Total synthesis of the N,C-coupled naphthylisoquinoline alkaloids ancistrocladinium A and B and related analogues.
The N,C-coupled naphthyldihydroisoquinoline alkaloids ancistrocladinium A (3) and B (4), which possess an unprecedented iminium-aryl axis and show high in vitro antileishmanial activities, have been synthesized via a short sequence of eight linear steps, without the need of protecting groups. Key steps were a Buchwald-Hartwig amination and a Bischler-Napieralski cyclization, preferentially leading to the naturally predominant M-atropo-diastereomer in the case of 3, while the N,C-axis is configurationally semistable in 4. The highly convergent first access to this type of alkaloids will now facilitate the preparation of structural analogues for structure-activity relationship studies. Its general applicability was shown by the preparation of the sterically even more congested, as yet unnatural N,3'- and N,1'-coupled analogues, ancistrocladinium C (5) and D (6).
Bringmann
Gerhard
G
Institute of Organic Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany. bringman@chemie.uni-wuerzburg.de
Gulder
Tanja
T
Hertlein
Barbara
B
Hemberger
Yasmin
Y
Meyer
Frank
F
D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D013237:Stereoisomerism
D007546:Isoquinolines; C522869:ancistrocladinium A; C522870:ancistrocladinium B