Solid-phase synthesis of biaryl cyclic peptides containing a histidine-phenylalanine linkage
The feasibility of the solid-phase intramolecular 4(5)-arylation of a histidine residue to obtain biaryl cyclic peptides bearing a His-Phe linkage was established. The synthetic strategy involved the preparation of a linear peptidyl resin incorporating a 5-bromohistidine and a 4-boronophenylalanine,...
| Autores: | , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10256/18663 |
| Acceso en línea: | http://hdl.handle.net/10256/18663 |
| Access Level: | acceso abierto |
| Palabra clave: | Antibiòtics pèptids Peptide antibiotics Pèptids -- Síntesi Peptides -- Synthesis Ciclització (Química) Ring formation (Chemistry) |
| Sumario: | The feasibility of the solid-phase intramolecular 4(5)-arylation of a histidine residue to obtain biaryl cyclic peptides bearing a His-Phe linkage was established. The synthetic strategy involved the preparation of a linear peptidyl resin incorporating a 5-bromohistidine and a 4-boronophenylalanine, and its cyclization through the formation of the biaryl bond between the imidazole of histidine and the phenyl group of phenylalanine via a microwave-assisted Suzuki-Miyaura cross-coupling. This methodology was applied to the preparation of biaryl cyclic peptides consisting of a 3- or 5-residue ring, incorporating the His residue at the N- or the C-terminus and bearing a Leu-Leu spacer or a -NH2 group at the C-terminus. In the case of the 3-residue ring peptides, the position of the His did not influence the macrocyclization. In contrast, to obtain the 5-member ring biaryl cyclic peptides, the His residue should be located at the N-terminus. It was also observed that the Leu-Leu spacer is crucial for the intramolecular arylation. These results suggest that this approach could be useful for the preparation of a diversity of synthetic and natural biaryl cyclic peptides bearing a His-Phe linkage |
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