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One‐pot peptide cleavage and macrocyclization through direct amidation using triazabicyclodecene
Author(s) -
Hickey Jennifer L.,
Lin Songnian
Publication year - 2020
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.533
H-Index - 7
ISSN - 2475-8817
DOI - 10.1002/pep2.24161
Subject(s) - chemistry , cleavage (geology) , amine gas treating , peptide , combinatorial chemistry , intramolecular force , hydroxymethyl , benzamide , stereochemistry , organic chemistry , biochemistry , geotechnical engineering , fracture (geology) , engineering
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.