title: Copper(I)-Mediated Denitrogenative Macrocyclization for the Synthesis of Cyclic α3β-Tetrapeptide Analogues.
abstract: A copper(I)-mediated denitrogenative reaction has been successfully developed for the preparation of cyclic tetrapeptides. The key reactive intermediate, ketenimine, triggers intramolecular cyclization through attack of the terminal amine group to generate an internal β-amino acid with an amidine linkage. The chemistry developed herein provides a new synthetic route for the preparation of cyclic α3β-tetrapeptide analogues that contain important biological properties and results in rich structural information being obtained for conformational studies. With the success of this copper(I)-catalyzed macrocyclization, two histone deacetylase inhibitor analogues consisting of the cyclic α3β-tetrapeptide framework have been successfully synthesized.
authors.affiliation: Department of Chemistry, Nation Sun Yat-sen University, 70 Lienhai Rd., Kaohsiung, 80424, Taiwan.
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Chemistry, Nation Sun Yat-sen University, 70 Lienhai Rd., Kaohsiung, 80424, Taiwan.
authors.forename: Sheng-Fu
authors.initials: SF
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Nation Sun Yat-sen University, 70 Lienhai Rd., Kaohsiung, 80424, Taiwan.
authors.forename: Yung-Yu
authors.initials: YY
authors.lastname: Su
authors.affiliation: Department of Chemistry, Nation Sun Yat-sen University, 70 Lienhai Rd., Kaohsiung, 80424, Taiwan.
authors.forename: Yuya A
authors.initials: YA
authors.lastname: Lin
authors.affiliation: Department of Chemistry, Nation Sun Yat-sen University, 70 Lienhai Rd., Kaohsiung, 80424, Taiwan.
authors.forename: Po-Chiao
authors.initials: PC
authors.lastname: Lin
mesh_terms: D003300:Copper / Q000737:chemistry*; D003500:Cyclization; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D056572:Histone Deacetylase Inhibitors; D009842:Oligopeptides; D010456:Peptides, Cyclic; D003300:Copper
keywords: copper; inhibitors; macrocycles; peptides; synthesis design