Syntheses of (+)-Complanadine A and Lycodine Derivatives by Regioselective [2 + 2 + 2] Cycloadditions

The
dimeric alkaloid complanadine A has shown promise in regenerative
science, promoting neuronal growth by inducing the secretion of growth
factors from glial cells. Through the use of tandem, cobalt-mediated
[2 + 2 + 2] cycloaddition reactions, two synthetic routes have been
developed with different sequences for the formation of the unsymmetric
bipyridyl core. The regioselective formation of each of the pyridines
was achieved based on the inherent selectivity of the molecules or
by reversing the regioselectivity through the addition of Lewis bases.
This strategy has been successfully employed to provide laboratory
access to complanadine A as well as structurally related compounds
possessing the lycodine core.