Synthesis of pindikamine A, a michellamine-related dimer of a non-natural, 'skew' naphthylisoquinoline

Article abstract of DOI:10.1016/0040-4020(96)00813-7

The synthesis of an unnatural dimeric naphthylisoquinoline, pindikamine A (3), as a 'skew' analog of antiviral michellamines, is described. Because of the unusual coupling positions, this C₂-symmetric quateraryl is the first michellamine analog without axial chirality. Key steps of total synthesis are the preparation of the molecular precursor 9 by intermolecular biaryl coupling, followed by a highly efficient oxidative 'dimerization' to give 8, which is transformed to 3. Pindikamine A (3) and its monomeric 'half' 10 show good antimalarial activity against plasmodium falciparum in vitro.