title: Quaternary α,α-2-oxoazepane α-amino acids: synthesis from ornithine-derived β-lactams and incorporation into model dipeptides.
abstract: To explore further the chemistry of amino acid-derived β-lactams, their conversion to α,α-heterocyclic quaternary amino acid derivatives is investigated. The latter derivatives, containing 2-oxoazepane as the α,α-substituent, are synthesized by a simple Pd-C-catalyzed hydrogenolysis of Orn(Z)-derived 2-azetidinones. The rearrangement from four- to seven-membered lactam ring is driven by the key intramolecular opening of the 1-Boc-β-lactam, initiated by 7-exotrig ring closure from the NH(2) of the Orn side chain. The synthetic route is applied to the stereoselective preparation of enantiomerically pure 4-amino-3-methyl-2-oxoazepane-4-carboxylate derivatives, for which the structure and configuration is confirmed by X-ray diffraction. Molecular modeling and NMR experiments indicate that these quaternary amino acids are able to drive the adoption of β-turn secondary structures when incorporated in model dipeptide derivatives.
authors: Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
authors: Diego
authors: D
authors: Núñez-Villanueva
authors: M Ángeles
authors: MÁ
authors: Bonache
authors: Lourdes
authors: L
authors: Infantes
authors: M Teresa
authors: MT
authors: García-López
authors: Mercedes
authors: M
authors: Martín-Martínez
authors: Rosario
authors: R
authors: González-Muñiz
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry*; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D004151:Dipeptides / Q000737:chemistry*; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry*; D009952:Ornithine / Q000737:chemistry*; D010077:Oxazepines / Q000737:chemistry*; D014961:X-Ray Diffraction; D047090:beta-Lactams / Q000737:chemistry*
chemical_list: C568371:4-amino-3-methyl-2-oxoazepane-4-carboxylate; D000596:Amino Acids; D001381:Azepines; D002264:Carboxylic Acids; D004151:Dipeptides; D009842:Oligopeptides; D010077:Oxazepines; D047090:beta-Lactams; D009952:Ornithine