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 (1a) and B (1b) 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 (1a) and B (1b), were obtained by completion of the second naphthalene ring, starting from the previous "bridgehead" C1 unit.
Bringmann
G
G
Institut für Organische Chemie, Universität Würzburg, Germany. bringman@chemie.uni-wuerzburg.de
Ochse
M
M
Götz
R
R
D000962:Antimalarials / Q000138:chemical synthesis*; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D007546:Isoquinolines / Q000138:chemical synthesis*; D007783:Lactones / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D009281:Naphthalenes / Q000138:chemical synthesis*; D010165:Palladium; D010946:Plants, Medicinal / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D000962:Antimalarials; D007546:Isoquinolines; D007783:Lactones; D009281:Naphthalenes; C110657:korupensamine A; D010165:Palladium