title: Solid-phase synthesis of peptide thioureas and thiazole-containing macrocycles through Ru-catalyzed ring-closing metathesis.
abstract: N-Terminally modified α-thiourea peptides can selectively be synthesized on solid support under mild reaction conditions using N,N'-di-Boc-thiourea and Mukaiyama's reagent (2-chloro-1-methyl-pyridinium iodide). This N-terminal modification applies to the 20 proteinogenic amino acid residues on three commonly used resins for solid-phase synthesis. Complementary methods for the synthesis of α-guanidino peptides have also been developed. The thiourea products underwent quantitative reactions with α-halo ketones to form thiazoles in excellent purities and yields. When strategically installed between two alkene moieties, said thiazole core was conveniently embedded in peptide macrocycles via Ru-catalyzed ring-closing metathesis reactions. Various 15-17 membered macrocycles were easily accessible in all diastereomeric forms using this methodology. The developed "build/couple/pair" strategy is well suited for the generation of larger and stereochemically complete screening libraries of thiazole-containing peptide macrocycles.
authors.affiliation: Department of Chemistry, Technical University of Denmark , DK-2800 Kongens Lyngby, Denmark.
authors.forename: A Emil
authors.initials: AE
authors.lastname: Cohrt
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Nielsen
mesh_terms: D002384:Catalysis; D003500:Cyclization; D047028:Macrocyclic Compounds / Q000138:chemical synthesis*; D010455:Peptides / Q000138:chemical synthesis*; D012428:Ruthenium / Q000737:chemistry*; D060327:Solid-Phase Synthesis Techniques / Q000379:methods*; D013844:Thiazoles / Q000138:chemical synthesis*; D013890:Thiourea / Q000138:chemical synthesis*
chemical_list: D047028:Macrocyclic Compounds; D010455:Peptides; D013844:Thiazoles; D012428:Ruthenium; D013890:Thiourea