Synthesis of L-cyclic tetrapeptides by backbone amide activation CyClick strategy

Tetrahedron. 2022 Nov 5;126:133071. doi: 10.1016/j.tet.2022.133071. Epub 2022 Oct 5.ABSTRACTCyclic tetrapeptides exhibit high cellular permeability and a wide range of biological properties and thus have gained great interest in the field of medicinal chemistry. We synthesized highly strained 12-membered head to tail cyclic peptides with varying reactive amino acids, without oligomerization using the exclusively intramolecular CyClick chemistry. This occurs by a two-step process involving the low-energy formation of a 15 atom-containing cyclic imine, followed by a chemoselective ring contraction of the peptide backbone generating a highly strained 12 atom-containing cyclic tetrapeptide. This reaction exhibited high substrate scope and generated head to tail cyclic tetrapeptides with varying amino acids at the N-terminus, showing chemoselectivity without the need for side group protection.PMID:37994371 | PMC:PMC10664817 | DOI:10.1016/j.tet.2022.133071

Source: Tetrahedron - November 23, 2023 Category: Chemistry Authors: Rachel Wills Victor Adebomi Caroline Spancake Ryan D Cohen Monika Raj Source Type: research