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.
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.
Miyazaki
Anna
A
Faculty of Pharmaceutical Sciences, Kobe Gakuin University; Nishi-ku, Kobe 651-2180, Japan.
Fujisawa
Yutaka
Y
Shiotani
Kimitaka
K
Fujita
Yoshio
Y
Li
Tingyou
T
Tsuda
Yuko
Y
Yokoi
Toshio
T
Bryant
Sharon D
SD
Lazarus
Lawrence H
LH
Okada
Yoshio
Y
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
C505016:1,2-dihydropyrazin-2-one; D000590:Amino Acid Chloromethyl Ketones; D007202:Indicators and Reagents; D011719:Pyrazines; D012997:Solvents; D003903:Deuterium