title: Regioselective incorporation of backbone constraints compatible with traditional solid-phase peptide synthesis.
abstract: A protected aldehyde was attached via a two-carbon spacer to a peptide backbone amide nitrogen during a traditional Merrifield solid-phase synthesis. Acid-mediated unmasking of the aldehyde triggered the regioselective formation of cyclic N-acyliminiums between the aldehyde and the neighboring peptide amide nitrogen. In the absence of an internal nucleophile, the cyclic iminiums formed dihydropyrazinones, a six-membered peptide backbone constraint between two peptide amides. In the presence of an internal nucleophile, tetrahydropyrazinopyrimidinediones or tetrahydroimidazopyrazinediones were formed via tandem N-acyliminium ion cyclization-nucleophilic addition. The outcome of this nucleophilic addition was dependent on the substituent on the nitrogen nucleophile.
authors.affiliation: Department of Organic Chemistry, Faculty of Science, Institute of Molecular and Translational Medicine, Palacky University , 771 46 Olomouc, Czech Republic.
authors.forename: Agustina
authors.initials: A
authors.lastname: La Venia
authors.forename: Barbora
authors.initials: B
authors.lastname: Lemrová
authors.forename: Viktor
authors.initials: V
authors.lastname: Krchňák
mesh_terms: D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D003500:Cyclization; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D060327:Solid-Phase Synthesis Techniques / Q000379:methods*; D013237:Stereoisomerism
chemical_list: D010455:Peptides