericio Fernando guestEditor.; Toniolo Claudio guestEditor.
• Is Part Of: Peptide science. Volume 112:Issue 4(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-03-24
• Subjects: cyclic peptides -- macrocycles -- peptides; Peptides -- Periodicals; 572.6505
• DOI: 10.1002/pep2.24161
• Languages: English
• ISSNs: 2475-8817

Abstract

Abstract: We have developed a novel protocol for a one‐pot cleavage from solid support and subsequent cyclization to form small macrocyclic peptides. Synthesized on a 4‐hydroxymethyl benzamide (HMBA) resin, the peptides are cleaved from the solid support through a 1, 5, 7‐triazabicyclo[4.4.0]dec‐5‐ene (TBD) assisted acyl transfer reaction. The resulting linear peptides then undergo an intramolecular cyclization, presumably upon in situ attack of the N ‐terminal amine on the TBD‐activated ester. This protocol requires catalytic quantities of TBD and eliminates the need for orthogonal side chain deprotection strategies and ether trituration/work‐up steps, streamlining the synthesis of head‐to‐tail macrocyclic peptides. Abstract :