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.

二聚生物碱科普兰定A（complanadine A）在再生科学领域展现出应用潜力，可通过诱导神经胶质细胞分泌生长因子以促进神经元生长。研究人员借助串联钴介导的[2+2+2]环加成反应，开发了两条成环顺序各异的合成路径，用于构建不对称联吡啶核心结构。两种吡啶环的区域选择性构建可依托分子自身的固有选择性实现，或通过添加路易斯碱逆转区域选择性来完成。该策略已成功应用，实现了科普兰定A及带有石松定母核（lycodine core）的结构相关化合物的实验室合成。