Iminium cyclization/azomethine ylid cycloaddition cascades for alkaloid syntheses - synthèse d'alcaloïdes par cyclisations d'iminiums/cycloaddition d'ylure d'axométhine en tandem

亚胺环化/偶氮甲亚胺YLID环加成级联合成生物碱在本研究方案中，我们打算开发两种通过级联环化反应构建天然产物的创新方法。在我们的一个项目中，我们正在双环化级联中使用亚胺离子。我们从设置第一个环化(Vilsmeier-Haack)开始，这是非常有挑战性的，最终产生了两个出版物(Org.让我们来吧。2005、7、4431和J.Org.化学。2006、71、704)。双环化的初步结果表明，该策略在模型系统上是有效的。因此，拟议的研究旨在确定双环化策略的范围和局限性，并利用这一新的合成策略构建天然产物，以显示其适用性。我们的第二个项目也利用了我们最近开发的Vilsmeier-Hack环化，但目标完全不同。事实上，Vilsmeier-Haack环化产物仍然是我们用来生成偶氮甲亚胺YLID的亚胺离子，与第一个项目中发现的第二次亚胺环化相比，它可能经历完全不同类型的环化(环加成)。这一策略(亚胺环化-甲亚胺叶立德环加成)现在提供了在一次操作中创建具有生物意义的生物碱的三环核心的可能性。我们正在推进这一项目，通过对起始化合物进行简单的调制，将该反应级联的范围扩大到各种不同的生物碱骨架。我们还打算将这一综合策略应用于天然产品的构建。

IMINIUM CYCLIZATIONS/AZOMETHINE YLID CYCLOADDITION CASCADES FOR ALKALOID SYNTHESESIn this research proposal, we intend to develop two innovative ways of constructing natural products through cyclization reactions in cascade. In one of our projects, we are using iminium ions in a double cyclization cascade. We started by setting the first cyclization (Vilsmeier-Haack), which was greatly challenging and ended up giving rise to two publications (Org. Lett. 2005, 7, 4431 and J. Org. Chem. 2006, 71, 704). Our preliminary results of double cyclization showed that the strategy works on a model systems. The proposed research is thus aimed at determining the scope and limitation of the double cyclization strategy and at constructing natural products with this new synthetic strategy to show its applicability. Our second project is also taking advantage of our recently developed Vilsmeier-Hack cyclization but toward a completely different end. In fact, the Vilsmeier-Haack cyclization product is still an iminium ion that we used to generate an azomethine ylid that could undergo a completely different type of cyclization (cycliaddition) compared to a second iminium cyclization as found in the first project presented. This strategy (iminium cyclization - azomethine ylid cycloaddition) now offers the possibility to create tricyclic cores of biologically interesting alkaloids in one operation. We are pursuing this project by expanding the scope of this reaction cascade to a wide range of different alkaloid skeletons by simple modulation on the starting compound. We also intend to apply this synthetic strategy to the construction of natural product as well.