Quaternary α,α-2-Oxoazepane α-Amino Acids: Synthesis from Ornithine-Derived β-Lactams and Incorporation into Model Dipeptides

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)-derive...

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Veröffentlicht in:Journal of organic chemistry 2011-08, Vol.76 (16), p.6592-6603
Hauptverfasser: Núñez-Villanueva, Diego, Bonache, M. Ángeles, Infantes, Lourdes, García-López, M. Teresa, Martín-Martínez, Mercedes, González-Muñiz, Rosario
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Sprache:eng
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Zusammenfassung: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 NH2 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.
ISSN:0022-3263
1520-6904
DOI:10.1021/jo200894d