ALKALOID SYNTHESIS VIA 2-AZAALLYL ANION CYCLOADDITIONS

本文提出的研究的主要目标是开发 一种新的和一般的合成方案，用于制备各种 药用重要生物碱及其他含氮天然 产品. 一个统一的战略，综合各种各样的这些 材料将是有吸引力的，而不是更传统的方法 针对每个目标采取不同的策略 目标子结构，a 在2-和3-位与另一个环稠合的吡咯烷是广泛存在的 在自然界中。 为了制备该亚基， 2-提出了氮杂烯丙基阴离子到烯烃上。 这种方法的灵活性将通过合成来证明 生物医学上重要的含氮化合物，如石斛碱， Scandine，石蒜碱和其他，包括一些血管紧张素转换 酶抑制剂 一个共同的目标是调查了解甚少的化学 2-氮杂烯丙基阴离子本身。 模型工作表明， 这些物种的分子内环加成是可行的，但许多工作 关于它们的产生和范围，立体化学， 必须解决环加成的区域化学。 内 天然产物合成的框架，这些未开发的领域， 这些迷人的中间体的化学将得到解决。

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.