Studies on Hepatic Agents. I. Synthesis of Aminoacyl (and Hydroxyacyl) Aminoacetonitriles

For the purpose of elucidating the structural relationship between lathyrism and inhibition of necrosis induced by CCl4 in the liver of the rat, many compounds related to aminoacetonitrile were synthesized. N-Aminoacylaminoacetonitriles (VIII, XIV) were synthesized from phthaloylaminoacylaminoacetonitriles. VIII were converted to 2-hydroxyimino-5-oxopiperazine derivatives (XV) and 5-oxo-2-thio-piperazines (XX). Preparations of N-(N-acylaminoacyl) aminoacetonitriles were also described. Further, N-α-hydroxyacylaminoacetonitriles were prepared from chloralides of α-hydroxyacids with aminoacetonitrile. In addition, XV (R=H) was converted to 2-acetamino-5-acetoxypyrazine by treatment with acetic anhydride.