Synthesis of 1, 2, 3, 4-Tetrahydro-[beta]-carboline Derivatives as Hepatoprotective Agents. I. Dithiocarbamates of Several [alpha]-Amino Acids

A series of dithiocarbamates of α-amino acids was synthesized and tested for hepatoprotective activity against CCl4-induced liver damage in mice. Reaction of the amino acids (2, 4, 6 and 8) with carbon disulfide followed by methylation gave the corresponding dithiocarbamates. Among the compounds synthesized, the β-carboline derivative (9a) exhibited remarkable hepatoprotective activity. The oxa analogues (9b-d) with respect to the dithiocarbamate group of 9a were also prepared. The activity of 9a-d decreased in the following order : dithiocarbamate (9a) > S-methyl thiocarbamate (9b) > O-methyl thiocarbamate (9c) > carbamate (9d). The structure-activity relationships are discussed.