title: Studies on the mechanism of 1,2-dihydropyrazin-2-one ring formation from dipeptidyl chloromethyl ketone and its chemical properties: immediate deamination during catalytic hydrogenation.
abstract: 1,2-Dihydropyrazin-2-one derivatives, which have two aminoalkyl groups at the positions 3 and 6, were found to be efficient tools for the construction of potent, selective and long-acting opioid mimetics. During the course of preparation, we found that the catalytic hydrogenation of 3,6-bis(benzyloxycarbonylaminomethyl)-5-methyl-1,2-dihydropyrazin-2-one to remove the benzyloxycarbonyl groups resulted in a side reaction. By MS and NMR studies and by preparation of additional 1,2-dihydropyrazin-2-one derivatives, the structure of the by-product was identified as 3-aminomethyl-5,6-dimethyl-1,2-dihydropyrazin-2-one. Preparation of additional compounds substituted with deuterium provided us with sufficient information to confirm the structure of the product and to support a cyclization mechanism in its formation.
authors.affiliation: Faculty of Pharmaceutical Sciences, Kobe Gakuin University; Nishi-ku, Kobe 651-2180, Japan.
authors.forename: Anna
authors.initials: A
authors.lastname: Miyazaki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Fujisawa
authors.forename: Kimitaka
authors.initials: K
authors.lastname: Shiotani
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujita
authors.forename: Tingyou
authors.initials: T
authors.lastname: Li
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tsuda
authors.forename: Toshio
authors.initials: T
authors.lastname: Yokoi
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Bryant
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Lazarus
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Okada
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000737:chemistry*; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D003500:Cyclization; D003641:Deamination; D003903:Deuterium; D006865:Hydrogenation; D007202:Indicators and Reagents; D011719:Pyrazines / Q000737:chemistry*; D012997:Solvents; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: C505016:1,2-dihydropyrazin-2-one; D000590:Amino Acid Chloromethyl Ketones; D007202:Indicators and Reagents; D011719:Pyrazines; D012997:Solvents; D003903:Deuterium