Atroposelective biaryl coupling with chiral catalysts: total synthesis of the antileishmanial naphthylisoquinoline alkaloids ancistrotanzanine B and ancistroealaine A.
[reaction: see text] The first total synthesis of the naphthylisoquinoline alkaloid ancistrotanzanine B and its atropo-diastereomer, ancistroealaine A, is described. The key step is the construction of the rotationally hindered and thus stereogenic biaryl axis by Suzuki coupling. While only weak internal asymmetric inductions by the stereogenic center in the dihydroisoquinoline part were observed, much better atropisomeric ratios in favor of ancistrotanzanine B were achieved by the use of chiral catalysts. Both alkaloids, in particular ancistrotanzanine B, show high antileishmanial activities.
Bringmann
Gerhard
G
Institut für Organische Chemie, Universität Würzburg, Am Hubland, 97074 Würzburg, Germany. brigman@chemie.uni-wuerzburg.de
Hamm
Andreas
A
Schraut
Michaela
M