title: Two-step one-pot synthesis of dihydropyrazinones as Xaa-Ser dipeptide isosteres through morpholine acetal rearrangement.
abstract: The synthesis of the uncommon dihydropyrazinone ring was accomplished by a two-step one pot process taking advantage of the ring rearrangement of N-acylated morpholine acetal derived from serine under acidic treatment in the presence of 2,6-lutidine. The mechanism involves an N-acyl iminium intermediate resulting from morpholine acetal ring opening, which occurs after a nucleophilic attack of the amino acid nitrogen atom to the acetal carbonyl atom. X-Ray diffraction analysis of the dihydropyrazinone, which may be exploited as a constrained Xaa-Ser dipeptide isostere, showed a planar assembly and the internal side-chain in axial orientation with respect to the cyclic molecular scaffold.
authors.affiliation: Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 13, 50019, Sesto Fiorentino, Florence, Italy. andrea.trabocchi@unifi.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Lenci
authors.forename: Riccardo
authors.initials: R
authors.lastname: Innocenti
authors.forename: Gloria
authors.initials: G
authors.lastname: Menchi
authors.forename: Cristina
authors.initials: C
authors.lastname: Faggi
authors.forename: Andrea
authors.initials: A
authors.lastname: Trabocchi
mesh_terms: D000080:Acetals / Q000138:chemical synthesis / Q000737:chemistry*; D000215:Acylation; D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry*; D008958:Models, Molecular; D009025:Morpholines / Q000138:chemical synthesis / Q000737:chemistry*; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry; D012694:Serine / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D000080:Acetals; D004151:Dipeptides; D009025:Morpholines; D011719:Pyrazines; D011725:Pyridines; C013093:2,6-lutidine; D012694:Serine; C037574:morpholine