Synthesis and antitumor activity of cis-dichloridoplatinum(II) complexes of 1,1'-biisoquinolines.

A simple approach to 1,1',2,2',3,3',4,4'-octahydro-1,1'-biisoquinolines is described. Reaction of phenethylamines with oxalyl chloride led to N,N'-bis(phenethyl) oxamides (1). Cyclization of oxamides by using Bischler-Napieralski conditions gave 3,3',4,4'-tetrahydro-1,1'-biisoquinoline (3) and unusual products 2, 4, 5. Reduction of 3,3',4,4'-tetrahydro-1,1'-biisoquinolines with sodium boron hydride gave both rac-1,1',2,2',3,3',4,4'-octahydro-1,1'-biisoquinolines (6) and meso-1,1',2,2',3,3',4,4' -octahydro-1,1'-biisoquinolines (7). Compound 6 was resolved to (1S, 1S') (8) and (1R, 1R') (9) furtherly. By treating all the biisoquinolines with K2PtCl4 afforded their cis-dichloridoplatinum (II) complexes (12-18). The antitumor activity of these complexes was evaluated.