title: Incorporation of CF3-pseudoprolines into peptides: a methodological study.
abstract: The peptide coupling reactions allowing the incorporation of trifluoromethyl substituted oxazolidine-type pseudoprolines (CF3-ΨPro) into peptide chains have been studied. While standard protocols can be used for the peptide coupling reaction at the C-terminal position of the CF3-ΨPro, acid chloride activation has to be used for the peptide coupling reaction at the N-terminal position to overcome the decrease of nucleophilicity of the CF3-ΨPro. We demonstrate that the N-amidification of a diastereomeric mixture of CF3-ΨPro using Fmoc-protected amino acid chloride without base gave the corresponding dipeptides as a single diastereomer (6 examples). The ratio of the cis and trans amide bond conformers was determined by NMR study, highlighting the role of the Xaa side chains in the control of the peptide backbone conformation. Finally a tripeptide bearing a central CF3-ΨPro has been successfully synthesized.
authors.affiliation: Laboratoire SOSCO, Université de Cergy-Pontoise , EA 4505, 5 Mail Gay-Lussac, 95000 Cergy-Pontoise, France.
authors.forename: Grégory
authors.initials: G
authors.lastname: Chaume
authors.forename: Julien
authors.initials: J
authors.lastname: Simon
authors.forename: Caroline
authors.initials: C
authors.lastname: Caupène
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lensen
authors.forename: Emeric
authors.initials: E
authors.lastname: Miclet
authors.forename: Thierry
authors.initials: T
authors.lastname: Brigaud
mesh_terms: D000577:Amides / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D005466:Fluorocarbons / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry*; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry*
chemical_list: D000577:Amides; D000596:Amino Acids; D005466:Fluorocarbons; D010455:Peptides; D013844:Thiazoles; C505976:pseudoproline; D011392:Proline