First atropo-divergent total synthesis of the antimalarial korupensamines A and B by the lactone method

The stereoselective total synthesis of the antimalarial korupensamines A (la) and B (Ib) by application of the lactone method is described. Key steps of this first atropo-selective access to 5,8'-coupled naphthylisoquinoline alkaloids were the regioselective intramolecular coupling of ester 8 to give the configurationally labile lactone-bridged biaryl 9 and its atropisomer-selective cleavage with a variety of chiral and achiral H-nucleophiles, yielding the configurationally stable P-diol 10a or, optionally, the M-product 10b. From the axially chiral phenylisoquinolines thus obtained atropo-diastereodivergently, the authentic natural naphthylisoquinolines with the respective axial configurations, korupensamines A (la) and B (Ib), were obtained by completion of the second naphthalene ring, starting from the previous bridgehead C-1 unit.