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.

Two-step one-pot synthesis of dihydropyrazinones as Xaa-Ser dipeptide isosteres through morpholine acetal rearrangement / Lenci, Elena; Innocenti, Riccardo; Menchi, Gloria; Faggi, Cristina; Trabocchi, Andrea. - In: ORGANIC & BIOMOLECULAR CHEMISTRY. - ISSN 1477-0520. - STAMPA. - 13(2015), pp. 7013-7019. [10.1039/C5OB00783F]

Two-step one-pot synthesis of dihydropyrazinones as Xaa-Ser dipeptide isosteres through morpholine acetal rearrangement

LENCI, ELENA;INNOCENTI, RICCARDO;MENCHI, GLORIA;FAGGI, CRISTINA;TRABOCCHI, ANDREA
2015

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.
13
7013
7019
Lenci, Elena; Innocenti, Riccardo; Menchi, Gloria; Faggi, Cristina; Trabocchi, Andrea
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2158/1008152
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