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 |
| |
Authors: | Miyazaki Anna Fujisawa Yutaka Shiotani Kimitaka Fujita Yoshio Li Tingyou Tsuda Yuko Yokoi Toshio Bryant Sharon D Lazarus Lawrence H Okada Yoshio |
| |
Institution: | Faculty of Pharmaceutical Sciences, Kobe Gakuin University; Nishi-ku, Kobe 651-2180, Japan. |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|