ALKALOID SYNTHESIS VIA 2-AZAALLYL ANION CYCLOADDITIONS

在此提出的研究的主要目标是发展 一种新的、通用的合成方案，用于制备各种 重要的药用生物碱和其他含氮天然化合物 产品。一种统一的战略，用于综合各种不同的 材料将是有吸引力的，而不是更传统的方法 对每个目标采取不同的策略。目标子结构，一个 吡咯烷在2位和3位与另一个环融合在一起，这种现象很普遍 在自然界中。为了制备这个亚基，一个分子内的环加成反应 提出了2-氮杂烯丙基阴离子在烯烃上的合成方法。 这种方法的灵活性将通过综合得到证明。 生物医学上重要的含氮化合物，如树突碱， 雪花碱、石蒜碱和其他药物，包括一些血管紧张素转换 酶抑制剂。 同时的一个目标是对鲜为人知的化学进行研究。 2-氮烯丙基阴离子本身。模型工作表明， 这些物种的分子内环加成是可行的，但工作量很大 关于它们的产生和范围，立体化学，以及 必须解决环加成反应的区域化学问题。在 天然产物合成的框架，这些未开发的领域 这些令人着迷的中间体的化学将被讨论。

The principal objective of the research proposed herein is the development of a new and general synthetic protocol for the preparation of a variety of medicinally important alkaloids and other nitrogen-containing natural products. A unified strategy for the synthesis of a diverse array of these materials would be attractive, as opposed to the more traditional approach involving a different strategy for each target. The target substructure, a pyrrolidine fused to another ring at the 2- and 3-positions, is widespread in nature. To prepare this subunit, the intramolecular cycloaddition of a 2-azaallyl anion onto an olefin is proposed. The flexibility of this method will be demonstrated through the synthesis of biomedically important nitrogen-containing compounds such as dendrobine, scandine, lycorine, and others, including some angiotension converting enzyme inhibitors. A concurrent goal is the investigation of the poorly understood chemistry of 2-azaallyl anions themselves. Model work has shown that the intramolecular cycloadditions of these species are feasible, but much work regarding their generation and the scope, stereochemistry, and regiochemistry of the cycloadditions must be addressed. Within the framework of natural products synthesis, these unexplored areas in the chemistry of these fascinating intermediates will be addressed.