Synthesis of tetracyclic dioxygenated isoquinolines and their cytotoxic activity

An efficient synthesis of new dioxygenated isoquinolines is reported. The novelty of this approach derives from its use of tricyclic-nitril (3) as a building block in a synthetic sequence of seven steps for the preparation of the tetracyclic isoquinoline (14) and its derivatives. The isoquinoline 16 was 10-fold more active against leukemia L1210 than the corresponding tetrahydroisoquinoline 14.