Synthetic Studies of Dimeric Alkaloids which Control Neuronal Differentiation

石松碱类生物碱的二聚体生物碱，诱导1321 N1细胞分泌神经营养因子，其促进PC-12细胞的神经元分化并增强神经生长因子（NGF）的mRNA表达。由于其独特的结构和有趣的生物活性，我们开始了合成研究，以揭示其生物活性的起源。至此，我们建立了一条简便的合成（±）-番茄红素的Diels-Alder反应和分子内Mizoroki-Heck反应路线。这一策略将很容易地适用于相关天然产物的全合成，包括companantinase和合成类似物的构效关系研究。

Complanadines, dimeric alkaloids in the lycodine class alkaloids, induce secretion of neurotrophic factors from 1321N1 cells, which promotes neuronal differentiation of PC-12 cells and enhances expression of mRNA for nerve growing factor (NGF). Because of the unique structure and interesting biological activities, we started synthetic studies for disclose the origin of biological activities. So far, we established a convenient synthetic route to (±)-lycodine by using Diels-Alder and intramolecular Mizoroki-Heck reactions. This strategy will be readily applicable to the total syntheses of related natural products including complanadines and synthetic analogues for structure-activity relationship studies.