New Synthesis of Benzo-δ-carbolines, Cryptolepines, and Their Salts: In vitro Cytotoxic, Antiplasmodial, and Antitrypanosomal Activities of δ-Carbolines, Benzo-δ-carbolines, and Cryptolepines.

The paper describes, in its first part, a new synthesis of benzo-δ-carbolines, cryptolepines, and their salts. The strategy is based on the association between halogen-dance and hetero-ring cross-coupling. It is fully convergent and regioselective with interesting overall yields from 27% to 70%. A halogen-dance mechanism in quinoline series is also proposed. The formal synthesis of potential antimalarial compounds and the first total synthesis of 11-isopropylcryptolepine are also described. In the second part, cytotoxic activity against mammalian cells and activities against Plasmodium falciparum and Trypanosoma cruzi of benzo-δ-carbolines and δ-carbolines were evaluated in vitro to study the structure−activity relationships. For benzo-δ-carbolines, methylation at N-5 increases the cytotoxic and antiparasitic activities. A further alkylation on C-11 generally increases the cytotoxic activity but not the antiparasitic activity, cryptolepine and 11-methylcryptolepine being the most active on both parasites....