Directed joint total synthesis of the three naphthylisoquinoline alkaloids dioncolactone A, dioncopeltine A, and 5′-O-demethyldioncophylline A

The first total synthesis of the three antimalarial naphthylisoquinoline alkaloids dioncolactone A (4), dioncopeltine A (5), and 5'-O-demethyldioncophylline A (6) is described. The regio- and stereoselective construction of the biaryl axes was achieved through the 'lactone methodology', by ester-type prefixation of the two molecular moieties, intramolecular coupling, and atropo-diastereoselective cleavage of the lactone auxiliary bridge. As a novel alternative, the configuration at the axis may be installed by atroposelective hydroxy aldehyde reduction through dynamic kinetic resolution. (C) 1998 Elsevier Science Ltd. All rights reserved.