Synthesis of 3-Amino-5H-pyridoindoles, Carcinogenic γ-Carbolines

Article abstract of DOI:10.1246/bcsj.58.123

The carcinogenic γ-carbolines 3-amino-1,4-dimethyl-5H-pyrido<4,3-b>indole (1) and 3-amino-1-methyl-5H-pyrido<4,3-b>indole (2) were synthesized efficiently by the following procedures.The key method involved the acid-catalyzed cyclization of 2-acetamido-3-(2-indolyl)alkanoic acids to 1,2-dihydro-γ-carbolines.This was followed by dehydrogenation to the γ-carbolinecarboxylates and conversion of the ester group to the carboxyl and finally to the amino one by Curtius rearrangement.Alternative methods involved the thermolysis of 4-(1-benzotriazolyl)-3,6-dimethyl-2-pyridinamine to synthesize 1 and the condensation of 3-acetylindole-2-acetonitrile with ammonia to synthesize 2.The structures of γ-carbolines 1 and 2 were unambiguously established by comparing samples of each synthesized by the two different routes.A selective and one-step synthesis of ethyl 2-acetamido-3-(2-indolyl)alkanoates was newly exploited starting from diethyl acetamidomalonate and quaternary ammonium salts of 2-<1-(dimethylamino)alkyl>indoles.