title: Solution- and Solid-Phase Macrocyclization of Peptides by the Ugi-Smiles Multicomponent Reaction: Synthesis of N-Aryl-Bridged Cyclic Lipopeptides.
abstract: A new multicomponent methodology for the solution- and solid-phase macrocyclization of peptides is described. The approach comprises the utilization of the Ugi-Smiles reaction for the cyclization of 3-nitrotyrosine-containing peptides either by the N-terminus or the lysine side-chain amino groups. Both the on-resin and solution cyclizations took place with good to excellent efficiency in the presence of an aldehyde and a lipidic isocyanide, while the use of paraformaldehyde required an aminocatalysis-mediated imine formation prior to the on-resin Ugi-Smiles ring closure. The introduction of a turn motif in the peptide sequence facilitated the cyclization step, shortened the reaction time, and delivered crude products with >90% purity. This powerful method provided a variety of structurally novel N-aryl-bridged cyclic lipopeptides occurring as single atropisomers.
authors: Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry , Weinberg 3, 06120 Halle/Saale, Germany.|Center for Natural Products Research, Faculty of Chemistry, University of Havana , Zapata y G, 10400 Havana, Cuba.
authors: Micjel C
authors: MC
authors: Morejón
authors: Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry , Weinberg 3, 06120 Halle/Saale, Germany.
authors: Annegret
authors: A
authors: Laub
authors: Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry , Weinberg 3, 06120 Halle/Saale, Germany.
authors: Bernhard
authors: B
authors: Westermann
authors: Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry , Weinberg 3, 06120 Halle/Saale, Germany.|Center for Natural Products Research, Faculty of Chemistry, University of Havana , Zapata y G, 10400 Havana, Cuba.
authors: Daniel G
authors: DG
authors: Rivera
authors: Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry , Weinberg 3, 06120 Halle/Saale, Germany.
authors: Ludger A
authors: LA
authors: Wessjohann
mesh_terms: D003500:Cyclization; D055666:Lipopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D012996:Solutions
chemical_list: D055666:Lipopeptides; D010455:Peptides; D010456:Peptides, Cyclic; D012996:Solutions