title: From amino acids to nature-inspired molecular scaffolds: incorporation of medium-sized bridged heterocycles into a peptide backbone.
abstract: Novel molecular scaffolds comprising two to four bridged and fused heterocycles were synthesized from amino acids using seven-membered endocyclic N-acyliminium ions as key intermediates in acid-mediated tandem reactions with internal nucleophiles. This complexity-generating synthesis proceeds with high efficiency and with full stereocontrol of the newly generated stereogenic center. These results have extended the scope of medium-sized cyclic iminium ion chemistry, making it applicable as a regio- and stereoselective synthetic strategy for the generation of complex polycyclic structures. Furthermore, its compatibility with the traditional Merrifield synthesis of peptides on solid supports allowed the incorporation of the previously unexplored conformationally restricted cyclic systems into peptides without a need to independently synthesize the scaffold.
authors.affiliation: Department of Organic Chemistry, Faculty of Science, Institute of Molecular and Translational Medicine, Palacky University , 17. Listopadu 12, 771 46 Olomouc, Czech Republic.
authors.forename: Agustina
authors.initials: A
authors.lastname: La-Venia
authors.forename: Pilar
authors.initials: P
authors.lastname: Ventosa-Andrés
authors.forename: Ludmila
authors.initials: L
authors.lastname: Hradilová
authors.forename: Viktor
authors.initials: V
authors.lastname: Krchňák
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D002384:Catalysis; D006572:Heterocyclic Compounds, Bridged-Ring / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000596:Amino Acids; D006572:Heterocyclic Compounds, Bridged-Ring; D010455:Peptides