Solid-phase synthesis of cyclic lipopeptidotriazoles
The solid-phase synthesis of cyclic lipopeptidotriazoles derived from the cyclic decapeptide c(Lys-Lys(2)-Leu-Lys-Lys(5)-Phe-Lys-Lys-Leu-Gln) (BPC194), incorporating a triazolyl ring at Lys(2) and a hexanoyl group at Lys(5), was studied. Four different strategies that required the use of five orthog...
| Autores: | , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2014 |
| 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:10256/10935 |
| Acceso en línea: | http://hdl.handle.net/10256/10935 |
| Access Level: | acceso embargado |
| Palabra clave: | Pèptids -- Síntesi Peptides -- Synthesis Compostos orgànics -- Síntesi Organic compounds -- Synthesis Compostos heterocíclics -- Síntesi Heterocyclic compounds -- Synthesis |
| Sumario: | The solid-phase synthesis of cyclic lipopeptidotriazoles derived from the cyclic decapeptide c(Lys-Lys(2)-Leu-Lys-Lys(5)-Phe-Lys-Lys-Leu-Gln) (BPC194), incorporating a triazolyl ring at Lys(2) and a hexanoyl group at Lys(5), was studied. Four different strategies that required the use of five orthogonal protecting groups (Fmoc, tBu, All, pNZ, ivDde) were explored. The influence of the side-chain protection of Lys(2) and Lys(5) with the ivDde and pNZ groups was evaluated by incorporating Lys(2)(ivDde)/Lys(5)(pNZ) or Lys(2)(pNZ)/Lys(5)(ivDde). The order of removal of these protecting groups and of the introduction of the hexanoyl and triazolyl moieties was also studied. The best strategy included: (i) synthesis of a cyclic peptidyl resin bearing Lys(2)(ivDde) and Lys(5)(pNZ); (ii) pNZ group removal; (iii) acylation with hexanoic acid; (iv) ivDde group removal; and (v) acylation with propiolic acid followed by an azide-alkyne 1,3-dipolar cycloaddition. By using this protocol, a set of cyclic lipopeptidotriazoles was prepared in high purities |
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