title: Aminocatalysis-Mediated on-Resin Ugi Reactions: Application in the Solid-Phase Synthesis of N-Substituted and Tetrazolo Lipopeptides and Peptidosteroids.
abstract: A new solid-phase protocol for the synthesis of N-substituted and tetrazolo peptides is described. The strategy relies on the combination of aminocatalysis-mediated on-resin Ugi reactions and peptide couplings for the N-alkylation of peptides at selected sites, including the N-terminal double lipidation, the simultaneous lipidation/biotinylation, and the steroid/lipid conjugation via tetrazole ring formation. The solid-phase Ugi four-component reactions were enabled by on-resin transimination steps prior to addition of the acid and isocyanide components. The strategy proved to be suitable for the feasible incorporation of complex N-substituents at both termini and at internal positions, which is not easily achievable by other solid-phase methods.
authors.affiliation: †Center for Natural Products Research, Faculty of Chemistry, University of Havana, Zapata y G, 10400, La Habana, Cuba.|‡Synthetic Peptides Group, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, La Habana, Cuba.
authors.forename: Fidel E
authors.initials: FE
authors.lastname: Morales
authors.affiliation: ‡Synthetic Peptides Group, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, La Habana, Cuba.
authors.forename: Hilda E
authors.initials: HE
authors.lastname: Garay
authors.affiliation: †Center for Natural Products Research, Faculty of Chemistry, University of Havana, Zapata y G, 10400, La Habana, Cuba.
authors.forename: Daniela F
authors.initials: DF
authors.lastname: Muñoz
authors.affiliation: †Center for Natural Products Research, Faculty of Chemistry, University of Havana, Zapata y G, 10400, La Habana, Cuba.
authors.forename: Yarelys E
authors.initials: YE
authors.lastname: Augusto
authors.affiliation: §Center for Protein Studies, Faculty of Biology, University of Havana, La Habana, Cuba.
authors.forename: Anselmo J
authors.initials: AJ
authors.lastname: Otero-González
authors.affiliation: ‡Synthetic Peptides Group, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, La Habana, Cuba.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Reyes Acosta
authors.affiliation: †Center for Natural Products Research, Faculty of Chemistry, University of Havana, Zapata y G, 10400, La Habana, Cuba.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Rivera
mesh_terms: D000478:Alkylation; D055666:Lipopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D060327:Solid-Phase Synthesis Techniques; D013256:Steroids / Q000737:chemistry*; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D055666:Lipopeptides; D013256:Steroids; D013777:Tetrazoles